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Does Breast or Ovarian Cancer Run in Your Family?

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... Does Breast or Ovarian Cancer Run in Your Family? Recommend on Facebook Tweet Share Compartir If you ... get ovarian cancer by age 70. Does Your Family Health History Put You At Risk? Collect your ...
Penetrance of breast cancer, ovarian cancer and contralateral breast cancer in BRCA1 and BRCA2 families : high cancer incidence at older age

NARCIS (Netherlands)

van der Kolk, Dorina M.; de Bock, Geertruida H.; Leegte, Beike K.; Schaapveld, Michael; Mourits, Marian J. E.; de Vries, J; van der Hout, Annemieke H.; Oosterwijk, Jan C.

Accurate estimations of lifetime risks of breast and ovarian cancer are crucial for counselling women from BRCA1/2 families. We therefore determined breast and ovarian cancer penetrance in BRCA1/2 mutation families in the northern Netherlands and compared them with the incidence of cancers in the
Population prevalence of first- and second-degree family history of breast and ovarian cancer.

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Moghimi-Dehkordi, B; Safaee, A; Vahedi, M; Pourhoseingholi, M A; Pourhoseingholi, A; Zali, M R

2011-12-01

Family cancer history is an important risk factor for common cancers, thus, recognizing pattern of familial cancer can help us to identify individuals who may have higher chance to develop specified cancers. This cross-sectional survey assessed family history of cancer in first- and second degree relatives. Totally, 7,300 persons aged > or = 20 years selected by random sampling from Tehran general population. Age- and sex-specified prevalence of breast and ovarian cancer in respondent's family was calculated. Of all, 279(4.3%) individuals reported a history of breast or ovarian cancer in their relatives. The prevalence of breast cancer family history was 1.8% among first-degree relatives and 2.5% among second- degree relatives. For ovarian cancer, first- and second-degree prevalence ranged from 0.05 to 0.12%. Those with family history of cancer were more often young and female. Overall, the estimates of prevalence presented here are likely to be conservative compared with actual current prevalence because of some limitations. While family history is an important risk factor for common cancers such as breast cancer, recognizing pattern of familial cancer that signify increased risk can help us to identify individuals who may have higher chance to develop specified cancers.
Analysis of PALB2 gene in BRCA1/BRCA2 negative Spanish hereditary breast/ovarian cancer families with pancreatic cancer cases.

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Ana Blanco

Full Text Available BACKGROUND: The PALB2 gene, also known as FANCN, forms a bond and co-localizes with BRCA2 in DNA repair. Germline mutations in PALB2 have been identified in approximately 1% of familial breast cancer and 3-4% of familial pancreatic cancer. The goal of this study was to determine the prevalence of PALB2 mutations in a population of BRCA1/BRCA2 negative breast cancer patients selected from either a personal or family history of pancreatic cancer. METHODS: 132 non-BRCA1/BRCA2 breast/ovarian cancer families with at least one pancreatic cancer case were included in the study. PALB2 mutational analysis was performed by direct sequencing of all coding exons and intron/exon boundaries, as well as multiplex ligation-dependent probe amplification. RESULTS: Two PALB2 truncating mutations, the c.1653T>A (p.Tyr551Stop previously reported, and c.3362del (p.Gly1121ValfsX3 which is a novel frameshift mutation, were identified. Moreover, several PALB2 variants were detected; some of them were predicted as pathological by bioinformatic analysis. Considering truncating mutations, the prevalence rate of our population of BRCA1/2-negative breast cancer patients with pancreatic cancer is 1.5%. CONCLUSIONS: The prevalence rate of PALB2 mutations in non-BRCA1/BRCA2 breast/ovarian cancer families, selected from either a personal or family pancreatic cancer history, is similar to that previously described for unselected breast/ovarian cancer families. Future research directed towards identifying other gene(s involved in the development of breast/pancreatic cancer families is required.
RAD51C germline mutations in breast and ovarian cancer cases from high-risk families.

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Jessica Clague

Full Text Available BRCA1 and BRCA2 are the most well-known breast cancer susceptibility genes. Additional genes involved in DNA repair have been identified as predisposing to breast cancer. One such gene, RAD51C, is essential for homologous recombination repair. Several likely pathogenic RAD51C mutations have been identified in BRCA1- and BRCA2-negative breast and ovarian cancer families. We performed complete sequencing of RAD51C in germline DNA of 286 female breast and/or ovarian cancer cases with a family history of breast and ovarian cancers, who had previously tested negative for mutations in BRCA1 and BRCA2. We screened 133 breast cancer cases, 119 ovarian cancer cases, and 34 with both breast and ovarian cancers. Fifteen DNA sequence variants were identified; including four intronic, one 5' UTR, one promoter, three synonymous, and six non-synonymous variants. None were truncating. The in-silico SIFT and Polyphen programs were used to predict possible pathogenicity of the six non-synonomous variants based on sequence conservation. G153D and T287A were predicted to be likely pathogenic. Two additional variants, A126T and R214C alter amino acids in important domains of the protein such that they could be pathogenic. Two-hybrid screening and immunoblot analyses were performed to assess the functionality of these four non-synonomous variants in yeast. The RAD51C-G153D protein displayed no detectable interaction with either XRCC3 or RAD51B, and RAD51C-R214C displayed significantly decreased interaction with both XRCC3 and RAD51B (p<0.001. Immunoblots of RAD51C-Gal4 activation domain fusion peptides showed protein levels of RAD51C-G153D and RAD51C-R214C that were 50% and 60% of the wild-type, respectively. Based on these data, the RAD51C-G153D variant is likely to be pathogenic, while the RAD51C- R214C variant is hypomorphic of uncertain pathogenicity. These results provide further support that RAD51C is a rare breast and ovarian cancer susceptibility gene.
Analysis of large deletions in BRCA1, BRCA2 and PALB2 genes in Finnish breast and ovarian cancer families

International Nuclear Information System (INIS)

Pylkäs, Katri; Erkko, Hannele; Nikkilä, Jenni; Sólyom, Szilvia; Winqvist, Robert

2008-01-01

BRCA1 and BRCA2 are the two most important genes associated with familial breast and ovarian cancer susceptibility. In addition, PALB2 has recently been identified as a breast cancer susceptibility gene in several populations. Here we have evaluated whether large genomic rearrangement in these genes could explain some of Finnish breast and/or ovarian cancer families. Altogether 61 index patients of Northern Finnish breast and/or ovarian cancer families were analyzed by Multiplex ligation-dependent probe amplification (MLPA) method in order to identify exon deletions and duplications in BRCA1, BRCA2 and PALB2. The families have been comprehensively screened for germline mutation in these genes by conventional methods of mutation analysis and were found negative. We identified one large deletion in BRCA1, deleting the most part of the gene (exon 1A-13) in one family with family history of ovarian cancer. No large genomic rearrangements were identified in either BRCA2 or PALB2. In Finland, women eligible for BRCA1 or BRCA2 mutation screening, when found negative, could benefit from screening for large genomic rearrangements at least in BRCA1. On the contrary, the genomic rearrangements in PALB2 seem not to contribute to the hereditary breast cancer susceptibility
Adherence to the breast cancer surveillance program for women at risk for familial breast and ovarian cancer versus overscreening: a monocenter study in Germany.

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Vetter, Lisa; Keller, Monika; Bruckner, Thomas; Golatta, Michael; Eismann, Sabine; Evers, Christina; Dikow, Nicola; Sohn, Christof; Heil, Jörg; Schott, Sarah

2016-04-01

Breast cancer (BC) is the leading cancer among women worldwide and in 5-10 % of cases is of hereditary origin, mainly due to BRCA1/2 mutations. Therefore, the German Consortium for Familial Breast and Ovarian Cancer (HBOC) with its 15 specialized academic centers offers families at high risk for familial/hereditary cancer a multimodal breast cancer surveillance program (MBCS) with regular breast MRI, mammography, ultrasound, and palpation. So far, we know a lot about the psychological effects of genetic testing, but we know little about risk-correlated adherence to MBCS or prophylactic surgery over time. The aim of this study was to investigate counselees' adherence to recommendations for MBCS in order to adjust the care supply and define predictors for incompliance. All counselees, who attended HBOC consultation at the University Hospital Heidelberg between July 01, 2009 and July 01, 2011 were eligible to participate. A tripartite questionnaire containing sociodemographic information, psychological parameters, behavioral questions, and medical data collection from the German consortium were used. A high participation rate was achieved among the study population, with 72 % returning the questionnaire. This study showed a rate of 59 % of full-adherers to the MBCS. Significant predictors for partial or full adherence were having children (p = 0.0221), younger daughters (p = 0.01795), a higher awareness of the topic HBOC (p = 0.01795, p breast cancer risk (p breast cancer surveillance program for women at risk for familial breast and ovarian cancer versus overscreening-a monocenter study in Germany.
Hereditary association between testicular cancer and familial ovarian cancer: A Familial Ovarian Cancer Registry study.

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Etter, John Lewis; Eng, Kevin; Cannioto, Rikki; Kaur, Jasmine; Almohanna, Hani; Alqassim, Emad; Szender, J Brian; Joseph, Janine M; Lele, Shashikant; Odunsi, Kunle; Moysich, Kirsten B

2018-04-01

Although family history of testicular cancer is well-established as a risk factor for testicular cancer, it is unknown whether family history of ovarian cancer is associated with risk of testicular cancer. Using data from the Familial Ovarian Cancer Registry on 2636 families with multiple cases of ovarian cancer, we systematically compared relative frequencies of ovarian cancer among relatives of men with testicular and non-testicular cancers. Thirty-one families with cases of both ovarian and testicular cancer were identified. We observed that, among men with cancer, those with testicular cancer were more likely to have a mother with ovarian cancer than those with non-testicular cancers (OR = 3.32, p = 0.004). Zero paternal grandmothers of men with testicular cancer had ovarian cancer. These observations provide compelling preliminary evidence for a familial association between ovarian and testicular cancers Future studies should be designed to further investigate this association and evaluate X-linkage. Copyright © 2018 Elsevier Ltd. All rights reserved.
Is there a genetic anticipation in breast and/or ovarian cancer families with the germline c.3481_3491del11 mutation?

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El Tannouri, R; Albuisson, E; Jonveaux, P; Luporsi, E

2018-01-01

The aim of the current analysis is to evaluate any differences of breast or ovarian cancer age at diagnosis between mothers and daughters carrying the c.3481_3491del11 mutation in the BRCA1 gene. A study cohort of 38 women carrying the c.3481_3491del11 mutation and affected by first breast or ovarian cancer who reported a first breast or ovarian cancer in their mother carrying the c.3481_3491del11 mutation, was identified in 37 different families including members with breast and/or ovarian cancer at the Oncology Institute of Lorraine. Twelve mothers underwent genetic testing. Twenty-five pairs of the 38 mothers-daughters pairs with c.3481_3491del11 mutation were affected by breast cancer and 13 pairs by ovarian cancer. Clinical and genetic data were collected from medical files and family pedigrees. Analyses were conducted for each cancer type. We investigated an early breast cancer detection effect due to early screening programs and also an increased breast tumor aggression. Since major improvements in breast cancer clinical management and imaging techniques appeared after 1980, we compared the age at breast cancer diagnosis and the age at death in mothers and daughters before and after 1980, first, in the group of women including mothers and daughters taken together and then in mothers and daughters separately. The mean age at breast cancer diagnosis was 45.28 ± 10.27 years in mothers and 39.80 ± 7.79 years in daughters (p = 0.026). The difference of age at ovarian cancer diagnosis in mother-daughter pairs was 8.62 ± 12.76 years (p = 0.032). When considering the group of women including mothers and daughters taken together, no significant difference of age at breast cancer diagnosis was found between women affected before 1980 and those affected after 1980 (p = 0.577). However, the age at death increased in these women after 1980 (p = 0.026). Comparison of age at breast cancer diagnosis in mothers and daughters separately
Sisters in hereditary breast and ovarian cancer families: communal coping, social integration, and psychological well-being.

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Koehly, Laura M; Peters, June A; Kuhn, Natalia; Hoskins, Lindsey; Letocha, Anne; Kenen, Regina; Loud, Jennifer; Greene, Mark H

2008-08-01

We investigated the association between psychological distress and indices of social integration and communal coping among sisters from hereditary breast and ovarian cancer (HBOC) families. Sixty-five sisters from 31 HBOC families completed the Brief Symptom Inventory-18 and the Colored Eco-Genetic Relationship Map, which identified members of participants' social support networks. Hierarchical linear models were used for all analyses to account for the clustering of sisters within families. Intra-family correlation coefficients suggested that sisters shared perceptions of breast cancer risk and worry, but not ovarian cancer risk and worry. Further, sisters demonstrated shared levels of anxiety and somatization, but not depressive symptoms. Communal coping indices quantifying shared support resources were negatively related to anxiety and somatization. The number of persons with whom cancer risk information was shared exhibited a positive trend with somatization. Social integration, as measured by the size of participants' emotional support network, was negatively associated with anxiety. Lower depression scores were observed among participants with more persons playing multiple support roles and fewer persons providing tangible assistance. Understanding how support relationships impact well-being among persons adjusting to HBOC risk, and the particular role of family in that process, will facilitate developing appropriate management approaches to help cancer-prone families adjust to their cancer risk.
Familial breast cancer: what the radiologist needs to know

International Nuclear Information System (INIS)

Kuhl, C.K.

2006-01-01

About 10% of breast cancers are ''hereditary'', i.e. caused by a pathogenic mutation in one of the ''breast and ovarian cancer susceptibility genes'' (BRCA). The BRCA genes 1 and 2 identified to date follow an autosomal dominant inheritance pattern. A clustering of breast cancer in a family without a documented mutation and without a recognizable inheritance pattern is usually referred to as ''familial cancer''. A distinction between hereditary and familial is difficult in the individual case because not all of the genetic mutations that cause breast cancer susceptibility are known and thus amenable to genetic testing. Women who are suspected of or documented as carrying a breast cancer susceptibility gene face a substantially increased lifetime risk of breast (and ovarian) cancer ranging from 60-80% for breast and up to 40% for ovarian cancer. In addition, the disease develops at a young age (the personal risk starts increasing at age 25; average age of diagnosis is 40). BRCA-associated breast cancers tend to exhibit histologic and histochemical evidence of aggressive biologic behavior (usually grade 3, receptor negative) with very fast growth rates. In particular BRCA1-associated breast cancer may be indistinguishable from fibroadenomas: They appear as well-defined, roundish, hypoechoic masses with smooth borders, without posterior acoustic shadowing on ultrasound, without associated microcalcifications on mammography, and with strong wash-out phenomenon on breast MRI. This article reviews the different options that exist for the prevention of familial or hereditary breast cancer and the specific difficulties that are associated with the radiological diagnosis of these cancers. Lastly, an overview is given of the current evidence regarding the effectiveness of the different imaging modalities for early diagnosis of familial and hereditary breast cancer. (orig.)
Family stories and the use of heuristics: women from suspected hereditary breast and ovarian cancer (HBOC) families.

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Kenen, Regina; Ardern-Jones, Audrey; Eeles, Rosalind

2003-11-01

The practice of medicine will increasingly be medicine of the family rather than the traditional physician/patient dyad, especially where a genetic condition is involved. This study explores how clients from suspected hereditary breast and ovarian cancer (HBOC) families seeking cancer genetics risk counselling are influenced by family stories and the use of heuristics (inferential shortcuts used to make sense of complicated information) in interpreting and applying genetic information they receive, and suggests ways in which genetic counsellors can integrate family context into their traditional counselling practices. We conducted an exploratory, qualitative study at a major clinical and research cancer centre in the United Kingdom from January to June 2000 which was reviewed by the hospital clinical research and ethics committees. Twenty-one semi-structured, in-depth interviews were conducted using a purposive sample of women coming to the cancer genetics clinic for the first time, supplemented by five months of clinical observation at weekly clinics. In addition to many family stories based on the number and outcomes of the cancers in their families, we noted: (1) fragments of stories, (2) secret stories, (3) emerging explanations and (4) misconceptions, We did not find widespread intergenerational family myths, The women used three main heuristics in interpreting their breast/ ovarian cancer risk: (1) representativeness, (2) availability and (3) illusion of control, as well as what Kahneman refers to as the Peak and End rule. Recent psychological research indicates that illusions of control may have positive affects on both physical and mental health. This may pose a future ethical issue for genetic counsellors in determining how to balance the benefit of positive illusions with the delivery of statistical probabilities of risk.
Hereditary breast/ovarian cancer--pitfalls in genetic counseling.

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Dagan, E; Gershoni-Baruch, R

2001-10-01

Genetic counseling and risk assessment, given to women with a family history of breast/ovarian cancer, are regularly based on pedigree analysis. In the Ashkenazi Jewish population, hereditary breast/ovarian cancer is mainly attributed to three founder mutations, namely, 185delAG, 5382insC, and 6174delT, in BRCA1/2 genes. The overall frequency of these mutations, in the Jewish Ashkenazi population, is as high as 2.5%. Based on clinical and family history data, the results of BRCA molecular testing, in Ashkenazi individuals at risk, are appropriately anticipated in most cases. Here we report on five families, in which the segregation of BRCA1/2 mutations, in affected and unaffected family members, was unexpected, emphasizing the need to test, for founder mutations, every Ashkenazi individual at risk, irrespective of the genotype of affected family members. Ultimately, risk assessments and recommendations, in Ashkenazi women, should be invariably based on the results of genetic testing.
Family history of cancer other than breast or ovarian cancer in first-degree relatives is associated with poor breast cancer prognosis.

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Song, Jun-Long; Chen, Chuang; Yuan, Jing-Ping; Li, Juan-Juan; Sun, Sheng-Rong

2017-04-01

Whether a first-degree family history of others cancers (FHOC) than breast or ovarian cancer (BOC) is associated with breast cancer prognosis remains unknown. Thus, the aim of the present study was to clarify this issue. Women who were diagnosed with invasive breast cancer at the Renmin Hospital of Wuhan University from 2010 to 2013 were included in the study. The demographic and clinicopathological characteristics of these patients were extracted. FHOC was considered positive for any patient who had a relative who had been diagnosed with cancer other than BOC. Disease-free survival (DFS) was calculated based on the date of diagnosis. DFS was analyzed using the Cox proportional hazards model. A total of 434 breast cancer patients were included in this study. Among these patients, 61 (14.06%) had a positive FHOC in first-degree relatives. Patients with a positive FHOC tended to have HER2-positive breast cancer (p = 0.03). In the survival analysis, FHOC was associated with poor DFS in both univariate (HR = 2.21 (1.28-3.83), 95% CI: 1.28-3.83, p breast cancer patients with FHOC, especially in patients with luminal A subtype. Copyright © 2017 Elsevier Ltd. All rights reserved.
Modeling familial clustered breast cancer using published data

NARCIS (Netherlands)

Jonker, MA; Jacobi, CE; Hoogendoorn, WE; Nagelkerke, NJD; de Bock, GH; van Houwelingen, JC

2003-01-01

The purpose of this research was to model the familial clustering of breast cancer and to provide an accurate risk estimate for individuals from the general population, based on their family history of breast and ovarian cancer. We constructed a genetic model as an extension of a model by Claus et
Mutations in BRCA1 and BRCA2 Uruguayan families with breast / ovarian

International Nuclear Information System (INIS)

Delgado, L.; Fernández, G.; González, A.; Cataldi, S.; Castillo, C.; Heguaburu, M.; Lluberas, N.; Sabini, G.; Roca, R.; Musé, I.; Bressac-de Paillerets, B.; Bombled, J.

2004-01-01

Germline mutations in BRCA1 and BRCA2 are associated with susceptibility hereditary to breast (CM) and ovarian cancer (OC). The proportion of high risk families carrying mutations in BRCA1 / 2 (20% -70%) and the spectrum of mutations are variable and dependent on the location and type of families studied. In this communication we update our results on the frequency and type of mutations in BRCA1 / 2 families in Uruguayan breast / ovarian cancer. Patients and methods. 39 selected families were included in the study from patients referred to the Unit of the Hospital de Clinicas Oncogene tics for genetic risk assessment and who had at least 3 cases of CM (at least one diagnosed before age 50) or 2 cases with any of the following sub: Parental transmittance, bilateral breast cancer, breast cancer male, ovarian cancer. Results. 8 8 families different mutations (20%), 6 were identified in BRCA1 and BRCA2 2, all resulting in premature termination codon. Regarding family history, 33 families had history of CM and 6 remaining history of CM and CO. Among the first 6 mutations diagnosed (Five in BRCA1 and one in BRCA2) and between the latter 2 mutations (1 in BRCA1 and 1 in BRCA2). Regarding the index cases, all BRCA2 mutations were detected in patients in whom the disease was diagnosed before the 50, 5 of them carrying CM and CO. The BRCA1 were found in a patient with CO diagnosed at age 55 and a patient with CM diagnosed before 50 years. Conclusions. The proportion of flamilies with BRCA1 / 2 is of agreement with that reported in previous studies involving selected families based on similar criteria, but the relative frequency of engagement
Prevalence of BRCA1 mutations in familial and sporadic greek ovarian cancer cases.

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Alexandra V Stavropoulou

Full Text Available Germline mutations in the BRCA1 and BRCA2 genes contribute to approximately 18% of hereditary ovarian cancers conferring an estimated lifetime risk from 15% to 50%. A variable incidence of mutations has been reported for these genes in ovarian cancer cases from different populations. In Greece, six mutations in BRCA1 account for 63% of all mutations detected in both BRCA1 and BRCA2 genes. This study aimed to determine the prevalence of BRCA1 mutations in a Greek cohort of 106 familial ovarian cancer patients that had strong family history or metachronous breast cancer and 592 sporadic ovarian cancer cases. All 698 patients were screened for the six recurrent Greek mutations (including founder mutations c.5266dupC, p.G1738R and the three large deletions of exon 20, exons 23-24 and exon 24. In familial cases, the BRCA1 gene was consequently screened for exons 5, 11, 12, 20, 21, 22, 23, 24. A deleterious BRCA1 mutation was found in 43/106 (40.6% of familial cancer cases and in 27/592 (4.6% of sporadic cases. The variant of unknown clinical significance p.V1833M was identified in 9/698 patients (1.3%. The majority of BRCA1 carriers (71.2% presented a high-grade serous phenotype. Identifying a mutation in the BRCA1 gene among breast and/or ovarian cancer families is important, as it enables carriers to take preventive measures. All ovarian cancer patients with a serous phenotype should be considered for genetic testing. Further studies are warranted to determine the prevalence of mutations in the rest of the BRCA1 gene, in the BRCA2 gene, and other novel predisposing genes for breast and ovarian cancer.
Molecular genetics analysis of hereditary breast and ovarian cancer patients in India

OpenAIRE

Soumittra, Nagasamy; Meenakumari, Balaiah; Parija, Tithi; Sridevi, Veluswami; Nancy, Karunakaran N; Swaminathan, Rajaraman; Rajalekshmy, Kamalalayam R; Majhi, Urmila; Rajkumar, Thangarajan

2009-01-01

Abstract Background Hereditary cancers account for 5–10% of cancers. In this study BRCA1, BRCA2 and CHEK2*(1100delC) were analyzed for mutations in 91 HBOC/HBC/HOC families and early onset breast and early onset ovarian cancer cases. Methods PCR-DHPLC was used for mutation screening followed by DNA sequencing for identification and confirmation of mutations. Kaplan-Meier survival probabilities were computed for five-year survival data on Breast and Ovarian cancer cases separately, and differe...
Screening of 1331 Danish breast and/or ovarian cancer families identified 40 novel BRCA1 and BRCA2 mutations

DEFF Research Database (Denmark)

Hansen, Thomas V O; Jønson, Lars; Steffensen, Ane Y

2011-01-01

Germ-line mutations in the tumour suppressor genes BRCA1 and BRCA2 predispose to breast and ovarian cancer. Since 1999 we have performed mutational screening of breast and/or ovarian cancer patients in East Denmark. During this period we have identified 40 novel sequence variations in BRCA1...... and BRCA2 in high risk breast and/or ovarian cancer families. The mutations were detected via pre-screening using dHPLC or high-resolution melting and direct sequencing. We identified 16 variants in BRCA1, including 9 deleterious frame-shift mutations, 2 intronic variants, 4 missense mutations, and 1......, the presumed significance of the missense mutations was predicted in silico using the align GVGD algorithm. In conclusion, the mutation screening identified 40 novel variants in the BRCA1 and BRCA2 genes and thereby extends the knowledge of the BRCA1/BRCA2 mutation spectrum. Nineteen of the mutations were...
[The clinical study of familial breast cancer - now and the problems].

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Nomizu, Tadashi; Matsuzaki, Masami; Katagata, Naoto; Watanabe, Fumiaki; Akama, Yoshinori

2012-04-01

The clinical features of familial breast cancer are characterized by early onset, high frequency of bilateral breast cancer, and multiple malignancies of other organs. It is strongly suggested that genetic factors contribute to familial breast cancer. The causative genes now identified are BRCA1 and BRCA2. This disease is called hereditary breast ovarian cancer syndrome (HBOC)because breast cancer and ovarian cancer are clustered in the kindred confirmed BRCA mutation. As for BRCA related breast cancer, early onset and highly frequent bilateral breast cancer are characteristic. In addition, the histological grade is high and the positive rate of estrogen receptors is low in BRCA1-related breast cancer. Gene diagnosis of BRCA is useful when choosing a surgical method, chemotherapy, or a surveillance of mutation carriers. The problem in Japan is that the treatment is very expensive, with poor understanding of HBOC of by clinicians and as yet immature genetic counseling system.

Mutation analysis and characterization of ATR sequence variants in breast cancer cases from high-risk French Canadian breast/ovarian cancer families

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Pichette Roxane

2006-09-01

Full Text Available Abstract Background Ataxia telangiectasia-mutated and Rad3-related (ATR is a member of the PIK-related family which plays, along with ATM, a central role in cell-cycle regulation. ATR has been shown to phosphorylate several tumor suppressors like BRCA1, CHEK1 and TP53. ATR appears as a good candidate breast cancer susceptibility gene and the current study was designed to screen for ATR germline mutations potentially involved in breast cancer predisposition. Methods ATR direct sequencing was performed using a fluorescent method while widely available programs were used for linkage disequilibrium (LD, haplotype analyses, and tagging SNP (tSNP identification. Expression analyses were carried out using real-time PCR. Results The complete sequence of all exons and flanking intronic sequences were analyzed in DNA samples from 54 individuals affected with breast cancer from non-BRCA1/2 high-risk French Canadian breast/ovarian families. Although no germline mutation has been identified in the coding region, we identified 41 sequence variants, including 16 coding variants, 3 of which are not reported in public databases. SNP haplotypes were established and tSNPs were identified in 73 healthy unrelated French Canadians, providing a valuable tool for further association studies involving the ATR gene, using large cohorts. Our analyses led to the identification of two novel alternative splice transcripts. In contrast to the transcript generated by an alternative splicing site in the intron 41, the one resulting from a deletion of 121 nucleotides in exon 33 is widely expressed, at significant but relatively low levels, in both normal and tumoral cells including normal breast and ovarian tissue. Conclusion Although no deleterious mutations were identified in the ATR gene, the current study provides an haplotype analysis of the ATR gene polymorphisms, which allowed the identification of a set of SNPs that could be used as tSNPs for large-scale association
Ovarian, Fallopian Tube, and Primary Peritoneal Cancer Prevention

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... black women, but have decreased in both groups. Women who have a family history of ovarian cancer and/or certain inherited gene ... ovarian, fallopian tube, and primary peritoneal cancer: Personal history of breast cancer A woman who has had breast cancer has an increased ...
The Prevention of Hereditary Breast and Ovarian Cancer: A Personal View

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Narod Steven

2004-02-01

Full Text Available Abstract Options for the prevention of hereditary breast and ovarian cancer include screening, preventive surgery and chemoprevention. Screening studies with magnetic resonance imaging of the breast are promising but the technology is not widespread and MRI is unlikely to be available as a screening tool in the near future. Prophylactic oophorectomy and mastectomy are effective preventive measures and are gaining in acceptance by patients and physicians. Preventive mastectomy is effective against both primary and contralateral breast cancer. Oophorectomy prevents ovarian cancer, and if done prior to menopause, will prevent breast cancer as well. Tamoxifen has been shown to prevent contralateral breast cancers in BRCA1 and BRCA2 carriers but is not widely accepted as a means of primary prevention. Oral contraceptives and tubal ligation will reduce the risk of hereditary ovarian cancer and should be considered in women who wish to retain ovarian function.
Breast Cancer

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Breast cancer affects one in eight women during their lives. No one knows why some women get breast cancer, but there are many risk factors. Risks that ... who have family members with breast or ovarian cancer may wish to be tested for the genes. ...
Investigation of mammographic breast density as a risk factor for ovarian cancer.

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Wernli, Karen J; O'Meara, Ellen S; Kerlikowske, Karla; Miglioretti, Diana L; Muller, Carolyn Y; Onega, Tracy; Sprague, Brian L; Henderson, Louise M; Buist, Diana S M

2014-01-01

Endogenous hormones and growth factors that increase mammographic breast density could increase ovarian cancer risk. We examined whether high breast density is associated with ovarian cancer risk. We conducted a cohort study of 724,603 women aged 40 to 79 years with 2,506,732 mammograms participating in the Breast Cancer Surveillance Consortium from 1995 to 2009. Incident epithelial ovarian cancer was diagnosed in 1373 women. We used partly conditional Cox regression to estimate the association between breast density and 5-year risk of incident epithelial ovarian cancer overall and stratified by 10-year age group. All statistical tests were two-sided. Compared with women with scattered fibroglandular densities, women with heterogeneously dense and extremely dense breast tissue had 20% and 18% increased 5-year risk of incident epithelial ovarian cancer (hazard ratio [HR] = 1.20, 95% confidence interval [CI] = 1.06 to 1.36; HR = 1.18, 95% CI = 0.93 to 1.50, respectively; P(trend) = .01). Among women aged 50 to 59 years, we observed a trend in elevated risk associated with increased breast density (P(trend) = .02); women with heterogeneously and extremely dense breast tissue had 30% (HR = 1.30; 95% CI = 1.03 to 1.64) and 65% (HR = 1.65; 95% CI = 1.12 to 2.44) increased risk, respectively, compared with women with scattered fibroglandular densities. The pattern was similar but not statistically significant at age 40 to 49 years. There were no consistent patterns of breast density and ovarian cancer risk at age 60 to 79 years. Dense breast tissue was associated with a modest increase in 5-year ovarian cancer risk in women aged 50 to 59 years but was not associated with ovarian cancer at ages 40 to 49 or 60 to 79 years.
No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer

Science.gov (United States)

Hollestelle, Antoinette; van der Baan, Frederieke H.; Berchuck, Andrew; Johnatty, Sharon E.; Aben, Katja K.; Agnarsson, Bjarni A.; Aittomäki, Kristiina; Alducci, Elisa; Andrulis, Irene L.; Anton-Culver, Hoda; Antonenkova, Natalia N.; Antoniou, Antonis C.; Apicella, Carmel; Arndt, Volker; Arnold, Norbert; Arun, Banu K.; Arver, Brita; Ashworth, Alan; Baglietto, Laura; Balleine, Rosemary; Bandera, Elisa V.; Barrowdale, Daniel; Bean, Yukie T.; Beckmann, Lars; Beckmann, Matthias W.; Benitez, Javier; Berger, Andreas; Berger, Raanan; Beuselinck, Benoit; Bisogna, Maria; Bjorge, Line; Blomqvist, Carl; Bogdanova, Natalia V.; Bojesen, Anders; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Brand, Judith S.; Brauch, Hiltrud; Brenner, Hermann; Brinton, Louise; Brooks-Wilson, Angela; Bruinsma, Fiona; Brunet, Joan; Brüning, Thomas; Budzilowska, Agnieszka; Bunker, Clareann H.; Burwinkel, Barbara; Butzow, Ralf; Buys, Saundra S.; Caligo, Maria A.; Campbell, Ian; Carter, Jonathan; Chang-Claude, Jenny; Chanock, Stephen J.; Claes, Kathleen B.M.; Collée, J. Margriet; Cook, Linda S.; Couch, Fergus J.; Cox, Angela; Cramer, Daniel; Cross, Simon S.; Cunningham, Julie M.; Cybulski, Cezary; Czene, Kamila; Damiola, Francesca; Dansonka-Mieszkowska, Agnieszka; Darabi, Hatef; de la Hoya, Miguel; deFazio, Anna; Dennis, Joseph; Devilee, Peter; Dicks, Ed M.; Diez, Orland; Doherty, Jennifer A.; Domchek, Susan M.; Dorfling, Cecilia M.; Dörk, Thilo; Santos Silva, Isabel Dos; du Bois, Andreas; Dumont, Martine; Dunning, Alison M.; Duran, Mercedes; Easton, Douglas F.; Eccles, Diana; Edwards, Robert P.; Ehrencrona, Hans; Ejlertsen, Bent; Ekici, Arif B.; Ellis, Steve D.; Engel, Christoph; Eriksson, Mikael; Fasching, Peter A.; Feliubadalo, Lidia; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Fontaine, Annette; Fortuzzi, Stefano; Fostira, Florentia; Fridley, Brooke L.; Friebel, Tara; Friedman, Eitan; Friel, Grace; Frost, Debra; Garber, Judy; García-Closas, Montserrat; Gayther, Simon A.; Gentry-Maharaj, Aleksandra; Gerdes, Anne-Marie; Giles, Graham G.; Glasspool, Rosalind; Glendon, Gord; Godwin, Andrew K.; Goodman, Marc T.; Gore, Martin; Greene, Mark H.; Grip, Mervi; Gronwald, Jacek; Kaulich, Daphne Gschwantler; Guénel, Pascal; Guzman, Starr R.; Haeberle, Lothar; Haiman, Christopher A.; Hall, Per; Halverson, Sandra L.; Hamann, Ute; Hansen, Thomas V.O.; Harter, Philipp; Hartikainen, Jaana M.; Healey, Sue; Hein, Alexander; Heitz, Florian; Henderson, Brian E.; Herzog, Josef; Hildebrandt, Michelle A. T.; Høgdall, Claus K.; Høgdall, Estrid; Hogervorst, Frans B.L.; Hopper, John L.; Humphreys, Keith; Huzarski, Tomasz; Imyanitov, Evgeny N.; Isaacs, Claudine; Jakubowska, Anna; Janavicius, Ramunas; Jaworska, Katarzyna; Jensen, Allan; Jensen, Uffe Birk; Johnson, Nichola; Jukkola-Vuorinen, Arja; Kabisch, Maria; Karlan, Beth Y.; Kataja, Vesa; Kauff, Noah; Kelemen, Linda E.; Kerin, Michael J.; Kiemeney, Lambertus A.; Kjaer, Susanne K.; Knight, Julia A.; Knol-Bout, Jacoba P.; Konstantopoulou, Irene; Kosma, Veli-Matti; Krakstad, Camilla; Kristensen, Vessela; Kuchenbaecker, Karoline B.; Kupryjanczyk, Jolanta; Laitman, Yael; Lambrechts, Diether; Lambrechts, Sandrina; Larson, Melissa C.; Lasa, Aadriana; Laurent-Puig, Pierre; Lazaro, Conxi; Le, Nhu D.; Le Marchand, Loic; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Li, Jingmei; Liang, Dong; Lindblom, Annika; Lindor, Noralane; Lissowska, Jolanta; Long, Jirong; Lu, Karen H.; Lubinski, Jan; Lundvall, Lene; Lurie, Galina; Mai, Phuong L.; Mannermaa, Arto; Margolin, Sara; Mariette, Frederique; Marme, Frederik; Martens, John W.M.; Massuger, Leon F.A.G.; Maugard, Christine; Mazoyer, Sylvie; McGuffog, Lesley; McGuire, Valerie; McLean, Catriona; McNeish, Iain; Meindl, Alfons; Menegaux, Florence; Menéndez, Primitiva; Menkiszak, Janusz; Menon, Usha; Mensenkamp, Arjen R.; Miller, Nicola; Milne, Roger L.; Modugno, Francesmary; Montagna, Marco; Moysich, Kirsten B.; Müller, Heiko; Mulligan, Anna Marie; Muranen, Taru A.; Narod, Steven A.; Nathanson, Katherine L.; Ness, Roberta B.; Neuhausen, Susan L.; Nevanlinna, Heli; Neven, Patrick; Nielsen, Finn C.; Nielsen, Sune F.; Nordestgaard, Børge G.; Nussbaum, Robert L.; Odunsi, Kunle; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I.; Olson, Janet E.; Olson, Sara H.; Oosterwijk, Jan C.; Orlow, Irene; Orr, Nick; Orsulic, Sandra; Osorio, Ana; Ottini, Laura; Paul, James; Pearce, Celeste L.; Pedersen, Inge Sokilde; Peissel, Bernard; Pejovic, Tanja; Pelttari, Liisa M.; Perkins, Jo; Permuth-Wey, Jenny; Peterlongo, Paolo; Peto, Julian; Phelan, Catherine M.; Phillips, Kelly-Anne; Piedmonte, Marion; Pike, Malcolm C.; Platte, Radka; Plisiecka-Halasa, Joanna; Poole, Elizabeth M.; Poppe, Bruce; Pylkäs, Katri; Radice, Paolo; Ramus, Susan J.; Rebbeck, Timothy R.; Reed, Malcolm W.R.; Rennert, Gad; Risch, Harvey A.; Robson, Mark; Rodriguez, Gustavo C.; Romero, Atocha; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo; Salani, Ritu; Salvesen, Helga B.; Sawyer, Elinor J.; Schildkraut, Joellen M.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Schneeweiss, Andreas; Schoemaker, Minouk J.; Schrauder, Michael G.; Schumacher, Fredrick; Schwaab, Ira; Scuvera, Giulietta; Sellers, Thomas A.; Severi, Gianluca; Seynaeve, Caroline M.; Shah, Mitul; Shrubsole, Martha; Siddiqui, Nadeem; Sieh, Weiva; Simard, Jacques; Singer, Christian F.; Sinilnikova, Olga M.; Smeets, Dominiek; Sohn, Christof; Soller, Maria; Song, Honglin; Soucy, Penny; Southey, Melissa C.; Stegmaier, Christa; Stoppa-Lyonnet, Dominique; Sucheston, Lara; Swerdlow, Anthony; Tangen, Ingvild L.; Tea, Muy-Kheng; Teixeira, Manuel R.; Terry, Kathryn L.; Terry, Mary Beth; Thomassen, Madas; Thompson, Pamela J.; Tihomirova, Laima; Tischkowitz, Marc; Toland, Amanda Ewart; Tollenaar, Rob A.E.M.; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Tsimiklis, Helen; Tung, Nadine; Tworoger, Shelley S.; Tyrer, Jonathan P.; Vachon, Celine M.; Van 't Veer, Laura J.; van Altena, Anne M.; Van Asperen, C.J.; van den Berg, David; van den Ouweland, Ans M.W.; van Doorn, Helena C.; Van Nieuwenhuysen, Els; van Rensburg, Elizabeth J.; Vergote, Ignace; Verhoef, Senno; Vierkant, Robert A.; Vijai, Joseph; Vitonis, Allison F.; von Wachenfeldt, Anna; Walsh, Christine; Wang, Qin; Wang-Gohrke, Shan; Wappenschmidt, Barbara; Weischer, Maren; Weitzel, Jeffrey N.; Weltens, Caroline; Wentzensen, Nicolas; Whittemore, Alice S.; Wilkens, Lynne R.; Winqvist, Robert; Wu, Anna H.; Wu, Xifeng; Yang, Hannah P.; Zaffaroni, Daniela; Zamora, M. Pilar; Zheng, Wei; Ziogas, Argyrios; Chenevix-Trench, Georgia; Pharoah, Paul D.P.; Rookus, Matti A.; Hooning, Maartje J.; Goode, Ellen L.

2015-01-01

Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR= 0.99, 95% CI 0.94–1.04,p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94–1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97–1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97–1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71–1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94–1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83–1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87–1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers. PMID:25940428
No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer.

Science.gov (United States)

Hollestelle, Antoinette; van der Baan, Frederieke H; Berchuck, Andrew; Johnatty, Sharon E; Aben, Katja K; Agnarsson, Bjarni A; Aittomäki, Kristiina; Alducci, Elisa; Andrulis, Irene L; Anton-Culver, Hoda; Antonenkova, Natalia N; Antoniou, Antonis C; Apicella, Carmel; Arndt, Volker; Arnold, Norbert; Arun, Banu K; Arver, Brita; Ashworth, Alan; Baglietto, Laura; Balleine, Rosemary; Bandera, Elisa V; Barrowdale, Daniel; Bean, Yukie T; Beckmann, Lars; Beckmann, Matthias W; Benitez, Javier; Berger, Andreas; Berger, Raanan; Beuselinck, Benoit; Bisogna, Maria; Bjorge, Line; Blomqvist, Carl; Bogdanova, Natalia V; Bojesen, Anders; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Brand, Judith S; Brauch, Hiltrud; Brenner, Hermann; Brinton, Louise; Brooks-Wilson, Angela; Bruinsma, Fiona; Brunet, Joan; Brüning, Thomas; Budzilowska, Agnieszka; Bunker, Clareann H; Burwinkel, Barbara; Butzow, Ralf; Buys, Saundra S; Caligo, Maria A; Campbell, Ian; Carter, Jonathan; Chang-Claude, Jenny; Chanock, Stephen J; Claes, Kathleen B M; Collée, J Margriet; Cook, Linda S; Couch, Fergus J; Cox, Angela; Cramer, Daniel; Cross, Simon S; Cunningham, Julie M; Cybulski, Cezary; Czene, Kamila; Damiola, Francesca; Dansonka-Mieszkowska, Agnieszka; Darabi, Hatef; de la Hoya, Miguel; deFazio, Anna; Dennis, Joseph; Devilee, Peter; Dicks, Ed M; Diez, Orland; Doherty, Jennifer A; Domchek, Susan M; Dorfling, Cecilia M; Dörk, Thilo; Silva, Isabel Dos Santos; du Bois, Andreas; Dumont, Martine; Dunning, Alison M; Duran, Mercedes; Easton, Douglas F; Eccles, Diana; Edwards, Robert P; Ehrencrona, Hans; Ejlertsen, Bent; Ekici, Arif B; Ellis, Steve D; Engel, Christoph; Eriksson, Mikael; Fasching, Peter A; Feliubadalo, Lidia; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Fontaine, Annette; Fortuzzi, Stefano; Fostira, Florentia; Fridley, Brooke L; Friebel, Tara; Friedman, Eitan; Friel, Grace; Frost, Debra; Garber, Judy; García-Closas, Montserrat; Gayther, Simon A; Gentry-Maharaj, Aleksandra; Gerdes, Anne-Marie; Giles, Graham G; Glasspool, Rosalind; Glendon, Gord; Godwin, Andrew K; Goodman, Marc T; Gore, Martin; Greene, Mark H; Grip, Mervi; Gronwald, Jacek; Gschwantler Kaulich, Daphne; Guénel, Pascal; Guzman, Starr R; Haeberle, Lothar; Haiman, Christopher A; Hall, Per; Halverson, Sandra L; Hamann, Ute; Hansen, Thomas V O; Harter, Philipp; Hartikainen, Jaana M; Healey, Sue; Hein, Alexander; Heitz, Florian; Henderson, Brian E; Herzog, Josef; T Hildebrandt, Michelle A; Høgdall, Claus K; Høgdall, Estrid; Hogervorst, Frans B L; Hopper, John L; Humphreys, Keith; Huzarski, Tomasz; Imyanitov, Evgeny N; Isaacs, Claudine; Jakubowska, Anna; Janavicius, Ramunas; Jaworska, Katarzyna; Jensen, Allan; Jensen, Uffe Birk; Johnson, Nichola; Jukkola-Vuorinen, Arja; Kabisch, Maria; Karlan, Beth Y; Kataja, Vesa; Kauff, Noah; Kelemen, Linda E; Kerin, Michael J; Kiemeney, Lambertus A; Kjaer, Susanne K; Knight, Julia A; Knol-Bout, Jacoba P; Konstantopoulou, Irene; Kosma, Veli-Matti; Krakstad, Camilla; Kristensen, Vessela; Kuchenbaecker, Karoline B; Kupryjanczyk, Jolanta; Laitman, Yael; Lambrechts, Diether; Lambrechts, Sandrina; Larson, Melissa C; Lasa, Adriana; Laurent-Puig, Pierre; Lazaro, Conxi; Le, Nhu D; Le Marchand, Loic; Leminen, Arto; Lester, Jenny; Levine, Douglas A; Li, Jingmei; Liang, Dong; Lindblom, Annika; Lindor, Noralane; Lissowska, Jolanta; Long, Jirong; Lu, Karen H; Lubinski, Jan; Lundvall, Lene; Lurie, Galina; Mai, Phuong L; Mannermaa, Arto; Margolin, Sara; Mariette, Frederique; Marme, Frederik; Martens, John W M; Massuger, Leon F A G; Maugard, Christine; Mazoyer, Sylvie; McGuffog, Lesley; McGuire, Valerie; McLean, Catriona; McNeish, Iain; Meindl, Alfons; Menegaux, Florence; Menéndez, Primitiva; Menkiszak, Janusz; Menon, Usha; Mensenkamp, Arjen R; Miller, Nicola; Milne, Roger L; Modugno, Francesmary; Montagna, Marco; Moysich, Kirsten B; Müller, Heiko; Mulligan, Anna Marie; Muranen, Taru A; Narod, Steven A; Nathanson, Katherine L; Ness, Roberta B; Neuhausen, Susan L; Nevanlinna, Heli; Neven, Patrick; Nielsen, Finn C; Nielsen, Sune F; Nordestgaard, Børge G; Nussbaum, Robert L; Odunsi, Kunle; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I; Olson, Janet E; Olson, Sara H; Oosterwijk, Jan C; Orlow, Irene; Orr, Nick; Orsulic, Sandra; Osorio, Ana; Ottini, Laura; Paul, James; Pearce, Celeste L; Pedersen, Inge Sokilde; Peissel, Bernard; Pejovic, Tanja; Pelttari, Liisa M; Perkins, Jo; Permuth-Wey, Jenny; Peterlongo, Paolo; Peto, Julian; Phelan, Catherine M; Phillips, Kelly-Anne; Piedmonte, Marion; Pike, Malcolm C; Platte, Radka; Plisiecka-Halasa, Joanna; Poole, Elizabeth M; Poppe, Bruce; Pylkäs, Katri; Radice, Paolo; Ramus, Susan J; Rebbeck, Timothy R; Reed, Malcolm W R; Rennert, Gad; Risch, Harvey A; Robson, Mark; Rodriguez, Gustavo C; Romero, Atocha; Rossing, Mary Anne; Rothstein, Joseph H; Rudolph, Anja; Runnebaum, Ingo; Salani, Ritu; Salvesen, Helga B; Sawyer, Elinor J; Schildkraut, Joellen M; Schmidt, Marjanka K; Schmutzler, Rita K; Schneeweiss, Andreas; Schoemaker, Minouk J; Schrauder, Michael G; Schumacher, Fredrick; Schwaab, Ira; Scuvera, Giulietta; Sellers, Thomas A; Severi, Gianluca; Seynaeve, Caroline M; Shah, Mitul; Shrubsole, Martha; Siddiqui, Nadeem; Sieh, Weiva; Simard, Jacques; Singer, Christian F; Sinilnikova, Olga M; Smeets, Dominiek; Sohn, Christof; Soller, Maria; Song, Honglin; Soucy, Penny; Southey, Melissa C; Stegmaier, Christa; Stoppa-Lyonnet, Dominique; Sucheston, Lara; Swerdlow, Anthony; Tangen, Ingvild L; Tea, Muy-Kheng; Teixeira, Manuel R; Terry, Kathryn L; Terry, Mary Beth; Thomassen, Mads; Thompson, Pamela J; Tihomirova, Laima; Tischkowitz, Marc; Toland, Amanda Ewart; Tollenaar, Rob A E M; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Tsimiklis, Helen; Tung, Nadine; Tworoger, Shelley S; Tyrer, Jonathan P; Vachon, Celine M; Van 't Veer, Laura J; van Altena, Anne M; Van Asperen, C J; van den Berg, David; van den Ouweland, Ans M W; van Doorn, Helena C; Van Nieuwenhuysen, Els; van Rensburg, Elizabeth J; Vergote, Ignace; Verhoef, Senno; Vierkant, Robert A; Vijai, Joseph; Vitonis, Allison F; von Wachenfeldt, Anna; Walsh, Christine; Wang, Qin; Wang-Gohrke, Shan; Wappenschmidt, Barbara; Weischer, Maren; Weitzel, Jeffrey N; Weltens, Caroline; Wentzensen, Nicolas; Whittemore, Alice S; Wilkens, Lynne R; Winqvist, Robert; Wu, Anna H; Wu, Xifeng; Yang, Hannah P; Zaffaroni, Daniela; Pilar Zamora, M; Zheng, Wei; Ziogas, Argyrios; Chenevix-Trench, Georgia; Pharoah, Paul D P; Rookus, Matti A; Hooning, Maartje J; Goode, Ellen L

2016-05-01

Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3' UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). We found no association with risk of ovarian cancer (OR=0.99, 95% CI 0.94-1.04, p=0.74) or breast cancer (OR=0.98, 95% CI 0.94-1.01, p=0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR=1.09, 95% CI 0.97-1.23, p=0.14, breast cancer HR=1.04, 95% CI 0.97-1.12, p=0.27; BRCA2, ovarian cancer HR=0.89, 95% CI 0.71-1.13, p=0.34, breast cancer HR=1.06, 95% CI 0.94-1.19, p=0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR=0.94, 95% CI 0.83-1.07, p=0.38), breast cancer (HR=0.96, 95% CI 0.87-1.06, p=0.38), and all other previously-reported associations. rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers. Copyright © 2015 Elsevier Inc. All rights reserved.
Mathematical Models of Breast and Ovarian Cancers

Science.gov (United States)

Botesteanu, Dana-Adriana; Lipkowitz, Stanley; Lee, Jung-Min; Levy, Doron

2016-01-01

Women constitute the majority of the aging United States (US) population, and this has substantial implications on cancer population patterns and management practices. Breast cancer is the most common women's malignancy, while ovarian cancer is the most fatal gynecological malignancy in the US. In this review we focus on these subsets of women's cancers, seen more commonly in postmenopausal and elderly women. In order to systematically investigate the complexity of cancer progression and response to treatment in breast and ovarian malignancies, we assert that integrated mathematical modeling frameworks viewed from a systems biology perspective are needed. Such integrated frameworks could offer innovative contributions to the clinical women's cancers community, since answers to clinical questions cannot always be reached with contemporary clinical and experimental tools. Here, we recapitulate clinically known data regarding the progression and treatment of the breast and ovarian cancers. We compare and contrast the two malignancies whenever possible, in order to emphasize areas where substantial contributions could be made by clinically inspired and validated mathematical modeling. We show how current paradigms in the mathematical oncology community focusing on the two malignancies do not make comprehensive use of, nor substantially reflect existing clinical data, and we highlight the modeling areas in most critical need of clinical data integration. We emphasize that the primary goal of any mathematical study of women's cancers should be to address clinically relevant questions. PMID:27259061
Risk prediction for breast, endometrial, and ovarian cancer in white women aged 50 y or older: derivation and validation from population-based cohort studies.

Directory of Open Access Journals (Sweden)

Ruth M Pfeiffer

Full Text Available Breast, endometrial, and ovarian cancers share some hormonal and epidemiologic risk factors. While several models predict absolute risk of breast cancer, there are few models for ovarian cancer in the general population, and none for endometrial cancer.Using data on white, non-Hispanic women aged 50+ y from two large population-based cohorts (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial [PLCO] and the National Institutes of Health-AARP Diet and Health Study [NIH-AARP], we estimated relative and attributable risks and combined them with age-specific US-population incidence and competing mortality rates. All models included parity. The breast cancer model additionally included estrogen and progestin menopausal hormone therapy (MHT use, other MHT use, age at first live birth, menopausal status, age at menopause, family history of breast or ovarian cancer, benign breast disease/biopsies, alcohol consumption, and body mass index (BMI; the endometrial model included menopausal status, age at menopause, BMI, smoking, oral contraceptive use, MHT use, and an interaction term between BMI and MHT use; the ovarian model included oral contraceptive use, MHT use, and family history or breast or ovarian cancer. In independent validation data (Nurses' Health Study cohort the breast and ovarian cancer models were well calibrated; expected to observed cancer ratios were 1.00 (95% confidence interval [CI]: 0.96-1.04 for breast cancer and 1.08 (95% CI: 0.97-1.19 for ovarian cancer. The number of endometrial cancers was significantly overestimated, expected/observed = 1.20 (95% CI: 1.11-1.29. The areas under the receiver operating characteristic curves (AUCs; discriminatory power were 0.58 (95% CI: 0.57-0.59, 0.59 (95% CI: 0.56-0.63, and 0.68 (95% CI: 0.66-0.70 for the breast, ovarian, and endometrial models, respectively.These models predict absolute risks for breast, endometrial, and ovarian cancers from easily obtainable risk factors and may
General Information About Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

Science.gov (United States)

... black women, but have decreased in both groups. Women who have a family history of ovarian cancer and/or certain inherited gene ... ovarian, fallopian tube, and primary peritoneal cancer: Personal history of breast cancer A woman who has had breast cancer has an increased ...
Polygenic risk score is associated with increased disease risk in 52 Finnish breast cancer families

OpenAIRE

Muranen, Taru A.; Mavaddat, Nasim; Khan, Sofia; Fagerholm, Rainer; Pelttari, Liisa; Lee, Andrew; Aittom?ki, Kristiina; Blomqvist, Carl; Easton, Douglas F.; Nevanlinna, Heli

2016-01-01

The risk of developing breast cancer is increased in women with family history of breast cancer and particularly in families with multiple cases of breast or ovarian cancer. Nevertheless, many women with a positive family history never develop the disease. Polygenic risk scores (PRSs) based on the risk effects of multiple common genetic variants have been proposed for individual risk assessment on a population level. We investigate the applicability of the PRS for risk prediction within breas...
Risk of breast cancer after a diagnosis of ovarian cancer in BRCA mutation carriers: Is preventive mastectomy warranted?

Science.gov (United States)

McGee, Jacob; Giannakeas, Vasily; Karlan, Beth; Lubinski, Jan; Gronwald, Jacek; Rosen, Barry; McLaughlin, John; Risch, Harvey; Sun, Ping; Foulkes, William D; Neuhausen, Susan L; Kotsopoulos, Joanne; Narod, Steven A

2017-05-01

Preventive breast surgery and MRI screening are offered to unaffected BRCA mutation carriers. The clinical benefit of these two modalities has not been evaluated among mutation carriers with a history of ovarian cancer. Thus, we sought to determine whether or not BRCA mutation carriers with ovarian cancer would benefit from preventive mastectomy or from MRI screening. First, the annual mortality rate for ovarian cancer patients was estimated for a cohort of 178 BRCA mutation carriers from Ontario, Canada. Next, the actuarial risk of developing breast cancer was estimated using an international registry of 509 BRCA mutation carriers with ovarian cancer. A series of simulations was conducted to evaluate the reduction in the probability of death (from all causes) associated with mastectomy and with MRI-based breast surveillance. Cox proportional hazards models were used to evaluate the impacts of mastectomy and MRI screening on breast cancer incidence as well as on all-cause mortality. Twenty (3.9%) of the 509 patients developed breast cancer within ten years following ovarian cancer diagnosis. The actuarial risk of developing breast cancer at ten years post-diagnosis, conditional on survival from ovarian cancer and other causes of mortality was 7.8%. Based on our simulation results, among all BRCA mutation-carrying patients diagnosed with stage III/IV ovarian cancer at age 50, the chance of dying before age 80 was reduced by less than 1% with MRI and by less than 2% with mastectomy. Greater improvements in survival with MRI or mastectomy were observed for women who had already survived 10years after ovarian cancer, and for women with stage I or II ovarian cancer. Among BRCA mutation-carrying ovarian cancer patients without a personal history of breast cancer, neither preventive mastectomy nor MRI screening is warranted, except for those who have survived ovarian cancer without recurrence for ten years and for those with early stage ovarian cancer. Copyright © 2017
Hereditary breast and ovarian cancer

DEFF Research Database (Denmark)

Nielsen, Finn Cilius; Hansen, Thomas van Overeem; Sørensen, Claus Storgaard

2016-01-01

Genetic abnormalities in the DNA repair genes BRCA1 and BRCA2 predispose to hereditary breast and ovarian cancer (HBOC). However, only approximately 25% of cases of HBOC can be ascribed to BRCA1 and BRCA2 mutations. Recently, exome sequencing has uncovered substantial locus heterogeneity among...... of putative causal variants and the clinical application of new HBOC genes in cancer risk management and treatment decision-making....
Five recurrent BRCA1/2 mutations are responsible for cancer predisposition in the majority of Slovenian breast cancer families

Directory of Open Access Journals (Sweden)

Novakovic Srdjan

2008-09-01

Full Text Available Abstract Background Both recurrent and population specific mutations have been found in different areas of the world and more specifically in ethnically defined or isolated populations. The population of Slovenia has over several centuries undergone limited mixing with surrounding populations. The current study was aimed at establishing the mutation spectrum of BRCA1/2 in the Slovenian breast/ovarian cancer families taking advantage of a complete cancer registration database. A second objective was to determine the cancer phenotype of these families. Methods The original population database was composed of cancer patients from the Institute of Oncology Ljubljana in Slovenia which also includes current follow-up status on these patients. The inclusion criteria for the BRCA1/2 screening were: (i probands with at least two first degree relatives with breast and ovarian cancer; (ii probands with only two first degree relatives of breast cancer where one must be diagnosed less than 50 years of age; and (iii individual patients with breast and ovarian cancer, bilateral breast cancer, breast cancer diagnosed before the age of 40 and male breast cancer without any other cancer in the family. Results Probands from 150 different families met the inclusion criteria for mutation analysis of which 145 consented to testing. A BRCA1/2 mutation was found in 56 (39%. Two novel large deletions covering consecutive exons of BRCA1 were found. Five highly recurrent specific mutations were identified (1806C>T, 300T>G, 300T>A, 5382insC in the BRCA1 gene and IVS16-2A>G in the BRCA2 gene. The IVS16-2A>G in the BRCA2 gene appears to be a unique founder mutation in the Slovenian population. A practical implication is that only 4 PCR fragments can be used in a first screen and reveal the cancer predisposing mutation in 67% of the BRCA1/2 positive families. We also observed an exceptionally high frequency of 4 different pathogenic missense mutations, all affecting one of
Cancer risks in BRCA2 families: estimates for sites other than breast and ovary

NARCIS (Netherlands)

van Asperen, C. J.; Brohet, R. M.; Meijers-Heijboer, E. J.; Hoogerbrugge, N.; Verhoef, S.; Vasen, H. F. A.; Ausems, M. G. E. M.; Menko, F. H.; Gomez Garcia, E. B.; Klijn, J. G. M.; Hogervorst, F. B. L.; van Houwelingen, J. C.; van't Veer, L. J.; Rookus, M. A.; van Leeuwen, F. E.

2005-01-01

In BRCA2 mutation carriers, increased risks have been reported for several cancer sites besides breast and ovary. As most of the families included in earlier reports were selected on the basis of multiple breast/ovarian cancer cases, it is possible that risk estimates may differ in mutation carriers
No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer

DEFF Research Database (Denmark)

Hollestelle, Antoinette; van der Baan, Frederieke H; Berchuck, Andrew

2015-01-01

,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). RESULTS: We found no association with risk of ovarian cancer (OR=0...
Update on fertility preservation in young women undergoing breast cancer and ovarian cancer therapy.

Science.gov (United States)

Lambertini, Matteo; Ginsburg, Elizabeth S; Partridge, Ann H

2015-02-01

The purpose of the article is to review the available options for fertility preservation in patients with breast and ovarian cancer, and the special issues faced by BRCA mutation carriers. Future fertility is an important consideration for many young patients with cancer. There are both experimental and standard available strategies for patients with breast and ovarian cancer to preserve fertility, and each has potential advantages and disadvantages. Embryo cryopreservation is widely available with a highly successful track record. Improvements in laboratory techniques have led to oocyte cryopreservation recently being recategorized as nonexperimental. Conservative gynecologic surgery is a standard consideration for patients with stage I ovarian cancer who desire future fertility. Ovarian tissue cryopreservation as well as ovarian suppression with luteinizing hormone-releasing hormone analogs during chemotherapy are considered experimental methods at this time, although recent data suggest both safety and efficacy for the use of luteinizing hormone-releasing hormone analogs in women receiving (neo)adjuvant chemotherapy for breast cancer. Special issues should be considered for women with BRCA mutations because of the need to undergo preventive surgery at young age. Multidisciplinary teams and well functioning relationships between the oncology and reproductive units are crucial to manage the fertility issues of young women with cancer.
Large BRCA1 and BRCA2 genomic rearrangements in Danish high risk breast-ovarian cancer families

DEFF Research Database (Denmark)

Hansen, Thomas v O; Jønson, Lars; Albrechtsen, Anders

2009-01-01

BRCA1 and BRCA2 germ-line mutations predispose to breast and ovarian cancer. Large genomic rearrangements of BRCA1 account for 0-36% of all disease causing mutations in various populations, while large genomic rearrangements in BRCA2 are more rare. We examined 642 East Danish breast and/or ovaria...
Endogenous estrogens and the risk of breast, endometrial, and ovarian cancers.

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Brown, Susan B; Hankinson, Susan E

2015-07-01

Data from laboratory and epidemiologic studies support a relationship between endogenous hormones and the increased risk of several female cancers. In epidemiologic studies, consistent associations have been observed between risk of breast, ovarian and endometrial cancers and reproductive and hormonal risk factors such as high postmenopausal body mass index (BMI) and postmenopausal hormone use, which suggest the importance of endogenous hormones in the etiology of these diseases. The relationship between circulating estrogen levels in postmenopausal women and the risk of breast cancer is well established, with an approximately 2-fold higher risk among women in the top 20-25% (versus bottom 20-25%) of levels. However, data evaluating the relationship between endogenous estrogens and premenopausal breast cancer risk are more limited and less consistent. Two studies to date have evaluated the relationship between circulating estrogens and breast cancer risk by menstrual cycle phase at blood collection and only one study has examined this relationship by menopausal status at diagnosis. Three prospective studies have evaluated circulating estrogen levels and endometrial cancer risk in postmenopausal women, with consistent strong positive associations reported (with relative risks of 2-4 comparing high versus low hormone levels), while this relationship has not been studied in premenopausal women. Compared to breast and endometrial cancers, reproductive and hormonal characteristics such as postmenopausal hormone use are generally weaker and less consistent risk factors for ovarian cancer, and the only small prospective study conducted to date indicated a non-significant positive relationship between circulating estrogen levels and ovarian cancer risk. In this review, we summarize current evidence and identify key areas to be addressed in future epidemiologic studies of endogenous estrogens and the risk of breast, endometrial, and ovarian cancers. Copyright © 2015
"It was an Emotional Baby": Previvors' Family Planning Decision-Making Styles about Hereditary Breast and Ovarian Cancer Risk.

Science.gov (United States)

Dean, Marleah; Rauscher, Emily A

2017-12-01

Women who test positive for a BRCA genetic mutation are at an increased risk for developing hereditary breast and ovarian cancer and have a 50% chance of passing on their genetic mutation to their children. The purpose of this study was to investigate how women who test positive for a BRCA mutation but have not been diagnosed with cancer make decisions regarding family planning. Analysis of interviews with 20 women revealed they engage in logical and emotional decision-making styles. Although women want to be logical to reduce their hereditary cancer risk, emotions often complicate their decision-making. Women experience fear and worry about a future cancer diagnosis, yet also desire to create a family, particularly having children through natural conception. That is, women negotiate having preventative surgeries in a logical doctor-recommended timeframe but also organize those decisions around emotional desires of motherhood. Overall, this study demonstrates the complex decisions women who test positive for a BRCA mutation must make in regards to genetic testing timing, family planning, and overall quality of life.

Completeness of pedigree and family cancer history for ovarian cancer patients.

Science.gov (United States)

Son, Yedong; Lim, Myong Cheol; Seo, Sang Soo; Kang, Sokbom; Park, Sang Yoon

2014-10-01

To investigate the completeness of pedigree and of number of pedigree analysis to know the acceptable familial history in Korean women with ovarian cancer. Interview was conducted in 50 ovarian cancer patients for obtaining familial history three times over the 6 weeks. The completeness of pedigree is estimated in terms of familial history of disease (cancer), health status (health living, disease and death), and onset age of disease and death. The completion of pedigree was 79.3, 85.1, and 85.6% at the 1st, 2nd, and 3rd time of interview and the time for pedigree analysis was 34.3, 10.8, and 3.1 minutes, respectively. The factors limiting pedigree analysis were as follows: out of contact with their relatives (38%), no living ancestors who know the family history (34%), dispersed family member because of the Korean War (16%), unknown cause of death (12%), reluctance to ask medical history of relatives (10%), and concealing their ovarian cancer (10%). The percentage of cancers revealed in 1st (2%) and 2nd degree (8%) relatives were increasing through surveys, especially colorectal cancer related with Lynch syndrome (4%). Analysis of pedigree at least two times is acceptable in Korean woman with ovarian cancer from the first study. The completion of pedigree is increasing, while time to take family history is decreasing during three time survey.
Cryopreservation of ovarian tissue for fertility preservation: no evidence of malignant cell contamination in ovarian tissue from patients with breast cancer

DEFF Research Database (Denmark)

Rosendahl, Mikkel; Timmermans Wielenga, Vera; Nedergaard, Lotte

2011-01-01

Cryopreserved ovarian cortical biopsies from 51 patients with breast cancer were examined by histologic and immunohistochemical analysis and showed no sign of metastases. Autotransplantation of ovarian cortex to patients with low-stage breast cancer disease appears safe, but confirmatory studies ...
A non-synonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers

Science.gov (United States)

Ding, Yuan C.; McGuffog, Lesley; Healey, Sue; Friedman, Eitan; Laitman, Yael; Shani-Shimon–Paluch; Kaufman, Bella; Liljegren, Annelie; Lindblom, Annika; Olsson, Håkan; Kristoffersson, Ulf; Stenmark-Askmalm, Marie; Melin, Beatrice; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Gronwald, Jacek; Huzarski, Tomasz; Cybulski, Cezary; Byrski, Tomasz; Osorio, Ana; Cajal, Teresa Ramóny; Stavropoulou, Alexandra V; Benítez, Javier; Hamann, Ute; Rookus, Matti; Aalfs, Cora M.; de Lange, Judith L.; Meijers-Heijboer, Hanne E.J.; Oosterwijk, Jan C.; van Asperen, Christi J.; García, Encarna B. Gómez; Hoogerbrugge, Nicoline; Jager, Agnes; van der Luijt, Rob B.; Easton, Douglas F.; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Evans, D. Gareth; Lalloo, Fiona; Izatt, Louise; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Brewer, Carole; Tischkowitz, Marc; Godwin, Andrew K.; Pathak, Harsh; Stoppa-Lyonnet, Dominique; Sinilnikova, Olga M.; Mazoyer, Sylvie; Barjhoux, Laure; Léoné, Mélanie; Gauthier-Villars, Marion; Caux-Moncoutier, Virginie; de Pauw, Antoine; Hardouin, Agnès; Berthet, Pascaline; Dreyfus, Hélène; Ferrer, Sandra Fert; Collonge-Rame, Marie-Agnès; Sokolowska, Johanna; Buys, Saundra; Daly, Mary; Miron, Alex; Terry, Mary Beth; Chung, Wendy; John, Esther M; Southey, Melissa; Goldgar, David; Singer, Christian F; Maria, Muy-Kheng Tea; Gschwantler-Kaulich, Daphne; Fink-Retter, Anneliese; Hansen, Thomas v. O.; Ejlertsen, Bent; Johannsson, Oskar Th.; Offit, Kenneth; Sarrel, Kara; Gaudet, Mia M.; Vijai, Joseph; Robson, Mark; Piedmonte, Marion R; Andrews, Lesley; Cohn, David; DeMars, Leslie R.; DiSilvestro, Paul; Rodriguez, Gustavo; Toland, Amanda Ewart; Montagna, Marco; Agata, Simona; Imyanitov, Evgeny; Isaacs, Claudine; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Ignacio; Ramus, Susan J; Sucheston, Lara; Karlan, Beth Y.; Gross, Jenny; Ganz, Patricia A.; Beattie, Mary S.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Meindl, Alfons; Arnold, Norbert; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorotehea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Nevanlinna, Heli; Aittomäki, Kristiina; Simard, Jacques; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Tomlinson, Gail E.; Weitzel, Jeffrey; Garber, Judy E.; Olopade, Olufunmilayo I.; Rubinstein, Wendy S.; Tung, Nadine; Blum, Joanne L.; Narod, Steven A.; Brummel, Sean; Gillen, Daniel L.; Lindor, Noralane; Fredericksen, Zachary; Pankratz, Vernon S.; Couch, Fergus J.; Radice, Paolo; Peterlongo, Paolo; Greene, Mark H.; Loud, Jennifer T.; Mai, Phuong L.; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Gerdes, Anne-Marie; Thomassen, Mads; Jensen, Uffe Birk; Skytte, Anne-Bine; Caligo, Maria A.; Lee, Andrew; Chenevix-Trench, Georgia; Antoniou, Antonis C; Neuhausen, Susan L.

2012-01-01

Background We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers. Methods IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers. Results Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 [Hazard ratio (HR) = 1.43; 95% CI: 1.06–1.92; p = 0.019] and BRCA2 mutation carriers (HR=2.21; 95% CI: 1.39–3.52, p=0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class 2 mutations than class 1 (mutations (class 2 HR=1.86, 95% CI: 1.28–2.70; class 1 HR=0.86, 95%CI:0.69–1.09; p-for difference=0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class 2 mutation carriers (HR = 2.42; p = 0.03). Conclusion The IRS1 Gly972Arg SNP, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class 2 mutation carriers. Impact These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers. PMID:22729394
A novel duplication polymorphism in the FANCA promoter and its association with breast and ovarian cancer

International Nuclear Information System (INIS)

Thompson, Ella; Dragovic, Rebecca L; Stephenson, Sally-Anne; Eccles, Diana M; Campbell, Ian G; Dobrovic, Alexander

2005-01-01

The FANCA gene is one of the genes in which mutations lead to Fanconi anaemia, a rare autosomal recessive disorder characterised by congenital abnormalities, bone marrow failure, and predisposition to malignancy. FANCA is also a potential breast and ovarian cancer susceptibility gene. A novel allele was identified which has a tandem duplication of a 13 base pair sequence in the promoter region. We screened germline DNA from 352 breast cancer patients, 390 ovarian cancer patients and 256 normal controls to determine if the presence of either of these two alleles was associated with an increased risk of breast or ovarian cancer. The duplication allele had a frequency of 0.34 in the normal controls. There was a non-significant decrease in the frequency of the duplication allele in breast cancer patients. The frequency of the duplication allele was significantly decreased in ovarian cancer patients. However, when malignant and benign tumours were considered separately, the decrease was only significant in benign tumours. The allele with the tandem duplication does not appear to modify breast cancer risk but may act as a low penetrance protective allele for ovarian cancer
A novel duplication polymorphism in the FANCA promoter and its association with breast and ovarian cancer.

Science.gov (United States)

Thompson, Ella; Dragovic, Rebecca L; Stephenson, Sally-Anne; Eccles, Diana M; Campbell, Ian G; Dobrovic, Alexander

2005-04-29

The FANCA gene is one of the genes in which mutations lead to Fanconi anaemia, a rare autosomal recessive disorder characterised by congenital abnormalities, bone marrow failure, and predisposition to malignancy. FANCA is also a potential breast and ovarian cancer susceptibility gene. A novel allele was identified which has a tandem duplication of a 13 base pair sequence in the promoter region. We screened germline DNA from 352 breast cancer patients, 390 ovarian cancer patients and 256 normal controls to determine if the presence of either of these two alleles was associated with an increased risk of breast or ovarian cancer. The duplication allele had a frequency of 0.34 in the normal controls. There was a non-significant decrease in the frequency of the duplication allele in breast cancer patients. The frequency of the duplication allele was significantly decreased in ovarian cancer patients. However, when malignant and benign tumours were considered separately, the decrease was only significant in benign tumours. The allele with the tandem duplication does not appear to modify breast cancer risk but may act as a low penetrance protective allele for ovarian cancer.
A novel duplication polymorphism in the FANCA promoter and its association with breast and ovarian cancer

Directory of Open Access Journals (Sweden)

Campbell Ian G

2005-04-01

Full Text Available Abstract The FANCA gene is one of the genes in which mutations lead to Fanconi anaemia, a rare autosomal recessive disorder characterised by congenital abnormalities, bone marrow failure, and predisposition to malignancy. FANCA is also a potential breast and ovarian cancer susceptibility gene. A novel allele was identified which has a tandem duplication of a 13 base pair sequence in the promoter region. Methods We screened germline DNA from 352 breast cancer patients, 390 ovarian cancer patients and 256 normal controls to determine if the presence of either of these two alleles was associated with an increased risk of breast or ovarian cancer. Results The duplication allele had a frequency of 0.34 in the normal controls. There was a non-significant decrease in the frequency of the duplication allele in breast cancer patients. The frequency of the duplication allele was significantly decreased in ovarian cancer patients. However, when malignant and benign tumours were considered separately, the decrease was only significant in benign tumours. Conclusion The allele with the tandem duplication does not appear to modify breast cancer risk but may act as a low penetrance protective allele for ovarian cancer.
A novel approach to breast cancer prevention: reducing excessive ovarian androgen production in elderly women.

Science.gov (United States)

Secreto, Giorgio; Sieri, Sabina; Agnoli, Claudia; Grioni, Sara; Muti, Paola; Zumoff, Barnett; Sant, Milena; Meneghini, Elisabetta; Krogh, Vittorio

2016-08-01

Minimizing endogenous estrogen production and activity in women at high risk for breast cancer is a prominent approach to prevention of the disease. A number of clinical trials have shown that the administration of selective-estrogen receptor modulators or aromatase inhibitors significantly reduces the incidence of breast cancer in healthy women. Unfortunately, these drugs often produce adverse effects on the quality of life and are, therefore, poorly accepted by many women, even those who are at high risk for breast cancer. We propose a novel alternative approach to decreasing estrogen production: suppression of ovarian synthesis of the androgen precursors of estrogens by administration of long-acting gonadotropin-releasing hormone analogs to women with ovarian stromal hyperplasia. The specific target population would be elderly postmenopausal women, at increased risk of breast cancer, and with high blood levels of testosterone, marker of ovarian hyperandrogenemia, and recognized factor of risk for breast cancer. Testosterone levels are measured at baseline to identify women at risk and during the follow-up to evaluate the effectiveness of therapy. The postmenopausal ovary is an important source of excessive androgen production which originates from the ovarian interstitial cell hyperplasia frequently present in breast cancer patients. We propose to counter the source of androgen excess in women with ovarian stromal hyperplasia, thus reducing the substrate for estrogen formation without completely inhibiting estrogen synthesis. Available evidence indicates that gonadotropin-releasing hormone analogs can be safely used for breast cancer prevention in postmenopausal women.
Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

Energy Technology Data Exchange (ETDEWEB)

Erez, Neta, E-mail: netaerez@post.tau.ac.il [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Glanz, Sarah [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Raz, Yael [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Department of Obstetrics and Gynecology, LIS Maternity Hospital, Tel Aviv Sourasky Medical Center, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Avivi, Camilla [Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Barshack, Iris [Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel-Aviv 69978 (Israel); Department of Pathology, Sheba Medical Center, Tel Hashomer, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel)

2013-08-02

Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- Abstract: Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics.
Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

International Nuclear Information System (INIS)

Erez, Neta; Glanz, Sarah; Raz, Yael; Avivi, Camilla; Barshack, Iris

2013-01-01

Highlights: •CAFs in human breast and ovarian tumors express pro-inflammatory factors. •Expression of pro-inflammatory factors correlates with tumor invasiveness. •Expression of pro-inflammatory factors is associated with NF-κb activation in CAFs. -- Abstract: Inflammation has been established in recent years as a hallmark of cancer. Cancer Associated Fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation and invasion. We previously demonstrated that CAFs also mediate tumor-enhancing inflammation in a mouse model of skin carcinoma. Breast and ovarian carcinomas are amongst the leading causes of cancer-related mortality in women and cancer-related inflammation is linked with both these tumor types. However, the role of CAFs in mediating inflammation in these malignancies remains obscure. Here we show that CAFs in human breast and ovarian tumors express high levels of the pro-inflammatory factors IL-6, COX-2 and CXCL1, previously identified to be part of a CAF pro-inflammatory gene signature. Moreover, we show that both pro-inflammatory signaling by CAFs and leukocyte infiltration of tumors are enhanced in invasive ductal carcinoma as compared with ductal carcinoma in situ. The pro-inflammatory genes expressed by CAFs are known NF-κB targets and we show that NF-κB is up-regulated in breast and ovarian CAFs. Our data imply that CAFs mediate tumor-promoting inflammation in human breast and ovarian tumors and thus may be an attractive target for stromal-directed therapeutics
Ovarian and Breast Cancer Spheres Are Similar in Transcriptomic Features and Sensitive to Fenretinide

Directory of Open Access Journals (Sweden)

Haiwei Wang

2013-01-01

Full Text Available Cancer stem cells (CSCs are resistant to chemotherapy and are ability to regenerate cancer cell populations, thus attracting much attention in cancer research. In this report, we first demonstrated that sphere cells from ovarian cancer cell line A2780 shared many features of CSCs, such as resistance to cisplatin and able to initiate tumors in an efficient manner. Then, we conducted cDNA microarray analysis on spheres from ovarian A2780 cells, and from breast MCF7 and SUM159 cells, and found that molecular pathways underlying spheres from these cancer cell lines were similar to a large extent, suggesting that similar mechanisms are involved in the genesis of CSCs in both ovarian and breast cancer types. In addition, we showed that spheres from these cancer types were highly sensitive to fenretinide, a stimulus of oxidative stress-mediated apoptosis in cancer cells. Thus, our results not only provide important insights into mechanisms underlying CSCs in ovarian and breast cancer, but also lead to the development of more sophisticated protocols of cancer therapy in near future.
Prevention and Screening in Hereditary Breast and Ovarian Cancer.

Science.gov (United States)

Zeichner, Simon B; Stanislaw, Christine; Meisel, Jane L

2016-10-15

In recent years, we have learned a great deal about pathogenic mutations that increase the risk of breast and ovarian cancer, particularly mutations in the BRCA1 and BRCA2 genes. Here we review current guidelines on breast and ovarian cancer screening, prophylactic surgery, and other risk-reduction strategies in patients with these mutations, and we detail the data that drive these recommendations. We also discuss guidelines on screening and management for other cancers associated with BRCA1 and BRCA2, such as male breast cancer, pancreatic cancer, and prostate cancer. Discussions about genetic testing have become more complex with the advent of panel testing, which often allows for testing of a more comprehensive panel of genes than traditional BRCA1 and BRCA2 testing, but which is also associated with a higher likelihood of obtaining results with less clear data to inform management. It is difficult to come to a consensus on how best to address the varied and potentially challenging situations that may arise from genetic testing. The complexity inherent in managing these cases makes a multidisciplinary team-including medical oncologists, surgical oncologists, genetic counselors, reproductive endocrinologists, and medical ethicists-critical to optimization of care.
Pizza consumption and the risk of breast, ovarian and prostate cancer.

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Gallus, Silvano; Talamini, Renato; Bosetti, Cristina; Negri, Eva; Montella, Maurizio; Franceschi, Silvia; Giacosa, Attilio; La Vecchia, Carlo

2006-02-01

Pizza has been favourably related to the risk of prostate cancer in North America. Scanty information, however, is available on sex hormone-related cancer sites. We therefore studied the role of pizza consumption on the risk of breast, ovarian and prostate cancers using data from three hospital-based case-control studies conducted in Italy between 1991 and 2002. These included 2569 women with breast cancer, 1031 with ovarian cancer, 1294 men with prostate cancer, and a total of 4864 controls. Compared with non-pizza eaters, the multivariate odds ratios for eaters were 0.97 (95% confidence interval (CI) 0.86-1.10) for breast, 1.06 (95% CI 0.89-1.26) for ovarian and 1.04 (95% CI 0.88-1.23) for prostate cancer. Corresponding estimates for regular eaters (i.e. > or =1 portion per week) were 0.92 (95% CI 0.78-1.08), 1.00 (95% CI 0.80-1.25) and 1.12 (95% CI 0.88-1.43), respectively. Our results do not show a relevant role of pizza on the risk of sex hormone-related cancers. The difference with selected studies from North America suggests that dietary and lifestyle correlates of pizza eating vary between different populations and social groups.
Lactose intolerance and risk of lung, breast and ovarian cancers: aetiological clues from a population-based study in Sweden.

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Ji, J; Sundquist, J; Sundquist, K

2015-01-06

Individuals with lactose intolerance are recommended to avoid milk or dairy products, which may affect the development of cancer. We identified individuals with lactose intolerance from several Swedish Registers linked to the Swedish Cancer Registry to calculate standardised incidence ratios (SIRs) for cancers in the breast, lung, and ovary. A total of 22,788 individuals with lactose intolerance were identified, and their risks of lung (SIR=0.55), breast (SIR=0.79), and ovarian (SIR=0.61) cancers were significantly decreased. Cancer incidences in the siblings and parents of individuals with lactose intolerance were similar to those in the general population. In this large cohort study, people with lactose intolerance, characterised by low consumption of milk and other dairy products, had decreased risks of lung, breast, and ovarian cancers, but the decreased risks were not found in their family members, suggesting that the protective effects against these cancers may be related to their specific dietary pattern.
Effective Referral of Low-Income Women at Risk for Hereditary Breast and Ovarian Cancer to Genetic Counseling: A Randomized Delayed Intervention Control Trial.

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Pasick, Rena J; Joseph, Galen; Stewart, Susan; Kaplan, Celia; Lee, Robin; Luce, Judith; Davis, Sharon; Marquez, Titas; Nguyen, Tung; Guerra, Claudia

2016-10-01

To determine the effectiveness of a statewide telephone service in identifying low-income women at risk for hereditary breast and ovarian cancer and referring them to free genetic counseling. From June 2010 through August 2011, eligible callers to California's toll-free breast and cervical cancer telephone service were screened for their family histories of breast and ovarian cancer. High-risk women were identified and called for a baseline survey and randomization to an immediate offer of genetic counseling or a mailed brochure on how to obtain counseling. Clinic records were used to assess receipt of genetic counseling after 2 months. Among 1212 eligible callers, 709 (58.5%) agreed to answer family history questions; 102 (14%) were at high risk (25% Hispanic, 46% White, 10% Black, 16% Asian, 3% of other racial/ethnic backgrounds). Of the high-risk women offered an immediate appointment, 39% received counseling during the intervention period, as compared with 4.5% of those receiving the brochure. A public health approach to the rare but serious risk of hereditary breast and ovarian cancer can be successful when integrated into the efforts of existing safety net organizations.
Paternal lineage early onset hereditary ovarian cancers: A Familial Ovarian Cancer Registry study.

Directory of Open Access Journals (Sweden)

Kevin H Eng

2018-02-01

Full Text Available Given prior evidence that an affected woman conveys a higher risk of ovarian cancer to her sister than to her mother, we hypothesized that there exists an X-linked variant evidenced by transmission to a woman from her paternal grandmother via her father. We ascertained 3,499 grandmother/granddaughter pairs from the Familial Ovarian Cancer Registry at the Roswell Park Cancer Institute observing 892 informative pairs with 157 affected granddaughters. We performed germline X-chromosome exome sequencing on 186 women with ovarian cancer from the registry. The rate of cancers was 28.4% in paternal grandmother/granddaughter pairs and 13.9% in maternal pairs consistent with an X-linked dominant model (Chi-square test X2 = 0.02, p = 0.89 and inconsistent with an autosomal dominant model (X2 = 20.4, p<0.001. Paternal grandmother cases had an earlier age-of-onset versus maternal cases (hazard ratio HR = 1.59, 95%CI: 1.12-2.25 independent of BRCA1/2 status. Reinforcing the X-linked hypothesis, we observed an association between prostate cancer in men and ovarian cancer in his mother and daughters (odds ratio, OR = 2.34, p = 0.034. Unaffected mothers with affected daughters produced significantly more daughters than sons (ratio = 1.96, p<0.005. We performed exome sequencing in reported BRCA negative cases from the registry. Considering age-of-onset, one missense variant (rs176026 in MAGEC3 reached chromosome-wide significance (Hazard ratio HR = 2.85, 95%CI: 1.75-4.65 advancing the age of onset by 6.7 years. In addition to the well-known contribution of BRCA, we demonstrate that a genetic locus on the X-chromosome contributes to ovarian cancer risk. An X-linked pattern of inheritance has implications for genetic risk stratification. Women with an affected paternal grandmother and sisters of affected women are at increased risk for ovarian cancer. Further work is required to validate this variant and to characterize carrier families.
The Impact of Mental Illness on Uptake of Genetic Counseling for Hereditary Breast Cancer and Ovarian Cancer in a Multiethnic Cohort of Breast Cancer Patients.

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Ackerman, Marra G; Shapiro, Peter A; Coe, Austin; Trivedi, Meghna S; Crew, Katherine D

2017-09-01

We evaluated whether mental illness is a barrier to genetic counseling for hereditary breast and ovarian cancer (HBOC) in multiethnic breast cancer patients. We conducted a retrospective analysis of 308 women with newly diagnosed breast cancer and eligible for HBOC genetic testing seen in the breast clinic of an academic, urban medical center from 2007 to 2015. Uptake of genetic services and history of mental health disorder (MHD), defined as a psychiatric diagnosis or treatment with an antidepressant, mood stabilizer, anxiolytic, or antipsychotic medication, were ascertained by medical chart review. The mean age at breast cancer diagnosis was 56 years, with 44% non-Hispanic whites, 37% Hispanics, and 15% non-Hispanic blacks. Ninety-nine (32%) women met study criteria for MHD, 73% had a genetics referral, 57% had genetic counseling, and 54% completed BRCA testing. Uptake of genetic counseling services did not differ by race/ethnicity or presence of MHD. In multivariable analysis, younger age at diagnosis, Ashkenazi Jewish heritage, and family history of breast cancer were associated with HBOC genetic counseling. A relatively high proportion of breast cancer patients eligible for HBOC genetic testing were referred to a genetic counselor and referral status did not vary by MHD or race/ethnicity. © 2017 Wiley Periodicals, Inc.
Does the diagnosis of breast or ovarian cancer trigger referral to genetic counseling?

Science.gov (United States)

Powell, C Bethan; Littell, Ramey; Hoodfar, Elizabeth; Sinclair, Fiona; Pressman, Alice

2013-03-01

Kaiser Permanente Northern California is a large integrated health care delivery system in the United States that has guidelines for referring women with newly diagnosed BRCA1-and BRCA2-associated cancers for genetic counseling. This study assesses adherence to genetic counseling referral guidelines within this health system. Chart review was performed to identify patients with cancer who met the following pathology-based Kaiser Permanente Northern California guidelines for referral for genetic counseling: invasive breast cancer, younger than age 40; nonmucinous epithelial ovarian, fallopian tube, or peritoneal cancer, younger than age 60; women with synchronous or metachronous primary cancers of the breast and ovaries; and male breast cancer. We assessed compliance with referral guidelines. An electronic notice was sent to the managing physician of patients with newly diagnosed cancer to assess the feasibility of this intervention. A total of 340 patients were identified with breast cancer at younger than age 40 or with ovarian, peritoneal, or tubal cancer between January and June, 2008. Upon chart review, 105 of these patients met pathology-based criteria for referral to genetic counseling, of whom 47 (45%) were referred within the 2-year study period. Of the 67 subjects with breast cancer, 40 subjects (60%) were referred. In contrast, only 7 (21%) of 33 patients with ovarian cancer were referred (P < 0.001). A pilot study was performed to test the feasibility of notifying managing oncologists with an electronic letter alerting them of eligibility for genetic referral of patients with new diagnosis (n = 21). In the 3 to 6 months after this notification, 12 of these 21 patients were referred for counseling including 5 of 7 patients with a diagnosis of ovarian cancer. There is a missed opportunity for referring patients to genetic counseling, especially among patients with ovarian cancer. A pilot study suggests that alerting treating physicians is a feasible
No germline mutations in the histone acetyltransferase gene EP300 in BRCA1 and BRCA2 negative families with breast cancer and gastric, pancreatic, or colorectal cancer

International Nuclear Information System (INIS)

Campbell, Ian G; Choong, David; Chenevix-Trench, Georgia

2004-01-01

Mutations in BRCA1, BRCA2, ATM, TP53, CHK2 and PTEN account for many, but not all, multiple-case breast and ovarian cancer families. The histone acetyltransferase gene EP300 may function as a tumour suppressor gene because it is sometimes somatically mutated in breast, colorectal, gastric and pancreatic cancers, and is located on a region of chromosome 22 that frequently undergoes loss of heterozygosity in many cancer types. We hypothesized that germline mutations in EP300 may account for some breast cancer families that include cases of gastric, pancreatic and/or colorectal cancer. We screened the entire coding region of EP300 for mutations in the youngest affected members of 23 non-BRCA1/BRCA2 breast cancer families with at least one confirmed case of gastric, pancreatic and/or colorectal cancer. These families were ascertained in Australia through the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer. Denaturing HPLC analysis identified a heterozygous alteration at codon 211, specifically a GGC to AGC (glycine to serine) alteration, in two individuals. This conservative amino acid change was not within any known functional domains of EP300. The frequency of the Ser211 variant did not differ significanlty between a series of 352 breast cancer patients (4.0%) and 254 control individuals (2.8%; P = 0.5). The present study does not support a major role for EP300 mutations in breast and ovarian cancer families with a history of gastric, pancreatic and/or colorectal cancer
Molecular genetics analysis of hereditary breast and ovarian cancer patients in India

Directory of Open Access Journals (Sweden)

Soumittra Nagasamy

2009-08-01

Full Text Available Abstract Background Hereditary cancers account for 5–10% of cancers. In this study BRCA1, BRCA2 and CHEK2*(1100delC were analyzed for mutations in 91 HBOC/HBC/HOC families and early onset breast and early onset ovarian cancer cases. Methods PCR-DHPLC was used for mutation screening followed by DNA sequencing for identification and confirmation of mutations. Kaplan-Meier survival probabilities were computed for five-year survival data on Breast and Ovarian cancer cases separately, and differences were tested using the Log-rank test. Results Fifteen (16% pathogenic mutations (12 in BRCA1 and 3 in BRCA2, of which six were novel BRCA1 mutations were identified. None of the cases showed CHEK2*1100delC mutation. Many reported polymorphisms in the exonic and intronic regions of BRCA1 and BRCA2 were also seen. The mutation status and the polymorphisms were analyzed for association with the clinico-pathological features like age, stage, grade, histology, disease status, survival (overall and disease free and with prognostic molecular markers (ER, PR, c-erbB2 and p53. Conclusion The stage of the disease at diagnosis was the only statistically significant (p
Activity of mevalonate pathway inhibitors against breast and ovarian cancers in the ATP-based tumour chemosensitivity assay

International Nuclear Information System (INIS)

Knight, Louise A; Kurbacher, Christian M; Glaysher, Sharon; Fernando, Augusta; Reichelt, Ralf; Dexel, Susanne; Reinhold, Uwe; Cree, Ian A

2009-01-01

Previous data suggest that lipophilic statins such as fluvastatin and N-bisphosphonates such as zoledronic acid, both inhibitors of the mevalonate metabolic pathway, have anti-cancer effects in vitro and in patients. We have examined the effect of fluvastatin alone and in combination with zoledronic acid in the ATP-based tumour chemosensitivity assay (ATP-TCA) for effects on breast and ovarian cancer tumour-derived cells. Both zoledronic acid and fluvastatin showed activity in the ATP-TCA against breast and ovarian cancer, though fluvastatin alone was less active, particularly against breast cancer. The combination of zoledronic acid and fluvastatin was more active than either single agent in the ATP-TCA with some synergy against breast and ovarian cancer tumour-derived cells. Sequential drug experiments showed that pre-treatment of ovarian tumour cells with fluvastatin resulted in decreased sensitivity to zoledronic acid. Addition of mevalonate pathway components with zoledronic acid with or without fluvastatin showed little effect, while mevalonate did reduced inhibition due to fluvastatin. These data suggest that the combination of zoledronic acid and fluvastatin may have activity against breast and ovarian cancer based on direct anti-cancer cell effects. A clinical trial to test this is in preparation

Validation of the Manchester scoring system for predicting BRCA1/2 mutations in 9,390 families suspected of having hereditary breast and ovarian cancer.

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Kast, Karin; Schmutzler, Rita K; Rhiem, Kerstin; Kiechle, Marion; Fischer, Christine; Niederacher, Dieter; Arnold, Norbert; Grimm, Tiemo; Speiser, Dorothee; Schlegelberger, Brigitte; Varga, Dominic; Horvath, Judit; Beer, Marit; Briest, Susanne; Meindl, Alfons; Engel, Christoph

2014-11-15

The Manchester scoring system (MSS) allows the calculation of the probability for the presence of mutations in BRCA1 or BRCA2 genes in families suspected of having hereditary breast and ovarian cancer. In 9,390 families, we determined the predictive performance of the MSS without (MSS-2004) and with (MSS-2009) consideration of pathology parameters. Moreover, we validated a recalibrated version of the MSS-2009 (MSS-recal). Families were included in the registry of the German Consortium for Hereditary Breast and Ovarian Cancer, using defined clinical criteria. Receiver operating characteristics (ROC) analysis was used to determine the predictive performance. The recalibrated model was developed using logistic regression analysis and tested using an independent random validation sample. The area under the ROC curves regarding a mutation in any of the two BRCA genes was 0.77 (95%CI 0.75-0.79) for MSS-2004, 0.80 (95%CI 0.78-0.82) for MSS-2009, and 0.82 (95%CI 0.80-0.83) for MSS-recal. Sensitivity at the 10% mutation probability cutoff was similar for all three models (MSS-2004 92.2%, MSS-2009 92.2%, and MSS-recal 90.3%), but specificity of MSS-recal (46.0%) was considerably higher than that of MSS-2004 (25.4%) and MSS-2009 (32.3%). In the MSS-recal model, almost all predictors of the original MSS were significantly predictive. However, the score values of some predictors, for example, high grade triple negative breast cancers, differed considerably from the originally proposed score values. The original MSS performed well in our sample of high risk families. The use of pathological parameters increased the predictive performance significantly. Recalibration improved the specificity considerably without losing much sensitivity. © 2014 UICC.
BRCA2 Polymorphic Stop Codon K3326X and the Risk of Breast, Prostate, and Ovarian Cancers

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Meeks, Huong D; Song, Honglin; Michailidou, Kyriaki

2016-01-01

3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1...... and for estrogen receptor-negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10(-5) and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10(-5), respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.......43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. CONCLUSIONS: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2...
Polycystic ovary syndrome and risk of endometrial, ovarian, and breast cancer: a systematic review.

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Harris, Holly R; Terry, Kathryn L

2016-01-01

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with an estimated prevalence of 4-21% in reproductive aged women. The altered metabolic and hormonal environment among women with PCOS may increase their risk of some types of cancer. We performed a comprehensive review of the literature using numerous search terms for all studies examining the associations between polycystic ovary syndrome and related characteristics and cancer published in English through October 2016. This review summarizes the epidemiological findings on the associations between PCOS and endometrial, ovarian, and breast cancers and discusses the methodological issues, complexities, and underlying mechanisms of these associations. We identified 11 individual studies and 3 meta-analyses on the associations between PCOS and endometrial cancer, 8 studies and 1 meta-analysis for ovarian cancer, and 10 studies and 1 meta-analysis for breast cancer. Multiple studies reported that women with PCOS were at a higher risk for endometrial cancer; however, many did not take into account body mass index (BMI), a strong and well-established risk factor for endometrial cancer. The association with ovarian cancer was less clear, but a potentially increased risk of the borderline serous subtype was reported by two studies. No consistent association between PCOS risk and breast cancer was observed. The associations between PCOS and endometrial, ovarian, and breast cancer are complex, with the need to consider many methodological issues in future analyses. Larger well-designed studies, or pooled analyses, may help clarify these complex associations.
Components of family history associated with women's disease perceptions for cancer: a report from the Family Healthware™ Impact Trial.

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Rubinstein, Wendy S; O'neill, Suzanne M; Rothrock, Nan; Starzyk, Erin J; Beaumont, Jennifer L; Acheson, Louise S; Wang, Catharine; Gramling, Robert; Galliher, James M; Ruffin, Mack T

2011-01-01

To determine the specific components of family history and personal characteristics related to disease perceptions about breast, colon, and ovarian cancers. Baseline, cross-sectional data on 2,505 healthy women aged 35-65 years enrolled from 41 primary care practices in the cluster-randomized Family Healthware™ Impact Trial, assessed for detailed family history and perceived risk, perceived severity, worry, and perceived control over getting six common diseases including breast, colon, and ovarian cancers. Participants provided family history information on 41,841 total relatives. We found evidence of underreporting of paternal family history and lower perceived breast cancer risk with cancer in the paternal versus maternal lineage. We observed cancer-specific perceived risks and worry for individual family history elements and also found novel "spillover" effects where a family history of one cancer was associated with altered disease perceptions of another. Having a mother with early-onset breast or ovarian cancer was strongly associated with perceived risk of breast cancer. Age, parenthood, and affected lineage were associated with disease perceptions and ran counter to empiric risks. Understanding patients' formulation of risk for multiple diseases is important for public health initiatives that seek to inform risk appraisal, influence disease perceptions, or match preventive interventions to existing risk perceptions.
Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study

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Song, Honglin; Ramus, Susan J; Kjaer, Susanne Krüger

2009-01-01

Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasiv...
Familial associations between polycystic ovarian syndrome and common diseases.

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Moini, Ashraf; Eslami, Bita

2009-03-01

The goal of this study was focused on two subjects. First, to determine possible association between PCOS and family history of breast cancer, ovarian cancer, endometrial cancer, heart attack, thrombosis, diabetes and cardiovascular disease (CVD). Second, to evaluate maternal and paternal transmission in PCOS patients with positive family history of a disease. A cross-sectional study was conducted in 549 infertile women (273 with PCOS and 276 controls) in Arash hospital of Tehran, Iran, between 2007 and 2008 by using questionnaire. In this analysis, there were significantly increased number of women with the positive family history of diabetes among PCOS group (28.21% vs. 19.20%, p=0.01). Meanwhile, four women in PCOS group had self history of diabetes while no one in the control group reported diabetes. A statistically significant positive family history of breast cancer was found among the control group (4.35% vs. 1.30%, p=0.02). Endometrial cancer and diabetes were observed in mother or mother's side of the family but heart attack and thrombosis manifested in father or father's side of the family more. There were no statistically significant differences in a positive individual or family history of ovarian cancer, endometrial cancer, heart attack, thrombosis and CVD between the two groups. In the present study, women and their relatives with PCOS had an increased prevalence of diabetes and it is more common in mother's side of the family.
Features of ovarian cancer in Lynch syndrome (Review).

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Nakamura, Kanako; Banno, Kouji; Yanokura, Megumi; Iida, Miho; Adachi, Masataka; Masuda, Kenta; Ueki, Arisa; Kobayashi, Yusuke; Nomura, Hiroyuki; Hirasawa, Akira; Tominaga, Eiichiro; Aoki, Daisuke

2014-11-01

Lynch syndrome is a hereditary ovarian cancer with a prevalence of 0.9-2.7%. Lynch syndrome accounts for 10-15% of hereditary ovarian cancers, while hereditary breast and ovarian cancer syndrome accounts for 65-75% of these cancers. The lifetime risk for ovarian cancer in families with Lynch syndrome is ~8%, which is lower than colorectal and endometrial cancers, and ovarian cancer is not listed in the Amsterdam Criteria II. More than half of sporadic ovarian cancers are diagnosed in stage III or IV, but ≥80% of ovarian cancers in Lynch syndrome are diagnosed in stage I or II. Ovarian cancers in Lynch syndrome mostly have non-serous histology and different properties from those of sporadic ovarian cancers. A screening method for ovarian cancers in Lynch syndrome has yet to be established and clinical studies of prophylactic administration of oral contraceptives are not available. However, molecular profiles at the genetic level indicate that ovarian cancer in Lynch syndrome has a more favorable prognosis than sporadic ovarian cancer. Inhibitors of the phosphatidylinositol 3-kinase/mammalian target of the rapamycin pathway and anti-epidermal growth factor antibodies may have efficacy for the disease. To the best of our knowledge, this is the first review focusing on ovarian cancer in Lynch syndrome.
A novel BRCA-1 mutation in Arab kindred from east Jerusalem with breast and ovarian cancer

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Nissan Aviram

2007-01-01

Full Text Available Abstract Background The incidence of breast cancer (BC in Arab women is lower compared to the incidence in the Jewish population in Israel; still, it is the most common malignancy among Arab women. There is a steep rise in breast cancer incidence in the Arab population in Israel over the last 10 years that can be attributed to life style changes. But, the younger age of BC onset in Arab women compared with that of the Jewish population is suggestive of a genetic component in BC occurrence in that population. Methods We studied the family history of 31 women of Palestinian Arab (PA origin affected with breast (n = 28, ovarian (n = 3 cancer. We used denaturing high performance liquid chromatography (DHPLC to screen for mutations of BRCA1/2 in 4 women with a personal and family history highly suggestive of genetic predisposition. Results A novel BRCA1 mutation, E1373X in exon 12, was found in a patient affected with ovarian cancer. Four of her family members, 3 BC patients and a healthy individual were consequently also found to carry this mutation. Of the other 27 patients, which were screened for this specific mutation none was found to carry it. Conclusion We found a novel BRCA1 mutation in a family of PA origin with a history highly compatible with BRCA1 phenotype. This mutation was not found in additional 30 PA women affected with BC or OC. Therefore full BRCA1/2 screening should be offered to patients with characteristic family history. The significance of the novel BRCA1 mutation we identified should be studied in larger population. However, it is likely that the E1373X mutation is not a founder frequent mutation in the PA population.
The current social, political, and medical role of genetic testing in familial breast and ovarian carcinomas.

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Weitzel, J N

1999-02-01

Few advances in medical science have yielded as much publicity and controversy as discoveries in genetics. Moving quickly from the bench to the bedside, genetic testing for inherited susceptibility to breast and ovarian cancer has had a significant impact on our paradigms for decisions about the treatment and prevention of disease. Assessment of cancer risk is developing into a distinct discipline, with rapidly evolving genetic technologies and models for estimating an individual's risk of cancer. Exciting developments in chemoprevention of breast cancer demonstrate the potential to offer a broader range of options for decreasing cancer risk. This article will consider recent advances in the understanding of cancer genetics, and describe the state-of-the-art in terms of management of individuals with inherited susceptibility to breast and ovarian cancer.
Pretreatment anti-Müllerian hormone predicts for loss of ovarian function after chemotherapy for early breast cancer

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Anderson, Richard A; Rosendahl, Mikkel; Kelsey, Thomas W

2013-01-01

Improving survival for women with early breast cancer (eBC) requires greater attention to the consequences of treatment, including risk to ovarian function. We have assessed whether biochemical markers of the ovarian reserve might improve prediction of chemotherapy related amenorrhoea.......Improving survival for women with early breast cancer (eBC) requires greater attention to the consequences of treatment, including risk to ovarian function. We have assessed whether biochemical markers of the ovarian reserve might improve prediction of chemotherapy related amenorrhoea....
Bilateral Salpingo-Oophorectomy Versus GnRH Analogue in the Adjuvant Treatment of Premenopausal Breast Cancer Patients: Cost-Effectiveness Evaluation of Breast Cancer Outcome, Ovarian Cancer Prevention and Treatment.

Science.gov (United States)

Ferrandina, Gabriella; Amadio, Giulia; Marcellusi, Andrea; Azzolini, Elena; Puggina, Anna; Pastorino, Roberta; Ricciardi, Walter; Scambia, Giovanni

2017-11-01

BACKGROUND AND OBJECTIVE: There is no available evidence to recommend gonadotropin-releasing hormone (GnRH) analogue-based ovarian suppression versus bilateral salpingo-oophorectomy (BSO) in the adjuvant treatment of early breast cancer, since the two approaches are considered equivalent in terms of oncologic outcome. The role of surgical ovarian ablation has been revitalized based on the advances of minimally invasive surgery, and a better understanding of clinical and molecular basis of hereditary breast/ovarian cancer syndromes. The aim of this study is to analyze the cost-effectiveness of laparoscopic BSO and GnRH analogue administration in patients aged 40-49 years with hormone-sensitive breast cancer. A probabilistic decision tree model was developed to evaluate costs and outcomes of ovarian ablation through laparoscopic BSO, or ovarian suppression through monthly injections of GnRH analogue. Results were expressed as incremental costs per quality-adjusted life years (QALYs) gained. Laparoscopic BSO strategy was associated with a lower mean total cost per patient than GnRH treatment, and considering the difference in terms of QALYs, the incremental effectiveness did not demonstrate a notable difference between the two approaches. From the National Health Service perspective, and for a time horizon of 5 years, laparoscopic BSO was the dominant option compared to GnRH treatment; laparoscopic BSO was less expensive than GnRH, €2385 [95% confidence interval (CI) = 2044, 2753] vs €7093 (95% CI = 3409, 12,105), respectively, and more effective. Surgical ovarian ablation is more cost-effective than GnRH administration in the adjuvant treatment of hormone-sensitive breast cancer patients aged 40-49 years, and the advantage of preventing ovarian cancer through laparoscopic BSO should be considered.
Molecular genetics analysis of hereditary breast and ovarian cancer patients in India

Science.gov (United States)

Soumittra, Nagasamy; Meenakumari, Balaiah; Parija, Tithi; Sridevi, Veluswami; Nancy, Karunakaran N; Swaminathan, Rajaraman; Rajalekshmy, Kamalalayam R; Majhi, Urmila; Rajkumar, Thangarajan

2009-01-01

Background Hereditary cancers account for 5–10% of cancers. In this study BRCA1, BRCA2 and CHEK2*(1100delC) were analyzed for mutations in 91 HBOC/HBC/HOC families and early onset breast and early onset ovarian cancer cases. Methods PCR-DHPLC was used for mutation screening followed by DNA sequencing for identification and confirmation of mutations. Kaplan-Meier survival probabilities were computed for five-year survival data on Breast and Ovarian cancer cases separately, and differences were tested using the Log-rank test. Results Fifteen (16%) pathogenic mutations (12 in BRCA1 and 3 in BRCA2), of which six were novel BRCA1 mutations were identified. None of the cases showed CHEK2*1100delC mutation. Many reported polymorphisms in the exonic and intronic regions of BRCA1 and BRCA2 were also seen. The mutation status and the polymorphisms were analyzed for association with the clinico-pathological features like age, stage, grade, histology, disease status, survival (overall and disease free) and with prognostic molecular markers (ER, PR, c-erbB2 and p53). Conclusion The stage of the disease at diagnosis was the only statistically significant (p < 0.0035) prognostic parameter. The mutation frequency and the polymorphisms were similar to reports on other ethnic populations. The lack of association between the clinico-pathological variables, mutation status and the disease status is likely to be due to the small numbers. PMID:19656415
Genetic testing for susceptibility to breast and ovarian cancer: evaluating the impact of a direct-to-consumer marketing campaign on physicians' knowledge and practices.

Science.gov (United States)

Myers, Melanie F; Chang, Man-Huei; Jorgensen, Cynthia; Whitworth, William; Kassim, Sidibe; Litch, James A; Armstrong, Lori; Bernhardt, Barbara; Faucett, W Andrew; Irwin, Debra; Mouchawar, Judy; Bradley, Linda A

2006-06-01

To assess the impact of direct-to-consumer marketing of genetic testing for risk of breast and ovarian cancer by a biotechnology company on: 1) physicians' knowledge; 2) reasons given when asking questions about the test; and 3) physicians' practice patterns in two pilot cities where the campaign took place and two control cities. Survey of randomly selected family physicians, internists, obstetrician-gynecologists, and oncologists from May 1-May 21, 2003. Physicians' knowledge did not differ between pilot and control cities. Significant differences (pilot versus control cities) were seen in the reasons patients gave for asking questions about testing. More physicians in pilot cities (14%) than control cities (7%) reported an increase in the number of times they ordered genetic testing for breast and ovarian cancer risk in the previous 6 months (adjusted odds ratio 1.9, 95% confidence interval, 1.2-3.1). Awareness of professional guidelines and being in a practice with a policy on genetic testing for risk of breast and ovarian cancer were associated with physicians' behaviors and interest among patients in testing. Given the complexity and limitations of genetic testing for risk of breast and ovarian cancer, the development and broad dissemination of clinical guidelines and education of physicians are needed.
Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk.

Directory of Open Access Journals (Sweden)

Fergus J Couch

Full Text Available BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer, with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 × 10(-8, HR = 1.14, 95% CI: 1.09-1.20. In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 × 10(-8, HR = 1.27, 95% CI: 1.17-1.38 and 4q32.3 (rs4691139, P = 3.4 × 10(-8, HR = 1.20, 95% CI: 1.17-1.38. The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2×10(-4. These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers.
Novel genetic variants in miR-191 gene and familial ovarian cancer

International Nuclear Information System (INIS)

Shen, Jie; DiCioccio, Richard; Odunsi, Kunle; Lele, Shashikant B; Zhao, Hua

2010-01-01

Half of the familial aggregation of ovarian cancer can't be explained by any known risk genes, suggesting the existence of other genetic risk factors. Some of these unknown factors may not be traditional protein encoding genes. MicroRNA (miRNA) plays a critical role in tumorigenesis, but it is still unknown if variants in miRNA genes lead to predisposition to cancer. Considering the fact that miRNA regulates a number of tumor suppressor genes (TSGs) and oncogenes, genetic variations in miRNA genes could affect the levels of expression of TSGs or oncogenes and, thereby, cancer risk. To test this hypothesis in familial ovarian cancer, we screened for genetic variants in thirty selected miRNA genes, which are predicted to regulate key ovarian cancer genes and are reported to be misexpressed in ovarian tumor tissues, in eighty-three patients with familial ovarian cancer. All of the patients are non-carriers of any known BRCA1/2 or mismatch repair (MMR) gene mutations. Seven novel genetic variants were observed in four primary or precursor miRNA genes. Among them, three rare variants were found in the precursor or primary precursor of the miR-191 gene. In functional assays, the one variant located in the precursor of miR-191 resulted in conformational changes in the predicted secondary structures, and consequently altered the expression of mature miR-191. In further analysis, we found that this particular variant exists in five family members who had ovarian cancer. Our findings suggest that there are novel genetic variants in miRNA genes, and those certain genetic variants in miRNA genes can affect the expression of mature miRNAs and, consequently, might alter the regulation of TSGs or oncogenes. Additionally, the variant might be potentially associated with the development of familial ovarian cancer
High prevalence of BRCA1 founder mutations in Greek breast/ovarian families.

Science.gov (United States)

Konstantopoulou, I; Tsitlaidou, M; Fostira, F; Pertesi, M; Stavropoulou, A-V; Triantafyllidou, O; Tsotra, E; Tsiftsoglou, A P; Tsionou, C; Droufakou, S; Dimitrakakis, C; Fountzilas, G; Yannoukakos, D

2014-01-01

We have screened 473 breast/ovarian cancer patients with family history, aiming to define the prevalence and enrich the spectrum of BRCA1/2 pathogenic mutations occurring in the Greek population. An overall mutation prevalence of 32% was observed. Six BRCA1 recurrent/founder mutations dominate the observed spectrum (58.5% of all mutations found). These include three mutations in exon 20 and three large genomic deletions. Of the 44 different deleterious mutations found in both genes, 16 are novel and reported here for the first time. Correlation with available histopathology data showed that 80% of BRCA1 carriers presented a triple-negative breast cancer phenotype while 82% of BRCA2 carriers had oestrogen receptor positive tumours. This study provides a comprehensive view of the frequency, type and distribution of BRCA1/2 mutations in the Greek population as well as an insight of the screening strategy of choice for patients of Greek origin. We conclude that the Greek population has a diverse mutation spectrum influenced by strong founder effects. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Molecular analysis of the eighteen most frequent mutations in the BRCA1 gene in 63 Chilean breast cancer families

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LILIAN JARA

2004-01-01

Full Text Available BRCA1 gene mutations account for nearly all families with multiple cases of both early onset breast and/or ovarian cancer and about 30% of hereditary breast cancer. Although to date more than 1,237 distinct mutations, polymorphisms, and variants have been described, several mutations have been found to be recurrent in this gene. We have analyzed 63 Chilean breast/ovarian cancer families for eighteen frequent BRCA1 mutations. The analysis of the five exons and two introns in which these mutations are located was made using mismatch PCR assay, ASO hybridization assay, restriction fragment analysis, allele specific PCR assay and direct sequentiation techniques. Two BRCA1 mutations (185delAG and C61G and one variant of unknown significance (E1250K were found in four of these families. Also, a new mutation (4185delCAAG and one previously described polymorphism (E1038G were found in two other families. The 185delAG was found in a 3.17 % of the families and the others were present only in one of the families of this cohort. Therefore these mutations are not prominent in the Chilean population. The variant of unknown significance and the polymorphism detected could represent a founder effect of Spanish origin
Endometriosis and risks for ovarian, endometrial and breast cancers

DEFF Research Database (Denmark)

Mogensen, Julie Brøchner; Kjær, Susanne K.; Mellemkjær, Lene

2016-01-01

Objective A growing body of evidence suggests that endometriosis increases the risk for ovarian cancer, but it is less well studied whether the excess risk is confined to certain histotypes. Furthermore, it is not fully resolved if endometriosis is associated with endometrial- and breast cancer....... The aim was to study overall- and histotype-specific risks for these hormone-dependent cancers in women with endometriosis. Methods In the Danish National Patient Register, we identified 45,790 women with a clinical diagnosis of endometriosis during 1977–2012. We linked the cohort to the Danish Cancer...... Register and calculated standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (CIs). Results Endometriosis was associated with increased risks for ovarian cancer (SIR 1.34; 95% CI: 1.16–1.55), due primarily to endometrioid (SIR 1.64; 95% CI: 1.09–2.37) and clear-cell types (SIR 3...
Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

NARCIS (Netherlands)

F.J. Couch (Fergus); X. Wang (Xing); L. McGuffog (Lesley); A. Lee (Andrew); C. Olswold (Curtis); K.B. Kuchenbaecker (Karoline); P. Soucy (Penny); Z. Fredericksen (Zachary); D. Barrowdale (Daniel); J. Dennis (Joe); M.M. Gaudet (Mia); E. Dicks (Ed); M. Kosel (Matthew); S. Healey (Sue); O. Sinilnikova (Olga); F. Bacot (Francois); D. Vincent (Daniel); F.B.L. Hogervorst (Frans); S. Peock (Susan); D. Stoppa-Lyonnet (Dominique); A. Jakubowska (Anna); P. Radice (Paolo); R.K. Schmutzler (Rita); S.M. Domchek (Susan); M. Piedmonte (Marion); C.F. Singer (Christian); E. Friedman (Eitan); M. Thomassen (Mads); T.V.O. Hansen (Thomas); S.L. Neuhausen (Susan); C. Szabo (Csilla); I. Blanco (Ignacio); M.H. Greene (Mark); B.Y. Karlan (Beth); J. Garber; C. Phelan (Catherine); J.N. Weitzel (Jeffrey); M. Montagna (Marco); E. Olah; I.L. Andrulis (Irene); A.K. Godwin (Andrew); D. Yannoukakos (Drakoulis); D. Goldgar (David); T. Caldes (Trinidad); H. Nevanlinna (Heli); A. Osorio (Ana); M.-B. Terry (Mary-Beth); M.B. Daly (Mary); E.J. van Rensburg (Elizabeth); U. Hamann (Ute); S.J. Ramus (Susan); A. Ewart-Toland (Amanda); M.A. Caligo (Maria); O.I. Olopade (Olofunmilayo); N. Tung (Nadine); K. Claes (Kathleen); M.S. Beattie (Mary); M.C. Southey (Melissa); E.N. Imyanitov (Evgeny); M. Tischkowitz (Marc); R. Janavicius (Ramunas); E.M. John (Esther); A. Kwong (Ava); O. Diez (Orland); J. Balmana (Judith); R.B. Barkardottir (Rosa); B.K. Arun (Banu); G. Rennert (Gad); S.-H. Teo (Soo-Hwang); P.A. Ganz (Patricia); I. Campbell (Ian); A.H. van der Hout (Annemarie); C.H.M. van Deurzen (Carolien); C.M. Seynaeve (Caroline); E.B. Gómez García (Encarna); F.E. van Leeuwen (F.); H. Meijers-Heijboer (Hanne); J.J. Gille (Johan); M.G.E.M. Ausems (Margreet); M.J. Blok (Marinus); M.J. Ligtenberg (Marjolijn); M.A. Rookus (Matti); P. Devilee (Peter); S. Verhoef; T.A.M. van Os (Theo); J.T. Wijnen (Juul); D. Frost (Debra); S. Ellis (Steve); E. Fineberg (Elena); R. Platte (Radka); D.G. Evans (Gareth); L. Izatt (Louise); R. Eeles (Rosalind); J.W. Adlard (Julian); D. Eccles (Diana); J. Cook (Jackie); C. Brewer (C.); F. Douglas (Fiona); S.V. Hodgson (Shirley); P.J. Morrison (Patrick); L. Side (Lucy); A. Donaldson (Alan); C. Houghton (Catherine); M.T. Rogers (Mark); H. Dorkins (Huw); J. Eason (Jacqueline); H. Gregory (Helen); E. McCann (Emma); A. Murray (Alexandra); A. Calender (Alain); A. Hardouin (Agnès); P. Berthet (Pascaline); C.D. Delnatte (Capucine); C. Nogues (Catherine); C. Lasset (Christine); C. Houdayer (Claude); D. Leroux (Dominique); E. Rouleau (Etienne); F. Prieur (Fabienne); F. Damiola (Francesca); H. Sobol (Hagay); I. Coupier (Isabelle); L. Vénat-Bouvet (Laurence); L. Castera (Laurent); M. Gauthier-Villars (Marion); M. Léone (Mélanie); P. Pujol (Pascal); S. Mazoyer (Sylvie); Y.-J. Bignon (Yves-Jean); E. Złowocka-Perłowska (Elzbieta); J. Gronwald (Jacek); J. Lubinski (Jan); K. Durda (Katarzyna); K. Jaworska (Katarzyna); T. Huzarski (Tomasz); A.B. Spurdle (Amanda); A. Viel (Alessandra); B. Peissel (Bernard); B. Bonnani (Bernardo); G. Melloni (Giulia); L. Ottini (Laura); L. Papi (Laura); L. Varesco (Liliana); M.G. Tibiletti (Maria Grazia); P. Peterlongo (Paolo); S. Volorio (Sara); S. Manoukian (Siranoush); V. Pensotti (Valeria); N. Arnold (Norbert); C. Engel (Christoph); H. Deissler (Helmut); D. Gadzicki (Dorothea); P.A. Gehrig (Paola A.); K. Kast (Karin); K. Rhiem (Kerstin); A. Meindl (Alfons); D. Niederacher (Dieter); N. Ditsch (Nina); H. Plendl (Hansjoerg); S. Preisler-Adams (Sabine); S. Engert (Stefanie); C. Sutter (Christian); R. Varon-Mateeva (Raymonda); B. Wapenschmidt (Barbara); B.H.F. Weber (Bernhard); B. Arver (Brita Wasteson); M. Stenmark-Askmalm (M.); N. Loman (Niklas); R. Rosenquist (R.); Z. Einbeigi (Zakaria); K.L. Nathanson (Katherine); R. Rebbeck (Timothy); S.V. Blank (Stephanie); D.E. Cohn (David); G.C. Rodriguez (Gustavo); L. Small (Laurie); M. Friedlander (Michael); V.L. Bae-Jump (Victoria L.); A. Fink-Retter (Anneliese); C. Rappaport (Christine); D. Gschwantler-Kaulich (Daphne); G. Pfeiler (Georg); M.-K. Tea; N.M. Lindor (Noralane); B. Kaufman (Bella); S. Shimon Paluch (Shani); Y. Laitman (Yael); A.-B. Skytte (Anne-Bine); A-M. Gerdes (Anne-Marie); I.S. Pedersen (Inge Sokilde); S.T. Moeller (Sanne Traasdahl); T.A. Kruse (Torben); U.B. Jensen; J. Vijai (Joseph); K. Sarrel (Kara); M. Robson (Mark); N. Kauff (Noah); A.M. Mulligan (Anna Marie); G. Glendon (Gord); H. Ozcelik (Hilmi); B. Ejlertsen (Bent); F.C. Nielsen (Finn); L. Jønson (Lars); M.K. Andersen (Mette); Y.C. Ding (Yuan); L. Steele (Linda); L. Foretova (Lenka); A. Teulé (A.); C. Lazaro (Conxi); J. Brunet (Joan); M.A. Pujana (Miguel); P.L. Mai (Phuong); J.T. Loud (Jennifer); C.S. Walsh (Christine); K.J. Lester (Kathryn); S. Orsulic (Sandra); S. Narod (Steven); J. Herzog (Josef); S.R. Sand (Sharon); S. Tognazzo (Silvia); S. Agata (Simona); T. Vaszko (Tibor); J. Weaver (JoEllen); A. Stavropoulou (Alexandra); S.S. Buys (Saundra); A. Romero (Alfonso); M. de La Hoya (Miguel); K. Aittomäki (Kristiina); T.A. Muranen (Taru); M. Durán (Mercedes); W.K. Chung (Wendy); A. Lasa (Adriana); C.M. Dorfling (Cecelia); A. Miron (Alexander); J. Benítez (Javier); L. Senter (Leigha); D. Huo (Dezheng); S. Chan (Salina); A. Sokolenko (Anna); J. Chiquette (Jocelyne); L. Tihomirova (Laima); M.O.W. Friebel (Mark ); B.A. Agnarsson (Bjarni); K.H. Lu (Karen); F. Lejbkowicz (Flavio); P.A. James (Paul ); A.S. Hall (Alistair); A.M. Dunning (Alison); Y. Tessier (Yann); J. Cunningham (Jane); S. Slager (Susan); C. Wang (Chen); S. Hart (Stewart); K. Stevens (Kristen); J. Simard (Jacques); T. Pastinen (Tomi); V.S. Pankratz (Shane); K. Offit (Kenneth); D.F. Easton (Douglas); G. Chenevix-Trench (Georgia); A.C. Antoniou (Antonis); H. Thorne (Heather); E. Niedermayr (Eveline); Å. Borg (Åke); H. Olsson; H. Jernström (H.); K. Henriksson (Karin); K. Harbst (Katja); M. Soller (Maria); U. Kristoffersson (Ulf); A. Öfverholm (Anna); M. 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Hoffman (Jonathan); M. James (Margaret); J. Paterson (Joan); A. Taylor (Amy); A. Murray (Anna); M.J. Kennedy (John); D.E. Barton (David); M.E. Porteous (Mary); S. Drummond (Sarah); C. Brewer (Carole); E. Kivuva (Emma); A. Searle (Anne); S. Goodman (Selina); R. Davidson (Rosemarie); V. Murday (Victoria); N. Bradshaw (Nicola); L. Snadden (Lesley); M. Longmuir (Mark); C. Watt (Catherine); S. Gibson (Sarah); E. Haque (Eshika); E. Tobias (Ed); A. Duncan (Alexis); L. Izatt (Louise); C. Jacobs (Chris); C. Langman (Caroline); A.F. Brady (Angela); S.A. Melville (Scott); K. Randhawa (Kashmir); J. Barwell (Julian); G. Serra-Feliu (Gemma); I.O. Ellis (Ian); F. Lalloo (Fiona); J. Taylor (James); A. Male (Alison); C. Berlin (Cheryl); R. Collier (Rebecca); F. Douglas (Fiona); O. Claber (Oonagh); I. Jobson (Irene); L.J. Walker (Lisa); D. McLeod (Diane); D. Halliday (Dorothy); S. Durell (Sarah); B. Stayner (Barbara); S. Shanley (Susan); N. Rahman (Nazneen); R. Houlston (Richard); A. Stormorken (Astrid); E.K. Bancroft (Elizabeth); E. Page (Elizabeth); A. Ardern-Jones (Audrey); K. Kohut (Kelly); J. Wiggins (Jennifer); E. Castro (Elena); S.R. Killick; S. Martin (Sue); D. Rea (Dan); A. Kulkarni (Anjana); O. Quarrell (Oliver); C. Bardsley (Cathryn); S. Goff (Sheila); G. Brice (Glen); L. Winchester (Lizzie); C. Eddy (Charlotte); V. Tripathi (Vishakha); V. Attard (Virginia); A. Lehmann (Anna); A. Lucassen (Anneke); G. Crawford (Gabe); D. McBride (Donna); S. Smalley (Sarah); S. Mazoyer (Sylvie); F. Damiola (Francesca); L. Barjhoux (Laure); C. Verny-Pierre (Carole); S. Giraud (Sophie); D. Stoppa-Lyonnet (Dominique); B. Buecher (Bruno); V. Moncoutier (Virginie); M. Belotti (Muriel); C. Tirapo (Carole); A. de Pauw (Antoine); B. Bressac-de Paillerets (Brigitte); O. Caron (Olivier); Y.-J. Bignon (Yves-Jean); N. Uhrhammer (Nancy); V. Bonadona (Valérie); S. Handallou (Sandrine); A. hardouin (Agnès); H. Sobol (Hagay); V. Bourdon (Violaine); T. Noguchi (Tetsuro); A. Remenieras (Audrey); F. Eisinger (François); J.-P. Peyrat; J. Fournier (Joëlle); F. Révillion (Françoise); P. Vennin (Philippe); C. Adenis (Claude); R. Lidereau (Rosette); L. Demange (Liliane); D.W. Muller (Danièle); J.P. Fricker (Jean Pierre); E. Barouk-Simonet (Emmanuelle); F. Bonnet (Françoise); V. Bubien (Virginie); N. Sevenet (Nicolas); M. Longy (Michel); C. Toulas (Christine); R. Guimbaud (Rosine); L. Gladieff (Laurence); V. Feillel (Viviane); H. Dreyfus (Hélène); C. Rebischung (Christine); M. Peysselon (Magalie); F. Coron (Fanny); L. Faivre (Laurence); M. Lebrun (Marine); C. Kientz (Caroline); S.F. Ferrer; M. Frenay (Marc); I. Mortemousque (Isabelle); F. Coulet (Florence); C. Colas (Chrystelle); F. Soubrier; J. Sokolowska (Johanna); M. Bronner (Myriam); H. Lynch (Henry); C.L. Snyder (Carrie); M. Angelakos (Maggie); J. Maskiell (Judi); G.S. Dite (Gillian)

2013-01-01

textabstractBRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer),
Antidepressants and breast and ovarian cancer risk: a review of the literature and researchers' financial associations with industry.

Science.gov (United States)

Cosgrove, Lisa; Shi, Ling; Creasey, David E; Anaya-McKivergan, Maria; Myers, Jessica A; Huybrechts, Krista F

2011-04-06

Antidepressant (AD) use has been purported to increase the risk of breast and ovarian cancer, although both epidemiological and pre-clinical studies have reported mixed results. Previous studies in a variety of biomedical fields have found that financial ties to drug companies are associated with favorable study conclusions. We searched English-language articles in MEDLINE, PsychINFO, the Science Citations Index and the Cochrane Central Register of Controlled Clinical Trials (through November 2010). A total of 61 articles that assessed the relationship between breast and ovarian cancer and AD use and articles that examined the effect of ADs on cell growth were included. Multi-modal screening techniques were used to investigate researchers' financial ties with industry. A random effects meta-analysis was used to pool the findings from the epidemiological literature. Thirty-three percent (20/61) of the studies reported a positive association between ADs and cancer. Sixty-seven percent (41/61) of the studies reported no association or antiproliferative effect. The pooled odds ratio for the association between AD use and breast/ovarian cancer in the epidemiologic studies was 1.11 (95% CI, 1.03-1.20). Researchers with industry affiliations were significantly less likely than researchers without those ties to conclude that ADs increase the risk of breast or ovarian cancer. (0/15 [0%] vs 20/46 [43.5%] (Fisher's Exact test P = 0.0012). Both the pre-clinical and clinical data are mixed in terms of showing an association between AD use and breast and ovarian cancer. The possibility that ADs may exhibit a bi-phasic effect, whereby short-term use and/or low dose antidepressants may increase the risk of breast and ovarian cancer, warrants further investigation. Industry affiliations were significantly associated with negative conclusions regarding cancer risk. The findings have implications in light of the 2009 USPSTF guidelines for breast cancer screening and for the

Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk

NARCIS (Netherlands)

Couch, Fergus J.; Wang, Xianshu; McGuffog, Lesley; Lee, Andrew; Olswold, Curtis; Kuchenbaecker, Karoline B.; Soucy, Penny; Fredericksen, Zachary; Barrowdale, Daniel; Dennis, Joe; Gaudet, Mia M.; Dicks, Ed; Kosel, Matthew; Healey, Sue; Sinilnikova, Olga M.; Lee, Adam; Bacot, François; Vincent, Daniel; Hogervorst, Frans B. L.; Peock, Susan; Stoppa-Lyonnet, Dominique; Jakubowska, Anna; Radice, Paolo; Schmutzler, Rita Katharina; Domchek, Susan M.; Piedmonte, Marion; Singer, Christian F.; Friedman, Eitan; Thomassen, Mads; Hansen, Thomas V. O.; Neuhausen, Susan L.; Szabo, Csilla I.; Blanco, Ignacio; Greene, Mark H.; Karlan, Beth Y.; Garber, Judy; Phelan, Catherine M.; Weitzel, Jeffrey N.; Montagna, Marco; Olah, Edith; Andrulis, Irene L.; Godwin, Andrew K.; Yannoukakos, Drakoulis; Goldgar, David E.; Caldes, Trinidad; Nevanlinna, Heli; Osorio, Ana; Terry, Mary Beth; Daly, Mary B.; van Rensburg, Elizabeth J.; Hamann, Ute; Ramus, Susan J.; Toland, Amanda Ewart; Caligo, Maria A.; Olopade, Olufunmilayo I.; Tung, Nadine; Claes, Kathleen; Beattie, Mary S.; Southey, Melissa C.; Imyanitov, Evgeny N.; Tischkowitz, Marc; Janavicius, Ramunas; John, Esther M.; Kwong, Ava; Diez, Orland; Balmaña, Judith; Barkardottir, Rosa B.; Arun, Banu K.; Rennert, Gad; teo, Soo-Hwang; Ganz, Patricia A.; Campbell, Ian; van der Hout, Annemarie H.; van Deurzen, Carolien H. M.; Seynaeve, Caroline; Gómez Garcia, Encarna B.; van Leeuwen, Flora E.; Meijers-Heijboer, Hanne E. J.; Gille, Johannes J. P.; Ausems, Margreet G. E. M.; Blok, Marinus J.; Ligtenberg, Marjolijn J. L.; Rookus, Matti A.; Devilee, Peter; Verhoef, Senno; van Os, Theo A. M.; Wijnen, Juul T.; Frost, Debra; Ellis, Steve; Fineberg, Elena; Platte, Radka; Evans, D. Gareth; Izatt, Louise; Eeles, Rosalind A.; Adlard, Julian; Eccles, Diana M.; Cook, Jackie; Brewer, Carole; Douglas, Fiona; Hodgson, Shirley; Morrison, Patrick J.; Side, Lucy E.; Donaldson, Alan; Houghton, Catherine; Rogers, Mark T.; Dorkins, Huw; Eason, Jacqueline; Gregory, Helen; McCann, Emma; Murray, Alex; Calender, Alain; Hardouin, Agnès; Berthet, Pascaline; Delnatte, Capucine; Nogues, Catherine; Lasset, Christine; Houdayer, Claude; Leroux, Dominique; Rouleau, Etienne; Prieur, Fabienne; Damiola, Francesca; Sobol, Hagay; Coupier, Isabelle; Venat-Bouvet, Laurence; Castera, Laurent; Gauthier-Villars, Marion; Léoné, Mélanie; Pujol, Pascal; Mazoyer, Sylvie; Bignon, Yves-Jean; Złowocka-Perłowska, Elżbieta; Gronwald, Jacek; Lubinski, Jan; Durda, Katarzyna; Jaworska, Katarzyna; Huzarski, Tomasz; Spurdle, Amanda B.; Viel, Alessandra; Peissel, Bernard; Bonanni, Bernardo; Melloni, Giulia; Ottini, Laura; Papi, Laura; Varesco, Liliana; Tibiletti, Maria Grazia; Peterlongo, Paolo; Volorio, Sara; Manoukian, Siranoush; Pensotti, Valeria; Arnold, Norbert; Engel, Christoph; Deissler, Helmut; Gadzicki, Dorothea; Gehrig, Andrea; Kast, Karin; Rhiem, Kerstin; Meindl, Alfons; Niederacher, Dieter; Ditsch, Nina; Plendl, Hansjoerg; Preisler-Adams, Sabine; Engert, Stefanie; Sutter, Christian; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Weber, Bernhard H. F.; Arver, Brita; Stenmark-Askmalm, Marie; Loman, Niklas; Rosenquist, Richard; Einbeigi, Zakaria; Nathanson, Katherine L.; Rebbeck, Timothy R.; Blank, Stephanie V.; Cohn, David E.; Rodriguez, Gustavo C.; Small, Laurie; Friedlander, Michael; Bae-Jump, Victoria L.; Fink-Retter, Anneliese; Rappaport, Christine; Gschwantler-Kaulich, Daphne; Pfeiler, Georg; tea, Muy-Kheng; Lindor, Noralane M.; Kaufman, Bella; Shimon Paluch, Shani; Laitman, Yael; Skytte, Anne-Bine; Gerdes, Anne-Marie; Pedersen, Inge Sokilde; Moeller, Sanne Traasdahl; Kruse, Torben A.; Jensen, Uffe Birk; Vijai, Joseph; Sarrel, Kara; Robson, Mark; Kauff, Noah; Mulligan, Anna Marie; Glendon, Gord; Ozcelik, Hilmi; Ejlertsen, Bent; Nielsen, Finn C.; Jønson, Lars; Andersen, Mette K.; Ding, Yuan Chun; Steele, Linda; Foretova, Lenka; Teulé, Alex; Lazaro, Conxi; Brunet, Joan; Pujana, Miquel Angel; Mai, Phuong L.; Loud, Jennifer T.; Walsh, Christine; Lester, Jenny; Orsulic, Sandra; Narod, Steven A.; Herzog, Josef; Sand, Sharon R.; Tognazzo, Silvia; Agata, Simona; Vaszko, Tibor; Weaver, Joellen; Stavropoulou, Alexandra V.; Buys, Saundra S.; Romero, Atocha; de la Hoya, Miguel; Aittomäki, Kristiina; Muranen, Taru A.; Duran, Mercedes; Chung, Wendy K.; Lasa, Adriana; Dorfling, Cecilia M.; Miron, Alexander; Benitez, Javier; Senter, Leigha; Huo, Dezheng; Chan, Salina B.; Sokolenko, Anna P.; Chiquette, Jocelyne; Tihomirova, Laima; Friebel, Tara M.; Agnarsson, Bjarni A.; Lu, Karen H.; Lejbkowicz, Flavio; James, Paul A.; Hall, Per; Dunning, Alison M.; Tessier, Daniel; Cunningham, Julie; Slager, Susan L.; Wang, Chen; Hart, Steven; Stevens, Kristen; Simard, Jacques; Pastinen, Tomi; Pankratz, Vernon S.; Offit, Kenneth; Easton, Douglas F.; Chenevix-Trench, Georgia; Antoniou, Antonis C.

2013-01-01

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a
Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk

DEFF Research Database (Denmark)

Couch, Fergus J; Wang, Xianshu; McGuffog, Lesley

2013-01-01

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a fur...
Breast and ovarian cancers: a survey and possible roles for the cell surface heparan sulfate proteoglycans

DEFF Research Database (Denmark)

Yoneda, Atsuko; Lendorf, Maria E; Couchman, John R

2012-01-01

. Occurrence of breast and ovarian cancer is high in older women. Common known risk factors of developing these cancers in addition to age are not having children or having children at a later age, the use of hormone replacement therapy, and mutations in certain genes. In addition, women with a history......Tumor markers are widely used in pathology not only for diagnostic purposes but also to assess the prognosis and to predict the treatment of the tumor. Because tumor marker levels may change over time, it is important to get a better understanding of the molecular changes during tumor progression...... of breast cancer may also develop ovarian cancer. Here, the authors review the different tumor markers of breast and ovarian carcinoma and discuss the expression, mutations, and possible roles of cell surface heparan sulfate proteoglycans during tumorigenesis of these carcinomas. The focus is on two groups...
Association study of prostate cancer susceptibility variants with risks of invasive ovarian, breast, and colorectal cancer

DEFF Research Database (Denmark)

Song, H.; Koessler, T.; Ahmed, S.

2008-01-01

allele OR, 0.95; 95% CI, 0.91-0.99; P(trend) = 0.028). This association was somewhat stronger for estrogen receptor-positive tumors (OR, 0.92; 95% CI, 0.87-0.98; P = 0.011). None of these tag SNPs were associated with risk of colorectal cancer. In conclusion, loci associated with risk of prostate cancer......Several prostate cancer susceptibility loci have recently been identified by genome-wide association studies. These loci are candidates for susceptibility to other epithelial cancers. The aim of this study was to test these tag single nucleotide polymorphisms (SNP) for association with invasive...... ovarian, colorectal, and breast cancer. Twelve prostate cancer-associated tag SNPs were genotyped in ovarian (2,087 cases/3,491 controls), colorectal (2,148 cases/2,265 controls) and breast (first set, 4,339 cases/4,552 controls; second set, 3,800 cases/3,995 controls) case-control studies. The primary...
Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

Science.gov (United States)

Wang, Xianshu; McGuffog, Lesley; Lee, Andrew; Olswold, Curtis; Kuchenbaecker, Karoline B.; Soucy, Penny; Fredericksen, Zachary; Barrowdale, Daniel; Dennis, Joe; Gaudet, Mia M.; Dicks, Ed; Kosel, Matthew; Healey, Sue; Sinilnikova, Olga M.; Lee, Adam; Bacot, François; Vincent, Daniel; Hogervorst, Frans B. L.; Peock, Susan; Stoppa-Lyonnet, Dominique; Jakubowska, Anna; Investigators, kConFab; Radice, Paolo; Schmutzler, Rita Katharina; Domchek, Susan M.; Piedmonte, Marion; Singer, Christian F.; Friedman, Eitan; Thomassen, Mads; Hansen, Thomas V. O.; Neuhausen, Susan L.; Szabo, Csilla I.; Blanco, Ignacio; Greene, Mark H.; Karlan, Beth Y.; Garber, Judy; Phelan, Catherine M.; Weitzel, Jeffrey N.; Montagna, Marco; Olah, Edith; Andrulis, Irene L.; Godwin, Andrew K.; Yannoukakos, Drakoulis; Goldgar, David E.; Caldes, Trinidad; Nevanlinna, Heli; Osorio, Ana; Terry, Mary Beth; Daly, Mary B.; van Rensburg, Elizabeth J.; Hamann, Ute; Ramus, Susan J.; Ewart Toland, Amanda; Caligo, Maria A.; Olopade, Olufunmilayo I.; Tung, Nadine; Claes, Kathleen; Beattie, Mary S.; Southey, Melissa C.; Imyanitov, Evgeny N.; Tischkowitz, Marc; Janavicius, Ramunas; John, Esther M.; Kwong, Ava; Diez, Orland; Balmaña, Judith; Barkardottir, Rosa B.; Arun, Banu K.; Rennert, Gad; Teo, Soo-Hwang; Ganz, Patricia A.; Campbell, Ian; van der Hout, Annemarie H.; van Deurzen, Carolien H. M.; Seynaeve, Caroline; Gómez Garcia, Encarna B.; van Leeuwen, Flora E.; Meijers-Heijboer, Hanne E. J.; Gille, Johannes J. P.; Ausems, Margreet G. E. M.; Blok, Marinus J.; Ligtenberg, Marjolijn J. L.; Rookus, Matti A.; Devilee, Peter; Verhoef, Senno; van Os, Theo A. M.; Wijnen, Juul T.; Frost, Debra; Ellis, Steve; Fineberg, Elena; Platte, Radka; Evans, D. Gareth; Izatt, Louise; Eeles, Rosalind A.; Adlard, Julian; Eccles, Diana M.; Cook, Jackie; Brewer, Carole; Douglas, Fiona; Hodgson, Shirley; Morrison, Patrick J.; Side, Lucy E.; Donaldson, Alan; Houghton, Catherine; Rogers, Mark T.; Dorkins, Huw; Eason, Jacqueline; Gregory, Helen; McCann, Emma; Murray, Alex; Calender, Alain; Hardouin, Agnès; Berthet, Pascaline; Delnatte, Capucine; Nogues, Catherine; Lasset, Christine; Houdayer, Claude; Leroux, Dominique; Rouleau, Etienne; Prieur, Fabienne; Damiola, Francesca; Sobol, Hagay; Coupier, Isabelle; Venat-Bouvet, Laurence; Castera, Laurent; Gauthier-Villars, Marion; Léoné, Mélanie; Pujol, Pascal; Mazoyer, Sylvie; Bignon, Yves-Jean; Złowocka-Perłowska, Elżbieta; Gronwald, Jacek; Lubinski, Jan; Durda, Katarzyna; Jaworska, Katarzyna; Huzarski, Tomasz; Spurdle, Amanda B.; Viel, Alessandra; Peissel, Bernard; Bonanni, Bernardo; Melloni, Giulia; Ottini, Laura; Papi, Laura; Varesco, Liliana; Tibiletti, Maria Grazia; Peterlongo, Paolo; Volorio, Sara; Manoukian, Siranoush; Pensotti, Valeria; Arnold, Norbert; Engel, Christoph; Deissler, Helmut; Gadzicki, Dorothea; Gehrig, Andrea; Kast, Karin; Rhiem, Kerstin; Meindl, Alfons; Niederacher, Dieter; Ditsch, Nina; Plendl, Hansjoerg; Preisler-Adams, Sabine; Engert, Stefanie; Sutter, Christian; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Weber, Bernhard H. F.; Arver, Brita; Stenmark-Askmalm, Marie; Loman, Niklas; Rosenquist, Richard; Einbeigi, Zakaria; Nathanson, Katherine L.; Rebbeck, Timothy R.; Blank, Stephanie V.; Cohn, David E.; Rodriguez, Gustavo C.; Small, Laurie; Friedlander, Michael; Bae-Jump, Victoria L.; Fink-Retter, Anneliese; Rappaport, Christine; Gschwantler-Kaulich, Daphne; Pfeiler, Georg; Tea, Muy-Kheng; Lindor, Noralane M.; Kaufman, Bella; Shimon Paluch, Shani; Laitman, Yael; Skytte, Anne-Bine; Gerdes, Anne-Marie; Pedersen, Inge Sokilde; Moeller, Sanne Traasdahl; Kruse, Torben A.; Jensen, Uffe Birk; Vijai, Joseph; Sarrel, Kara; Robson, Mark; Kauff, Noah; Mulligan, Anna Marie; Glendon, Gord; Ozcelik, Hilmi; Ejlertsen, Bent; Nielsen, Finn C.; Jønson, Lars; Andersen, Mette K.; Ding, Yuan Chun; Steele, Linda; Foretova, Lenka; Teulé, Alex; Lazaro, Conxi; Brunet, Joan; Pujana, Miquel Angel; Mai, Phuong L.; Loud, Jennifer T.; Walsh, Christine; Lester, Jenny; Orsulic, Sandra; Narod, Steven A.; Herzog, Josef; Sand, Sharon R.; Tognazzo, Silvia; Agata, Simona; Vaszko, Tibor; Weaver, Joellen; Stavropoulou, Alexandra V.; Buys, Saundra S.; Romero, Atocha; de la Hoya, Miguel; Aittomäki, Kristiina; Muranen, Taru A.; Duran, Mercedes; Chung, Wendy K.; Lasa, Adriana; Dorfling, Cecilia M.; Miron, Alexander; Benitez, Javier; Senter, Leigha; Huo, Dezheng; Chan, Salina B.; Sokolenko, Anna P.; Chiquette, Jocelyne; Tihomirova, Laima; Friebel, Tara M.; Agnarsson, Bjarni A.; Lu, Karen H.; Lejbkowicz, Flavio; James, Paul A.; Hall, Per; Dunning, Alison M.; Tessier, Daniel; Cunningham, Julie; Slager, Susan L.; Wang, Chen; Hart, Steven; Stevens, Kristen; Simard, Jacques; Pastinen, Tomi; Pankratz, Vernon S.; Offit, Kenneth; Antoniou, Antonis C.

2013-01-01

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10−8, HR = 1.14, 95% CI: 1.09–1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10−8, HR = 1.27, 95% CI: 1.17–1.38) and 4q32.3 (rs4691139, P = 3.4×10−8, HR = 1.20, 95% CI: 1.17–1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2×10−4). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%–50% compared to 81%–100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers. PMID:23544013
Familial breast cancer - targeted therapy in secondary and tertiary prevention.

Science.gov (United States)

Kast, Karin; Rhiem, Kerstin

2015-02-01

The introduction of an increasing number of individualized molecular targeted therapies into clinical routine mirrors their importance in modern cancer prevention and treatment. Well-known examples for targeted agents are the monoclonal antibody trastuzumab and the selective estrogen receptor modulator tamoxifen. The identification of an unaltered gene in tumor tissue in colon cancer (KRAS) is a predictor for the patient's response to targeted therapy with a monoclonal antibody (cetuximab). Targeted therapy for hereditary breast and ovarian cancer has become a reality with the approval of olaparib for platin-sensitive late relapsed BRCA-associated ovarian cancer in December 2014. This manuscript reviews the status quo of poly-ADP-ribose polymerase inhibitors (PARPi) in the therapy of breast and ovarian cancer as well as the struggle for carboplatin as a potential standard of care for triple-negative and, in particular, BRCA-associated breast cancer. Details of the mechanism of action with information on tumor development are provided, and an outlook for further relevant research is given. The efficacy of agents against molecular targets together with the identification of an increasing number of cancer-associated genes will open the floodgates to a new era of treatment decision-making based on molecular tumor profiles. Current clinical trials involving patients with BRCA-associated cancer explore the efficacy of the molecular targeted therapeutics platinum and PARPi.
Frequency of the ATM IVS10-6T→G variant in Australian multiple-case breast cancer families

International Nuclear Information System (INIS)

Lindeman, Geoffrey J; Suthers, Graeme; Kirk, Judy; Hiew, Melody; Visvader, Jane E; Leary, Jennifer; Field, Michael; Gaff, Clara L; Gardner, RJ McKinlay; Trainor, Kevin; Cheetham, Glenice

2004-01-01

Germline mutations in the genes BRCA1 and BRCA2 account for only a proportion of hereditary breast cancer, suggesting that additional genes contribute to hereditary breast cancer. Recently a heterozygous variant in the ataxia–telangiectasia mutated (ATM) gene, IVS10-6T→G, was reported by an Australian multiple-case breast cancer family cohort study (the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer) to confer a substantial breast cancer risk. Although this variant can result in a truncated ATM product, its clinical significance as a high-penetrance breast cancer allele or its role as a low-penetrance risk-modifier is controversial. We determined the frequency of ATM IVS10-6T→G variants in a cohort of individuals affected by breast and/or ovarian cancer who underwent BRCA1 and BRCA2 genetic testing at four major Australian familial cancer clinics. Seven of 495 patients (1.4%) were heterozygous for the IVS10-6T→G variant; the carrier rate in unselected Australian women with no family history of breast cancer is reported to be 6 of 725 (0.83%) (P = 0.4). Two of the seven probands also harboured a pathogenic BRCA1 mutation and one patient had a BRCA1 unclassified variant of uncertain significance. These findings indicate that the ATM IVS10-6T→G variant does not seem to occur at a significantly higher frequency in affected individuals from high-risk families than in the general population. A role for this variant as a low-penetrance allele or as a modifying gene in association with other genes (such as BRCA1) remains possible. Routine testing for ATM IVS10-6T→G is not warranted in mutation screening of affected individuals from high-risk families
Levels of Distress in Women With a Family History of Ovarian Cancer

National Research Council Canada - National Science Library

Kash, Kathryn

2005-01-01

The overall goal of this study is to determine the levels of distress in women with a family history of ovarian cancer and to identify the mediating factors between risk of developing ovarian cancer...
Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.

Science.gov (United States)

Peterlongo, Paolo; Chang-Claude, Jenny; Moysich, Kirsten B; Rudolph, Anja; Schmutzler, Rita K; Simard, Jacques; Soucy, Penny; Eeles, Rosalind A; Easton, Douglas F; Hamann, Ute; Wilkening, Stefan; Chen, Bowang; Rookus, Matti A; Schmidt, Marjanka K; van der Baan, Frederieke H; Spurdle, Amanda B; Walker, Logan C; Lose, Felicity; Maia, Ana-Teresa; Montagna, Marco; Matricardi, Laura; Lubinski, Jan; Jakubowska, Anna; Gómez Garcia, Encarna B; Olopade, Olufunmilayo I; Nussbaum, Robert L; Nathanson, Katherine L; Domchek, Susan M; Rebbeck, Timothy R; Arun, Banu K; Karlan, Beth Y; Orsulic, Sandra; Lester, Jenny; Chung, Wendy K; Miron, Alex; Southey, Melissa C; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Dorfling, Cecilia M; van Rensburg, Elizabeth J; Ding, Yuan Chun; Neuhausen, Susan L; Hansen, Thomas V O; Gerdes, Anne-Marie; Ejlertsen, Bent; Jønson, Lars; Osorio, Ana; Martínez-Bouzas, Cristina; Benitez, Javier; Conway, Edye E; Blazer, Kathleen R; Weitzel, Jeffrey N; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Scuvera, Giulietta; Barile, Monica; Ficarazzi, Filomena; Mariette, Frederique; Fortuzzi, Stefano; Viel, Alessandra; Giannini, Giuseppe; Papi, Laura; Martayan, Aline; Tibiletti, Maria Grazia; Radice, Paolo; Vratimos, Athanassios; Fostira, Florentia; Garber, Judy E; Donaldson, Alan; Brewer, Carole; Foo, Claire; Evans, D Gareth R; Frost, Debra; Eccles, Diana; Brady, Angela; Cook, Jackie; Tischkowitz, Marc; Adlard, Julian; Barwell, Julian; Walker, Lisa; Izatt, Louise; Side, Lucy E; Kennedy, M John; Rogers, Mark T; Porteous, Mary E; Morrison, Patrick J; Platte, Radka; Davidson, Rosemarie; Hodgson, Shirley V; Ellis, Steve; Cole, Trevor; Godwin, Andrew K; Claes, Kathleen; Van Maerken, Tom; Meindl, Alfons; Gehrig, Andrea; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Plendl, Hansjoerg; Kast, Karin; Rhiem, Kerstin; Ditsch, Nina; Arnold, Norbert; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Wang-Gohrke, Shan; Bressac-de Paillerets, Brigitte; Buecher, Bruno; Delnatte, Capucine; Houdayer, Claude; Stoppa-Lyonnet, Dominique; Damiola, Francesca; Coupier, Isabelle; Barjhoux, Laure; Venat-Bouvet, Laurence; Golmard, Lisa; Boutry-Kryza, Nadia; Sinilnikova, Olga M; Caron, Olivier; Pujol, Pascal; Mazoyer, Sylvie; Belotti, Muriel; Piedmonte, Marion; Friedlander, Michael L; Rodriguez, Gustavo C; Copeland, Larry J; de la Hoya, Miguel; Segura, Pedro Perez; Nevanlinna, Heli; Aittomäki, Kristiina; van Os, Theo A M; Meijers-Heijboer, Hanne E J; van der Hout, Annemarie H; Vreeswijk, Maaike P G; Hoogerbrugge, Nicoline; Ausems, Margreet G E M; van Doorn, Helena C; Collée, J Margriet; Olah, Edith; Diez, Orland; Blanco, Ignacio; Lazaro, Conxi; Brunet, Joan; Feliubadalo, Lidia; Cybulski, Cezary; Gronwald, Jacek; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Sukiennicki, Grzegorz; Arason, Adalgeir; Chiquette, Jocelyne; Teixeira, Manuel R; Olswold, Curtis; Couch, Fergus J; Lindor, Noralane M; Wang, Xianshu; Szabo, Csilla I; Offit, Kenneth; Corines, Marina; Jacobs, Lauren; Robson, Mark E; Zhang, Liying; Joseph, Vijai; Berger, Andreas; Singer, Christian F; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng M; Phelan, Catherine M; Greene, Mark H; Mai, Phuong L; Rennert, Gad; Mulligan, Anna Marie; Glendon, Gord; Tchatchou, Sandrine; Andrulis, Irene L; Toland, Amanda Ewart; Bojesen, Anders; Pedersen, Inge Sokilde; Thomassen, Mads; Jensen, Uffe Birk; Laitman, Yael; Rantala, Johanna; von Wachenfeldt, Anna; Ehrencrona, Hans; Askmalm, Marie Stenmark; Borg, Åke; Kuchenbaecker, Karoline B; McGuffog, Lesley; Barrowdale, Daniel; Healey, Sue; Lee, Andrew; Pharoah, Paul D P; Chenevix-Trench, Georgia; Antoniou, Antonis C; Friedman, Eitan

2015-01-01

BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes. Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies. ©2014 American Association for Cancer Research.
RAD51B in Familial Breast Cancer.

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Liisa M Pelttari

Full Text Available Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC that were genotyped on a custom chip (iCOGS. We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259 and population controls (n = 3586 from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR: 1.15, 95% confidence interval (CI: 1.11-1.19, P = 8.88 x 10-16 and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 x 10-11, compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.
RAD51B in Familial Breast Cancer

Science.gov (United States)

Pelttari, Liisa M.; Khan, Sofia; Vuorela, Mikko; Kiiski, Johanna I.; Vilske, Sara; Nevanlinna, Viivi; Ranta, Salla; Schleutker, Johanna; Winqvist, Robert; Kallioniemi, Anne; Dörk, Thilo; Bogdanova, Natalia V.; Figueroa, Jonine; Pharoah, Paul D. P.; Schmidt, Marjanka K.; Dunning, Alison M.; García-Closas, Montserrat; Bolla, Manjeet K.; Dennis, Joe; Michailidou, Kyriaki; Wang, Qin; Hopper, John L.; Southey, Melissa C.; Rosenberg, Efraim H.; Fasching, Peter A.; Beckmann, Matthias W.; Peto, Julian; dos-Santos-Silva, Isabel; Sawyer, Elinor J.; Tomlinson, Ian; Burwinkel, Barbara; Surowy, Harald; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E.; Nordestgaard, Børge G.; Benitez, Javier; González-Neira, Anna; Neuhausen, Susan L.; Anton-Culver, Hoda; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K.; Brauch, Hiltrud; Brüning, Thomas; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Hartikainen, Jaana M.; Chenevix-Trench, Georgia; Van Dyck, Laurien; Janssen, Hilde; Chang-Claude, Jenny; Rudolph, Anja; Radice, Paolo; Peterlongo, Paolo; Hallberg, Emily; Olson, Janet E.; Giles, Graham G.; Milne, Roger L.; Haiman, Christopher A.; Schumacher, Fredrick; Simard, Jacques; Dumont, Martine; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Zheng, Wei; Beeghly-Fadiel, Alicia; Grip, Mervi; Andrulis, Irene L.; Glendon, Gord; Devilee, Peter; Seynaeve, Caroline; Hooning, Maartje J.; Collée, Margriet; Cox, Angela; Cross, Simon S.; Shah, Mitul; Luben, Robert N.; Hamann, Ute; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Couch, Fergus J.; Yannoukakos, Drakoulis; Orr, Nick; Swerdlow, Anthony; Darabi, Hatef; Li, Jingmei; Czene, Kamila; Hall, Per; Easton, Douglas F.; Mattson, Johanna; Blomqvist, Carl; Aittomäki, Kristiina; Nevanlinna, Heli

2016-01-01

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11–1.19, P = 8.88 x 10−16) and among familial cases (OR: 1.24, 95% CI: 1.16–1.32, P = 6.19 x 10−11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk. PMID:27149063
Levels of Distress in Women With a Family History of Ovarian Cancer

National Research Council Canada - National Science Library

Kash, Kathryn

2001-01-01

The overall goal of this study is to determine the levels of distress in women with a family history of ovarian cancer and to identify the mediating factors between risk of developing ovarian cancer and distress...
Feelings of Women With Strong Family Histories Who Subsequent to Their Breast Cancer Diagnosis Tested BRCA Positive.

Science.gov (United States)

Joseph, Meera; Rab, Faiza; Panabaker, Karen; Nisker, Jeff

2015-05-01

Family physicians in Canada as reported in several studies do not recognize the importance of family history in relation to breast/ovarian cancer and thus Canadian women with strong family histories continue to develop early-onset breast cancer without the knowledge of or ability to make choices regarding increased surveillance or preventative strategies. This study explored the feelings of women who learned about their hereditary risk only after their diagnosis younger than 52 years and who eventually tested positive for a BRCA gene mutation. Thirty-four such women were mailed an invitation to participate in this research including a letter of information, consent form, and discussion prompts for their written narrative response. Rigorous mixed method analyses were performed using Charmaz-based qualitative analyses as well as quantitative analyses. Thirteen women (38.2%) responded with narratives for qualitative analysis from which 4 themes were coconstructed as follows: I, types of emotions; II, emotional response; III, coping with emotions; and IV, advice to women at similar risk. Women felt they should have learned about their hereditary risk from their family physician and through public education before their diagnosis. Although not experienced at the time of diagnosis, anger, frustration, and regret were experienced after receiving their BRCA results. These emotions arose from our research participants' lack of opportunity for prior genetic counseling and testing opportunity for genetic counseling and testing. With increased public and physician education, it is hoped that women with significant family histories of breast/ovarian cancer will be identified before diagnosis and given options regarding cancer surveillance and risk reduction strategies.
Biological Basis for Chemoprevention of Ovarian Cancer

Science.gov (United States)

2006-10-01

Concealing Clothing” Sukru Hatun, Omer Islam, Filiz Cizmecioglu, Bulent Kara, Kadir Babaoglu, Fatma Berk,and Ayse Sevim Go¨ kalp J. Nutr. 135: 218–222...to studies in ovarian caner , analyses of the relationship between the short AR CAG repeat length polymorphism and prostate cancer risk also have...pregnant, months of OC use, BMI, tubal ligation, family history of breast or ovarian caner in a first degree relative, waist-to-hip ratio 23 Table 6
Family history of cancer and risk of Pancreatic Cancer: A Pooled Analysis from the Pancreatic Cancer Cohort Consortium (PanScan)

Science.gov (United States)

Jacobs, Eric J.; Chanock, Stephen J.; Fuchs, Charles S.; LaCroix, Andrea; McWilliams, Robert R.; Steplowski, Emily; Stolzenberg-Solomon, Rachael Z.; Arslan, Alan A.; Bueno-de-Mesquita, H. Bas; Gross, Myron; Helzlsouer, Kathy; Petersen, Gloria; Zheng, Wei; Agalliu, Ilir; Allen, Naomi E.; Amundadottir, Laufey; Boutron-Ruault, Marie-Christine; Buring, Julie E.; Canzian, Federico; Clipp, Sandra; Dorronsoro, Miren; Gaziano, J. Michael; Giovannucci, Edward L.; Hankinson, Susan E.; Hartge, Patricia; Hoover, Robert N.; Hunter, David J.; Jacobs, Kevin B.; Jenab, Mazda; Kraft, Peter; Kooperberg, Charles; Lynch, Shannon M.; Sund, Malin; Mendelsohn, Julie B.; Mouw, Tracy; Newton, Christina C.; Overvad, Kim; Palli, Domenico; Peeters, Petra H.M.; Rajkovic, Aleksandar; Shu, Xiao-Ou; Thomas, Gilles; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Wactawski-Wende, Jean; Wolpin, Brian M.; Yu, Kai; Zeleniuch-Jacquotte, Anne

2010-01-01

A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.e. ovarian, breast, and colorectal) could also be associated, although not as strongly, with increased risk of pancreatic cancer. We examined the association between a family history of five types of cancer (pancreas, prostate, ovarian, breast, and colorectal) and risk of pancreatic cancer using data from a collaborative nested case-control study conducted by the Pancreatic Cancer Cohort Consortium. Cases and controls were from cohort studies from the United States, Europe, and China, and a case-control study from the Mayo Clinic. Analyses of family history of pancreatic cancer included 1,183 cases and 1,205 controls. A family history of pancreatic cancer in a parent, sibling, or child was associated with increased risk of pancreatic cancer (multivariate-adjusted OR = 1.76, 95% CI 1.19–2.61). A family history of prostate cancer was also associated with increased risk (OR = 1.45, 95% CI 1.12–1.89). There were no statistically significant associations with a family history of ovarian cancer (OR = 0.82, 95% CI 0.52–1.31), breast cancer (OR = 1.21, 95% CI 0.97–1.51), or colorectal cancer (OR = 1.17, 95% CI 0.93–1.47). Our results confirm a moderate sized association between a family history of pancreatic cancer and risk of pancreatic cancer and also provide evidence for an association with a family history of prostate cancer worth further study. PMID:20049842
Family history and risk of breast cancer: an analysis accounting for family structure.

Science.gov (United States)

Brewer, Hannah R; Jones, Michael E; Schoemaker, Minouk J; Ashworth, Alan; Swerdlow, Anthony J

2017-08-01

Family history is an important risk factor for breast cancer incidence, but the parameters conventionally used to categorize it are based solely on numbers and/or ages of breast cancer cases in the family and take no account of the size and age-structure of the woman's family. Using data from the Generations Study, a cohort of over 113,000 women from the general UK population, we analyzed breast cancer risk in relation to first-degree family history using a family history score (FHS) that takes account of the expected number of family cases based on the family's age-structure and national cancer incidence rates. Breast cancer risk increased significantly (P trend history was that combining FHS and age of relative at diagnosis. A family history score based on expected as well as observed breast cancers in a family can give greater risk discrimination on breast cancer incidence than conventional parameters based solely on cases in affected relatives. Our modeling suggests that a yet stronger predictor of risk might be a combination of this score and age at diagnosis in relatives.
Relationship of family history and outcome after breast conservation therapy in women with ductal carcinoma in situ of the breast

International Nuclear Information System (INIS)

Harris, Eleanor E.R.; Schultz, Delray J.; Peters, Christopher A.; Solin, Lawrence J.

2000-01-01

Purpose: The purpose of this study was to evaluate the relationship between a family history of breast or ovarian cancer and outcome after breast-conserving surgery and radiation in women presenting with an initial diagnosis of ductal carcinoma in situ (DCIS) of the breast. Methods and Materials: A total of 146 consecutive women with a pathologic diagnosis of ductal carcinoma in situ as their first diagnosis of any breast cancer were identified; 28 (19%) had a positive family history of breast or ovarian cancer in a first-degree relative, 27 (19%) had a positive family history in a second-degree relative, and 91 (62%) had no family history. Pathologic, clinical, and treatment factors, and clinical outcomes for each family history group were compared. Cosmesis and complications were recorded at each follow-up. Patients were treated between 1978 and 1995, and the median follow-up was 7.1 years. Results: Patients with a positive family history in a first- or second-degree relative each had an 8% incidence of local failure at 10 years, while the negative family history group demonstrated a 16% local failure rate (p = 0.33). Overall survival at 10 years for patients with a positive family history in a first- or second-degree relative was 100% and for those with a negative family history was 91% (p = 0.08). The negative family history group had a higher median age that may account for the difference in overall survival. Cause-specific survival (CSS) was 97%, 100%, and 99%, respectively, at 10 years (p = 0.25). There were no differences in the cosmetic results or complication rates between women with a positive or negative family history. Conclusion: We have shown that a family history of breast and/or ovarian cancer is not associated with an adverse outcome for women treated with breast conservation therapy for DCIS. Local recurrence, cause-specific survival, overall survival, cosmesis, and complication rates were comparable to that of similarly treated women with
Breast and Ovarian Cancer Risk and Risk Reduction in Jewish BRCA1/2 Mutation Carriers

Science.gov (United States)

Finkelman, Brian S.; Rubinstein, Wendy S.; Friedman, Sue; Friebel, Tara M.; Dubitsky, Shera; Schonberger, Niecee Singer; Shoretz, Rochelle; Singer, Christian F.; Blum, Joanne L.; Tung, Nadine; Olopade, Olufunmilayo I.; Weitzel, Jeffrey N.; Lynch, Henry T.; Snyder, Carrie; Garber, Judy E.; Schildkraut, Joellen; Daly, Mary B.; Isaacs, Claudine; Pichert, Gabrielle; Neuhausen, Susan L.; Couch, Fergus J.; van't Veer, Laura; Eeles, Rosalind; Bancroft, Elizabeth; Evans, D. Gareth; Ganz, Patricia A.; Tomlinson, Gail E.; Narod, Steven A.; Matloff, Ellen; Domchek, Susan; Rebbeck, Timothy R.

2012-01-01

Purpose Mutations in BRCA1/2 dramatically increase the risk of both breast and ovarian cancers. Three mutations in these genes (185delAG, 5382insC, and 6174delT) occur at high frequency in Ashkenazi Jews. We evaluated how these common Jewish mutations (CJMs) affect cancer risks and risk reduction. Methods Our cohort comprised 4,649 women with disease-associated BRCA1/2 mutations from 22 centers in the Prevention and Observation of Surgical End Points Consortium. Of these women, 969 were self-identified Jewish women. Cox proportional hazards models were used to estimate breast and ovarian cancer risks, as well as risk reduction from risk-reducing salpingo-oophorectomy (RRSO), by CJM and self-identified Jewish status. Results Ninety-one percent of Jewish BRCA1/2-positive women carried a CJM. Jewish women were significantly more likely to undergo RRSO than non-Jewish women (54% v 41%, respectively; odds ratio, 1.87; 95% CI, 1.44 to 2.42). Relative risks of cancer varied by CJM, with the relative risk of breast cancer being significantly lower in 6174delT mutation carriers than in non-CJM BRCA2 carriers (hazard ratio, 0.35; 95% CI, 0.18 to 0.69). No significant difference was seen in cancer risk reduction after RRSO among subgroups. Conclusion Consistent with previous results, risks for breast and ovarian cancer varied by CJM in BRCA1/2 carriers. In particular, 6174delT carriers had a lower risk of breast cancer. This finding requires additional confirmation in larger prospective and population-based cohort studies before being integrated into clinical care. PMID:22430266
Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers

Science.gov (United States)

Peterlongo, Paolo; Chang-Claude, Jenny; Moysich, Kirsten B.; Rudolph, Anja; Schmutzler, Rita K.; Simard, Jacques; Soucy, Penny; Eeles, Rosalind A.; Easton, Douglas F.; Hamann, Ute; Wilkening, Stefan; Chen, Bowang; Rookus, Matti A.; Schmidt, Marjanka K; van der Baan, Frederieke H.; Spurdle, Amanda B.; Walker, Logan C.; Lose, Felicity; Maia, Ana-Teresa; Montagna, Marco; Matricardi, Laura; Lubinski, Jan; Jakubowska, Anna; Gómez Garcia, Encarna B.; Olopade, Olufunmilayo I.; Nussbaum, Robert L.; Nathanson, Katherine L.; Domchek, Susan M.; Rebbeck, Timothy R.; Arun, Banu K.; Karlan, Beth Y.; Orsulic, Sandra; Lester, Jenny; Chung, Wendy K.; Miron, Alex; Southey, Melissa C.; Goldgar, David E.; Buys, Saundra S.; Janavicius, Ramunas; Dorfling, Cecilia M.; van Rensburg, Elizabeth J.; Ding, Yuan Chun; Neuhausen, Susan L.; Hansen, Thomas V. O.; Gerdes, Anne-Marie; Ejlertsen, Bent; Jønson, Lars; Osorio, Ana; Martínez-Bouzas, Cristina; Benitez, Javier; Conway, Edye E.; Blazer, Kathleen R.; Weitzel, Jeffrey N.; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Scuvera, Giulietta; Barile, Monica; Ficarazzi, Filomena; Mariette, Frederique; Fortuzzi, Stefano; Viel, Alessandra; Giannini, Giuseppe; Papi, Laura; Martayan, Aline; Tibiletti, Maria Grazia; Radice, Paolo; Vratimos, Athanassios; Fostira, Florentia; Garber, Judy E.; Donaldson, Alan; Brewer, Carole; Foo, Claire; Evans, D. Gareth R.; Frost, Debra; Eccles, Diana; Brady, Angela; Cook, Jackie; Tischkowitz, Marc; Adlard, Julian; Barwell, Julian; Walker, Lisa; Izatt, Louise; Side, Lucy E.; Kennedy, M. John; Rogers, Mark T.; Porteous, Mary E.; Morrison, Patrick J.; Platte, Radka; Davidson, Rosemarie; Hodgson, Shirley V.; Ellis, Steve; Cole, Trevor; Godwin, Andrew K.; Claes, Kathleen; Van Maerken, Tom; Meindl, Alfons; Gehrig, Andrea; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Plendl, Hansjoerg; Kast, Karin; Rhiem, Kerstin; Ditsch, Nina; Arnold, Norbert; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Wang-Gohrke, Shan; Bressac-de Paillerets, Brigitte; Buecher, Bruno; Delnatte, Capucine; Houdayer, Claude; Stoppa-Lyonnet, Dominique; Damiola, Francesca; Coupier, Isabelle; Barjhoux, Laure; Venat-Bouvet, Laurence; Golmard, Lisa; Boutry-Kryza, Nadia; Sinilnikova, Olga M.; Caron, Olivier; Pujol, Pascal; Mazoyer, Sylvie; Belotti, Muriel; Piedmonte, Marion; Friedlander, Michael L.; Rodriguez, Gustavo C.; Copeland, Larry J; de la Hoya, Miguel; Segura, Pedro Perez; Nevanlinna, Heli; Aittomäki, Kristiina; van Os, Theo A.M.; Meijers-Heijboer, Hanne E.J.; van der Hout, Annemarie H.; Vreeswijk, Maaike P.G.; Hoogerbrugge, Nicoline; Ausems, Margreet G.E.M.; van Doorn, Helena C.; Collée, J. Margriet; Olah, Edith; Diez, Orland; Blanco, Ignacio; Lazaro, Conxi; Brunet, Joan; Feliubadalo, Lidia; Cybulski, Cezary; Gronwald, Jacek; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Sukiennicki, Grzegorz; Arason, Adalgeir; Chiquette, Jocelyne; Teixeira, Manuel R.; Olswold, Curtis; Couch, Fergus J.; Lindor, Noralane M.; Wang, Xianshu; Szabo, Csilla I.; Offit, Kenneth; Corines, Marina; Jacobs, Lauren; Robson, Mark E.; Zhang, Liying; Joseph, Vijai; Berger, Andreas; Singer, Christian F.; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng M.; Phelan, Catherine M.; Greene, Mark H.; Mai, Phuong L.; Rennert, Gad; Mulligan, Anna Marie; Glendon, Gord; Tchatchou, Sandrine; Andrulis, Irene L.; Toland, Amanda Ewart; Bojesen, Anders; Pedersen, Inge Sokilde; Thomassen, Mads; Jensen, Uffe Birk; Laitman, Yael; Rantala, Johanna; von Wachenfeldt, Anna; Ehrencrona, Hans; Askmalm, Marie Stenmark; Borg, Åke; Kuchenbaecker, Karoline B.; McGuffog, Lesley; Barrowdale, Daniel; Healey, Sue; Lee, Andrew; Pharoah, Paul D.P.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Friedman, Eitan

2014-01-01

Background BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and non-genetic modifying factors. In this study we evaluated the putative role of variants in many candidate modifier genes. Methods Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n=3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. Results The observed p-values of association ranged between 0.005-1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. Conclusion There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. Impact Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies. PMID:25336561
Predictors of pretreatment CA125 at ovarian cancer diagnosis

DEFF Research Database (Denmark)

Babic, Ana; Cramer, Daniel W; Kelemen, Linda E

2017-01-01

PURPOSE: Cancer antigen 125 (CA125) is a glycoprotein expressed by epithelial cells of several normal tissue types and overexpressed by several epithelial cancers. Serum CA125 levels are mostly used as an aid in the diagnosis of ovarian cancer patients, to monitor response to treatment and detect...... in CA125 between studies and linear regression to estimate the association between epidemiologic factors and tumor characteristics and pretreatment CA125 levels. RESULTS: In age-adjusted models, older age, history of pregnancy, history of tubal ligation, family history of breast cancer, and family...... cancer recurrence. Besides tumor characteristics, CA125 levels are also influenced by several epidemiologic factors, such as age, parity, and oral contraceptive use. Identifying factors that influence CA125 levels in ovarian cancer patients could aid in the interpretation of CA125 values for individuals...

Fertility after breast cancer treatment.

Science.gov (United States)

Kasum, Miro; Beketić-Orešković, Lidija; Peddi, Parvin F; Orešković, Slavko; Johnson, Rebecca H

2014-02-01

In many countries of the developed world, there is an increasing trend toward delay in childbearing from 30 to 40 years of age for various reasons. This is unfortunately concordant with an increasing incidence of breast cancer in women who have not yet completed their family. The current choice for premenopausal women with breast cancer is adjuvant therapy which includes cytotoxic chemotherapy, ovarian ablation (by surgery, irradiation, or chemical ovarian suppression), anti-estrogen therapy, or any combination of these. Although the use of adjuvant therapies with cytotoxic drugs can significantly reduce mortality, it raises issues of the long-term toxicity, such as induction of an early menopause and fertility impairment. The risk of infertility is a potential hardship to be faced by the patients following treatment of breast cancer. The offspring of patients who became pregnant after completion of chemotherapy have shown no adverse effects and congenital anomalies from the treatment, but sometimes high rates of abortion (29%) and premature deliveries with low birth weight (40%) have been demonstrated. Therefore, the issue of recent cytotoxic treatment remains controversial and further research is required to define a "safety period" between cessation of treatment and pregnancy. Preservation of fertility in breast cancer survivors of reproductive age has become an important issue regarding the quality of life. Currently, there are several potential options, including all available assisted technologies, such as in vitro fertilization and embryo transfer, in vitro maturation, oocyte and embryo cryopreservation, and cryopreservation of ovarian tissue. Because increased estrogen levels are thought to be potentially risky in breast cancer patients, recently developed ovarian stimulation protocols with the aromatase inhibitor letrozole and tamoxifen appear to provide safe stimulation with endogenous estrogen. Embryo cryopreservation seems to be the most established
RAD51B in Familial Breast Cancer

OpenAIRE

Pelttari, L.M.; Khan, S.; et al.,

2016-01-01

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737\\ud and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast\\ud cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer\\ud predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the\\ud coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for\\ud identifi...
RAD51B in familial breast cancer

OpenAIRE

Pelttari, LM; Khan, S; Vuorela, M; Kiiski, JI; Vilske, S; Nevanlinna, V; Ranta, S; Schleutker, J; Winqvist, R; Kallioniemi, A; Dörk, T; Bogdanova, NV; Figueroa, J; Pharoah, PDP; Schmidt, MK

2016-01-01

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possi...
Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

DEFF Research Database (Denmark)

Lawrenson, Kate; Kar, Siddhartha; McCue, Karen

2016-01-01

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10(-20)), ER......'-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk....
Establishing a family risk assessment clinic for breast cancer.

LENUS (Irish Health Repository)

Mulsow, Jurgen

2012-02-01

Breast cancer is the most common cancer affecting European women and the leading cause of cancer-related death. A total of 15-20% of women who develop breast cancer have a family history and 5-10% a true genetic predisposition. The identification and screening of women at increased risk may allow early detection of breast cancer and improve prognosis. We established a family risk assessment clinic in May 2005 to assess and counsel women with a family history of breast cancer, to initiate surveillance, and to offer risk-reducing strategies for selected high-risk patients. Patients at medium or high risk of developing breast cancer according to NICE guidelines were accepted. Family history was determined by structured questionnaire and interview. Lifetime risk of developing breast cancer was calculated using Claus and Tyrer-Cuzick scoring. Risk of carrying a breast cancer-related gene mutation was calculated using the Manchester system. One thousand two hundred and forty-three patients have been referred. Ninety-two percent were at medium or high risk of developing breast cancer. Formal assessment of risk has been performed in 368 patients, 73% have a high lifetime risk of developing breast cancer, and 72% a Manchester score >or=16. BRCA1\\/2 mutations have been identified in 14 patients and breast cancer diagnosed in two. Our initial experience of family risk assessment has shown there to be a significant demand for this service. Identification of patients at increased risk of developing breast cancer allows us to provide individuals with accurate risk profiles, and enables patients to make informed choices regarding their follow-up and management.
Prevalance of BRCA1 and BRCA2 mutations in familial breast cancer patients in Lebanon

Directory of Open Access Journals (Sweden)

Jalkh Nadine

2012-06-01

Full Text Available Abstract Breast cancer is the most prevalent malignancy in women in Western countries, currently accounting for one third of all female cancers. Familial aggregation is thought to account for 5–10 % of all BC cases, and germline mutations in BRCA1 and BRCA2 account for less of the half of these inherited cases. In Lebanon, breast cancer represents the principal death-causing malignancy among women, with 50 % of the cases diagnosed before the age of 50 years. In order to study BRCA1/2 mutation spectra in the Lebanese population, 72 unrelated patients with a reported family history of breast and/or ovarian cancers or with an early onset breast cancer were tested. Fluorescent direct sequencing of the entire coding region and intronic sequences flanking each exon was performed. A total of 38 BRCA1 and 40 BRCA2 sequence variants were found. Seventeen of them were novel. Seven confirmed deleterious mutations were identified in 9 subjects providing a frequency of mutations of 12.5 %. Fifteen variants were considered of unknown clinical significance according to BIC and UMD-BRCA1/BRCA2 databases. In conclusion, this study represents the first evaluation of the deleterious and unclassified genetic variants in the BRCA1/2 genes found in a Lebanese population with a relatively high risk of breast cancer.
Identification and Functional Testing of ERCC2 Mutations in a Multi-national Cohort of Patients with Familial Breast- and Ovarian Cancer.

Directory of Open Access Journals (Sweden)

Andreas Rump

2016-08-01

Full Text Available The increasing application of gene panels for familial cancer susceptibility disorders will probably lead to an increased proposal of susceptibility gene candidates. Using ERCC2 DNA repair gene as an example, we show that proof of a possible role in cancer susceptibility requires a detailed dissection and characterization of the underlying mutations for genes with diverse cellular functions (in this case mainly DNA repair and basic cellular transcription. In case of ERCC2, panel sequencing of 1345 index cases from 587 German, 405 Lithuanian and 353 Czech families with breast and ovarian cancer (BC/OC predisposition revealed 25 mutations (3 frameshift, 2 splice-affecting, 20 missense, all absent or very rare in the ExAC database. While 16 mutations were unique, 9 mutations showed up repeatedly with population-specific appearance. Ten out of eleven mutations that were tested exemplarily in cell-based functional assays exert diminished excision repair efficiency and/or decreased transcriptional activation capability. In order to provide evidence for BC/OC predisposition, we performed familial segregation analyses and screened ethnically matching controls. However, unlike the recently published RECQL example, none of our recurrent ERCC2 mutations showed convincing co-segregation with BC/OC or significant overrepresentation in the BC/OC cohort. Interestingly, we detected that some deleterious founder mutations had an unexpectedly high frequency of > 1% in the corresponding populations, suggesting that either homozygous carriers are not clinically recognized or homozygosity for these mutations is embryonically lethal. In conclusion, we provide a useful resource on the mutational landscape of ERCC2 mutations in hereditary BC/OC patients and, as our key finding, we demonstrate the complexity of correct interpretation for the discovery of "bonafide" breast cancer susceptibility genes.
Almost 2% of Spanish breast cancer families are associated to germline pathogenic mutations in the ATM gene.

Science.gov (United States)

Tavera-Tapia, A; Pérez-Cabornero, L; Macías, J A; Ceballos, M I; Roncador, G; de la Hoya, M; Barroso, A; Felipe-Ponce, V; Serrano-Blanch, R; Hinojo, C; Miramar-Gallart, M D; Urioste, M; Caldés, T; Santillan-Garzón, S; Benitez, J; Osorio, A

2017-02-01

There is still a considerable percentage of hereditary breast and ovarian cancer (HBOC) cases not explained by BRCA1 and BRCA2 genes. In this report, next-generation sequencing (NGS) techniques were applied to identify novel variants and/or genes involved in HBOC susceptibility. Using whole exome sequencing, we identified a novel germline mutation in the moderate-risk gene ATM (c.5441delT; p.Leu1814Trpfs*14) in a family negative for mutations in BRCA1/2 (BRCAX). A case-control association study was performed to establish its prevalence in Spanish population, in a series of 1477 BRCAX families and 589 controls further screened, and NGS panels were used for ATM mutational screening in a cohort of 392 HBOC Spanish BRCAX families and 350 patients affected with diseases not related to breast cancer. Although the interrogated mutation was not prevalent in case-control association study, a comprehensive mutational analysis of the ATM gene revealed 1.78% prevalence of mutations in the ATM gene in HBOC and 1.94% in breast cancer-only BRCAX families in Spanish population, where data about ATM mutations were very limited. ATM mutation prevalence in Spanish population highlights the importance of considering ATM pathogenic variants linked to breast cancer susceptibility.
Recruiting families at risk for hereditary breast and ovarian cancer from a statewide cancer registry: a methodological study.

Science.gov (United States)

Katapodi, Maria C; Duquette, Deb; Yang, James J; Mendelsohn-Victor, Kari; Anderson, Beth; Nikolaidis, Christos; Mancewicz, Emily; Northouse, Laurel L; Duffy, Sonia; Ronis, David; Milliron, Kara J; Probst-Herbst, Nicole; Merajver, Sofia D; Janz, Nancy K; Copeland, Glenn; Roberts, Scott

2017-03-01

Cancer genetic services (counseling/testing) are recommended for women diagnosed with breast cancer younger than 45 years old (young breast cancer survivors-YBCS) and at-risk relatives. We present recruitment of YBCS, identification and recruitment of at-risk relatives, and YBCS willingness to contact their cancer-free, female relatives. A random sample of 3,000 YBCS, stratified by race (Black vs. White/Other), was identified through a population-based cancer registry and recruited in a randomized trial designed to increase use of cancer genetic services. Baseline demographic, clinical, and family characteristics, and variables associated with the Theory of Planned Behavior (TPB) were assessed as predictors of YBCS' willingness to contact at-risk relatives. The 883 YBCS (33.2% response rate; 40% Black) who returned a survey had 1,875 at-risk relatives and were willing to contact 1,360 (72.5%). From 853 invited at-risk relatives (up to two relatives per YBCS), 442 responded (51.6% response rate). YBCS with larger families, with a previous diagnosis of depression, and motivated to comply with recommendations from family members were likely to contact a greater number of relatives. Black YBCS were more likely to contact younger relatives and those living further than 50 miles compared to White/Other YBCS. It is feasible to recruit diverse families at risk for hereditary cancer from a population-based cancer registry. This recruitment approach can be used as a paradigm for harmonizing processes and increasing internal and external validity of large-scale public health genomic initiatives in the era of precision medicine.
Analysis of BRCA1 involvement in breast cancer in Indian women

Indian Academy of Sciences (India)

The involvement of the familial breast-ovarian cancer gene (BRCA1) in the molecular pathogenesis of breast cancer among Indian women is unknown. We have used a set of microsatellite polymorphisms to examine the frequency of allele loss at the BRCA1 region on chromosome 17q21, in a panel of 80 human breast ...
Random start ovarian stimulation for fertility preservation appears unlikely to delay initiation of neoadjuvant chemotherapy for breast cancer.

Science.gov (United States)

Letourneau, Joseph M; Sinha, Nikita; Wald, Kaitlyn; Harris, Eve; Quinn, Molly; Imbar, Tal; Mok-Lin, Evelyn; Chien, A Jo; Rosen, Mitchell

2017-10-01

Is random start ovarian stimulation associated with delays in initiation of neoadjuvant chemotherapy for breast cancer? Among women who complete fertility preservation (FP) consultation, random start ovarian stimulation is unlikely to delay time to initiation of neoadjuvant chemotherapy start. Neoadjuvant chemotherapy is now a widely accepted treatment modality for operable breast cancer and random start ovarian stimulation is an increasingly-utilized modality for FP. While conventional ovarian stimulation does not appear to delay starting adjuvant chemotherapy, the relationship between random start ovarian stimulation and neoadjuvant chemotherapy start is not well-understood. Cross-sectional study of all women seen between from January 2011 to April 2017 for FP consultation prior to starting neoadjuvant chemotherapy for breast cancer. A chart-review was performed. Study inclusion criteria were female sex; age 18-45; non-metastatic breast cancer diagnosis; underwent FP consultation; underwent neoadjuvant chemotherapy. Referrals for FP evaluation came from a regional referral base of oncology clinics. Various time-points related to cancer diagnosis, FP or chemotherapy were obtained from medical record review. We compared time-points between those who underwent ovarian stimulation for FP versus those who did not using T-tests and linear modeling. A total of 89 women who had FP consultation prior to neoadjuvant chemotherapy were identified. Sixty-seven percent underwent ovarian stimulation prior to cancer treatment and 33% did not. Women who underwent ovarian stimulation were similar in parity and clinical cancer stage to those who did not. Overall, the average time from cancer diagnosis to chemotherapy start was similar between the group that did undergo ovarian stimulation and those who did not (38.1 ± 11.3 versus 39.4 ± 18.5 days, P = 0.672). Those that underwent ovarian stimulation were referred 9.4 ± 6.8 days after diagnosis versus 17.9 ± 15.3 days for those
G1738R is a BRCA1 founder mutation in Greek breast/ovarian cancer patients: evaluation of its pathogenicity and inferences on its genealogical history.

Science.gov (United States)

Anagnostopoulos, Theodore; Pertesi, Maroulio; Konstantopoulou, Irene; Armaou, Sofia; Kamakari, Smaragda; Nasioulas, George; Athanasiou, Athanassios; Dobrovic, Alex; Young, Mary-Anne; Goldgar, David; Fountzilas, George; Yannoukakos, Drakoulis

2008-07-01

We have performed screening in 287 breast/ovarian cancer families in Greece which has revealed that approximately 12% (8/65) of all index patients-carriers of a deleterious mutation in BRCA1 and BRCA2 genes, contain the base substitution G to A at position 5331 of BRCA1 gene. This generates the amino acid change G1738R for which based on a combination of genetic, in silico and histopathological analysis there are strong suggestions that it is a causative mutation. In this paper, we present further evidence suggesting the pathogenicity of this variant. Forty breast/ovarian cancer patients were reported in 11 Greek families: the above eight living in Greece, two living in Australia and one in USA, all containing G1738R. Twenty of these patients were screened and were all found to be carriers of the same base substitution. In addition, we have detected the same base change in five breast/ovarian cancer patients after screening 475 unselected patient samples with no apparent family history. The mean age of onset for all the above patients was 39.4 and 53.6 years for breast and ovarian cancer cases, respectively. A multi-factorial likelihood model for classification of unclassified variants in BRCA1 and BRCA2 developed previously was applied on G1738R and the odds of it being a deleterious mutation was estimated to be 11470:1. In order to explain the prevalence of this mutation mainly in the Greek population, its genealogical history was examined. DNA samples were collected from 11 carrier families living in Greece, Australia and USA. Screening of eight intragenic SNPs, three intragenic and seven extragenic microsatellite markers and comparison with control individuals, suggested a common origin for the mutation while the time to its most recent common ancestor was estimated to be 11 generations (about 275 years assuming a generational interval of 25 years) with a 1-lod support interval of 4-24 generations (100-600 years). Considering the large degree of genetic
Implementing a screening tool for identifying patients at risk for hereditary breast and ovarian cancer: a statewide initiative.

Science.gov (United States)

Brannon Traxler, L; Martin, Monique L; Kerber, Alice S; Bellcross, Cecelia A; Crane, Barbara E; Green, Victoria; Matthews, Roland; Paris, Nancy M; Gabram, Sheryl G A

2014-10-01

The Georgia Breast Cancer Genomic Health Consortium is a partnership created with funding from the Centers for Disease Control and Prevention (CDC) to the Georgia Department of Public Health to reduce cancer disparities among high-risk minority women. The project addresses young women at increased risk for hereditary breast and ovarian cancer (HBOC) syndrome through outreach efforts. The consortium provides education and collects surveillance data using the breast cancer genetics referral screening tool (B-RST) available at www.BreastCancerGeneScreen.org . The HBOC educational protocol was presented to 73 staff in 6 public health centers. Staff used the tool during the collection of medical history. Further family history assessments and testing for mutations in the BRCA1/2 genes were facilitated if appropriate. Data was collected from November 2012 through December 2013, including 2,159 screened women. The majority of patients identified as black/African American and were 18-49 years old. Also, 6.0 % (n = 130) had positive screens, and 60.9 % (n = 67) of the 110 patients who agreed to be contacted provided a detailed family history. A total of 47 patients (42.7 %) met National Comprehensive Cancer Network guidelines when family history was clarified. Fourteen (12.7 %) underwent genetic testing; 1 patient was positive for a BRCA2 mutation, and 1 patient was found to carry a variant of uncertain significance. The introduction of genomics practice within public health departments has provided access to comprehensive cancer care for uninsured individuals. The successful implementation of the B-RST into public health centers demonstrates the opportunity for integration of HBOC screening into primary care practices.
A Nonsynonymous Polymorphism in IRS1 Modifies Risk of Developing Breast and Ovarian Cancers in BRCA1 and Ovarian Cancer in BRCA2 Mutation Carriers

NARCIS (Netherlands)

Ding, Yuan C.; McGuffog, Lesley; Healey, Sue; Friedman, Eitan; Laitman, Yael; Paluch-Shimon, Shani-; Kaufman, Bella; Liljegren, Annelie; Lindblom, Annika; Olsson, Håkan; Kristoffersson, Ulf; Stenmark-Askmalm, Marie; Melin, Beatrice; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Gronwald, Jacek; Huzarski, Tomasz; Cybulski, Cezary; Byrski, Tomasz; Osorio, Ana; Cajal, Teresa Ramóny; Stavropoulou, Alexandra V.; Benítez, Javier; Hamann, Ute; Rookus, Matti; Aalfs, Cora M.; de Lange, Judith L.; Meijers-Heijboer, Hanne E. J.; Oosterwijk, Jan C.; van Asperen, Christi J.; Gómez García, Encarna B.; Hoogerbrugge, Nicoline; Jager, Agnes; van der Luijt, Rob B.; Easton, Douglas F.; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Evans, D. Gareth; Lalloo, Fiona; Izatt, Louise; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Brewer, Carole; Tischkowitz, Marc; Godwin, Andrew K.; Pathak, Harsh; Stoppa-Lyonnet, Dominique; Sinilnikova, Olga M.; Mazoyer, Sylvie; Barjhoux, Laure; Léoné, Mélanie; Gauthier-Villars, Marion; Caux-Moncoutier, Virginie; de Pauw, Antoine; Hardouin, Agnès; Berthet, Pascaline; Dreyfus, Hélène; Ferrer, Sandra Fert; Collonge-Rame, Marie-Agnès; Sokolowska, Johanna; Buys, Saundra; Daly, Mary; Miron, Alex; Terry, Mary Beth; Chung, Wendy; John, Esther M.; Southey, Melissa; Goldgar, David; Singer, Christian F.; tea, Muy-Kheng Maria; Gschwantler-Kaulich, Daphne; Fink-Retter, Anneliese; Hansen, Thomas V. O.; Ejlertsen, Bent; Johannsson, Oskar T.; Offit, Kenneth; Sarrel, Kara; Gaudet, Mia M.; Vijai, Joseph; Robson, Mark; Piedmonte, Marion R.; Andrews, Lesley; Cohn, David; DeMars, Leslie R.; DiSilvestro, Paul; Rodriguez, Gustavo; Toland, Amanda Ewart; Montagna, Marco; Agata, Simona; Imyanitov, Evgeny; Isaacs, Claudine; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Ignacio; Ramus, Susan J.; Sucheston, Lara; Karlan, Beth Y.; Gross, Jenny; Ganz, Patricia A.; Beattie, Mary S.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Meindl, Alfons; Arnold, Norbert; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorotehea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Nevanlinna, Heli; Aittomäki, Kristiina; Simard, Jacques; Spurdle, Amanda B.; Beesley, Jonathan; Chen, Xiaoqing; Tomlinson, Gail E.; Weitzel, Jeffrey; Garber, Judy E.; Olopade, Olufunmilayo I.; Rubinstein, Wendy S.; Tung, Nadine; Blum, Joanne L.; Narod, Steven A.; Brummel, Sean; Gillen, Daniel L.; Lindor, Noralane; Fredericksen, Zachary; Pankratz, Vernon S.; Couch, Fergus J.; Radice, Paolo; Peterlongo, Paolo; Greene, Mark H.; Loud, Jennifer T.; Mai, Phuong L.; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Gerdes, Anne-Marie; Thomassen, Mads; Jensen, Uffe Birk; Skytte, Anne-Bine; Caligo, Maria A.; Lee, Andrew; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Neuhausen, Susan L.

2012-01-01

Background: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were
A Nonsynonymous Polymorphism in IRS1 Modifies Risk of Developing Breast and Ovarian Cancers in BRCA1 and Ovarian Cancer in BRCA2 Mutation Carriers.

NARCIS (Netherlands)

Ding, Y.C.; McGuffog, L.; Healey, S.; Friedman, E.; Laitman, Y.; Paluch-Shimon, S.; Kaufman, B.; Liljegren, A.; Lindblom, A.; Olsson, H.; Kristoffersson, U.; Stenmark-Askmalm, M.; Melin, B.; Domchek, S.M.; Nathanson, K.L.; Rebbeck, T.R.; Jakubowska, A.; Lubinski, J.; Jaworska, K.; Durda, K.; Gronwald, J.; Huzarski, T.; Cybulski, C.; Byrski, T.; Osorio, A.; Cajal, T.R.; Stavropoulou, A.V.; Benitez, J.; Hamann, U.; Rookus, M.; Aalfs, C.M.; Lange, J.L. de; Meijers-Heijboer, H.E.; Oosterwijk, J.C.; Asperen, C.J. van; Gomez Garcia, E.B.; Hoogerbrugge, N.; Jager, A.; Luijt, R.B. van der; Easton, D.F.; Peock, S.; Frost, D.; Ellis, S.D.; Platte, R.; Fineberg, E.; Evans, D.G.; Lalloo, F.; Izatt, L.; Eeles, R.; Adlard, J.; Davidson, R.; Eccles, D.; Cole, T.; Cook, J.; Brewer, C.; Tischkowitz, M.; Godwin, A.K.; Pathak, H.; Stoppa-Lyonnet, D.; Sinilnikova, O.M.; Mazoyer, S.; Barjhoux, L.; Leone, M.; Gauthier-Villars, M.; Caux-Moncoutier, V.; Pauw, A. de; Hardouin, A.; Berthet, P.; Dreyfus, H.; Ferrer, S.F.; Collonge-Rame, M.A.; Sokolowska, J.; Buys, S.; Daly, M.; Miron, A.; Terry, M.B.; Chung, W.; John, E.M.; Southey, M.; Goldgar, D.; Singer, C.F.; Tea, M.K.; Gschwantler-Kaulich, D.; Fink-Retter, A.; Hansen, T.V.; Ejlertsen, B.; Johannsson, O.T.; Offit, K.; Sarrel, K.; Gaudet, M.M.; Vijai, J.; Robson, M.; Piedmonte, M.R.; Andrews, L.; Cohn, D.; Demars, L.R.; Disilvestro, P.; Rodriguez, G.; Toland, A.E.; Montagna, M.; Agata, S.; Imyanitov, E.; Isaacs, C.; Janavicius, R.; Lazaro, C.; Blanco, I.; Ramus, S.J.; Sucheston, L.; Karlan, B.Y.; Gross, J.; Ganz, P.A.; Beattie, M.S.; Schmutzler, R.K.; Wappenschmidt, B.; Meindl, A.; Arnold, N.; Niederacher, D.; Preisler-Adams, S.; Gadzicki, D.; Varon-Mateeva, R.; Deissler, H.; Gehrig, A.; Sutter, C.; Kast, K.; Nevanlinna, H.; Aittomaki, K.; Simard, J.; Spurdle, A.B.; Beesley, J.; Chen, X.; Tomlinson, G.E.; Weitzel, J.; Garber, J.E.; Olopade, O.I.; Rubinstein, W.S.; Tung, N.; Blum, J.L.; Narod, S.A.; Brummel, S.; Gillen, D.L.; Lindor, N.; Fredericksen, Z.; Pankratz, V.S.; Couch, F.J.; Radice, P.; Peterlongo, P.; Greene, M.H.; Loud, J.T.; Mai, P.L.; Andrulis, I.L.; Glendon, G.; Ozcelik, H.; Gerdes, A.M.; Thomassen, M.; Jensen, U.B.; Skytte, A.B.; Caligo, M.A.; Lee, A.; Chenevix-Trench, G.; Antoniou, A.C.; Neuhausen, S.L.

2012-01-01

BACKGROUND: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were
A Nonsynonymous Polymorphism in IRS1 Modifies Risk of Developing Breast and Ovarian Cancers in BRCA1 and Ovarian Cancer in BRCA2 Mutation Carriers

NARCIS (Netherlands)

Ding, Yuan C.; McGuffog, Lesley; Healey, Sue; Friedman, Eitan; Laitman, Yael; Shani-Paluch-Shimon, [No Value; Kaufman, Bella; Liljegren, Annelie; Lindblom, Annika; Olsson, Hakan; Kristoffersson, Ulf; Stenmark-Askmalm, Marie; Melin, Beatrice; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Gronwald, Jacek; Huzarski, Tomasz; Cybulski, Cezary; Byrski, Tomasz; Osorio, Ana; Ramony Cajal, Teresa; Stavropoulou, Alexandra V.; Benitez, Javier; Hamann, Ute; Rookus, Matti; Aalfs, Cora M.; de Lange, Judith L.; Meijers-Heijboer, Hanne E. J.; Oosterwijk, Jan C.; van Asperen, Christi J.; Garcia, Encarna B. Gomez; Hoogerbrugge, Nicoline; Jager, Agnes; van der Luijt, Rob B.; Easton, Douglas F.; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Evans, D. Gareth; Lalloo, Fiona; Izatt, Louise; Eeles, Ros; Adlard, Julian

Background: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were
A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers

NARCIS (Netherlands)

Y.C. Ding (Yuan); L. McGuffog (Lesley); S. Healey (Sue); E. Friedman (Eitan); Y. Laitman (Yael); S.-P. Shimon (Shani-Paluch); B. Kaufman (Bella); A. Liljegren (Annelie); A. Lindblom (Annika); H. Olsson; U. Kristoffersson (Ulf); M. Stenmark-Askmalm (M.); B. Melin (Beatrice); S.M. Domchek (Susan); K.L. Nathanson (Katherine); R. Rebbeck (Timothy); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska (Katarzyna); K. Durda (Katarzyna); J. Gronwald (Jacek); T. Huzarski (Tomasz); C. Cybulski (Cezary); T. Byrski (Tomasz); A. Osorio (Ana); T.R. Cajal; A. Stavropoulou (Alexandra); J. Benítez (Javier); U. Hamann (Ute); M.A. Rookus (Matti); C.M. Aalfs (Cora); J.L. de Lange (J.); E.J. Meijers-Heijboer (Hanne); J.C. Oosterwijk (Jan); C.J. van Asperen (Christi); E.B. Gómez García (Encarna); N. Hoogerbrugge (Nicoline); A. Jager (Agnes); R.B. van der Luijt (Rob); D.F. Easton (Douglas); S. Peock (Susan); D. Frost (Debra); S.D. Ellis (Steve); R. Platte (Radka); E. Fineberg (Elena); D.G. Evans (Gareth); F. Lalloo (Fiona); L. Izatt (Louise); R. Eeles (Rosalind); J.W. Adlard (Julian); R. Davidson (Rosemarie); D. Eccles (Diana); T.J. Cole (Trevor); J. Cook (Jackie); C. Brewer (Carole); M. Tischkowitz (Marc); A.K. Godwin (Andrew); S.S. Pathak; D. Stoppa-Lyonnet (Dominique); O. Sinilnikova (Olga); S. Mazoyer (Sylvie); L. Barjhoux (Laure); M. Léone (Mélanie); M. Gauthier-Villars (Marion); V. Caux-Moncoutier (Virginie); A. de Pauw (Antoine); A. Hardouin (Agnès); P. Berthet (Pascaline); H. Dreyfus (Hélène); S.F. Ferrer; M.-A. Collonge-Rame; J. Sokolowska (Johanna); S.S. Buys (Saundra); M.B. Daly (Mary); A. Miron (Alexander); M.-B. Terry (Mary-Beth); W. Chung (Wendy); E.M. John (Esther); M.C. Southey (Melissa); D. Goldgar (David); C.F. Singer (Christian); M.-K. Tea; D. Gschwantler-Kaulich (Daphne); A. Fink-Retter (Anneliese); T.V.O. Hansen (Thomas); B. Ejlertsen (Bent); O.T. Johannson (Oskar); K. Offit (Kenneth); K. Sarrel (Kara); M.M. Gaudet (Mia); J. Vijai (Joseph); M. Robson (Mark); M. Piedmonte (Marion); L. Andrews (Lesley); D.E. Cohn (David); L.R. DeMars (Leslie); P. DiSilvestro (Paul); G.C. Rodriguez (Gustavo); A.E. Toland (Amanda); M. Montagna (Marco); S. Agata (Simona); E.N. Imyanitov (Evgeny); C. Isaacs (Claudine); R. Janavicius (Ramunas); C. Lazaro (Conxi); I. Blanco (Ignacio); S.J. Ramus (Susan); L. Sucheston (Lara); B.Y. Karlan (Beth); J. Gross (Jenny); P.A. Ganz (Patricia); M.S. Beattie (Mary); R.K. Schmutzler (Rita); B. Wapenschmidt (Barbara); A. Meindl (Alfons); N. Arnold (Norbert); D. Niederacher (Dieter); S. Preisler-Adams (Sabine); D. Gadzicki (Dorothea); R. Varon-Mateeva (Raymonda); H. Deissler (Helmut); P.A. Gehrig (Paola A.); C. Sutter (Christian); K. Kast (Karin); H. Nevanlinna (Heli); K. Aittomäki (Kristiina); J. Simard (Jacques); A.B. Spurdle (Amanda); J. Beesley (Jonathan); X. Chen (Xiaoqing); G. Tomlinson (Gail); J.N. Weitzel (Jeffrey); J. Garber; O.I. Olopade (Olofunmilayo); W.S. Rubinstein (Wendy); N. Tung (Nadine); J.L. Blum (Joanne); S. Narod (Steven); S. Brummel (Sean); D.L. Gillen (Daniel); N.M. Lindor (Noralane); Z. Fredericksen (Zachary); V.S. Pankratz (Shane); F.J. Couch (Fergus); P. Radice (Paolo); P. Peterlongo (Paolo); M.H. Greene (Mark); J.T. Loud (Jennifer); P.L. Mai (Phuong); I.L. Andrulis (Irene); G. Glendon (Gord); H. Ozcelik (Hilmi); A-M. Gerdes (Anne-Marie); M. Thomassen (Mads); U.B. Jensen; A.-B. Skytte (Anne-Bine); M.A. Caligo (Maria); A. Lee (Andrew); G. Chenevix-Trench (Georgia); A.C. Antoniou (Antonis); S.L. Neuhausen (Susan)

2012-01-01

textabstractBackground: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk inwomen carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and
The prevalence of BRCA1 mutations among young women with triple-negative breast cancer

International Nuclear Information System (INIS)

Young, SR; DeSai, Damini; Zandvakili, Inuk; Royer, Robert; Li, Song; Narod, Steven A; Pilarski, Robert T; Donenberg, Talia; Shapiro, Charles; Hammond, Lyn S; Miller, Judith; Brooks, Karen A; Cohen, Stephanie; Tenenholz, Beverly

2009-01-01

Molecular screening for BRCA1 and BRCA2 mutations is now an established component of risk evaluation and management of familial breast cancer. Features of hereditary breast cancer include an early age-of-onset and over-representation of the 'triple-negative' phenotype (negative for estrogen-receptor, progesterone-receptor and HER2). The decision to offer genetic testing to a breast cancer patient is usually based on her family history, but in the absence of a family history of cancer, some women may qualify for testing based on the age-of-onset and/or the pathologic features of the breast cancer. We studied 54 women who were diagnosed with high-grade, triple-negative invasive breast cancer at or before age 40. These women were selected for study because they had little or no family history of breast or ovarian cancer and they did not qualify for genetic testing using conventional family history criteria. BRCA1 screening was performed using a combination of fluorescent multiplexed-PCR analysis, BRCA1 exon-13 6 kb duplication screening, the protein truncation test (PTT) and fluorescent multiplexed denaturing gradient gel electrophoresis (DGGE). All coding exons of BRCA1 were screened. The two large exons of BRCA2 were also screened using PTT. All mutations were confirmed with direct sequencing. Five deleterious BRCA1 mutations and one deleterious BRCA2 mutation were identified in the 54 patients with early-onset, triple-negative breast cancer (11%). Women with early-onset triple-negative breast cancer are candidates for genetic testing for BRCA1, even in the absence of a family history of breast or ovarian cancer
A novel loss-of-function heterozygous BRCA2 c.8946_8947delAG mutation found in a Chinese woman with family history of breast cancer.

Science.gov (United States)

Ma, Jing; Yang, Jichun; Jian, Wenjing; Wang, Xianming; Xiao, Deyong; Xia, Wenjun; Xiong, Likuan; Ma, Duan

2017-04-01

Breast cancer is the most frequent female malignancy worldwide. Among them, some cases have hereditary susceptibility in two leading genes, BRCA1 and BRCA2. Heterozygous germ line mutations in them are related with increased risk of breast, ovarian and other cancer, following autosomal dominant inheritance mode. For purpose of early finding, early diagnosis and early treatment, mutation detecting of BRCA1/2 genes was performed in unselected 300 breast or ovarian patients and unaffected women using next-generation sequencing and then confirmed by Sanger sequencing. A non-previously reported heterozygous mutation c.8946_8947delAG (p.D2983FfsX34) of BRCA2 gene was identified in an unaffected Chinese woman with family history of breast cancer (her breast cancer mother, also carrying this mutation). The BRCA2-truncated protein resulted from the frame shift mutation was found to lose two putative nuclear localization signals and a Rad51-binding motif in the extreme C-terminal region by bioinformatic prediction. And then in vitro experiments showed that nearly all the mutant protein was unable to translocate to the nucleus to perform DNA repair activity. This novel mutant BRCA2 protein is dysfunction. We classify the mutation into disease causing and conclude that it is the risk factor for breast cancer in this family. So, conducting the same mutation test and providing genetic counseling for this family is practically meaningful and significant. Meanwhile, the identification of this new mutation enriches the Breast Cancer Information Core database, especially in China.
A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers

DEFF Research Database (Denmark)

Ding, Yuan C; McGuffog, Lesley; Healey, Sue

2012-01-01

We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated wit...

A genomic and transcriptomic approach for a differential diagnosis between primary and secondary ovarian carcinomas in patients with a previous history of breast cancer

International Nuclear Information System (INIS)

Meyniel, Jean-Philippe; Alran, Séverine; Rapinat, Audrey; Gentien, David; Roman-Roman, Sergio; Mignot, Laurent; Sastre-Garau, Xavier; Cottu, Paul H; Decraene, Charles; Stern, Marc-Henri; Couturier, Jérôme; Lebigot, Ingrid; Nicolas, André; Weber, Nina; Fourchotte, Virginie

2010-01-01

The distinction between primary and secondary ovarian tumors may be challenging for pathologists. The purpose of the present work was to develop genomic and transcriptomic tools to further refine the pathological diagnosis of ovarian tumors after a previous history of breast cancer. Sixteen paired breast-ovary tumors from patients with a former diagnosis of breast cancer were collected. The genomic profiles of paired tumors were analyzed using the Affymetrix GeneChip ® Mapping 50 K Xba Array or Genome-Wide Human SNP Array 6.0 (for one pair), and the data were normalized with ITALICS (ITerative and Alternative normaLIzation and Copy number calling for affymetrix Snp arrays) algorithm or Partek Genomic Suite, respectively. The transcriptome of paired samples was analyzed using Affymetrix GeneChip ® Human Genome U133 Plus 2.0 Arrays, and the data were normalized with gc-Robust Multi-array Average (gcRMA) algorithm. A hierarchical clustering of these samples was performed, combined with a dataset of well-identified primary and secondary ovarian tumors. In 12 of the 16 paired tumors analyzed, the comparison of genomic profiles confirmed the pathological diagnosis of primary ovarian tumor (n = 5) or metastasis of breast cancer (n = 7). Among four cases with uncertain pathological diagnosis, genomic profiles were clearly distinct between the ovarian and breast tumors in two pairs, thus indicating primary ovarian carcinomas, and showed common patterns in the two others, indicating metastases from breast cancer. In all pairs, the result of the transcriptomic analysis was concordant with that of the genomic analysis. In patients with ovarian carcinoma and a previous history of breast cancer, SNP array analysis can be used to distinguish primary and secondary ovarian tumors. Transcriptomic analysis may be used when primary breast tissue specimen is not available
Anthropometric characteristics and ovarian cancer risk and survival.

Science.gov (United States)

Minlikeeva, Albina N; Moysich, Kirsten B; Mayor, Paul C; Etter, John L; Cannioto, Rikki A; Ness, Roberta B; Starbuck, Kristen; Edwards, Robert P; Segal, Brahm H; Lele, Sashikant; Odunsi, Kunle; Diergaarde, Brenda; Modugno, Francesmary

2018-02-01

Multiple studies have examined the role of anthropometric characteristics in ovarian cancer risk and survival; however, their results have been conflicting. We investigated the associations between weight change, height and height change and risk and outcome of ovarian cancer using data from a large population-based case-control study. Data from 699 ovarian cancer cases and 1,802 controls who participated in the HOPE study were included. We used unconditional logistic regression adjusted for age, race, number of pregnancies, use of oral contraceptives, and family history of breast or ovarian cancer to examine the associations between self-reported height and weight and height change with ovarian cancer risk. Cox proportional hazards regression models adjusted for age and stage were used to examine the association between the exposure variables and overall and progression-free survival among ovarian cancer cases. We observed an increased risk of ovarian cancer mortality and progression for gaining more than 20 pounds between ages 18-30, HR 1.36; 95% CI 1.05-1.76, and HR 1.31; 95% CI 1.04-1.66, respectively. Losing weight and gaining it back multiple times was inversely associated with both ovarian cancer risk, OR 0.78; 95% CI 0.63-0.97 for 1-4 times and OR 0.73; 95% CI 0.54-0.99 for 5-9 times, and mortality, HR 0.63; 95% CI 0.40-0.99 for 10-14 times. Finally, being taller during adolescence and adulthood was associated with increased risk of mortality. Taller stature and weight gain over lifetime were not related to ovarian cancer risk. Our results suggest that height and weight and their change over time may influence ovarian cancer risk and survival. These findings suggest that biological mechanisms underlying these associations may be hormone driven and may play an important role in relation to ovarian carcinogenesis and tumor progression.
Breast cancer risks and risk prediction models.

Science.gov (United States)

Engel, Christoph; Fischer, Christine

2015-02-01

BRCA1/2 mutation carriers have a considerably increased risk to develop breast and ovarian cancer. The personalized clinical management of carriers and other at-risk individuals depends on precise knowledge of the cancer risks. In this report, we give an overview of the present literature on empirical cancer risks, and we describe risk prediction models that are currently used for individual risk assessment in clinical practice. Cancer risks show large variability between studies. Breast cancer risks are at 40-87% for BRCA1 mutation carriers and 18-88% for BRCA2 mutation carriers. For ovarian cancer, the risk estimates are in the range of 22-65% for BRCA1 and 10-35% for BRCA2. The contralateral breast cancer risk is high (10-year risk after first cancer 27% for BRCA1 and 19% for BRCA2). Risk prediction models have been proposed to provide more individualized risk prediction, using additional knowledge on family history, mode of inheritance of major genes, and other genetic and non-genetic risk factors. User-friendly software tools have been developed that serve as basis for decision-making in family counseling units. In conclusion, further assessment of cancer risks and model validation is needed, ideally based on prospective cohort studies. To obtain such data, clinical management of carriers and other at-risk individuals should always be accompanied by standardized scientific documentation.
Modeling the dyadic effects of parenting, stress, and coping on parent-child communication in families tested for hereditary breast-ovarian cancer risk.

Science.gov (United States)

Hamilton, Jada G; Mays, Darren; DeMarco, Tiffani; Tercyak, Kenneth P

2016-10-01

Genetic testing for BRCA genes, associated with hereditary breast-ovarian cancer risk, is an accepted cancer control strategy. BRCA genetic testing has both medical and psychosocial implications for individuals seeking testing and their family members. However, promoting open and adaptive communication about cancer risk in the family is challenging for parents of minor children. Using prospective data collected from mothers undergoing BRCA genetic testing and their untested co-parents (N = 102 parenting dyads), we examined how maternal and co-parent characteristics independently and conjointly influenced the overall quality of parent-child communication with minor children. Statistical associations were tested in accordance with the Actor-Partner Interdependence Model. Significant Actor effects were observed among mothers, such that open parent-child communication prior to genetic testing was positively associated with open communication 6 months following receipt of genetic test results; and among co-parents, more open parent-child communication at baseline and greater perceived quality of the parenting relationship were associated with more open parent-child communication at follow-up. Partner effects were also observed: co-parents' baseline communication and confidence in their ability to communicate with their minor children about genetic testing was positively associated with open maternal parent-child communication at follow-up. These results demonstrate that for families facing the prospect of cancer genetic testing, perceptions and behaviors of both members of child-rearing couples have important implications for the overall quality of communication with their minor children, including communication about cancer risk.
RAD51B in Familial Breast Cancer

DEFF Research Database (Denmark)

Pelttari, Liisa M; Khan, Sofia; Vuorela, Mikko

2016-01-01

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition......, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD......51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients...
Ovarian Cancer Risk Factors by Histologic Subtype: An Analysis From the Ovarian Cancer Cohort Consortium.

Science.gov (United States)

Wentzensen, Nicolas; Poole, Elizabeth M; Trabert, Britton; White, Emily; Arslan, Alan A; Patel, Alpa V; Setiawan, V Wendy; Visvanathan, Kala; Weiderpass, Elisabete; Adami, Hans-Olov; Black, Amanda; Bernstein, Leslie; Brinton, Louise A; Buring, Julie; Butler, Lesley M; Chamosa, Saioa; Clendenen, Tess V; Dossus, Laure; Fortner, Renee; Gapstur, Susan M; Gaudet, Mia M; Gram, Inger T; Hartge, Patricia; Hoffman-Bolton, Judith; Idahl, Annika; Jones, Michael; Kaaks, Rudolf; Kirsh, Victoria; Koh, Woon-Puay; Lacey, James V; Lee, I-Min; Lundin, Eva; Merritt, Melissa A; Onland-Moret, N Charlotte; Peters, Ulrike; Poynter, Jenny N; Rinaldi, Sabina; Robien, Kim; Rohan, Thomas; Sandler, Dale P; Schairer, Catherine; Schouten, Leo J; Sjöholm, Louise K; Sieri, Sabina; Swerdlow, Anthony; Tjonneland, Anna; Travis, Ruth; Trichopoulou, Antonia; van den Brandt, Piet A; Wilkens, Lynne; Wolk, Alicja; Yang, Hannah P; Zeleniuch-Jacquotte, Anne; Tworoger, Shelley S

2016-08-20

An understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention, early detection, and therapeutic approaches. We evaluated 14 hormonal, reproductive, and lifestyle factors by histologic subtype in the Ovarian Cancer Cohort Consortium (OC3). Among 1.3 million women from 21 studies, 5,584 invasive epithelial ovarian cancers were identified (3,378 serous, 606 endometrioid, 331 mucinous, 269 clear cell, 1,000 other). By using competing-risks Cox proportional hazards regression stratified by study and birth year and adjusted for age, parity, and oral contraceptive use, we assessed associations for all invasive cancers by histology. Heterogeneity was evaluated by likelihood ratio test. Most risk factors exhibited significant heterogeneity by histology. Higher parity was most strongly associated with endometrioid (relative risk [RR] per birth, 0.78; 95% CI, 0.74 to 0.83) and clear cell (RR, 0.68; 95% CI, 0.61 to 0.76) carcinomas (P value for heterogeneity [P-het] < .001). Similarly, age at menopause, endometriosis, and tubal ligation were only associated with endometrioid and clear cell tumors (P-het ≤ .01). Family history of breast cancer (P-het = .008) had modest heterogeneity. Smoking was associated with an increased risk of mucinous (RR per 20 pack-years, 1.26; 95% CI, 1.08 to 1.46) but a decreased risk of clear cell (RR, 0.72; 95% CI, 0.55 to 0.94) tumors (P-het = .004). Unsupervised clustering by risk factors separated endometrioid, clear cell, and low-grade serous carcinomas from high-grade serous and mucinous carcinomas. The heterogeneous associations of risk factors with ovarian cancer subtypes emphasize the importance of conducting etiologic studies by ovarian cancer subtypes. Most established risk factors were more strongly associated with nonserous carcinomas, which demonstrate challenges for risk prediction of serous cancers, the most fatal subtype. © 2016 by American Society of Clinical Oncology.
Predictive genetic testing for hereditary breast and ovarian cancer: psychological distress and illness representations 1 year following disclosure.

Science.gov (United States)

Claes, E; Evers-Kiebooms, G; Denayer, L; Decruyenaere, M; Boogaerts, A; Philippe, K; Legius, E

2005-10-01

This prospective study evaluates emotional functioning and illness representations in 68 unaffected women (34 carriers/34 noncarriers) 1 year after predictive testing for BRCA1/2 mutations when offered within a multidisciplinary approach. Carriers had higher subjective risk perception of breast cancer than noncarriers. Carriers who did not have prophylactic oophorectomy had the highest risk perception of ovarian cancer. No differences were found between carriers and noncarriers regarding perceived seriousness and perceived control of breast and ovarian cancer. Mean levels of distress were within normal ranges. Only few women showed an overall pattern of clinically elevated distress. Cancer-specific distress and state-anxiety significantly decreased in noncarriers from pre- to posttest while general distress remained about the same. There were no significant changes in distress in the group of carriers except for ovarian cancer distress which significantly decreased from pre- to posttest. Our study did not reveal adverse effects of predictive testing when offered in the context of a multidisciplinary approach.
Rate and Time of Ovarian Function Restoration in Menopausal Breast Cancer Patients Who Received Letrozole Following Chemotherapy

Directory of Open Access Journals (Sweden)

Shapour Omidvari

2015-01-01

Full Text Available Background: The present study aimed to investigate the rate and time of ovarian function restoration in breast cancer patients between 40 and 60 years of age who were in menopause (biochemically documented and received letrozole after chemotherapy. We intended to further clarify the management strategy for breast cancer patients with different menopausal status. Methods: We prospectively measured the effects of replacing tamoxifen with letrozole on ovarian function recovery in 90 women from two age groups (40-50 and 51-60 years. All had breast cancer and were treated by chemotherapy. Patients had laboratory documentation of menopause (FSH >40 mIU/ml and estradiol <20 pg/mL. Patients did not have menstruation for at least one year. Study patients received letrozole. At three month intervals, we checked their FSH and estradiol levels. Results:At three months after beginning letrozole, 12 patients in the younger age group had laboratory ovarian function restoration, among which three had vaginal bleeding. In the older group, 8 patients had increased estradiol levels; however, there was no evidence of vaginal bleeding in this group. At 6, 9 and 12 months, no ovarian function restoration was seen in the older group. However in younger patients, 4 had laboratory evidence of ovarian function restoration at 6 months, 2 at 9 months and 1 patient showed laboratory ovarian function restoration at 12 months of follow-up. Totally, there was a significant difference in the occurrence of ovarian function restoration between the two groups (P=0.03. Conclusion: A remarkable portion of women with chemotherapy-induced amenorrhea may develop ovarian function restoration. Therefore, endocrine therapy using aromatase inhibitors in patients with chemotherapy-induced amenorrhea should be followed by a regular hormonal study.
Breast Cancer Rates by State

Science.gov (United States)

... Associated Lung Ovarian Prostate Skin Uterine Cancer Home Breast Cancer Rates by State Language: English (US) Español (Spanish) ... from breast cancer each year. Rates of Getting Breast Cancer by State The number of people who get ...
Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers

DEFF Research Database (Denmark)

Ramus, Susan J; Antoniou, Antonis C; Kuchenbaecker, Karoline B

2012-01-01

Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers ...
Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers

NARCIS (Netherlands)

Ramus, Susan J.; Antoniou, Antonis C.; Kuchenbaecker, Karoline B.; Soucy, Penny; Beesley, Jonathan; Chen, Xiaoqing; McGuffog, Lesley; Sinilnikova, Olga M.; Healey, Sue; Barrowdale, Daniel; Lee, Andrew; Thomassen, Mads; Gerdes, Anne-Marie; Kruse, Torben A.; Jensen, Uffe Birk; Skytte, Anne-Bine; Caligo, Maria A.; Liljegren, Annelie; Lindblom, Annika; Olsson, Håkan; Kristoffersson, Ulf; Stenmark-Askmalm, Marie; Melin, Beatrice; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Złowocka, Elżbieta; Gronwald, Jacek; Huzarski, Tomasz; Byrski, Tomasz; Cybulski, Cezary; Toloczko-Grabarek, Aleksandra; Osorio, Ana; Benitez, Javier; Duran, Mercedes; Tejada, Maria-Isabel; Hamann, Ute; Rookus, Matti; van Leeuwen, Flora E.; Aalfs, Cora M.; Meijers-Heijboer, Hanne E. J.; van Asperen, Christi J.; van Roozendaal, K. E. P.; Hoogerbrugge, Nicoline; Collée, J. Margriet; Kriege, Mieke; van der Luijt, Rob B.; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Evans, D. Gareth; Lalloo, Fiona; Jacobs, Chris; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Paterson, Joan; Douglas, Fiona; Brewer, Carole; Hodgson, Shirley; Morrison, Patrick J.; Walker, Lisa; Porteous, Mary E.; Kennedy, M. John; Pathak, Harsh; Godwin, Andrew K.; Stoppa-Lyonnet, Dominique; Caux-Moncoutier, Virginie; de Pauw, Antoine; Gauthier-Villars, Marion; Mazoyer, Sylvie; Léoné, Mélanie; Calender, Alain; Lasset, Christine; Bonadona, Valérie; Hardouin, Agnès; Berthet, Pascaline; Bignon, Yves-Jean; Uhrhammer, Nancy; Faivre, Laurence; Loustalot, Catherine; Buys, Saundra; Daly, Mary; Miron, Alex; Terry, Mary Beth; Chung, Wendy K.; John, Esther M.; Southey, Melissa; Goldgar, David; Singer, Christian F.; tea, Muy-Kheng; Pfeiler, Georg; Fink-Retter, Anneliese; Hansen, Thomas v O.; Ejlertsen, Bent; Johannsson, Oskar Th; Offit, Kenneth; Kirchhoff, Tomas; Gaudet, Mia M.; Vijai, Joseph; Robson, Mark; Piedmonte, Marion; Phillips, Kelly-Anne; van Le, Linda; Hoffman, James S.; Ewart Toland, Amanda; Montagna, Marco; Tognazzo, Silvia; Imyanitov, Evgeny; Issacs, Claudine; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Iganacio; Tornero, Eva; Navarro, Matilde; Moysich, Kirsten B.; Karlan, Beth Y.; Gross, Jenny; Olah, Edith; Vaszko, Tibor; teo, Soo-Hwang; Ganz, Patricia A.; Beattie, Mary S.; Dorfling, Cecelia M.; van Rensburg, Elizabeth J.; Diez, Orland; Kwong, Ava; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Heidemann, Simone; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorotehea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Fiebig, Britta; Schäfer, Dieter; Caldes, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomäki, Kristiina; Plante, Marie; Spurdle, Amanda B.; Neuhausen, Susan L.; Ding, Yuan Chun; Wang, Xianshu; Lindor, Noralane; Fredericksen, Zachary; Pankratz, V. Shane; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Bonanni, Bernardo; Bernard, Loris; Dolcetti, Riccardo; Papi, Laura; Ottini, Laura; Radice, Paolo; Greene, Mark H.; Mai, Phuong L.; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Pharoah, Paul D. P.; Gayther, Simon A.; Simard, Jacques; Easton, Douglas F.; Couch, Fergus J.; Chenevix-Trench, Georgia; Miedzybrodzka, Zosia; Gregory, Helen; Morrison, Patrick; Jeffers, Lisa; Ong, Kai-Ren; Hoffman, Jonathan; Donaldson, Alan; James, Margaret; Downing, Sarah; Taylor, Amy; Murray, Alexandra; Rogers, Mark T.; McCann, Emma; Barton, David; Porteous, Mary; Drummond, Sarah; Kivuva, Emma; Searle, Anne; Goodman, Selina; Hill, Kathryn; Murday, Victoria; Bradshaw, Nicola; Snadden, Lesley; Longmuir, Mark; Watt, Catherine; Gibson, Sarah; Haque, Eshika; Tobias, Ed; Duncan, Alexis; Izatt, Louise; Langman, Caroline; Whaite, Anna; Dorkins, Huw; Barwell, Julian; Serra-Feliu, Gemma; Ellis, Ian; Houghton, Catherine; Taylor, Jane; Side, Lucy; Male, Alison; Berlin, Cheryl; Eason, Jacqueline; Collier, Rebecca; Claber, Oonagh; Jobson, Irene; McLeod, Diane; Halliday, Dorothy; Durell, Sarah; Stayner, Barbara; Shanley, Susan; Rahman, Nazneen; Houlston, Richard; Bancroft, Elizabeth; D'Mello, Lucia; Page, Elizabeth; Ardern-Jones, Audrey; Kohut, Kelly; Wiggins, Jennifer; Castro, Elena; Mitra, Anita; Robertson, Lisa; Quarrell, Oliver; Bardsley, Cathryn; Goff, Sheila; Brice, Glen; Winchester, Lizzie; Eddy, Charlotte; Tripathi, Vishakha; Attard, Virginia; Lucassen, Anneke; Crawford, Gillian; McBride, Donna; Smalley, Sarah; Sinilnikova, Olga; Barjhoux, Laure; Verny-Pierre, Carole; Giraud, Sophie; Léone, Mélanie; Buecher, Bruno; Houdayer, Claude; Moncoutier, Virginie; Belotti, Muriel; Tirapo, Carole; Bressac-de-Paillerets, Brigitte; Remenieras, Audrey; Byrede, Véronique; Caron, Olivier; Lenoir, Gilbert; Urhammer, Nancy; Sobol, Hagay; Bourdon, Violaine; Noguchi, Tetsuro; Eisinger, François; Coulet, Florence; Colas, Chrystelle; Soubrier, Florent; Coupier, Isabelle; Pujol, Pascal; Peyrat, Jean-Philippe; Fournier, Joëlle; Révilliion, Françoise; Vennin, Philippe; Adenis, Claude; Rouleau, Etienne; Lidereau, Rosette; Demange, Liliane; Nogues, Catherine; Muller, Danièle; Fricker, Jean-Pierre; Barouk-Simonet, Emmanuelle; Bonnet, Françoise; Bubien, Virginie; Sevenet, Nicolas; Longy, Michel; Toulas, Christine; Guimbaud, Rosine; Gladieff, Laurence; Feillel, Viviane; Leroux, Dominique; Dreyfus, Hélène; Rebischung, Christine; Peysselon, Megalie; Coron, Fanny; Prieur, Fabienne; Lebrun, Marine; Kientz, Caroline; Frénay, Marc; Vénat-Bouvet, Laurence; Delnatte, Capucine; Mortemousque, Isabelle; Lynch, Henry T.; Snyder, Carrie L.; Hogervorst, F. B. L.; Verhoef, S.; Verheus, M.; van't Veer, L. J.; van Leeuwen, F. E.; Collée, M.; van den Ouweland, A. M. W.; Jager, A.; Hooning, M. J.; Tilanus-Linthorst, M. M. A.; Seynaeve, C.; van Asperen, C. J.; Wijnen, J. T.; Vreeswijk, M. P.; Tollenaar, R. A.; Devilee, P.; Ligtenberg, M. J.; Hoogerbrugge, N.; Ausems, M. G.; van der Luijt, R. B.; van Os, T. A.; Gille, J. J. P.; Waisfisz, Q.; Gomez-Garcia, E. B.; van Roozendaal, C. E.; Blok, Marinus J.; Caanen, B.; Oosterwijk, J. C.; van der Hout, A. H.; Mourits, M. J.; Vasen, H. F.; Thorne, Heather; Niedermayr, Eveline; Gill, Mona; Collins, Lucine; Gokgoz, Nalan; Selander, Teresa; Weerasooriya, Nayana; Karlsson, Per; Nordlilng, Margareta; Bergman, Annika; Einbeigi, Zakaria; Liedgren, Sigrun; Borg, Åke; Loman, Niklas; Soller, Maria; Jernström, Helena; Harbst, Katja; Henriksson, Karin; Arver, Brita; von Wachenfeldt, Anna; Barbany-Bustinza, Gisela; Rantala, Johanna; Grönberg, Henrik; Stattin, Eva-Lena; Emanuelsson, Monica; Ehrencrona, Hans; Rosenquist, Richard; Dahl, Niklas

2012-01-01

Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of
Low incidence of germline mutation in BRCA1 Exon 11 among early-onset and familial Filipino breast cancer patients

International Nuclear Information System (INIS)

Nato, Alejandro Q. Jr; Deocaris, Custer C.; Sajise, Sheila C.

2002-01-01

Breast cancer susceptibility gene, type 1 (BRCA1) has been thought to be responsible for about 45% of families with multiple breast carcinoma cases and for more than 80% of hereditary breast and ovarian cancer (HBOC) families. About 61-75% of the reported distinct alterations that result in truncated protein products have been found in exon 11 which comprises 61% (3427bp) of the coding sequence of BRCA1(5592bp). Protein truncation test (PTT) has become a popular method as an efficient means of screening mutations in a coding sequence that lead to a truncated protein product. In this study, 34 early-onset and/or familial breast cancer (FBC) patients were investigated. Twenty-six patients are early-onset B(o)C cases (diagnosed≤40 years old), 14 of which have familiality of the disease. Among the 8 patients that have been diagnosed above 40 years old, 7 have familial clustering. Through radioactive PTT analysis of the 34 BC cases in a 5-20% denaturing gradient polyacrylamide gel, we found only one mutation in exon 11 having a 29.7 kDa truncated protein product. Our results corroborate the findings of a recently reported study of unselected incident breast cancer cases in the Philippines where the prevalence of BRCA1 mutation is also low. This would, however, be the second documented mutation in BRCA1 exon 11 in a Filipino BC patient since 1998. (author)
Prevalence of deleterious germline variants in risk genes including BRCA1/2 in consecutive ovarian cancer patients (AGO-TR-1.

Directory of Open Access Journals (Sweden)

Philipp Harter

Full Text Available Identification of families at risk for ovarian cancer offers the opportunity to consider prophylactic surgery thus reducing ovarian cancer mortality. So far, identification of potentially affected families in Germany was solely performed via family history and numbers of affected family members with breast or ovarian cancer. However, neither the prevalence of deleterious variants in BRCA1/2 in ovarian cancer in Germany nor the reliability of family history as trigger for genetic counselling has ever been evaluated.Prospective counseling and germline testing of consecutive patients with primary diagnosis or with platinum-sensitive relapse of an invasive epithelial ovarian cancer. Testing included 25 candidate and established risk genes. Among these 25 genes, 16 genes (ATM, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, NBN, PMS2, PTEN, PALB2, RAD51C, RAD51D, STK11, TP53 were defined as established cancer risk genes. A positive family history was defined as at least one relative with breast cancer or ovarian cancer or breast cancer in personal history.In total, we analyzed 523 patients: 281 patients with primary diagnosis of ovarian cancer and 242 patients with relapsed disease. Median age at primary diagnosis was 58 years (range 16-93 and 406 patients (77.6% had a high-grade serous ovarian cancer. In total, 27.9% of the patients showed at least one deleterious variant in all 25 investigated genes and 26.4% in the defined 16 risk genes. Deleterious variants were most prevalent in the BRCA1 (15.5%, BRCA2 (5.5%, RAD51C (2.5% and PALB2 (1.1% genes. The prevalence of deleterious variants did not differ significantly between patients at primary diagnosis and relapse. The prevalence of deleterious variants in BRCA1/2 (and in all 16 risk genes in patients <60 years was 30.2% (33.2% versus 10.6% (18.9% in patients ≥60 years. Family history was positive in 43% of all patients. Patients with a positive family history had a prevalence of deleterious variants
Genetic variants of age at menopause are not related to timing of ovarian failure in breast cancer survivors.

Science.gov (United States)

Homer, Michael V; Charo, Lindsey M; Natarajan, Loki; Haunschild, Carolyn; Chung, Karine; Mao, Jun J; DeMichele, Angela M; Su, H Irene

2017-06-01

To determine if interindividual genetic variation in single-nucleotide polymorphisms (SNPs) related to age at natural menopause is associated with risk of ovarian failure in breast cancer survivors. A prospective cohort of 169 premenopausal breast cancer survivors recruited at diagnosis with stages 0 to III disease were followed longitudinally for menstrual pattern via self-reported daily menstrual diaries. Participants were genotyped for 13 SNPs previously found to be associated with age at natural menopause: EXO1, TLK1, HELQ, UIMC1, PRIM1, POLG, TMEM224, BRSK1, and MCM8. A risk variable summed the total number of risk alleles in each participant. The association between individual genotypes, and also the risk variable, and time to ovarian failure (>12 months of amenorrhea) was tested using time-to-event methods. Median age at enrollment was 40.5 years (range 20.6-46.1). The majority of participants were white (69%) and underwent chemotherapy (76%). Thirty-eight participants (22%) experienced ovarian failure. None of the candidate SNPs or the summary risk variable was significantly associated with time to ovarian failure. Sensitivity analysis restricted to whites or only to participants receiving chemotherapy yielded similar findings. Older age, chemotherapy exposure, and lower body mass index were related to shorter time to ovarian failure. Thirteen previously identified genetic variants associated with time to natural menopause were not related to timing of ovarian failure in breast cancer survivors.
No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer

NARCIS (Netherlands)

A. Hollestelle (Antoinette); F.H. Van Der Baan (Frederieke H.); A. Berchuck (Andrew); S.E. Johnatty (Sharon); K.K.H. Aben (Katja); B.A. Agnarsson (Bjarni); K. Aittomäki (Kristiina); E. Alducci (Elisa); I.L. Andrulis (Irene); H. Anton-Culver (Hoda); N.N. Antonenkova (Natalia); A.C. Antoniou (Antonis C.); C. Apicella (Carmel); V. Arndt (Volker); N. Arnold (Norbert); B.K. Arun (Banu); B. Arver (Brita Wasteson); A. Ashworth (Alan); L. Baglietto (Laura); R. Balleine (Rosemary); E.V. Bandera (Elisa); D. Barrowdale (Daniel); Y.T. Bean (Yukie); L. Beckmann (Lars); M.W. Beckmann (Matthias); J. Benítez (Javier); A. Berger (Andreas); R. Berger (Raanan); B. Beuselinck (B.); M. Bisogna (Maria); L. Bjorge (Line); C. Blomqvist (Carl); N.V. Bogdanova (Natalia); A. Bojesen (Anders); S.E. Bojesen (Stig); M.K. Bolla (Manjeet); B. Bonnani (Bernardo); J.S. Brand (Judith S.); H. Brauch (Hiltrud); H. Brenner (Hermann); L.A. Brinton (Louise); A. Brooks-Wilson (Angela); F. Bruinsma (Fiona); J. Brunet (Joan); T. Brüning (Thomas); A. Budzilowska (Agnieszka); C.H. Bunker (Clareann H.); B. Burwinkel (Barbara); R. Butzow (Ralf); S.S. Buys (Saundra S.); M.A. Caligo (Maria); I. Campbell (Ian); J. Carter (Jonathan); J. Chang-Claude (Jenny); S.J. Chanock (Stephen J.); K.B.M. Claes (Kathleen B.M.); J.M. Collée (Margriet); L.S. Cook (Linda S.); F.J. Couch (Fergus); A. Cox (Angela); D.W. Cramer (Daniel); S.S. Cross (Simon); J.M. Cunningham (Julie); C. Cybulski (Cezary); K. Czene (Kamila); F. Damiola (Francesca); A. Dansonka-Mieszkowska (Agnieszka); H. Darabi (Hatef); M. de La Hoya (Miguel); A. DeFazio (Anna); J. Dennis (Joe); P. Devilee (Peter); E. Dicks (Ed); O. Díez (Orland); J.A. Doherty (Jennifer A.); S.M. Domchek (Susan); C.M. Dorfling (Cecilia); T. Dörk (Thilo); I. dos Santos Silva (Isabel); A. Du Bois (Andreas); M. Dumont (Martine); A.M. Dunning (Alison); M. Duran (Mercedes); D.F. Easton (Douglas F.); D. Eccles (Diana); R. Edwards (Robert); H. Ehrencrona (Hans); B. Ejlertsen (Bent); A.B. Ekici (Arif); S.D. Ellis (Steve); C. Engel (Christoph); M. Eriksson (Mikael); P.A. Fasching (Peter); L. Feliubadaló (L.); J.D. Figueroa (Jonine); D. Flesch-Janys (Dieter); O. Fletcher (Olivia); A. Fontaine (Annette); S. Fortuzzi (S.); F. Fostira (Florentia); B.L. Fridley (Brooke); M.O.W. Friebel (Mark ); E. Friedman (Eitan); G. Friel (Grace); D. Frost (Debra); J. Garber (Judy); M. García-Closas (Montserrat); S.A. Gayther (Simon); A. Gentry-Maharaj (Aleksandra); A-M. Gerdes (Anne-Marie); G.G. Giles (Graham); R. Glasspool (Rosalind); G. Glendon (Gord); A.K. Godwin (Andrew K.); M.T. Goodman (Marc T.); M. Gore (Martin); M.H. Greene (Mark H.); M. Grip (Mervi); J. Gronwald (Jacek); D. Gschwantler-Kaulich (Daphne); P. Guénel (Pascal); S.R. Guzman (Starr R.); L. Haeberle (Lothar); C.A. Haiman (Christopher A.); P. Hall (Per); S.L. Halverson (Sandra L.); U. Hamann (Ute); T.V.O. Hansen (Thomas); P. Harter (Philipp); J.M. Hartikainen (J.); S. Healey (Sue); R. Hein (Rebecca); P.U. Heitz; B.E. Henderson (Brian); J. Herzog (Josef); M.A. T Hildebrandt (Michelle A.); C.K. Høgdall (Claus); E. Høgdall (Estrid); F.B.L. Hogervorst (Frans); J.L. Hopper (John); K. Humphreys (Keith); T. Huzarski (Tomasz); E.N. Imyanitov (Evgeny N.); C. Isaacs (Claudine); A. Jakubowska (Anna); R. Janavicius (Ramunas); K. Jaworska (Katarzyna); A. Jensen (Allan); U.B. Jensen; N. Johnson (Nichola); A. Jukkola-Vuorinen (Arja); M. Kabisch (Maria); B.Y. Karlan (Beth Y.); V. Kataja (Vesa); N. Kauff (Noah); L.E. Kelemen (Linda); M. Kerin (Michael); L.A.L.M. Kiemeney (Bart); M. Kjaer (Michael); J.A. Knight (Julia); J.P. Knol-Bout (Jacoba P.); I. Konstantopoulou (I.); V-M. Kosma (Veli-Matti); C. Krakstad (Camilla); V. Kristensen (Vessela); K.B. Kuchenbaecker (Karoline); J. Kupryjanczyk (Jolanta); Y. Laitman (Yael); D. Lambrechts (Diether); S. Lambrechts (Sandrina); M.C. Larson (Melissa); A. Lasa (Adriana); P. Laurent-Puig (Pierre); C. Lazaro (Conxi); N. Le (Nhu); L. Le Marchand (Loic); A. Leminen (Arto); K.J. Lester (Kathryn); D.A. Levine (Douglas); J. Li (Jingmei); D. Liang (Dong); A. Lindblom (Annika); N.M. Lindor (Noralane); J. Lissowska (Jolanta); J. Long (Jirong); K.H. Lu (Karen); J. Lubinski (Jan); L. Lundvall (Lene); G. Lurie (Galina); P.L. Mai (Phuong); A. Mannermaa (Arto); S. Margolin (Sara); F. Mariette (F.); F. Marme (Federick); J.W.M. Martens (John); L.F. Massuger (Leon); C. Maugard; S. Mazoyer (Sylvie); L. McGuffog (Lesley); W.P. McGuire; C.A. McLean (Catriona Ann); I. McNeish (Iain); A. Meindl (Alfons); F. Menegaux (Florence); P. Menéndez (Primitiva); J. Menkiszak (Janusz); U. Menon (Usha); A.R. Mensenkamp (Arjen); N. Miller (Nicola); R.L. Milne (Roger); F. Modugno (Francesmary); M. Montagna (Marco); K.B. Moysich (Kirsten B.); H. Mul̈ler (Heiko); A.-M. Mulligan (Anna-Marie); T.A. Muranen (Taru); S.A. Narod (Steven A.); K.L. Nathanson (Katherine); R.B. Ness (Roberta B.); S.L. Neuhausen (Susan); H. Nevanlinna (Heli); P. Neven (Patrick); F. Nielsen (Finn); S.F. Nielsen (Sune); B.G. Nordestgaard (Børge); R. Nussbaum (Robert); K. Odunsi (Kunle); K. Offit (Kenneth); E. Olah; O.I. Olopade (Olufunmilayo I.); J.E. Olson (Janet); S.H. Olson (Sara); J.C. Oosterwijk (Jan); I. Orlow (Irene); N. Orr (Nick); S. Orsulic (Sandra); A. Osorio (Ana); L. Ottini (Laura); J. Paul (James); C.L. Pearce (Celeste); I.S. Pedersen (Inge Sokilde); B. Peissel (Bernard); T. Pejovic (Tanja); L.M. Pelttari (Liisa); J. Perkins (Jo); J. Permuth-Wey (Jenny); P. Peterlongo (Paolo); J. Peto (Julian); C. Phelan (Catherine); K.-A. Phillips (Kelly-Anne); M. Piedmonte (Marion); M.C. Pike (Malcolm C.); R. Platte (Radka); J. Plisiecka-Halasa (Joanna); E.M. Poole (Elizabeth); B. Poppe (Bruce); K. Pykäs (Katri); P. Radice (Paolo); S.J. Ramus (Susan); R. Rebbeck (Timothy); M.W.R. Reed (Malcolm W.R.); G. Rennert (Gad); H. Risch (Harvey); M. Robson (Mark); G. Rodriguez (Gustavo); A. Romero (Atocha); M.A. Rossing (Mary Anne); J.H. Rothstein (Joseph H.); A. Rudolph (Anja); I.B. Runnebaum (Ingo); R. Salani (Ritu); H.B. Salvesen (Helga); E.J. Sawyer (Elinor); J.M. Schildkraut (Joellen); M.K. Schmidt (Marjanka); R.K. Schmutzler (Rita); A. Schneeweiss (Andreas); M. Schoemaker (Minouk); A. Schrauder (André); F.R. Schumacher (Fredrick); I. Schwaab (Ira); G. Scuvera (Giulietta); T.A. Sellers (Thomas A.); G. Severi (Gianluca); C.M. Seynaeve (Caroline); M. Shah (Mitul); M. Shrubsole (Martha); N. Siddiqui (Nadeem); W. Sieh (Weiva); J. Simard (Jacques); C.F. Singer (Christian); O. Sinilnikova (Olga); D. Smeets (Dominiek); C. Sohn (Christof); M. Soller (Maria); H. Song (Honglin); P. Soucy (Penny); M.C. Southey (Melissa); C. Stegmaier (Christa); D. Stoppa-Lyonnet (Dominique); L. Sucheston (Lara); A.J. Swerdlow (Anthony ); I.L. Tangen (Ingvild L.); M.-K. Tea; P.J. Teixeira; K.L. Terry (Kathryn); M.B. Terry (Mary Beth); M. Thomassen (Mads); P.J. Thompson (Pamela J.); L. Tihomirova (Laima); M. Tischkowitz (Marc); A.E. Toland (Amanda); R.A.E.M. Tollenaar (Rob); I. Tomlinson (Ian); D. Torres (Diana); T. Truong (Thérèse); H. Tsimiklis (Helen); N. Tung (Nadine); S. Tworoger (Shelley); J.P. Tyrer (Jonathan); C. Vachon (Celine); L.J. van 't Veer (Laura); A.M. van Altena (Anne); C.J. van Asperen (Christi); D. Van Den Berg (David); A.M.W. van den Ouweland (Ans); H.C. van Doorn (Helena); E. Van Nieuwenhuysen (Els); E.J. van Rensburg (Elizabeth); I. Vergote (Ignace); S. Verhoef; R.A. Vierkant (Robert); J. Vijai (Joseph); A.F. Vitonis (Allison); A. von Wachenfeldt (Anna); C.S. Walsh (Christine); Q. Wang (Qing); S. Wang-Gohrke (Shan); B. Wapenschmidt (Barbara); M. Weischer (Maren); J.N. Weitzel (Jeffrey); C. Weltens (Caroline); N. Wentzensen (N.); A.S. Whittemore (Alice S.); L.R. Wilkens (Lynne R.); R. Winqvist (Robert); A.H. Wu (Anna); X. Wu (Xifeng); H.P. Yang (Hannah P.); D. Zaffaroni (Daniela); M.P. Zamora (Pilar); W. Zheng (Wei); A. Ziogas (Argyrios); G. Chenevix-Trench (Georgia); P.D.P. Pharoah (Paul); M.A. Rookus (Matti); M.J. Hooning (Maartje); E.L. Goode (Ellen L.); Breast Cancer Family Register; EMBRACE; GENICA Network; HEBON; SWE-BRCA

2016-01-01

textabstractObjective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies,
Towards prevention of ovarian cancer.

Science.gov (United States)

Ali, Aus Tariq

2018-01-01

Ovarian cancer is the leading cause of death of all gynaecological cancers. To date, there is no reliable, specific screening procedure for detecting ovarian cancer. The risk factors of ovarian cancer include modifiable and non-modifiable factors. The main goal of the ovarian cancer prevention program is to significantly reduce the risk of development of ovarian cancer and other cancers such as breast and/or peritoneal cancer. The application of non-surgical preventive approaches such as oral contraceptives, parity and breastfeeding has been shown to be highly protective against ovarian cancer development. Targeting inflammation has been also reported to be associated with a protective trend against ovarian cancer and can be achieved through either non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin or lifestyle modifications or both. Lifestyle modification that includes regular exercise, healthy diet supplemented with anti-oxidants and anti-inflammatory elements reduces the risk of the disease even further. Surgical protective approaches include; tubal ligation, hysterectomy and prophylactic bilateral salpingo-oophorectomy and the former is the most effective approach to protect against ovarian cancer. A better understanding of the risk factors of ovarian cancer and the current approaches to prevent it may increase the awareness and help to decrease the incidence of ovarian cancer, increase the five-year survival rate and decrease the mortality rate significantly in the general population especially among those at high risk for ovarian cancer. This review is an attempt to outline a potential program of ovarian cancer prevention and the potential challenges. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Toxicity-adjusted dose (TAD) administration of chemotherapy: Effect of baseline and nadir neutrophil count in patients with breast, ovarian, and lung cancer?

DEFF Research Database (Denmark)

Carus, Andreas; Donskov, Frede; Gebski, Val

2011-01-01

Background: In some solid cancers a survival benefit has been observed for patients who had chemotherapy-induced neutropenia. The prognostic impact of baseline and nadir blood neutrophils was assessed in the present study. Methods: Data on patients with breast cancer st.I-IV, ovarian cancer st.......Survival data were updated 2010. Results: A total of 819 patients were identified, comprising 507 patients with breast cancer, 118 patients with ovarian cancer, 115 patients with NSCLC and 79 patients with SCLC. Median survival for ovarian cancer patients obtaining nadir neutropenia below 2.0 x 109/l was 56...... months. In contrast, median survival for ovarian cancer patients who had nadir neutropenia above 2.0 was 27 months. In a multivariate analysis, adjusting for well-known prognostic features, nadir neutropenia below 2.0 was statistically significant (HR 1.73;p=0.03). In patients with NSCLC, baseline...
Depression and family support in breast cancer patients

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Su JA

2017-09-01

Full Text Available Jian-An Su,1–3,* Dah-Cherng Yeh,4,* Ching-Chi Chang,5,* Tzu-Chin Lin,6,7 Ching-Hsiang Lai,8 Pei-Yun Hu,8 Yi-Feng Ho,9 Vincent Chin-Hung Chen,1,2 Tsu-Nai Wang,10,11 Michael Gossop12 1Chang Gung Medical Foundation, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; 2Department of Medicine, School of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Nursing, Chang Gung Institute of Technology, Taoyuan, Taiwan; 4Department of Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan; 5Institute of Medicine, Chung Shan Medical University and Department of Psychiatry, Chung Shan Medical University Hospital, Taichung, Taiwan; 6Department of Psychiatry, Chung Shan Medical University Hospital, Taichung, Taiwan; 7Department of Psychiatry, School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 8Department of Medical Informatics, Chung Shan Medical University, Taichung, Taiwan; 9Tsaotun Psychiatric Center, Ministry of Health and Welfare, Nan-Tou,Taiwan; 10Department of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan; 11Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 12King’s College London, Institute of Psychiatry, London, UK *These authors contributed equally to this work Background: Breast cancer is the most common cancer in women. Among the survivors, depression is one of the most common psychiatric comorbidities. This paper reports the point prevalence of major depressive disorder among breast cancer patients and the association between family support and major depressive disorder.Methods: Clinical data were collected from a breast cancer clinic of a general hospital in central Taiwan. Participants included 300 patients who were older than 18 years and diagnosed with breast cancer. Among these individuals, we used Mini International Neuropsychiatric Interview (a structural diagnostic tool for
Increased COX-2 expression in patients with ovarian cancer

African Journals Online (AJOL)

ajl yemi

2011-10-26

Oct 26, 2011 ... 10%) subtypes (Kristensen et al., 2003; Green et al.,. 1999). The disease ... history of ovarian and/or breast cancer, and nulliparity, whereas the oral ... and molecular mechanisms of ovarian cancer remain unclear. It is most ..... chemotherapy on the prognosis in advanced epithelial ovarian cancer. N. Engl.
Metastasis of Pregnancy-Associated Breast Cancer (Suspected to Be Hereditary Breast and Ovarian Cancer to the Brain, Diagnosed at 18 Weeks’ Gestation: A Case Report and Review of the Literature

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Tomohiro Okuda

2016-01-01

Full Text Available We report a case of pregnancy-associated breast cancer with metastasis to the brain, likely resulting from hereditary breast and ovarian cancer (HBOC. A 35-year-old woman (gravida 2, para 0-1-0-1 underwent a right mastectomy and right axillary dissection after a cesarean section at 30 years of age; her mother died at 47 years of age due to breast cancer. Histopathological examination indicated an invasive ductal carcinoma with triple-negative cancer (cancer stage 2B [pT3N0M0]. The patient refused adjuvant therapy because of the risk of infertility. After 4 years, she became pregnant naturally. At 18 weeks’ gestation, she experienced aphasia and dyslexia due to brain metastasis. The pregnancy was terminated at 21 weeks’ gestation after thorough counseling. Her family history, young-onset disease, and histopathological findings suggested HBOC. She declined genetic testing for BRCA1/2, though genetic counseling was provided. In cases of pregnancy-related breast cancer, consideration must be given to whether the pregnancy should be continued and to posttreatment fertility. HBOC should also be considered. Genetic counseling should be provided and the patient should be checked for the BRCA mutation, as it is meaningful for the future of any potential children. Genetic counseling should be provided even if the cancer is advanced or recurrent.

The Fanconi anemia family of genes and its correlation with breast cancer susceptibility and breast cancer features.

Science.gov (United States)

Barroso, E; Pita, G; Arias, J I; Menendez, P; Zamora, P; Blanco, M; Benitez, J; Ribas, G

2009-12-01

Fanconi anemia (FA) family of proteins participates in the DNA repair pathway by homologous recombination, and it is currently formed by 13 genes. Some of these proteins also confer susceptibility to hereditary breast and ovarian cancer (HBOC), since FANCD1 is the BRCA2 breast cancer susceptibility gene, and FANCN/PALB2 and FANCJ/BRIP1 explain 2% of non-BRCA1/2 HBOC families. Thus, there is an important connection between FA and BRCA pathways. In a previous case-control association study analysing FANCA, FANCD2 and FANCL, we reported an association between FANCD2 and sporadic breast cancer (BC) risk (OR = 1.35). In order to know whether variants in other FA genes could also be involved in this association, we have extended our study with the rest of FA genes and some others implicated in the BRCA pathway. We have also analyzed the correlation with survival, nodal metastasis and hormonal receptors (ER- and PR-). A total of 61 SNPs in ten FA genes (FANC-B, -C, -D1, -E, -F, -G, -I, -J, -M, -N) and five FA related genes (ATM, ATR, BRCA1, H2AX and USP1) were studied in a total of 547 consecutive and nonrelated sporadic BC cases and 552 unaffected controls from the Spanish population. Association analyses reported marginal statistically significant results with the minor allele of intronic SNPs in three genes: BRCA1, BRCA2/FANCD1, and ATM. Survival association with SNPs on FANCC and BRCA2/FANCD1 genes were also reported. Sub-group analyses revealed associations between SNPs on FANCI and ATM and nodal metastasis status and between FANCJ/BRIP1 and FANCN/PALB2 and PR- status.
Genetic profiles distinguish different types of hereditary ovarian cancer

DEFF Research Database (Denmark)

Domanska, Katarina; Malander, Susanne; Staaf, Johan

2010-01-01

(HBOC) syndrome and the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Genome-wide array comparative genomic hybridization was applied to 12 HBOC associated tumors with BRCA1 mutations and 8 HNPCC associated tumors with mismatch repair gene mutations with 24 sporadic ovarian cancers......Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian cancer...... that HBOC and HNPCC associated ovarian cancer develop along distinct genetic pathways and genetic profiles can thus be applied to distinguish between different types of hereditary ovarian cancer....
A Molecularly Targeted Theranostic Probe for Ovarian Cancer

Science.gov (United States)

Chen, Wenxue; Bardhan, Rizia; Bartels, Marc; Perez-Torres, Carlos; Pautler, Robia G.; Halas, Naomi J.; Joshi, Amit

2014-01-01

Overexpression of the human epidermal growth factor receptor (HER) family has been implicated in ovarian cancer because of its participation in signaling pathway regulating cellular proliferation, differentiation, motility, and survival. Currently, effective diagnostic and therapeutic schemes are lacking for treating ovarian cancer and consequently ovarian cancer has a high mortality rate. While HER2 receptor expression does not usually affect the survival rates of ovarian cancer to the same extent as in breast cancer, it can be employed as a docking site for directed nanotherapies in cases with de novo or acquired chemotherapy resistance. In this study, we have exploited a novel gold nanoshell-based complex (nanocomplex) for targeting, dual modal imaging, and photothermal therapy of HER2 overexpressing and drug resistant ovarian cancer OVCAR3 cells in vitro. The nanocomplexes are engineered to simultaneously provide contrast as fluorescence optical imaging probe and a magnetic resonance imaging (MRI) agent. Both immunofluorescence staining and MRI successfully demonstrate that nanocomplex-anti-HER2 conjugates specifically bind to OVCAR3 cells as opposed to the control, MDA-MB-231 cells, which have low HER2 expression. In addition, nanocomplexes targeted to OVCAR3 cells, when irradiated with near infrared (NIR) laser result in selective destruction of cancer cells through photothermal ablation. We also demonstrate that NIR light therapy and the nanocomplexes by themselves are non-cytotoxic in vitro. To the best of our knowledge, this is the first demonstration of a successful integration of dual modal bioimaging with photothermal cancer therapy for treatment of ovarian cancer. Based on their efficacy in vitro, these nanocomplexes are highly promising for image guided photo-thermal therapy of ovarian cancer as well as other HER2 overexpressing cancers. PMID:20371708
Prevention of ovarian cancer.

Science.gov (United States)

Hanna, Louise; Adams, Malcolm

2006-04-01

Ovarian cancer is the leading cause of death from gynaecological malignancy. The incidence is high in the Western world. The incidence of ovarian cancer is reduced by pregnancy, lactation, the oral contraceptive pill and tubal ligation. Lifestyle factors are important in the aetiology of ovarian cancer and current evidence suggests the risk can be reduced by eating a diet rich in fruit and vegetables, taking regular exercise, avoiding smoking, avoiding being overweight and avoiding long-term use of hormonal replacement therapy (HRT). Familial ovarian cancer is responsible for about 10% of ovarian cancer cases. Strategies available to high-risk women include screening (covered elsewhere) and prophylactic salpingo-oophorectomy. The precise role of chemoprevention for high-risk women in the form of the oral contraceptive pill is unclear.
Management of fertility preservation in young breast cancer patients in a large breast cancer centre.

Science.gov (United States)

Lawrenz, B; Neunhoeffer, E; Henes, M; Lessmann-Bechle, S; Krämer, B; Fehm, Tanja

2010-11-01

The increase of breast cancer in young women under 40 years and the increasing age of women at the time of the birth of their first child underlines the importance to implement counselling for fertility-preserving strategies in the management of breast cancer care. We present the fertility-preserving procedures performed after routine counselling for primary breast cancer patients in a large certified breast cancer centre. Since November 2006, patients aged below 40 years with histologically confirmed breast cancer are routinely counselled on fertility-preserving possibilities before breast surgery and chemotherapy in the fertility centre of the University Women's Hospital in Tuebingen. The recommendations are based on the treatment recommendations of the network FertiPROTEKT. During the last 40 months, 56 primary breast cancer patients were counselled. Forty-one of these patients were hormone receptor positive. Thirty-four patients (63%) underwent fertility-preserving strategies. The majority of the patients (n = 22) decided on ovarian tissue cryopreservation. GnRH protection was performed in 14 patients. In 12 patients an ovarian stimulation protocol was initiated to cryopreserve fertilized or unfertilized oocytes. A combination of different fertility-preserving methods was performed in 12 patients. The preservation of ovarian function and fertility are of great importance to young breast cancer patients. Counselling on fertility-preserving strategies is therefore critical in these patients and should be routinely performed.
Evaluation of mammographic surveillance services in women aged 40-49 years with a moderate family history of breast cancer: a single-arm cohort study.

Science.gov (United States)

Duffy, S W; Mackay, J; Thomas, S; Anderson, E; Chen, T H H; Ellis, I; Evans, G; Fielder, H; Fox, R; Gui, G; Macmillan, D; Moss, S; Rogers, C; Sibbering, M; Wallis, M; Warren, R; Watson, E; Whynes, D; Allgood, P; Caunt, J

2013-03-01

Women with a significant family history of breast cancer are often offered more intensive and earlier surveillance than is offered to the general population in the National Breast Screening Programme. Up to now, this strategy has not been fully evaluated. To evaluate the benefit of mammographic surveillance for women aged 40-49 years at moderate risk of breast cancer due to family history. The study is referred to as FH01. This was a single-arm cohort study with recruitment taking place between January 2003 and February 2007. Recruits were women aged women were offered annual mammography for at least 5 years and observed for the occurrence of breast cancer during the surveillance period. The age group 40-44 years was targeted so that they would still be aged women, 94% of whom were aged women aged 40-49 years with a significant family history of breast or ovarian cancer is both clinically effective in reducing breast cancer mortality and cost-effective. There is a need to further standardise familial risk assessment, to research the impact of digital mammography and to clarify the role of breast density in this population. National Research Register N0484114809. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 11. See the HTA programme website for further project information.
Women’s Satisfaction with Genetic Counseling for Hereditary Breast-Ovarian Cancer: Psychological Aspects

OpenAIRE

Tercyak, Kenneth P.; DeMarco, Tiffani A.; Mars, Bryn D.; Peshkin, Beth N.

2004-01-01

Women who participate in BRCA1/2 cancer genetic counseling do so for a variety of reasons, including learning quantitative risk information about their chances of developing hereditary breast-ovarian cancer at some point during their lifetimes. For these women, obtaining pre-test and disclosure genetic counseling with a professional affords them numerous potential benefits, including adequate preparation for, and accurate interpretation of, their test results. In consequence, women commonly r...
Targeted Therapies in Epithelial Ovarian Cancer

Directory of Open Access Journals (Sweden)

Jurjees Hasan

2010-02-01

Full Text Available Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the advantage of long-term therapy with a manageable toxicity profile enabling patients to enjoy a good quality of life. In this review we appraise the emerging data on novel targeted therapies in ovarian cancer. We discuss the role of these compounds in the front-line treatment of ovarian cancer and in relapsed disease; and describe how the development of predictive clinical, molecular and imaging biomarkers will define the role of biological agents in the treatment of ovarian cancer.
Targeted Therapies in Epithelial Ovarian Cancer

Energy Technology Data Exchange (ETDEWEB)

Dean, Emma; El-Helw, Loaie; Hasan, Jurjees, E-mail: jurjees.hasan@christie.nhs.uk [Christie Hospital NHS Foundation Trust / Wilmslow Road, Manchester, M20 4BX (United Kingdom)

2010-02-23

Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the advantage of long-term therapy with a manageable toxicity profile enabling patients to enjoy a good quality of life. In this review we appraise the emerging data on novel targeted therapies in ovarian cancer. We discuss the role of these compounds in the front-line treatment of ovarian cancer and in relapsed disease; and describe how the development of predictive clinical, molecular and imaging biomarkers will define the role of biological agents in the treatment of ovarian cancer.
ABRAXAS (FAM175A) and Breast Cancer Susceptibility: No Evidence of Association in the Breast Cancer Family Registry.

Science.gov (United States)

Renault, Anne-Laure; Lesueur, Fabienne; Coulombe, Yan; Gobeil, Stéphane; Soucy, Penny; Hamdi, Yosr; Desjardins, Sylvie; Le Calvez-Kelm, Florence; Vallée, Maxime; Voegele, Catherine; Hopper, John L; Andrulis, Irene L; Southey, Melissa C; John, Esther M; Masson, Jean-Yves; Tavtigian, Sean V; Simard, Jacques

2016-01-01

Approximately half of the familial aggregation of breast cancer remains unexplained. This proportion is less for early-onset disease where familial aggregation is greater, suggesting that other susceptibility genes remain to be discovered. The majority of known breast cancer susceptibility genes are involved in the DNA double-strand break repair pathway. ABRAXAS is involved in this pathway and mutations in this gene impair BRCA1 recruitment to DNA damage foci and increase cell sensitivity to ionizing radiation. Moreover, a recurrent germline mutation was reported in Finnish high-risk breast cancer families. To determine if ABRAXAS could be a breast cancer susceptibility gene in other populations, we conducted a population-based case-control mutation screening study of the coding exons and exon/intron boundaries of ABRAXAS in the Breast Cancer Family Registry. In addition to the common variant p.Asp373Asn, sixteen distinct rare variants were identified. Although no significant difference in allele frequencies between cases and controls was observed for the identified variants, two variants, p.Gly39Val and p.Thr141Ile, were shown to diminish phosphorylation of gamma-H2AX in MCF7 human breast adenocarcinoma cells, an important biomarker of DNA double-strand breaks. Overall, likely damaging or neutral variants were evenly represented among cases and controls suggesting that rare variants in ABRAXAS may explain only a small proportion of hereditary breast cancer.
Breast Cancer-Related Lymphedema: Implications for Family Leisure Participation

Science.gov (United States)

Radina, M. Elise

2009-01-01

An estimated 20% of breast cancer survivors face the chronic condition of breast cancer-related lymphedema. This study explored the ways in which women with this condition experienced changes in their participation in family leisure as one indicator of family functioning. Participants (N = 27) were interviewed regarding lifestyles before and after…
Tissue microarrays for testing basal biomarkers in familial breast cancer cases

Directory of Open Access Journals (Sweden)

Rozany Mucha Dufloth

Full Text Available CONTEXT AND OBJECTIVE: The proteins p63, p-cadherin and CK5 are consistently expressed by the basal and myoepithelial cells of the breast, although their expression in sporadic and familial breast cancer cases has yet to be fully defined. The aim here was to study the basal immunopro-file of a breast cancer case series using tissue microarray technology. DESIGN AND SETTING: This was a cross-sectional study at Universidade Estadual de Campinas, Brazil, and the Institute of Pathology and Mo-lecular Immunology, Porto, Portugal. METHODS: Immunohistochemistry using the antibodies p63, CK5 and p-cadherin, and also estrogen receptor (ER and Human Epidermal Receptor Growth Factor 2 (HER2, was per-formed on 168 samples from a breast cancer case series. The criteria for identifying women at high risk were based on those of the Breast Cancer Linkage Consortium. RESULTS: Familial tumors were more frequently positive for the p-cadherin (p = 0.0004, p63 (p < 0.0001 and CK5 (p < 0.0001 than was sporadic cancer. Moreover, familial tumors had coexpression of the basal biomarkers CK5+/ p63+, grouped two by two (OR = 34.34, while absence of coexpression (OR = 0.13 was associ-ated with the sporadic cancer phenotype. CONCLUSION: Familial breast cancer was found to be associated with basal biomarkers, using tissue microarray technology. Therefore, characterization of the familial breast cancer phenotype will improve the understanding of breast carcinogenesis.
Benefits and risks of ovarian function and reproduction for cancer development and prevention.

Science.gov (United States)

Schindler, Adolf E

2011-12-01

Ovarian function and menstrual cycle disturbances, pregnancy, and reproductive medicine procedures can either increase gynecological cancer risk or prevent cancer development. For ovarian cancer development, there are two hypotheses, which are connected with ovulation and gonadotropin secretion. Most of the ovarian cancers seem to be derived from displaced ovarian surfice epithelial cells. One year of ovulatory cycles increases the ovarian cancer risk by 6%. Ovulation between 22 and 29 years of age causes the highest risk increase per year. In contrast, progesterone or progestins appear to create protection. Lifestyle can affect or modify ovarian cancer risk. Breast cancer risk is very much related to age of menarche and menopause, pregnancy, and breast feeding. All of which are related to ovarian function and progestogenic impact that translates either into breast cancer risk increase or decrease. This is modified by body mass index, physical activity, and lifestyle in general. The risk of endometrial cancer is most closely related to endogenous progesterone during the menstrual cycle and pregnancy or by exogenous progestogens as in oral contraceptives. These effects are progestogen dose and time dependent. Endometrial cancer risk can also be increased by estrogen-producing tumors or long-term estrogen treatment.
Somatic mutations in breast and serous ovarian cancer young patients : a systematic review and meta-analysis

NARCIS (Netherlands)

Encinas, Giselly; Maistro, Simone; Pasini, Fatima Solange; Hirata Katayama, Maria Lucia; Brentani, Maria Mitzi; de Bock, Geertruida Hendrika; Azevedo Koike Folgueira, Maria Aparecida

2015-01-01

Objective: our aim was to evaluate whether somatic mutations in five genes were associated with an early age at presentation of breast cancer (BC) or serous ovarian cancer (SOC). Methods: COSMIC database was searched for the five most frequent somatic mutations in BC and SOC. A systematic review of
Public Health Approaches and Barriers to Educating Providers about Hereditary Breast and Ovarian Cancer Syndrome

Directory of Open Access Journals (Sweden)

Angela M. Trepanier

2016-03-01

Full Text Available The Michigan Department of Health and Human Services implemented and evaluated two initiatives designed to enhance provider knowledge of patients appropriate for breast and/or ovarian cancer genetic risk assessment and hereditary breast and ovarian cancer (HBOC syndrome testing. The first initiative targeted select providers who had diagnosed patients meeting HBOC risk criteria. Specifically, the initiative used 2008–2009 state cancer registry data to identify all providers who had diagnosed breast cancers in women ≤50 years of age, male breast cancers, and ovarian cancers in four health systems with newly established cancer genetics clinics. Using a method coined bidirectional reporting (BDR, reports highlighting how many of these cases each provider had seen were generated and mailed. Reports on 475 cancers (9.5% of the 5005 cases statewide meeting criteria were sent to 69 providers with information about how and why to refer such patients for genetic counseling. Providers who received a report were contacted to assess whether the reports increased awareness or resulted in action (genetic counseling/referral. Based on the few responses received, despite multiple attempts to contact, and attrition rate, it is not possible to ascertain the impact of this initiative on providers. However the project resulted in the MDHHS identifying which providers see the largest proportion of at-risk patients, creating an opportunity to target those providers with HBOC education efforts. The second initiative involved creating and broadly disseminating an online, interactive case-based educational module to increase awareness and referral decisions for HBOC using high- and low-risk patient scenarios. A total of 1835 unique users accessed the module in a one year. Collectively the users viewed topic pages 2724 times and the interactive case studies 1369 times. Point of care tools (fact sheets were viewed 1624 times and downloaded 764 times. Satisfaction
Setting the Threshold for Surgical Prevention in Women at Increased Risk of Ovarian Cancer.

Science.gov (United States)

Manchanda, Ranjit; Menon, Usha

2018-01-01

The number of ovarian cancer cases is predicted to rise by 14% in Europe and 55% worldwide over the next 2 decades. The current absence of a screening program, rising drug/treatment costs, and only marginal improvements in survival seen over the past 30 years suggest the need for maximizing primary surgical prevention to reduce the burden of ovarian cancer. Primary surgical prevention through risk-reducing salpingo-oophorectomy (RRSO) is well established as the most effective method for preventing ovarian cancer. In the UK, it has traditionally been offered to high-risk women (>10% lifetime risk of ovarian cancer) who have completed their family. The cost-effectiveness of RRSO in BRCA1/BRCA2 carriers older than 35 years is well established. Recently, RRSO has been shown to be cost-effective in postmenopausal women at lifetime ovarian cancer risks of 5% or greater and in premenopausal women at lifetime risks greater than 4%. The acceptability, uptake, and satisfaction with RRSO at these intermediate-risk levels remain to be established. Prospective outcome data on risk-reducing salpingectomy and delayed-oophorectomy for preventing ovarian cancer is lacking, and hence, this is best offered for primary prevention within the context and safe environment of a clinical trial. An estimated 63% of ovarian cancers occur in women with greater than 4% lifetime risk and 53% in those with 5% or greater lifetime-risk. Risk-reducing salpingo-oophorectomy can be offered for primary surgical prevention to women at intermediate risk levels (4%-5% to 10%). This includes unaffected women who have completed their family and have RAD51C, RAD51D, or BRIP1 gene mutations; first-degree relatives of women with invasive epithelial ovarian cancer; BRCA mutation-negative women from high-risk breast-and-ovarian cancer or ovarian-cancer-only families. In those with BRCA1, RAD51C/RAD51D/MMR mutations and the occasional families with a history of ovarian cancer in their 40s, surgery needs to be
Mammographic density and breast cancer risk in breast screening assessment cases and women with a family history of breast cancer.

Science.gov (United States)

Duffy, Stephen W; Morrish, Oliver W E; Allgood, Prue C; Black, Richard; Gillan, Maureen G C; Willsher, Paula; Cooke, Julie; Duncan, Karen A; Michell, Michael J; Dobson, Hilary M; Maroni, Roberta; Lim, Yit Y; Purushothaman, Hema N; Suaris, Tamara; Astley, Susan M; Young, Kenneth C; Tucker, Lorraine; Gilbert, Fiona J

2018-01-01

Mammographic density has been shown to be a strong independent predictor of breast cancer and a causative factor in reducing the sensitivity of mammography. There remain questions as to the use of mammographic density information in the context of screening and risk management, and of the association with cancer in populations known to be at increased risk of breast cancer. To assess the association of breast density with presence of cancer by measuring mammographic density visually as a percentage, and with two automated volumetric methods, Quantra™ and VolparaDensity™. The TOMosynthesis with digital MammographY (TOMMY) study of digital breast tomosynthesis in the Breast Screening Programme of the National Health Service (NHS) of the United Kingdom (UK) included 6020 breast screening assessment cases (of whom 1158 had breast cancer) and 1040 screened women with a family history of breast cancer (of whom two had breast cancer). We assessed the association of each measure with breast cancer risk in these populations at enhanced risk, using logistic regression adjusted for age and total breast volume as a surrogate for body mass index (BMI). All density measures showed a positive association with presence of cancer and all declined with age. The strongest effect was seen with Volpara absolute density, with a significant 3% (95% CI 1-5%) increase in risk per 10 cm 3 of dense tissue. The effect of Volpara volumetric density on risk was stronger for large and grade 3 tumours. Automated absolute breast density is a predictor of breast cancer risk in populations at enhanced risk due to either positive mammographic findings or family history. In the screening context, density could be a trigger for more intensive imaging. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

Science.gov (United States)

Bojesen, Stig E; Pooley, Karen A; Johnatty, Sharon E; Beesley, Jonathan; Michailidou, Kyriaki; Tyrer, Jonathan P; Edwards, Stacey L; Pickett, Hilda A; Shen, Howard C; Smart, Chanel E; Hillman, Kristine M; Mai, Phuong L; Lawrenson, Kate; Stutz, Michael D; Lu, Yi; Karevan, Rod; Woods, Nicholas; Johnston, Rebecca L; French, Juliet D; Chen, Xiaoqing; Weischer, Maren; Nielsen, Sune F; Maranian, Melanie J; Ghoussaini, Maya; Ahmed, Shahana; Baynes, Caroline; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Healey, Sue; Lush, Michael; Tessier, Daniel C; Vincent, Daniel; Bacot, Françis; Vergote, Ignace; Lambrechts, Sandrina; Despierre, Evelyn; Risch, Harvey A; González-Neira, Anna; Rossing, Mary Anne; Pita, Guillermo; Doherty, Jennifer A; Álvarez, Nuria; Larson, Melissa C; Fridley, Brooke L; Schoof, Nils; Chang-Claude, Jenny; Cicek, Mine S; Peto, Julian; Kalli, Kimberly R; Broeks, Annegien; Armasu, Sebastian M; Schmidt, Marjanka K; Braaf, Linde M; Winterhoff, Boris; Nevanlinna, Heli; Konecny, Gottfried E; Lambrechts, Diether; Rogmann, Lisa; Guénel, Pascal; Teoman, Attila; Milne, Roger L; Garcia, Joaquin J; Cox, Angela; Shridhar, Vijayalakshmi; Burwinkel, Barbara; Marme, Frederik; Hein, Rebecca; Sawyer, Elinor J; Haiman, Christopher A; Wang-Gohrke, Shan; Andrulis, Irene L; Moysich, Kirsten B; Hopper, John L; Odunsi, Kunle; Lindblom, Annika; Giles, Graham G; Brenner, Hermann; Simard, Jacques; Lurie, Galina; Fasching, Peter A; Carney, Michael E; Radice, Paolo; Wilkens, Lynne R; Swerdlow, Anthony; Goodman, Marc T; Brauch, Hiltrud; García-Closas, Montserrat; Hillemanns, Peter; Winqvist, Robert; Dürst, Matthias; Devilee, Peter; Runnebaum, Ingo; Jakubowska, Anna; Lubinski, Jan; Mannermaa, Arto; Butzow, Ralf; Bogdanova, Natalia V; Dörk, Thilo; Pelttari, Liisa M; Zheng, Wei; Leminen, Arto; Anton-Culver, Hoda; Bunker, Clareann H; Kristensen, Vessela; Ness, Roberta B; Muir, Kenneth; Edwards, Robert; Meindl, Alfons; Heitz, Florian; Matsuo, Keitaro; du Bois, Andreas; Wu, Anna H; Harter, Philipp; Teo, Soo-Hwang; Schwaab, Ira; Shu, Xiao-Ou; Blot, William; Hosono, Satoyo; Kang, Daehee; Nakanishi, Toru; Hartman, Mikael; Yatabe, Yasushi; Hamann, Ute; Karlan, Beth Y; Sangrajrang, Suleeporn; Kjaer, Susanne Krüger; Gaborieau, Valerie; Jensen, Allan; Eccles, Diana; Høgdall, Estrid; Shen, Chen-Yang; Brown, Judith; Woo, Yin Ling; Shah, Mitul; Azmi, Mat Adenan Noor; Luben, Robert; Omar, Siti Zawiah; Czene, Kamila; Vierkant, Robert A; Nordestgaard, Børge G; Flyger, Henrik; Vachon, Celine; Olson, Janet E; Wang, Xianshu; Levine, Douglas A; Rudolph, Anja; Weber, Rachel Palmieri; Flesch-Janys, Dieter; Iversen, Edwin; Nickels, Stefan; Schildkraut, Joellen M; Silva, Isabel Dos Santos; Cramer, Daniel W; Gibson, Lorna; Terry, Kathryn L; Fletcher, Olivia; Vitonis, Allison F; van der Schoot, C Ellen; Poole, Elizabeth M; Hogervorst, Frans B L; Tworoger, Shelley S; Liu, Jianjun; Bandera, Elisa V; Li, Jingmei; Olson, Sara H; Humphreys, Keith; Orlow, Irene; Blomqvist, Carl; Rodriguez-Rodriguez, Lorna; Aittomäki, Kristiina; Salvesen, Helga B; Muranen, Taru A; Wik, Elisabeth; Brouwers, Barbara; Krakstad, Camilla; Wauters, Els; Halle, Mari K; Wildiers, Hans; Kiemeney, Lambertus A; Mulot, Claire; Aben, Katja K; Laurent-Puig, Pierre; van Altena, Anne M; Truong, Thérèse; Massuger, Leon F A G; Benitez, Javier; Pejovic, Tanja; Perez, Jose Ignacio Arias; Hoatlin, Maureen; Zamora, M Pilar; Cook, Linda S; Balasubramanian, Sabapathy P; Kelemen, Linda E; Schneeweiss, Andreas; Le, Nhu D; Sohn, Christof; Brooks-Wilson, Angela; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Cybulski, Cezary; Henderson, Brian E; Menkiszak, Janusz; Schumacher, Fredrick; Wentzensen, Nicolas; Marchand, Loic Le; Yang, Hannah P; Mulligan, Anna Marie; Glendon, Gord; Engelholm, Svend Aage; Knight, Julia A; Høgdall, Claus K; Apicella, Carmel; Gore, Martin; Tsimiklis, Helen; Song, Honglin; Southey, Melissa C; Jager, Agnes; van den Ouweland, Ans M W; Brown, Robert; Martens, John W M; Flanagan, James M; Kriege, Mieke; Paul, James; Margolin, Sara; Siddiqui, Nadeem; Severi, Gianluca; Whittemore, Alice S; Baglietto, Laura; McGuire, Valerie; Stegmaier, Christa; Sieh, Weiva; Müller, Heiko; Arndt, Volker; Labrèche, France; Gao, Yu-Tang; Goldberg, Mark S; Yang, Gong; Dumont, Martine; McLaughlin, John R; Hartmann, Arndt; Ekici, Arif B; Beckmann, Matthias W; Phelan, Catherine M; Lux, Michael P; Permuth-Wey, Jenny; Peissel, Bernard; Sellers, Thomas A; Ficarazzi, Filomena; Barile, Monica; Ziogas, Argyrios; Ashworth, Alan; Gentry-Maharaj, Aleksandra; Jones, Michael; Ramus, Susan J; Orr, Nick; Menon, Usha; Pearce, Celeste L; Brüning, Thomas; Pike, Malcolm C; Ko, Yon-Dschun; Lissowska, Jolanta; Figueroa, Jonine; Kupryjanczyk, Jolanta; Chanock, Stephen J; Dansonka-Mieszkowska, Agnieszka; Jukkola-Vuorinen, Arja; Rzepecka, Iwona K; Pylkäs, Katri; Bidzinski, Mariusz; Kauppila, Saila; Hollestelle, Antoinette; Seynaeve, Caroline; Tollenaar, Rob A E M; Durda, Katarzyna; Jaworska, Katarzyna; Hartikainen, Jaana M; Kosma, Veli-Matti; Kataja, Vesa; Antonenkova, Natalia N; Long, Jirong; Shrubsole, Martha; Deming-Halverson, Sandra; Lophatananon, Artitaya; Siriwanarangsan, Pornthep; Stewart-Brown, Sarah; Ditsch, Nina; Lichtner, Peter; Schmutzler, Rita K; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Tseng, Chiu-Chen; Stram, Daniel O; van den Berg, David; Yip, Cheng Har; Ikram, M Kamran; Teh, Yew-Ching; Cai, Hui; Lu, Wei; Signorello, Lisa B; Cai, Qiuyin; Noh, Dong-Young; Yoo, Keun-Young; Miao, Hui; Iau, Philip Tsau-Choong; Teo, Yik Ying; McKay, James; Shapiro, Charles; Ademuyiwa, Foluso; Fountzilas, George; Hsiung, Chia-Ni; Yu, Jyh-Cherng; Hou, Ming-Feng; Healey, Catherine S; Luccarini, Craig; Peock, Susan; Stoppa-Lyonnet, Dominique; Peterlongo, Paolo; Rebbeck, Timothy R; Piedmonte, Marion; Singer, Christian F; Friedman, Eitan; Thomassen, Mads; Offit, Kenneth; Hansen, Thomas V O; Neuhausen, Susan L; Szabo, Csilla I; Blanco, Ignacio; Garber, Judy; Narod, Steven A; Weitzel, Jeffrey N; Montagna, Marco; Olah, Edith; Godwin, Andrew K; Yannoukakos, Drakoulis; Goldgar, David E; Caldes, Trinidad; Imyanitov, Evgeny N; Tihomirova, Laima; Arun, Banu K; Campbell, Ian; Mensenkamp, Arjen R; van Asperen, Christi J; van Roozendaal, Kees E P; Meijers-Heijboer, Hanne; Collée, J Margriet; Oosterwijk, Jan C; Hooning, Maartje J; Rookus, Matti A; van der Luijt, Rob B; van Os, Theo A M; Evans, D Gareth; Frost, Debra; Fineberg, Elena; Barwell, Julian; Walker, Lisa; Kennedy, M John; Platte, Radka; Davidson, Rosemarie; Ellis, Steve D; Cole, Trevor; Paillerets, Brigitte Bressac-de; Buecher, Bruno; Damiola, Francesca; Faivre, Laurence; Frenay, Marc; Sinilnikova, Olga M; Caron, Olivier; Giraud, Sophie; Mazoyer, Sylvie; Bonadona, Valérie; Caux-Moncoutier, Virginie; Toloczko-Grabarek, Aleksandra; Gronwald, Jacek; Byrski, Tomasz; Spurdle, Amanda B; Bonanni, Bernardo; Zaffaroni, Daniela; Giannini, Giuseppe; Bernard, Loris; Dolcetti, Riccardo; Manoukian, Siranoush; Arnold, Norbert; Engel, Christoph; Deissler, Helmut; Rhiem, Kerstin; Niederacher, Dieter; Plendl, Hansjoerg; Sutter, Christian; Wappenschmidt, Barbara; Borg, Åke; Melin, Beatrice; Rantala, Johanna; Soller, Maria; Nathanson, Katherine L; Domchek, Susan M; Rodriguez, Gustavo C; Salani, Ritu; Kaulich, Daphne Gschwantler; Tea, Muy-Kheng; Paluch, Shani Shimon; Laitman, Yael; Skytte, Anne-Bine; Kruse, Torben A; Jensen, Uffe Birk; Robson, Mark; Gerdes, Anne-Marie; Ejlertsen, Bent; Foretova, Lenka; Savage, Sharon A; Lester, Jenny; Soucy, Penny; Kuchenbaecker, Karoline B; Olswold, Curtis; Cunningham, Julie M; Slager, Susan; Pankratz, Vernon S; Dicks, Ed; Lakhani, Sunil R; Couch, Fergus J; Hall, Per; Monteiro, Alvaro N A; Gayther, Simon A; Pharoah, Paul D P; Reddel, Roger R; Goode, Ellen L; Greene, Mark H; Easton, Douglas F; Berchuck, Andrew; Antoniou, Antonis C; Chenevix-Trench, Georgia; Dunning, Alison M

2013-01-01

TERT-locus single nucleotide polymorphisms (SNPs) and leucocyte telomere measures are reportedly associated with risks of multiple cancers. Using the iCOGs chip, we analysed ~480 TERT-locus SNPs in breast (n=103,991), ovarian (n=39,774) and BRCA1 mutation carrier (11,705) cancer cases and controls. 53,724 participants have leucocyte telomere measures. Most associations cluster into three independent peaks. Peak 1 SNP rs2736108 minor allele associates with longer telomeres (P=5.8×10−7), reduced estrogen receptor negative (ER-negative) (P=1.0×10−8) and BRCA1 mutation carrier (P=1.1×10−5) breast cancer risks, and altered promoter-assay signal. Peak 2 SNP rs7705526 minor allele associates with longer telomeres (P=2.3×10−14), increased low malignant potential ovarian cancer risk (P=1.3×10−15) and increased promoter activity. Peak 3 SNPs rs10069690 and rs2242652 minor alleles increase ER-negative (P=1.2×10−12) and BRCA1 mutation carrier (P=1.6×10−14) breast and invasive ovarian (P=1.3×10−11) cancer risks, but not via altered telomere length. The cancer-risk alleles of rs2242652 and rs10069690 respectively increase silencing and generate a truncated TERT splice-variant. PMID:23535731
Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer.

Science.gov (United States)

Bojesen, Stig E; Pooley, Karen A; Johnatty, Sharon E; Beesley, Jonathan; Michailidou, Kyriaki; Tyrer, Jonathan P; Edwards, Stacey L; Pickett, Hilda A; Shen, Howard C; Smart, Chanel E; Hillman, Kristine M; Mai, Phuong L; Lawrenson, Kate; Stutz, Michael D; Lu, Yi; Karevan, Rod; Woods, Nicholas; Johnston, Rebecca L; French, Juliet D; Chen, Xiaoqing; Weischer, Maren; Nielsen, Sune F; Maranian, Melanie J; Ghoussaini, Maya; Ahmed, Shahana; Baynes, Caroline; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Healey, Sue; Lush, Michael; Tessier, Daniel C; Vincent, Daniel; Bacot, Françis; Vergote, Ignace; Lambrechts, Sandrina; Despierre, Evelyn; Risch, Harvey A; González-Neira, Anna; Rossing, Mary Anne; Pita, Guillermo; Doherty, Jennifer A; Alvarez, Nuria; Larson, Melissa C; Fridley, Brooke L; Schoof, Nils; Chang-Claude, Jenny; Cicek, Mine S; Peto, Julian; Kalli, Kimberly R; Broeks, Annegien; Armasu, Sebastian M; Schmidt, Marjanka K; Braaf, Linde M; Winterhoff, Boris; Nevanlinna, Heli; Konecny, Gottfried E; Lambrechts, Diether; Rogmann, Lisa; Guénel, Pascal; Teoman, Attila; Milne, Roger L; Garcia, Joaquin J; Cox, Angela; Shridhar, Vijayalakshmi; Burwinkel, Barbara; Marme, Frederik; Hein, Rebecca; Sawyer, Elinor J; Haiman, Christopher A; Wang-Gohrke, Shan; Andrulis, Irene L; Moysich, Kirsten B; Hopper, John L; Odunsi, Kunle; Lindblom, Annika; Giles, Graham G; Brenner, Hermann; Simard, Jacques; Lurie, Galina; Fasching, Peter A; Carney, Michael E; Radice, Paolo; Wilkens, Lynne R; Swerdlow, Anthony; Goodman, Marc T; Brauch, Hiltrud; Garcia-Closas, Montserrat; Hillemanns, Peter; Winqvist, Robert; Dürst, Matthias; Devilee, Peter; Runnebaum, Ingo; Jakubowska, Anna; Lubinski, Jan; Mannermaa, Arto; Butzow, Ralf; Bogdanova, Natalia V; Dörk, Thilo; Pelttari, Liisa M; Zheng, Wei; Leminen, Arto; Anton-Culver, Hoda; Bunker, Clareann H; Kristensen, Vessela; Ness, Roberta B; Muir, Kenneth; Edwards, Robert; Meindl, Alfons; Heitz, Florian; Matsuo, Keitaro; du Bois, Andreas; Wu, Anna H; Harter, Philipp; Teo, Soo-Hwang; Schwaab, Ira; Shu, Xiao-Ou; Blot, William; Hosono, Satoyo; Kang, Daehee; Nakanishi, Toru; Hartman, Mikael; Yatabe, Yasushi; Hamann, Ute; Karlan, Beth Y; Sangrajrang, Suleeporn; Kjaer, Susanne Krüger; Gaborieau, Valerie; Jensen, Allan; Eccles, Diana; Høgdall, Estrid; Shen, Chen-Yang; Brown, Judith; Woo, Yin Ling; Shah, Mitul; Azmi, Mat Adenan Noor; Luben, Robert; Omar, Siti Zawiah; Czene, Kamila; Vierkant, Robert A; Nordestgaard, Børge G; Flyger, Henrik; Vachon, Celine; Olson, Janet E; Wang, Xianshu; Levine, Douglas A; Rudolph, Anja; Weber, Rachel Palmieri; Flesch-Janys, Dieter; Iversen, Edwin; Nickels, Stefan; Schildkraut, Joellen M; Silva, Isabel Dos Santos; Cramer, Daniel W; Gibson, Lorna; Terry, Kathryn L; Fletcher, Olivia; Vitonis, Allison F; van der Schoot, C Ellen; Poole, Elizabeth M; Hogervorst, Frans B L; Tworoger, Shelley S; Liu, Jianjun; Bandera, Elisa V; Li, Jingmei; Olson, Sara H; Humphreys, Keith; Orlow, Irene; Blomqvist, Carl; Rodriguez-Rodriguez, Lorna; Aittomäki, Kristiina; Salvesen, Helga B; Muranen, Taru A; Wik, Elisabeth; Brouwers, Barbara; Krakstad, Camilla; Wauters, Els; Halle, Mari K; Wildiers, Hans; Kiemeney, Lambertus A; Mulot, Claire; Aben, Katja K; Laurent-Puig, Pierre; Altena, Anne Mvan; Truong, Thérèse; Massuger, Leon F A G; Benitez, Javier; Pejovic, Tanja; Perez, Jose Ignacio Arias; Hoatlin, Maureen; Zamora, M Pilar; Cook, Linda S; Balasubramanian, Sabapathy P; Kelemen, Linda E; Schneeweiss, Andreas; Le, Nhu D; Sohn, Christof; Brooks-Wilson, Angela; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Cybulski, Cezary; Henderson, Brian E; Menkiszak, Janusz; Schumacher, Fredrick; Wentzensen, Nicolas; Le Marchand, Loic; Yang, Hannah P; Mulligan, Anna Marie; Glendon, Gord; Engelholm, Svend Aage; Knight, Julia A; Høgdall, Claus K; Apicella, Carmel; Gore, Martin; Tsimiklis, Helen; Song, Honglin; Southey, Melissa C; Jager, Agnes; den Ouweland, Ans M Wvan; Brown, Robert; Martens, John W M; Flanagan, James M; Kriege, Mieke; Paul, James; Margolin, Sara; Siddiqui, Nadeem; Severi, Gianluca; Whittemore, Alice S; Baglietto, Laura; McGuire, Valerie; Stegmaier, Christa; Sieh, Weiva; Müller, Heiko; Arndt, Volker; Labrèche, France; Gao, Yu-Tang; Goldberg, Mark S; Yang, Gong; Dumont, Martine; McLaughlin, John R; Hartmann, Arndt; Ekici, Arif B; Beckmann, Matthias W; Phelan, Catherine M; Lux, Michael P; Permuth-Wey, Jenny; Peissel, Bernard; Sellers, Thomas A; Ficarazzi, Filomena; Barile, Monica; Ziogas, Argyrios; Ashworth, Alan; Gentry-Maharaj, Aleksandra; Jones, Michael; Ramus, Susan J; Orr, Nick; Menon, Usha; Pearce, Celeste L; Brüning, Thomas; Pike, Malcolm C; Ko, Yon-Dschun; Lissowska, Jolanta; Figueroa, Jonine; Kupryjanczyk, Jolanta; Chanock, Stephen J; Dansonka-Mieszkowska, Agnieszka; Jukkola-Vuorinen, Arja; Rzepecka, Iwona K; Pylkäs, Katri; Bidzinski, Mariusz; Kauppila, Saila; Hollestelle, Antoinette; Seynaeve, Caroline; Tollenaar, Rob A E M; Durda, Katarzyna; Jaworska, Katarzyna; Hartikainen, Jaana M; Kosma, Veli-Matti; Kataja, Vesa; Antonenkova, Natalia N; Long, Jirong; Shrubsole, Martha; Deming-Halverson, Sandra; Lophatananon, Artitaya; Siriwanarangsan, Pornthep; Stewart-Brown, Sarah; Ditsch, Nina; Lichtner, Peter; Schmutzler, Rita K; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Tseng, Chiu-Chen; Stram, Daniel O; van den Berg, David; Yip, Cheng Har; Ikram, M Kamran; Teh, Yew-Ching; Cai, Hui; Lu, Wei; Signorello, Lisa B; Cai, Qiuyin; Noh, Dong-Young; Yoo, Keun-Young; Miao, Hui; Iau, Philip Tsau-Choong; Teo, Yik Ying; McKay, James; Shapiro, Charles; Ademuyiwa, Foluso; Fountzilas, George; Hsiung, Chia-Ni; Yu, Jyh-Cherng; Hou, Ming-Feng; Healey, Catherine S; Luccarini, Craig; Peock, Susan; Stoppa-Lyonnet, Dominique; Peterlongo, Paolo; Rebbeck, Timothy R; Piedmonte, Marion; Singer, Christian F; Friedman, Eitan; Thomassen, Mads; Offit, Kenneth; Hansen, Thomas V O; Neuhausen, Susan L; Szabo, Csilla I; Blanco, Ignacio; Garber, Judy; Narod, Steven A; Weitzel, Jeffrey N; Montagna, Marco; Olah, Edith; Godwin, Andrew K; Yannoukakos, Drakoulis; Goldgar, David E; Caldes, Trinidad; Imyanitov, Evgeny N; Tihomirova, Laima; Arun, Banu K; Campbell, Ian; Mensenkamp, Arjen R; van Asperen, Christi J; van Roozendaal, Kees E P; Meijers-Heijboer, Hanne; Collée, J Margriet; Oosterwijk, Jan C; Hooning, Maartje J; Rookus, Matti A; van der Luijt, Rob B; Os, Theo A Mvan; Evans, D Gareth; Frost, Debra; Fineberg, Elena; Barwell, Julian; Walker, Lisa; Kennedy, M John; Platte, Radka; Davidson, Rosemarie; Ellis, Steve D; Cole, Trevor; Bressac-de Paillerets, Brigitte; Buecher, Bruno; Damiola, Francesca; Faivre, Laurence; Frenay, Marc; Sinilnikova, Olga M; Caron, Olivier; Giraud, Sophie; Mazoyer, Sylvie; Bonadona, Valérie; Caux-Moncoutier, Virginie; Toloczko-Grabarek, Aleksandra; Gronwald, Jacek; Byrski, Tomasz; Spurdle, Amanda B; Bonanni, Bernardo; Zaffaroni, Daniela; Giannini, Giuseppe; Bernard, Loris; Dolcetti, Riccardo; Manoukian, Siranoush; Arnold, Norbert; Engel, Christoph; Deissler, Helmut; Rhiem, Kerstin; Niederacher, Dieter; Plendl, Hansjoerg; Sutter, Christian; Wappenschmidt, Barbara; Borg, Ake; Melin, Beatrice; Rantala, Johanna; Soller, Maria; Nathanson, Katherine L; Domchek, Susan M; Rodriguez, Gustavo C; Salani, Ritu; Kaulich, Daphne Gschwantler; Tea, Muy-Kheng; Paluch, Shani Shimon; Laitman, Yael; Skytte, Anne-Bine; Kruse, Torben A; Jensen, Uffe Birk; Robson, Mark; Gerdes, Anne-Marie; Ejlertsen, Bent; Foretova, Lenka; Savage, Sharon A; Lester, Jenny; Soucy, Penny; Kuchenbaecker, Karoline B; Olswold, Curtis; Cunningham, Julie M; Slager, Susan; Pankratz, Vernon S; Dicks, Ed; Lakhani, Sunil R; Couch, Fergus J; Hall, Per; Monteiro, Alvaro N A; Gayther, Simon A; Pharoah, Paul D P; Reddel, Roger R; Goode, Ellen L; Greene, Mark H; Easton, Douglas F; Berchuck, Andrew; Antoniou, Antonis C; Chenevix-Trench, Georgia; Dunning, Alison M

2013-04-01

TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ∼480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 × 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 × 10(-8)) and BRCA1 mutation carrier (P = 1.1 × 10(-5)) breast cancers and altered promoter assay signal. The minor allele at the peak 2 SNP rs7705526 associates with longer telomeres (P = 2.3 × 10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 × 10(-15)) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 × 10(-12)) and BRCA1 mutation carrier (P = 1.6 × 10(-14)) breast and invasive ovarian (P = 1.3 × 10(-11)) cancer risks but not via altered telomere length. The cancer risk alleles of rs2242652 and rs10069690, respectively, increase silencing and generate a truncated TERT splice variant.
Temporary ovarian suppression during chemotherapy to preserve ovarian function and fertility in breast cancer patients: A GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology.

Science.gov (United States)

Lambertini, Matteo; Cinquini, Michela; Moschetti, Ivan; Peccatori, Fedro A; Anserini, Paola; Valenzano Menada, Mario; Tomirotti, Maurizio; Del Mastro, Lucia

2017-01-01

The development of premature ovarian failure and subsequent infertility are possible consequences of chemotherapy use in pre-menopausal women with early-stage breast cancer. Among the available strategies for fertility preservation, pharmacological protection of the ovaries using luteinising hormone-releasing hormone analogues (LHRHa) during chemotherapy has the potential to restore ovarian function and fertility after anticancer treatments; however, the possible efficacy and clinical application of this strategy has been highly debated in the last years. Following the availability of new data on this controversial topic, the Panel of the Italian Association of Medical Oncology (AIOM) Clinical Practice Guideline on fertility preservation in cancer patients decided to apply the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology around the relevant and current question on the clinical utility of temporary ovarian suppression with LHRHa during chemotherapy as a strategy to preserve ovarian function and fertility in breast cancer patients. To answer this question, preservation of ovarian function and fertility were judged as critical outcomes for the decision-making. Three possible outcomes of harm were identified: LHRHa-associated toxicities, potential antagonism between concurrent LHRHa and chemotherapy, and lack of the prognostic impact of chemotherapy-induced premature ovarian failure. According to the GRADE evaluation conducted, the result was a strong positive recommendation in favour of using this option to preserve ovarian function and fertility in breast cancer patients. The present manuscript aims to update and summarise the evidence for the use of this strategy in light of the new data published up to January 2016, according to the GRADE process. Copyright © 2016 Elsevier Ltd. All rights reserved.

Detection of ATM germline variants by the p53 mitotic centrosomal localization test in BRCA1/2-negative patients with early-onset breast cancer.

Science.gov (United States)

Prodosmo, Andrea; Buffone, Amelia; Mattioni, Manlio; Barnabei, Agnese; Persichetti, Agnese; De Leo, Aurora; Appetecchia, Marialuisa; Nicolussi, Arianna; Coppa, Anna; Sciacchitano, Salvatore; Giordano, Carolina; Pinnarò, Paola; Sanguineti, Giuseppe; Strigari, Lidia; Alessandrini, Gabriele; Facciolo, Francesco; Cosimelli, Maurizio; Grazi, Gian Luca; Corrado, Giacomo; Vizza, Enrico; Giannini, Giuseppe; Soddu, Silvia

2016-09-06

Variant ATM heterozygotes have an increased risk of developing cancer, cardiovascular diseases, and diabetes. Costs and time of sequencing and ATM variant complexity make large-scale, general population screenings not cost-effective yet. Recently, we developed a straightforward, rapid, and inexpensive test based on p53 mitotic centrosomal localization (p53-MCL) in peripheral blood mononuclear cells (PBMCs) that diagnoses mutant ATM zygosity and recognizes tumor-associated ATM polymorphisms. Fresh PBMCs from 496 cancer patients were analyzed by p53-MCL: 90 cases with familial BRCA1/2-positive and -negative breast and/or ovarian cancer, 337 with sporadic cancers (ovarian, lung, colon, and post-menopausal breast cancers), and 69 with breast/thyroid cancer. Variants were confirmed by ATM sequencing. A total of seven individuals with ATM variants were identified, 5/65 (7.7 %) in breast cancer cases of familial breast and/or ovarian cancer and 2/69 (2.9 %) in breast/thyroid cancer. No variant ATM carriers were found among the other cancer cases. Excluding a single case in which both BRCA1 and ATM were mutated, no p53-MCL alterations were observed in BRCA1/2-positive cases. These data validate p53-MCL as reliable and specific test for germline ATM variants, confirm ATM as breast cancer susceptibility gene, and highlight a possible association with breast/thyroid cancers.
A controlled study of mental distress and somatic complaints after risk-reducing salpingo-oophorectomy in women at risk for hereditary breast ovarian cancer.

Science.gov (United States)

Michelsen, Trond M; Dørum, Anne; Dahl, Alv A

2009-04-01

Risk-reducing salpingo-oophorectomy (RRSO) provides effective protection against ovarian cancer in BRCA mutation carriers and in women at risk for hereditary breast ovarian cancer, but little is known about non-oncologic morbidity after the procedure. We explored mental distress and somatic complaints in women after RRSO compared to controls from the general population. 503 women from hereditary breast ovarian cancer families who had undergone RRSO after genetic counseling received a mailed questionnaire. 361 (71%) responded and 338 (67%) delivered complete data (cases). Controls were five randomly allocated age-matched controls per case (N=1690) from the population-based Norwegian Nord-Trøndelag Health Study (HUNT-2). Mean age of cases and controls was 54.6 years at survey. Mean time since surgery was 5.3 years (median 6.0). Compared to controls, the RRSO group had more palpitations (p=0.02), constipation (p=0.01), pain and stiffness (p=0.02), osteoporosis (p=0.02) and musculoskeletal disease (p=0.01) even after adjustments for demographic factors including use of hormonal replacement therapy. The RRSO group had lower levels of depression (pdepression (p<0.001) and total mental distress (p=0.002). In this controlled observational study, we found more somatic morbidity such as osteoporosis, palpitations, constipation, musculoskeletal disease and pain and stiffness but lower levels of mental distress among women who had undergone RRSO compared to controls.
Mutation analysis of breast cancer gene BRCA among breast cancer Jordanian females

International Nuclear Information System (INIS)

Atoum, Manar F.; Al-Kayed, Sameer A.

2004-01-01

To screen mutations of the tumor suppressor breast cancer susceptibility gene 1 (BRCA1) within 3 exons among Jordanian breast cancer females. A total of 135 Jordanian breast cancer females were genetically analyzed by denaturing gradient electrophoresis (DGGE) for mutation detection in 3 BRCA1 exons (2, 11 and 20) between 2000-2002 in Al-Basheer Hospital, Amman, Jordan. Of the studied patients 50 had a family history of breast cancer, 28 had a family history of cancer other than breast cancer, and 57 had no family history of any cancer. Five germline mutations were detected among breast cancer females with a family history of breast cancers (one in exon 2 and 4 mutations in exon 11). Another germline mutation (within exon 11) was detected among breast cancer females with family history of cancer other than breast cancer, and no mutation was detected among breast cancer females with no family history of any cancer or among normal control females. Screening mutations within exon 2, exon 11 and exon 20 showed that most screened mutations were within BRCA1 exon 11 among breast cancer Jordanian families with a family history of breast cancer. (author)
Early detection of ovarian cancer in FB&H - role of family medicine team

Directory of Open Access Journals (Sweden)

Dž. Ljuca

2007-08-01

Full Text Available Assessment of problems with ovarian malignancy in the Federation B&H requires a comprehensive and precise analysis of the population characteristics with particular focus on risk factors such as age, parity, hereditary factors, menstrual cycle characteristics (short cycle, early menarche, late menopause. A retrospective study of medical documentation involving 272 patients with ovarian cancer within the Federation of BiH in the period from 1996 to 2000 was conducted. Usual statistical methods were used (T- test, 2 -Test, Fisher exact test. The research showed that the disease was in most cases diagnosed too late, in the stages III and IV (60% whereas histology of the tissue showed epithelial cancer in 88,6% cases, most frequently between the age of 55 to 70. Out of 272 patients null-parity was recorded in 16,9 %, whereas 19,8 % of patients had just one pregnancy. Menstrual cycle duration shorter than 21 days was recorded in 26,5% cases. Approximately 1,8% patients had close relatives that suffered of cancer of breast, ovary or colon. Prerequisites for application of algorhithms in diagnostic procedures would be met by identification of risk groups consisting of those with one or more risk factors in their history. Bearing in mind the role of the family doctors in the future health system reform, it can be concluded that they could have an important role in the process.
Short-term effects of night shift work on breast cancer risk

DEFF Research Database (Denmark)

Vistisen, H. T.; Garde, A. H.; Frydenberg, M.

2017-01-01

.80-1.01] was observed for workers ever working night shifts during the follow-up period compared with workers only working day shifts after adjustment for age, age at first child, parity, family history of breast or ovarian cancer, sex hormones, medications related to alcoholism, family educational level, mammography......Objectives: The objective was to examine if night shift work is a short-term risk factor for breast cancer, including combined estrogen receptor (ER) and human epidermal growth factor 2 (HER2) breast cancer subtypes. Methods: The cohort comprised 155 540 public sector female workers in Denmark who...... were followed from 2007-2012. Day-to-day work-hour information was available from payroll registers and 1245 incident cases of breast cancer were identified in national cancer registries together with receptor subtype information. Results: A rate ratio (RR) of 0.90 [95% confidence interval (95% CI) 0...
Family history in breast cancer is not a prognostic factor?

NARCIS (Netherlands)

Jobsen, J.J.; Meerwaldt, J.H.; van der Palen, Jacobus Adrianus Maria

2000-01-01

The aim of this study is to determine if breast conservative treatment is justified for patients with a positive family history of breast cancer and to investigate whether they have a worse prognosis. We performed a prospective cohort study of breast cancer patients, treated with breast conservative
Worry Is Good for Breast Cancer Screening: A Study of Female Relatives from the Ontario Site of the Breast Cancer Family Registry

International Nuclear Information System (INIS)

Zhang, L.; Knight, J. A.; Andrulis, I. L.; Chiarelli, A. M.; Glendon, G.; Ritvo, P.

2012-01-01

Few prospective studies have examined associations between breast cancer worry and screening behaviours in women with elevated breast cancer risks based on family history. Methods. This study included 901 high familial risk women, aged 23-71 years, from the Ontario site of the Breast Cancer Family Registry. Self-reported breast screening behaviours at year-one followup were compared between women at low (N=305), medium ( N=433), and high (N=163) levels of baseline breast cancer worry using logistic regression. Nonlinear relationships were assessed using likelihood ratio tests. Results. A significant non-linear inverted “U” relationship was observed between breast cancer worry and mammography screening (π=0. 034) for all women, where women at either low or high worry levels were less likely than those at medium to have a screening mammogram. A similar significant non-linear inverted “U” relationship was also found among all women and women at low familial risk for worry and screening clinical breast examinations (CBEs). Conclusions. Medium levels of cancer worries predicted higher rates of screening mammography and CBE among high-risk women
Gastrointestinal permeability in ovarian cancer and breast cancer patients treated with paclitaxel and platinum

International Nuclear Information System (INIS)

Melichar, Bohuslav; Hyšpler, Radomír; Dragounová, Emanuela; Dvořák, Josef; Kalábová, Hana; Tichá, Alena

2007-01-01

Combination of platinum derivatives with paclitaxel is currently the standard front line regimen for patients with epithelial ovarian carcinoma, and represents also an active regimen in patients with metastatic breast or unknown primary carcinomas. Measurement of intestinal permeability represents one of the potential methods of noninvasive laboratory assessment of gastrointestinal mucositis induced by chemotherapy, but little is known about intestinal permeability in patients treated with paclitaxel or platinum. Intestinal permeability was assessed in 36 breast and ovarian cancer patients treated with paclitaxel/platinum combination by measuring, using capillary gas chromatography, urinary sucrose, lactulose, xylose and mannitol after oral challenge. The significance of differences during the therapy compared to pre-treatment values was studied by Wilcoxon paired test. The differences between groups of patient were studied by Mann-Whitney U test. Fisher exact test was used to compare the frequency in different subgroups. After administration of the first dose, a significant (p < 0.05) decrease in xylose absorption and increased lactulose/mannitol, sucrose/mannitol, lactulose/xylose and sucrose/xylose ratios were observed, but these parameters returned subsequently to pre-treatment levels. Patients who experienced serious (grade 3 or 4) toxicity had at baseline significantly lower percentages of xylose, mannitol and sucrose, and higher lactulose/mannitol ratio. Nine of 13 (69%) patients with baseline lactulose/mannitol ratio 0.070 or above experienced serious toxicity compared to 4 out of 23 patients (17%) with the ratio below 0.070 (p = 0.002). Post-treatment lactulose, lactulose/mannitol, sucrose/mannitol and lactulose/xylose ratios were significantly increased in patients with serious toxicity. A transient significant increase in lactulose/monosaccharide and sucrose/monosaccharide ratios was observed in ovarian and breast cancer patients treated with paclitaxel
BACH1 Ser919Pro variant and breast cancer risk

Directory of Open Access Journals (Sweden)

Eerola Hannaleena

2006-01-01

Full Text Available Abstract Background BACH1 (BRCA1-associated C-terminal helicase 1; also known as BRCA1-interacting protein 1, BRIP1 is a helicase protein that interacts in vivo with BRCA1, the protein product of one of the major genes for hereditary predisposition to breast cancer. Previously, two BACH1 germ line missense mutations have been identified in early-onset breast cancer patients with and without family history of breast and ovarian cancer. In this study, we aimed to evaluate whether there are BACH1 genetic variants that contribute to breast cancer risk in Finland. Methods The BACH1 gene was screened for germ line alterations among probands from 43 Finnish BRCA1/2 negative breast cancer families. Recently, one of the observed common variants, Ser-allele of the Ser919Pro polymorphism, was suggested to associate with an increased breast cancer risk, and was here evaluated in an independent, large series of 888 unselected breast cancer patients and in 736 healthy controls. Results Six BACH1 germ line alterations were observed in the mutation analysis, but none of these were found to associate with the cancer phenotype. The Val193Ile variant that was seen in only one family was further screened in an independent series of 346 familial breast cancer cases and 183 healthy controls, but no additional carriers were observed. Individuals with the BACH1 Ser919-allele were not found to have an increased breast cancer risk when the Pro/Ser heterozygotes (OR 0.90; 95% CI 0.70–1.16; p = 0.427 or Ser/Ser homozygotes (OR 1.02; 95% CI 0.76–1.35; p = 0.91 were compared to Pro/Pro homozygotes, and there was no association of the variant with any breast tumor characteristics, age at cancer diagnosis, family history of cancer, or survival. Conclusion Our results suggest that the BACH1 Ser919 is not a breast cancer predisposition allele in the Finnish study population. Together with previous studies, our results also indicate that although some rare germ line variants
BACH1 Ser919Pro variant and breast cancer risk

International Nuclear Information System (INIS)

Vahteristo, Pia; Yliannala, Kristiina; Tamminen, Anitta; Eerola, Hannaleena; Blomqvist, Carl; Nevanlinna, Heli

2006-01-01

BACH1 (BRCA1-associated C-terminal helicase 1; also known as BRCA1-interacting protein 1, BRIP1) is a helicase protein that interacts in vivo with BRCA1, the protein product of one of the major genes for hereditary predisposition to breast cancer. Previously, two BACH1 germ line missense mutations have been identified in early-onset breast cancer patients with and without family history of breast and ovarian cancer. In this study, we aimed to evaluate whether there are BACH1 genetic variants that contribute to breast cancer risk in Finland. The BACH1 gene was screened for germ line alterations among probands from 43 Finnish BRCA1/2 negative breast cancer families. Recently, one of the observed common variants, Ser-allele of the Ser919Pro polymorphism, was suggested to associate with an increased breast cancer risk, and was here evaluated in an independent, large series of 888 unselected breast cancer patients and in 736 healthy controls. Six BACH1 germ line alterations were observed in the mutation analysis, but none of these were found to associate with the cancer phenotype. The Val193Ile variant that was seen in only one family was further screened in an independent series of 346 familial breast cancer cases and 183 healthy controls, but no additional carriers were observed. Individuals with the BACH1 Ser919-allele were not found to have an increased breast cancer risk when the Pro/Ser heterozygotes (OR 0.90; 95% CI 0.70–1.16; p = 0.427) or Ser/Ser homozygotes (OR 1.02; 95% CI 0.76–1.35; p = 0.91) were compared to Pro/Pro homozygotes, and there was no association of the variant with any breast tumor characteristics, age at cancer diagnosis, family history of cancer, or survival. Our results suggest that the BACH1 Ser919 is not a breast cancer predisposition allele in the Finnish study population. Together with previous studies, our results also indicate that although some rare germ line variants in BACH1 may contribute to breast cancer development, the
Significance of the tumor markers CA 125 and CA 15-3 in postoperative diagnosis of ovarian and breast cancer

International Nuclear Information System (INIS)

Johannsen, B.; Bartel, U.; Elling, D.

1989-01-01

In 271 patients with ovarian carcinoma, benign ovarian tumors, breast cancer, and two control groups, serum levels of CA 125, CA 15-3, CEA and, partly, CA 19-9 were determined immunoradiometrically. According to the results of the determination of CA 125 in the follow-up of ovarian carcinoma, CA 125 represents a useful marker for early detection of recurrences, especially in cases of diffuse carcinoma dissemination. In incomplete tumor debulking, postoperative CA 125 serum levels did not prove to be helpful except that a positive level renders invasive diagnostic investigation no longer necessary. Postoperative follow-up in breast cancer early reveals distant metastases, with very high levels in patients with bone metastases. By simultaneous measurement of CA 15-3 and CEA the sensitivity could be increased from 86% (CA 15-3 only) to 93%. (author)
Novel BRCA1 splice-site mutation in ovarian cancer patients of Slavic origin.

Science.gov (United States)

Krivokuca, Ana; Dragos, Vita Setrajcic; Stamatovic, Ljiljana; Blatnik, Ana; Boljevic, Ivana; Stegel, Vida; Rakobradovic, Jelena; Skerl, Petra; Jovandic, Stevo; Krajc, Mateja; Magic, Mirjana Brankovic; Novakovic, Srdjan

2018-04-01

Mutations in breast cancer susceptibility gene 1 (BRCA1) lead to defects in a number of cellular pathways including DNA damage repair and transcriptional regulation, resulting in the elevated genome instability and predisposing to breast and ovarian cancers. We report a novel mutation LRG_292t1:c.4356delA,p.(Ala1453Glnfs*3) in the 12th exon of BRCA1, in the splice site region near the donor site of intron 12. It is a frameshift mutation with the termination codon generated on the third amino acid position from the site of deletion. Human Splice Finder 3.0 and MutationTaster have assessed this variation as disease causing, based on the alteration of splicing, creation of premature stop codon and other potential alterations initiated by nucleotide deletion. Among the most important alterations are frameshift and splice site changes (score of the newly created donor splice site: 0.82). c.4356delA was associated with two ovarian cancer cases in two families of Slavic origin. It was detected by next generation sequencing, and confirmed with Sanger sequencing in both cases. Because of the fact that it changes the reading frame of the protein, novel mutation c.4356delA p.(Ala1453Glnfs*3) in BRCA1 gene might be of clinical significance for hereditary ovarian cancer. Further functional as well as segregation analyses within the families are necessary for appropriate clinical classification of this variant. Since it has been detected in two ovarian cancer patients of Slavic origin, it is worth investigating founder effect of this mutation in Slavic populations.
Hereditary Breast Cancer: Mutations Within BRCA1 and BRCA2 with Phenotypic Responses

National Research Council Canada - National Science Library

Lynch, Henry T

2000-01-01

To date we have seventy-three Hereditary Breast/Ovarian Cancer families with identified BRCA1 or BRCA2 genetic mutations, wherein 24 additional cases of slides and tissue blocks have been retrieved...
The Role of Ovarian Sex Steroids in Metabolic Homeostasis, Obesity, and Postmenopausal Breast Cancer: Molecular Mechanisms and Therapeutic Implications

Directory of Open Access Journals (Sweden)

Viroj Boonyaratanakornkit

2015-01-01

Full Text Available Obese postmenopausal women have an increased risk of breast cancer and are likely to have a worse prognosis than nonobese postmenopausal women. The cessation of ovarian function after menopause results in withdrawal of ovarian sex steroid hormones, estrogen, and progesterone. Accumulating evidence suggests that the withdrawal of estrogen and progesterone causes homeostasis imbalances, including decreases in insulin sensitivity and leptin secretion and changes in glucose and lipid metabolism, resulting in a total reduction in energy expenditure. Together with a decrease in physical activity and consumption of a high fat diet, these factors significantly contribute to obesity in postmenopausal women. Obesity may contribute to breast cancer development through several mechanisms. Obesity causes localized inflammation, an increase in local estrogen production, and changes in cellular metabolism. In addition, obese women have a higher risk of insulin insensitivity, and an increase in insulin and other growth factor secretion. In this review, we describe our current understanding of the molecular actions of estrogen and progesterone and their contributions to cellular metabolism, obesity, inflammation, and postmenopausal breast cancer. We also discuss how modifications of estrogen and progesterone actions might be used as a therapeutic approach for obesity and postmenopausal breast cancer.
Risk of breast cancer in women with a CHEK2 mutation with and without a family history of breast cancer.

Science.gov (United States)

Cybulski, Cezary; Wokołorczyk, Dominika; Jakubowska, Anna; Huzarski, Tomasz; Byrski, Tomasz; Gronwald, Jacek; Masojć, Bartłomiej; Deebniak, Tadeusz; Górski, Bohdan; Blecharz, Paweł; Narod, Steven A; Lubiński, Jan

2011-10-01

To estimate the risk of breast cancer in a woman who has a CHEK2 mutation depending on her family history of breast cancer. Seven thousand four hundred ninety-four BRCA1 mutation-negative patients with breast cancer and 4,346 control women were genotyped for four founder mutations in CHEK2 (del5395, IVS2+1G>A, 1100delC, and I157T). A truncating mutation (IVS2+1G>A, 1100delC, or del5395) was present in 227 patients (3.0%) and in 37 female controls (0.8%; odds ratio [OR], 3.6; 95% CI, 2.6 to 5.1). The OR was higher for women with a first- or second-degree relative with breast cancer (OR, 5.0; 95% CI, 3.3 to 7.6) than for women with no family history (OR, 3.3; 95% CI, 2.3 to 4.7). If both a first- and second-degree relative were affected with breast cancer, the OR was 7.3 (95% CI, 3.2 to 16.8). Assuming a baseline risk of 6%, we estimate the lifetime risks for carriers of CHEK2 truncating mutations to be 20% for a woman with no affected relative, 28% for a woman with one second-degree relative affected, 34% for a woman with one first-degree relative affected, and 44% for a woman with both a first- and second-degree relative affected. CHEK2 mutation screening detects a clinically meaningful risk of breast cancer and should be considered in all women with a family history of breast cancer. Women with a truncating mutation in CHEK2 and a positive family history of breast cancer have a lifetime risk of breast cancer of greater than 25% and are candidates for magnetic resonance imaging screening and for tamoxifen chemoprevention.
Genome-wide Meta-analyses of Breast, Ovarian and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by At Least Two Cancer Types

Science.gov (United States)

Kar, Siddhartha P.; Beesley, Jonathan; Al Olama, Ali Amin; Michailidou, Kyriaki; Tyrer, Jonathan; Kote-Jarai, ZSofia; Lawrenson, Kate; Lindstrom, Sara; Ramus, Susan J.; Thompson, Deborah J.; Kibel, Adam S.; Dansonka-Mieszkowska, Agnieszka; Michael, Agnieszka; Dieffenbach, Aida K.; Gentry-Maharaj, Aleksandra; Whittemore, Alice S.; Wolk, Alicja; Monteiro, Alvaro; Peixoto, Ana; Kierzek, Andrzej; Cox, Angela; Rudolph, Anja; Gonzalez-Neira, Anna; Wu, Anna H.; Lindblom, Annika; Swerdlow, Anthony; Ziogas, Argyrios; Ekici, Arif B.; Burwinkel, Barbara; Karlan, Beth Y.; Nordestgaard, Børge G.; Blomqvist, Carl; Phelan, Catherine; McLean, Catriona; Pearce, Celeste Leigh; Vachon, Celine; Cybulski, Cezary; Slavov, Chavdar; Stegmaier, Christa; Maier, Christiane; Ambrosone, Christine B.; Høgdall, Claus K.; Teerlink, Craig C.; Kang, Daehee; Tessier, Daniel C.; Schaid, Daniel J.; Stram, Daniel O.; Cramer, Daniel W.; Neal, David E.; Eccles, Diana; Flesch-Janys, Dieter; Velez Edwards, Digna R.; Wokozorczyk, Dominika; Levine, Douglas A.; Yannoukakos, Drakoulis; Sawyer, Elinor J.; Bandera, Elisa V.; Poole, Elizabeth M.; Goode, Ellen L.; Khusnutdinova, Elza; Høgdall, Estrid; Song, Fengju; Bruinsma, Fiona; Heitz, Florian; Modugno, Francesmary; Hamdy, Freddie C.; Wiklund, Fredrik; Giles, Graham G.; Olsson, Håkan; Wildiers, Hans; Ulmer, Hans-Ulrich; Pandha, Hardev; Risch, Harvey A.; Darabi, Hatef; Salvesen, Helga B.; Nevanlinna, Heli; Gronberg, Henrik; Brenner, Hermann; Brauch, Hiltrud; Anton-Culver, Hoda; Song, Honglin; Lim, Hui-Yi; McNeish, Iain; Campbell, Ian; Vergote, Ignace; Gronwald, Jacek; Lubiński, Jan; Stanford, Janet L.; Benítez, Javier; Doherty, Jennifer A.; Permuth, Jennifer B.; Chang-Claude, Jenny; Donovan, Jenny L.; Dennis, Joe; Schildkraut, Joellen M.; Schleutker, Johanna; Hopper, John L.; Kupryjanczyk, Jolanta; Park, Jong Y.; Figueroa, Jonine; Clements, Judith A.; Knight, Julia A.; Peto, Julian; Cunningham, Julie M.; Pow-Sang, Julio; Batra, Jyotsna; Czene, Kamila; Lu, Karen H.; Herkommer, Kathleen; Khaw, Kay-Tee; Matsuo, Keitaro; Muir, Kenneth; Offitt, Kenneth; Chen, Kexin; Moysich, Kirsten B.; Aittomäki, Kristiina; Odunsi, Kunle; Kiemeney, Lambertus A.; Massuger, Leon F.A.G.; Fitzgerald, Liesel M.; Cook, Linda S.; Cannon-Albright, Lisa; Hooning, Maartje J.; Pike, Malcolm C.; Bolla, Manjeet K.; Luedeke, Manuel; Teixeira, Manuel R.; Goodman, Marc T.; Schmidt, Marjanka K.; Riggan, Marjorie; Aly, Markus; Rossing, Mary Anne; Beckmann, Matthias W.; Moisse, Matthieu; Sanderson, Maureen; Southey, Melissa C.; Jones, Michael; Lush, Michael; Hildebrandt, Michelle A. T.; Hou, Ming-Feng; Schoemaker, Minouk J.; Garcia-Closas, Montserrat; Bogdanova, Natalia; Rahman, Nazneen; Le, Nhu D.; Orr, Nick; Wentzensen, Nicolas; Pashayan, Nora; Peterlongo, Paolo; Guénel, Pascal; Brennan, Paul; Paulo, Paula; Webb, Penelope M.; Broberg, Per; Fasching, Peter A.; Devilee, Peter; Wang, Qin; Cai, Qiuyin; Li, Qiyuan; Kaneva, Radka; Butzow, Ralf; Kopperud, Reidun Kristin; Schmutzler, Rita K.; Stephenson, Robert A.; MacInnis, Robert J.; Hoover, Robert N.; Winqvist, Robert; Ness, Roberta; Milne, Roger L.; Travis, Ruth C.; Benlloch, Sara; Olson, Sara H.; McDonnell, Shannon K.; Tworoger, Shelley S.; Maia, Sofia; Berndt, Sonja; Lee, Soo Chin; Teo, Soo-Hwang; Thibodeau, Stephen N.; Bojesen, Stig E.; Gapstur, Susan M.; Kjær, Susanne Krüger; Pejovic, Tanja; Tammela, Teuvo L.J.; Dörk, Thilo; Brüning, Thomas; Wahlfors, Tiina; Key, Tim J.; Edwards, Todd L.; Menon, Usha; Hamann, Ute; Mitev, Vanio; Kosma, Veli-Matti; Setiawan, Veronica Wendy; Kristensen, Vessela; Arndt, Volker; Vogel, Walther; Zheng, Wei; Sieh, Weiva; Blot, William J.; Kluzniak, Wojciech; Shu, Xiao-Ou; Gao, Yu-Tang; Schumacher, Fredrick; Freedman, Matthew L.; Berchuck, Andrew; Dunning, Alison M.; Simard, Jacques; Haiman, Christopher A.; Spurdle, Amanda; Sellers, Thomas A.; Hunter, David J.; Henderson, Brian E.; Kraft, Peter; Chanock, Stephen J.; Couch, Fergus J.; Hall, Per; Gayther, Simon A.; Easton, Douglas F.; Chenevix-Trench, Georgia; Eeles, Rosalind; Pharoah, Paul D.P.; Lambrechts, Diether

2016-01-01

Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P cancer meta-analysis. PMID:27432226
Familial Investigations of Childhood Cancer Predisposition

Science.gov (United States)

2018-01-03

Acute Leukemia; Adenomatous Polyposis; Adrenocortical Carcinoma; AML; BAP1 Tumor Predisposition Syndrome; Carney Complex; Choroid Plexus Carcinoma; Constitutional Mismatch Repair Deficiency Syndrome; Diamond-Blackfan Anemia; DICER1 Syndrome; Dyskeratosis Congenita; Emberger Syndrome; Familial Acute Myeloid Leukemia; Familial Adenomatous Polyposis; Fanconi Anemia; Familial Cancer; Familial Wilms Tumor; Familial Neuroblastoma; GIST; Hereditary Breast and Ovarian Cancer; Hereditary Paraganglioma-Pheochromocytoma Syndrome; Hodgkin Lymphoma; Juvenile Polyposis; Li-Fraumeni Syndrome; Lynch Syndrome; MDS; Melanoma Syndrome; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2; Neuroblastoma; Neurofibromatosis Type 1; Neurofibromatosis Type II; Nevoid Basal Cell Carcinoma Syndrome; Non Hodgkin Lymphoma; Noonan Syndrome and Other Rasopathy; Overgrowth Syndromes; Pancreatic Cancer; Peutz-Jeghers Syndrome; Pheochromocytoma/Paraganglioma; PTEN Hamartoma Tumor Syndrome; Retinoblastoma; Rhabdoid Tumor Predisposition Syndrome; Rhabdomyosarcoma; Rothmund-Thomson Syndrome; Tuberous Sclerosis; Von Hippel-Lindau Disease
Predictors for contralateral prophylactic mastectomy in breast cancer patients

Science.gov (United States)

Fu, Yun; Zhuang, Zhigang; Dewing, Michelle; Apple, Sophia; Chang, Helena

2015-01-01

Background: In recent years, radical breast cancer surgery has been largely replaced by breast conservation treatment, due to early diagnosis and more effective adjuvant treatment. While breast conservation is mostly preferred, the trend of bilateral mastectomy has risen in the United States. The aim of this study is to determine factors influencing patients’ choice for having contralateral prophylactic mastectomy (CPM). Methods: This is a retrospective study of 373 patients diagnosed with primary invasive breast cancer who were treated by bilateral or unilateral mastectomy (BM or UM) at the Revlon/UCLA Breast Center between Jan. 2002 and Dec. 2010. In the BM group, only those with unilateral breast cancer who chose CPM were included in the analysis. Results: When compared with the UM group, the following factors were found to be associated with BM: younger age, pre-menopausal, a family history of breast/ovarian cancer, BRCA mutation, more breast biopsies, history of breast augmentation, having MRI study within 6 months before the surgery, more likely to have reconstruction and sentinel lymph node biopsy (SLNB) and fewer had neoadjuvant/adjuvant chemotherapy/radiation. When patients with bilateral breast cancer were excluded, multivariate logistic regression analysis indicated younger patients with negative nodes, SLNB as the only nodal surgery and positive family history were significant factors predicting CPM and immediate reconstruction using tissue expanders or implants. Conclusion: Younger age, lower TN stage, requiring only SLNB and high risk family history predict contralateral prophylactic mastectomy. Tissue expander/implant-based reconstructions were more frequently chosen by patients with BM. PMID:26097557
Selected Aspects of Molecular Diagnostics of Constitutional Alterations in BRCA1 and BRCA2 Genes Associated with Increased Risk of Breast Cancer in the Polish Population

Directory of Open Access Journals (Sweden)

Górski Bohdan

2006-08-01

Full Text Available Abstract Objectives This study was undertaken to determine: 1 Type and prevalence of founder mutations BRCA1 and BRCA2 genes in Polish families with strong aggregation of breast and/or ovarian cancer. 2 Risk of breast and/or ovarian cancer depending on type of BRCA1 gene mutation. 3 Prevalence of BRCA1 mutation and of other alleles presumably linked with predisposition to breast cancer in unselected Polish patients with breast cancer. 4 Risk of breast cancer in patients with 5972C/T polymorphism that alters the BRCA2 protein structure. Summary of the results 1. Among 66 families from several regions in Poland with a strong aggregation of breast/ovarian cancer, founder mutation of the BRCA1 gene were disclosed in 34 families and of the BRCA2 gene in on family. Altogether, seven different mutations were disclosed. Five mutations were found in at least two families in this group. The most frequent mutation was 5382insC (18 families, followed by C61G (7 families and 4153delA (4 families. 2. Among 200 families representative for Poland with strong aggregation of breast/ovarian cancer, mutation of the BRCA1 gene were found in 122 families (61% and of the BRCA2 gene in seven families (3,5%. 119 out of 122 mutations of the BRCA1 gene (97,5% were repeatable. Three recurrent mutations of the BRCA1 gene (5382insC, C61G, 4153delA characteristic for the Polish population were disclosed in 111 families representing 86% of all pathogenic sequences of this gene. 3. The risk of ovarian cancer in carriers of the three most frequent recurrent mutation of the BRCA1 gene in Poland is similar (OR 43.6 for 5382insC and 50 for 4153delA. The risk of breast cancer is significantly different for 4153delA (OR 1 and for other mutations (OR 10.9. 4. Among 2012 unselected breast cancers diagnosed in hospitals of nine Polish cities, mutations of the BRCA1 gene (5382insC, C61G, 4153delA were disclosed in 2.9% patients. CHEK2 alternation (1100delC, IVS2+1G>A, I157T was
Nonbreast Second Malignancies After Treatment of Primary Breast Cancer

International Nuclear Information System (INIS)

Yadav, Budhi S.; Sharma, Suresh C.; Patel, Firuza D.; Ghoshal, Sushmita; Kapoor, Rakesh; Kumar, Rajinder

2009-01-01

Purpose: To determine the incidence and risk factors for nonbreast second malignancies (NBSMs) in women after treatment for primary breast cancer. Methods and Materials: Between January 1985 and December 1995, a total of 1,084 breast cancer patients were analyzed for NBSMs. Detailed analysis was carried out for age, family history, disease stage, radiation therapy, chemotherapy, hormone therapy, other clinical/pathologic characteristics, and site of NBSMs. The Cox proportional hazard regression model was used to estimate the relative risk of NBSMs. Results: Median follow-up was 12 years. In total, 33 cases of NBSMs were noted in 29 patients. The overall incidence of NBSM was 3%, and the median time for NBSMs was 7 years. The most common NBSMs were gynecologic (22 patients), gastrointestinal (4 patients), head and neck (3 patients), hematologic (2 patients), lung (1 patient), and thyroid (1 patient). The NBSMs rate at 12 years was 2.4% for both mastectomy and radiation therapy groups. In the subset of patients less than 45 years of age at the time of treatment, the NBSMs rate was 0.7% as compared with 4.6% in patients more than 45 years of age (p = 0.001). Statistically significant higher incidences of endometrial and ovarian cancer were seen in patients with hormonal therapy (5.2%) as compared with patients without hormonal therapy (1.8%, p = 0.002). Women with a family history of breast cancer had a higher incidence (6%) of endometrial and ovarian malignancy compared with women without such a history (2.1%, p = 0.003). Chemotherapy did not affect the risk of second malignancy. Conclusion: The most common NBSMs in this study were gynecologic. Family history of breast cancer was a high risk factor for NBSMs. No risk of NBSMs with radiotherapy was observed.

Trends in breast, ovarian and cervical cancer incidence in Mumbai, India over a 30-year period, 1976–2005: an age–period–cohort analysis

Science.gov (United States)

Dhillon, P K; Yeole, B B; Dikshit, R; Kurkure, A P; Bray, F

2011-01-01

Background: Demographic, socioeconomic and cultural changes in India have increased longevity, delayed childbearing, decreased parity and resulted in a more westernised lifestyle, contributing to the increasing burden of cancer, especially among women. Methods: We evaluated secular changes in the incidence of breast, cervical and ovarian cancer in Mumbai women aged 30–64 between 1976 and 2005. Age-standardised incidence rates were calculated and presented by site and calendar period. An age–period–cohort (APC) analysis quantified recent time trends and the significance of birth cohort and calendar period effects. The estimated annual percent change (EAPC) was obtained from the drift parameter, expressing the linear time trend common to both calendar period and birth cohort. Results: Over the 30-year study period, the age-standardised rates significantly increased for breast cancer (EAPC: 1.1% (95% confidence interval (CI): 1.0, 1.3)), significantly decreased for cervical cancer (EAPC: −1.8% (95% CI: −2.0, −1.6)) and there was no statistically significant change for ovarian cancer (EAPC: 0.3% (95% CI: −0.1, 0.6)). For breast and cervical cancer, the best-fitting model was the APC model. Conclusions: The rates of breast, cervical and ovarian cancer remain low in comparison with western countries, and the divergent trends of breast (increasing) and cervical cancer (decreasing) in Mumbai were similar to those observed in several other Asian countries. The changing risk profile in successive generations – improved education, higher socioeconomic status, later age at marriage and at first child, and lower parity – may in combination partially explain the diverging generational changes in breast and cervical cancer in Mumbai in the last decades. PMID:21829198
Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

NARCIS (Netherlands)

K. Lawrenson (Kate); S. Kar (Siddhartha); K. McCue (Karen); Kuchenbaeker, K. (Karoline); K. Michailidou (Kyriaki); J.P. Tyrer (Jonathan); J. Beesley (Jonathan); S.J. Ramus (Susan); Li, Q. (Qiyuan); Delgado, M.K. (Melissa K.); J.M. Lee (Janet M.); K. Aittomäki (Kristiina); I.L. Andrulis (Irene); H. Anton-Culver (Hoda); Arndt, V. (Volker); B.K. Arun (Banu); B. Arver (Brita Wasteson); E.V. Bandera (Elisa); M. Barile (Monica); Barkardottir, R.B. (Rosa B.); D. Barrowdale (Daniel); M.W. Beckmann (Matthias); J. Benítez (Javier); A. Berchuck (Andrew); M. Bisogna (Maria); L. Bjorge (Line); C. Blomqvist (Carl); W.J. Blot (William); N.V. Bogdanova (Natalia); Bojesen, A. (Anders); S.E. Bojesen (Stig); M.K. Bolla (Manjeet K.); B. Bonnani (Bernardo); A.-L. Borresen-Dale (Anne-Lise); H. Brauch (Hiltrud); P. Brennan (Paul); H. Brenner (Hermann); F. Bruinsma (Fiona); J. Brunet (Joan); S.A.B.S. Buhari (Shaik Ahmad Bin Syed); B. Burwinkel (Barbara); R. Butzow (Ralf); S.S. Buys (Saundra); Q. Cai (Qiuyin); T. Caldes (Trinidad); I. Campbell (Ian); Canniotto, R. (Rikki); J. Chang-Claude (Jenny); Chiquette, J. (Jocelyne); Choi, J.-Y. (Ji-Yeob); K.B.M. Claes (Kathleen B.M.); L.S. Cook (Linda S.); A. Cox (Angela); D.W. Cramer (Daniel); S.S. Cross (Simon); C. Cybulski (Cezary); K. Czene (Kamila); M.B. Daly (Mary B.); F. Damiola (Francesca); A. Dansonka-Mieszkowska (Agnieszka); H. Darabi (Hatef); J. Dennis (Joe); P. Devilee (Peter); O. Díez (Orland); J.A. Doherty (Jennifer A.); S.M. Domchek (Susan); C.M. Dorfling (Cecilia); T. Dörk (Thilo); M. Dumont (Martine); H. Ehrencrona (Hans); B. Ejlertsen (Bent); S.D. Ellis (Steve); C. Engel (Christoph); E. Lee (Eunjung); Evans, D.G. (D. Gareth); P.A. Fasching (Peter); L. Feliubadaló (L.); J.D. Figueroa (Jonine); D. Flesch-Janys (Dieter); O. Fletcher (Olivia); H. Flyger (Henrik); L. Foretova (Lenka); F. Fostira (Florentia); W.D. Foulkes (William); B.L. Fridley (Brooke); E. Friedman (Eitan); D. Frost (Debra); Gambino, G. (Gaetana); P.A. Ganz (Patricia A.); J. Garber (Judy); M. García-Closas (Montserrat); A. Gentry-Maharaj (Aleksandra); M. Ghoussaini (Maya); G.G. Giles (Graham); R. Glasspool (Rosalind); A.K. Godwin (Andrew K.); M.S. Goldberg (Mark); D. Goldgar (David); A. González-Neira (Anna); E.L. Goode (Ellen); M.T. Goodman (Marc); M.H. Greene (Mark H.); J. Gronwald (Jacek); P. Guénel (Pascal); C.A. Haiman (Christopher A.); P. Hall (Per); Hallberg, E. (Emily); U. Hamann (Ute); T.V.O. Hansen (Thomas); P. harrington (Patricia); J.M. Hartman (Joost); N. Hassan (Norhashimah); S. Healey (Sue); P.U. Heitz; J. Herzog (Josef); E. Høgdall (Estrid); C.K. Høgdall (Claus); F.B.L. Hogervorst (Frans); A. Hollestelle (Antoinette); J.L. Hopper (John); P.J. Hulick (Peter); T. Huzarski (Tomasz); E.N. Imyanitov (Evgeny); C. Isaacs (Claudine); H. Ito (Hidemi); A. Jakubowska (Anna); R. Janavicius (Ramunas); A. Jensen (Allan); E.M. John (Esther); Johnson, N. (Nichola); M. Kabisch (Maria); D. Kang (Daehee); M.K. 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Nathanson (Katherine); R.B. Ness (Roberta); S.L. Neuhausen (Susan); H. Nevanlinna (Heli); S. Nord (Silje); R.L. Nussbaum (Robert L.); K. Odunsi (Kunle); K. Offit (Kenneth); E. Olah; O.I. Olopade (Olufunmilayo I.); J.E. Olson (Janet); C. Olswold (Curtis); D.M. O'Malley (David M.); I. Orlow (Irene); N. Orr (Nick); A. Osorio (Ana); Park, S.K. (Sue Kyung); C.L. Pearce (Celeste); T. Pejovic (Tanja); P. Peterlongo (Paolo); G. Pfeiler (Georg); C. Phelan (Catherine); E.M. Poole (Elizabeth); K. Pykäs (Katri); P. Radice (Paolo); J. Rantala (Johanna); M.U. Rashid (Muhammad); G. Rennert (Gad); V. Rhenius (Valerie); K. Rhiem (Kerstin); H. Risch (Harvey); G.C. Rodriguez (Gustavo); M.A. Rossing (Mary Anne); Rudolph, A. (Anja); H.B. Salvesen (Helga); Sangrajrang, S. (Suleeporn); Sawyer, E.J. (Elinor J.); J.M. Schildkraut (Joellen); M.K. Schmidt (Marjanka); R.K. Schmutzler (Rita); T.A. Sellers (Thomas A.); C.M. Seynaeve (Caroline); Shah, M. (Mitul); C.-Y. Shen (Chen-Yang); X.-O. Shu (Xiao-Ou); W. Sieh (Weiva); C.F. Singer (Christian); O. Sinilnikova (Olga); S. Slager (Susan); H. Song (Honglin); Soucy, P. (Penny); M.C. Southey (Melissa); M. Stenmark-Askmalm (Marie); D. Stoppa-Lyonnet (Dominique); C. Sutter (Christian); A.J. Swerdlow (Anthony ); Tchatchou, S. (Sandrine); P.J. Teixeira; S.-H. Teo (Soo-Hwang); K.L. Terry (Kathryn); M.B. Terry (Mary Beth); M. Thomassen (Mads); M.G. Tibiletti (Maria Grazia); L. Tihomirova (Laima); S. Tognazzo (Silvia); A.E. Toland (Amanda); I.P. Tomlinson (Ian); D. Torres (Diana); T. Truong (Thérèse); C.-C. Tseng (Chiu-Chen); N. Tung (Nadine); Tworoger, S.S. (Shelley S.); C. Vachon (Celine); Van Den Ouweland, A.M.W. (Ans M.W.); Van Doorn, H.C. (Helena C.); E.J. van Rensburg (Elizabeth); L.J. van 't Veer (Laura); A. Vanderstichele (Adriaan); I. Vergote (Ignace); J. Vijai (Joseph); Wang, Q. (Qin); S. Wang-Gohrke (Shan); J.N. Weitzel (Jeffrey); N. Wentzensen (N.); A.S. Whittemore (Alice); H. Wildiers (Hans); R. Winqvist (Robert); A.H. Wu (Anna); Yannoukakos, D. (Drakoulis); S.-Y. Yoon (Sook-Yee); J-C. Yu (Jyh-Cherng); W. Zheng (Wei); Y. Zheng (Ying); Khanna, K.K. (Kum Kum); J. Simard (Jacques); A.N.A. Monteiro (Alvaro N.); J.D. French (Juliet); F.J. Couch (Fergus); M. Freedman (Matthew); D.F. Easton (Douglas F.); A.M. Dunning (Alison); P.D.P. Pharoah (Paul); S.L. Edwards (Stacey); G. Chenevix-Trench (Georgia); A.C. Antoniou (Antonis C.); S.A. Gayther (Simon); D. Bowtell (David); A. DeFazio (Anna); P. Webb (Penny); M.-A. Collonge-Rame; Damette, A. (Alexandre); E. Barouk-Simonet (Emmanuelle); F. Bonnet (Françoise); V. Bubien (Virginie); N. Sevenet (Nicolas); M. Longy (Michel); P. Berthet (Pascaline); D. Vaur (Dominique); L. Castera (Laurent); S.F. Ferrer; Y.-J. Bignon (Yves-Jean); N. Uhrhammer (Nancy); F. Coron (Fanny); L. Faivre (Laurence); Baurand, A. (Amandine); Jacquot, C. (Caroline); Bertolone, G. (Geoffrey); Lizard, S. (Sarab); D. Leroux (Dominique); H. Dreyfus (Hélène); C. Rebischung (Christine); Peysselon, M. 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Lebrun (Marine); C. Kientz (Caroline); D.W. Muller (Danièle); J.P. Fricker (Jean Pierre); C. Toulas (Christine); R. Guimbaud (Rosine); L. Gladieff (Laurence); V. Feillel (Viviane); I. Mortemousque (Isabelle); B. Bressac-de Paillerets (Brigitte); O. Caron (Olivier); M. Guillaud-Bataille (Marine); H. Gregory (Helen); Z. Miedzybrodzka (Zosia); P.J. Morrison (Patrick); A. Donaldson (Alan); M.T. Rogers (Mark); M.J. Kennedy (John); M.E. Porteous (Mary); A. Brady (A.); J. Barwell (Julian); Foo, C. (Claire); F. Lalloo (Fiona); L. Side (Lucy); J. Eason (Jacqueline); Henderson, A. (Alex); L.J. Walker (Lisa); J. Cook (Jackie); Snape, K. (Katie); A. Murray (Alexandra); E. McCann (Emma); M.A. Rookus (Matti); F.E. van Leeuwen (F.); L. van der Kolk (Lizet); M.K. Schmidt (Marjanka); N.S. Russell (Nicola); J.L. de Lange (J.); Wijnands, R.; J.M. Collée (Margriet); M.J. Hooning (Maartje); Seynaeve, C.; C.H.M. van Deurzen (Carolien); A.I.M. Obdeijn (Inge-Marie); C.J. van Asperen (Christi); R.A.E.M. Tollenaar (Rob); T.C.T.E.F. van Cronenburg; C.M. Kets; M.G.E.M. Ausems (Margreet); C. van der Pol (Carmen); T.A.M. van Os (Theo); Q. Waisfisz (Quinten); E.J. Meijers-Heijboer (Hanne); E.B. Gómez García (Encarna); J.C. Oosterwijk (Jan); M.J. Mourits (Marjan); G.H. de Bock (Geertruida); H. Vasen (Hans); Siesling, S.; Verloop, J.; L.I.H. Overbeek (Lucy); S.B. Fox (Stephen); J. Kirk (Judy); G.J. Lindeman; M. Price (Melanie)

2016-01-01

textabstractA locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 ×
Genetic testing for breast and ovarian cancer susceptibility: evaluating direct-to-consumer marketing--Atlanta, Denver, Raleigh-Durham, and Seattle, 2003.

Science.gov (United States)

2004-07-16

Breast and ovarian cancer are the second and fifth leading causes of cancer death, respectively, among women in the United States. One in eight women will have breast cancer during their lifetimes, and one in 70 will have ovarian cancer. Mutations in two genes, BRCA1 and BRCA2 (BRCA1/2), are associated with predisposition for inherited breast and ovarian cancer and are identified in 5%-10% of women with breast or ovarian cancer (BOC). Since 1996, genetic testing for these mutations has been available clinically; however, population-based screening is not recommended because of the complexity of test interpretation and limited data on clinical validity and utility. Despite the test's limited applicability in the general population, the U.S. provider of clinical BRCA1/2 testing (Myriad Genetic Laboratories, Inc., Salt Lake City, Utah) conducted a pilot direct-to-consumer (DTC) marketing campaign in two cities (Atlanta, Georgia, and Denver, Colorado) during September 2002-February 2003. Although DTC advertisements have been used to raise consumer awareness about pharmaceuticals, this was the first time an established genetic test was marketed to the public. To assess the impact of the campaign on consumer behaviors and health-care provider practices, CDC and the respective state health departments for the pilot cities and two comparison cities (Raleigh-Durham, North Carolina, and Seattle, Washington) surveyed consumers and providers. This report summarizes results of those surveys, which indicated that consumer and provider awareness of BRCA1/2 testing increased in the pilot cities and that providers in these cities perceived an impact on their practice (e.g., more questions asked about testing, more BRCA1/2 tests requested, and more tests ordered). However, in all four cities, providers often lacked knowledge to advise patients about inherited BOC and testing. These findings underscore the need for evidence-based recommendations on appropriate use of genetic tests
Susceptibility to breast cancer Cuban families and intervention strategy proposal

International Nuclear Information System (INIS)

Robaina, Martha S.; Menendez, Ibis; Valdes, Zodilina; Diaz, Milania

2009-01-01

In breast cancer, as in most cancers, mutations usually occur in somatic cells, but sometimes occur in germ cells. The carriers of these mutations germ have up to 80% risk of having the disease course of their lives and pass it on to their offspring, they are called hereditary cancers. In this work studied 50 tested history relatives of this neoplasm from consulting advice genetic hereditary breast cancer. The tree was made pedigree of the family of each test and been classified risk using the criteria of Hampel et al. Other malignancies were identified through the analysis of pedigrees and performed syndromic classification of families. It develops an algorithm for the care of breast cancer families hereditary and plotted strategies identified by risk taking that each category implies a different intervention. It recommended to continue studying the value of marking lesions subclinical and train staff to perform this technique for its widespread use in the country. (Author)
Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer.

Science.gov (United States)

Slamon, D J; Godolphin, W; Jones, L A; Holt, J A; Wong, S G; Keith, D E; Levin, W J; Stuart, S G; Udove, J; Ullrich, A

1989-05-12

Carcinoma of the breast and ovary account for one-third of all cancers occurring in women and together are responsible for approximately one-quarter of cancer-related deaths in females. The HER-2/neu proto-oncogene is amplified in 25 to 30 percent of human primary breast cancers and this alteration is associated with disease behavior. In this report, several similarities were found in the biology of HER-2/neu in breast and ovarian cancer, including a similar incidence of amplification, a direct correlation between amplification and over-expression, evidence of tumors in which overexpression occurs without amplification, and the association between gene alteration and clinical outcome. A comprehensive study of the gene and its products (RNA and protein) was simultaneously performed on a large number of both tumor types. This analysis identified several potential shortcomings of the various methods used to evaluate HER-2/neu in these diseases (Southern, Northern, and Western blots, and immunohistochemistry) and provided information regarding considerations that should be addressed when studying a gene or gene product in human tissue. The data presented further support the concept that the HER-2/neu gene may be involved in the pathogenesis of some human cancers.
Psychosocial factors and uptake of risk-reducing salpingo-oophorectomy in women at high risk for ovarian cancer.

Science.gov (United States)

Meiser, Bettina; Price, Melanie A; Butow, Phyllis N; Karatas, Janan; Wilson, Judy; Heiniger, Louise; Baylock, Brandi; Charles, Margaret; McLachlan, Sue-Anne; Phillips, Kelly-Anne

2013-03-01

Bilateral risk-reducing salpingo-oophorectomy (RRSO) has been shown to significantly reduce the risk of ovarian cancer. This study assessed factors predicting uptake of RRSO. Women participating in a large multiple-case breast cancer family cohort study who were at increased risk for ovarian and fallopian tube cancer (i.e. BRCA1 or BRCA2 mutation carrier or family history including at least one first- or second-degree relative with ovarian or fallopian tube cancer), with no personal history of cancer and with at least one ovary in situ at cohort enrolment, were eligible for this study. Women who knew they did not carry the BRCA1 or BRCA2 mutation segregating in their family (true negatives) were excluded. Sociodemographic, biological and psychosocial factors, including cancer-specific anxiety, perceived ovarian cancer risk, optimism and social support, were assessed using self-administered questionnaires and interviews at cohort enrolment. RRSO uptake was self-reported every three years during systematic follow-up. Of 2,859 women, 571 were eligible. Mean age was 43.3 years; 62 women (10.9 %) had RRSO a median of two years after cohort entry. Factors predicting RRSO were: being parous (OR 3.3, p = 0.015); knowing one's mutation positive status (OR 2.9, p cancer (OR 2.5, p = 0.013). Psychological variables measured at cohort entry were not associated with RRSO. These results suggest that women at high risk for ovarian cancer make decisions about RRSO based on risk and individual socio-demographic characteristics, rather than in response to psychological factors such as anxiety.
Consortium analysis of 7 candidate SNPs for ovarian cancer

DEFF Research Database (Denmark)

Ramus, S.J.; Vierkant, R.A.; Johnatty, S.E.

2008-01-01

The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H...... (rs144848) in BRCA2, rs2854344 in intron 17 of RB1, rs2811712 5' flanking CDKN2A, rs523349 in the 3' UTR of SRD5A2, D302H (rs1045485) in CASP8 and L10P (rs1982073) in TGFB1. Fourteen studies genotyped 4,624 invasive epithelial ovarian cancer cases and 8,113 controls of white non-Hispanic origin...... was suggestive although no longer statistically significant (ordinal OR 0.92, 95% CI 0.79-1.06). This SNP has also been shown to have an association with decreased risk in breast cancer. There was a suggestion of an association for AURKA, when one study that caused significant study heterogeneity was excluded...
Randomized trial of adjuvant ovarian suppression in 926 premenopausal patients with early breast cancer treated with adjuvant chemotherapy.

Science.gov (United States)

Arriagada, R; Lê, M G; Spielmann, M; Mauriac, L; Bonneterre, J; Namer, M; Delozier, T; Hill, C; Tursz, T

2005-03-01

The aim of this multicenter trial was to evaluate the role of ovarian suppression in patients with early breast cancer previously treated with local surgery and adjuvant chemotherapy. Nine hundred and twenty-six premenopausal patients with completely resected breast cancer and either axillary node involvement or histological grade 2 or 3 tumors were randomized after surgery to adjuvant chemotherapy alone (control arm) or adjuvant chemotherapy plus ovarian suppression (ovarian suppression arm). Ovarian suppression was obtained by either radiation-induced ovarian ablation or triptorelin for 3 years. The analyses were performed with Cox models stratified by center. Median follow-up was 9.5 years. Mean age was 43 years. Ninety per cent of patients had histologically proven positive axillary nodes, 63% positive hormonal receptors and 77% had received an anthracycline-based chemotherapy regimen. Ovarian suppression was by radiation-induced ovarian ablation (45% of patients) or with triptorelin (48%). At the time of randomization, all patients had regular menses or their follicle-stimulating hormone and estradiol levels indicated a premenopausal status. The 10-year disease-free survival rates were 49% [95% confidence interval (CI) 44% to 54%] in both arms (P = 0.51). The 10-year overall survival rates were 66% (95% CI 61% to 70%) for the ovarian suppression arm and 68% (95% CI 63% to 73%) for the control arm (P = 0.19). There were no variations in the treatment effect according to age, hormonal receptor status or ovarian suppression modality. However, in patients suppression significantly decreased the risk of recurrence (P = 0.01). The results of this trial, after at least 10 years of follow-up, do not favor the use of ovarian suppression after adjuvant chemotherapy. The potential beneficial effect in younger women with hormono-dependent tumors should be further assessed.
Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

DEFF Research Database (Denmark)

Lawrenson, Kate; Kar, Siddhartha; McCue, Karen

2016-01-01

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10(-20)), ER-n...
Family involvement for breast cancer decision making among Chinese-American women.

Science.gov (United States)

Lee, Shiuyu Katie C; Knobf, M Tish

2016-12-01

To describe family involvement in decision making for primary treatment in Chinese-American women with early-stage breast cancer. Qualitative data were collected in 2003 from semi-structured questions in interviews with a sample of Chinese-American (ChA) women with breast cancer, who were recruited from the metropolitan New York area. Responses to the questions were written in Chinese immediately during the interview and read back to the subject for accuracy and validation. Content analysis was used to inductively code and analyze the data to generate themes. The participants consisted of 123 ChA women with early stage breast cancer with a mean age of 48.7 years (±9.3) and who had lived in the United States a median of 13.6 years. Support and Caring was the major theme that described family involvement in the breast cancer decision-making process. Gathering Information, Being There, Navigating the Health Care System, Maintaining Family Life and Making the Decision described the aspects of family support in the process. The majority of women described the treatment decision making as a collaborative supportive process with the family, but limited English fluency, strong opinions, lack of a shared perspective, distant living proximity and competing work responsibilities of family members were stressful for the women and perceived as non-supportive. Family involvement in health care decision making is culturally embedded in Asian populations. Culturally sensitive patient and family consultation strategies are needed to assist informed treatment decision making in Chinese-American women diagnosed with breast cancer. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
Familial Breast and Bowel Cancer: Does It Exist?

Directory of Open Access Journals (Sweden)

Scott Rodney J

2004-02-01

Full Text Available Abstract There is much debate in the literature about familial predispositions to breast and bowel cancers yet little evidence is forthcoming to suggest that there are susceptibility genes that can account for such kindreds. Within the context of known susceptibility genes the most controversial syndrome is hereditary non-polyposis colorectal cancer (HNPCC. In HNPCC, breast cancers do occur yet their incidence overall is no different to that of the general population yet when studied at the molecular level these tumours often display DNA microsatellite instability suggesting that they do indeed belong to this genetic entity. In this review we examine the relationship between breast and bowel cancer and suggest a possible explanation for the diverse points of view described in the literature.
Candidate genetic modifiers for breast and ovarian cancer risk inBRCA1andBRCA2 mutation carriers

NARCIS (Netherlands)

P. Peterlongo (Paolo); J. Chang-Claude (Jenny); K.B. Moysich (Kirsten); A. Rudolph (Anja); R.K. Schmutzler (Rita); J. Simard (Jacques); P. Soucy (Penny); R. Eeles (Rosalind); D.F. Easton (Douglas); U. Hamann (Ute); S. Wilkening (Stefan); B. Chen (Bowang); M.A. Rookus (Matti); M.K. Schmidt (Marjanka); F.H. Van Der Baan (Frederieke H.); A.B. Spurdle (Amanda); L.C. Walker (Logan); F. Lose (Felicity); A.-T. Maia (Ana-Teresa); M. Montagna (Marco); L. Matricardi (Laura); J. Lubinski (Jan); A. Jakubowska (Anna); E.B.G. Garcia; O.I. Olopade (Olofunmilayo); R.L. Nussbaum (Robert L.); K.L. Nathanson (Katherine); S.M. Domchek (Susan); R. Rebbeck (Timothy); B.K. Arun (Banu); B.Y. Karlan (Beth); S. Orsulic (Sandra); K.J. Lester (Kathryn); W.K. Chung (Wendy K.); A. Miron (Alexander); M.C. Southey (Melissa); D. Goldgar (David); S.S. Buys (Saundra); R. Janavicius (Ramunas); C.M. Dorfling (Cecilia); E.J. van Rensburg (Elizabeth); Y.C. Ding (Yuan Chun); S.L. Neuhausen (Susan); T.V.O. Hansen (Thomas); A.-M. Gerdes (Anne-Marie); B. Ejlertsen (Bent); L. Jønson (Lars); A. Osorio (Ana); C. Martínez-Bouzas (Cristina); J. Benítez (Javier); E.E. Conway (Edye E.); K.R. Blazer (Kathleen R.); J.N. Weitzel (Jeffrey); S. Manoukian (Siranoush); B. Peissel (Bernard); D. Zaffaroni (Daniela); G. Scuvera (Giulietta); M. Barile (Monica); F. Ficarazzi (Filomena); F. Mariette (F.); S. Fortuzzi (S.); A. Viel (Alessandra); G. Giannini (Giuseppe); L. Papi (Laura); A. Martayan (Aline); M.G. Tibiletti (Maria Grazia); P. Radice (Paolo); A. Vratimos (Athanassios); F. Fostira (Florentia); J. Garber (Judy); A. Donaldson (Alan); C. Brewer (Carole); C. Foo (Claire); D.G. Evans (Gareth); D. Frost (Debra); D. Eccles (Diana); A. Brady (A.); J. Cook (Jackie); M. Tischkowitz (Marc); L. Adlard; J. Barwell (Julian); L.J. Walker (Lisa); L. Izatt (Louise); L. Side (Lucy); M.J. Kennedy (John); M.T. Rogers (Mark); M.E. Porteous (Mary); P.J. Morrison (Patrick); R. Platte (Radka); R. Davidson (Rosemarie); S. Hodgson (Shirley); S.D. Ellis (Steve); T. Cole (Trevor); A.K. Godwin (Andrew); K.B.M. Claes (Kathleen B.M.); T. Van Maerken (Tom); A. Meindl (Alfons); P.A. Gehrig (Paola A.); C. Sutter (Christian); C. Engel (Christoph); D. Niederacher (Dieter); D. Steinemann (Doris); H. Plendl (Hansjoerg); K. Kast (Karin); K. Rhiem (Kerstin); N. Ditsch (Nina); N. Arnold (Norbert); R. Varon-Mateeva (Raymonda); B. Wapenschmidt (Barbara); S. Wang-Gohrke (Shan); B. Bressac-de Paillerets (Brigitte); B. Buecher (Bruno); C.D. Delnatte (Capucine); C. Houdayer (Claude); D. Stoppa-Lyonnet (Dominique); F. Damiola (Francesca); I. Coupier (Isabelle); L. Barjhoux (Laure); L. Vénat-Bouvet (Laurence); L. Golmard (Lisa); N. Boutry-Kryza (N.); O. Sinilnikova (Olga); O. Caron (Olivier); P. Pujol (Pascal); S. Mazoyer (Sylvie); M. Belotti (Muriel); M. Piedmonte (Marion); M.L. Friedlander (Michael L.); G. Rodriguez (Gustavo); L.J. Copeland (Larry J.); M. de La Hoya (Miguel); P. Perez-Segura (Pedro); H. Nevanlinna (Heli); K. Aittomäki (Kristiina); T.A.M. van Os (Theo); E.J. Meijers-Heijboer (Hanne); A.H. van der Hout (Annemarie); M.P. Vreeswijk (Maaike); N. Hoogerbrugqe (N.); M.G.E.M. Ausems (Margreet); H.C. van Doorn (Helena); J.M. Collée (Margriet); E. Olah; O. Díez (Orland); I. Blanco (Ignacio); C. Lazaro (Conxi); J. Brunet (Joan); L. Feliubadaló (L.); C. Cybulski (Cezary); J. Gronwald (Jacek); K. Durda (Katarzyna); K. Jaworska-Bieniek (Katarzyna); G. Sukiennicki (Grzegorz); A. Arason (Adalgeir); J. Chiquette (Jocelyne); P.J. Teixeira; C. Olswold (Curtis); F.J. Couch (Fergus); N.M. Lindor (Noralane); X. Wang (X.); C. Szabo (Csilla); K. Offit (Kenneth); M. Corines (Marina); L. Jacobs (Lauren); M.E. Robson (Mark E.); L. Zhang (Lingling); V. Joseph (Vijai); A. Berger (Andreas); C.F. Singer (Christian); C. Rappaport (Christine); D.G. Kaulich (Daphne Gschwantler); G. Pfeiler (Georg); M.-K. Tea; C. Phelan (Catherine); M.H. Greene (Mark); P.L. Mai (Phuong); G. Rennert (Gad); A.-M. Mulligan (Anna-Marie); G. Glendon (Gord); S. Tchatchou (Sandrine); I.L. Andrulis (Irene); A.E. Toland (Amanda); A. Bojesen (Anders); I.S. Pedersen (Inge Sokilde); M. Thomassen (Mads); U.B. Jensen; Y. Laitman (Yael); J. Rantala (Johanna); A. von Wachenfeldt (Anna); H. Ehrencrona (Hans); M.S. Askmalm (Marie); Å. Borg (Åke); K.B. Kuchenbaecker (Karoline); L. McGuffog (Lesley); D. Barrowdale (Daniel); S. Healey (Sue); A. Lee (Andrew); P.D.P. Pharoah (Paul D.P.); G. Chenevix-Trench (Georgia); A.C. Antoniou (Antonis C.); E. Friedman (Eitan)

2015-01-01

textabstractBackground: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying
Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers

DEFF Research Database (Denmark)

Peterlongo, Paolo; Chang-Claude, Jenny; Moysich, Kirsten B

2015-01-01

BACKGROUND: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In ...
Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers

NARCIS (Netherlands)

Peterlongo, P.; Chang-Claude, J.; Moysich, K.B.; Rudolph, A.; Schmutzler, R.K.; Simard, J.; Soucy, P.; Eeles, R.A.; Easton, D.F.; Hamann, U.; Wilkening, S.; Chen, B.; Rookus, M.A.; Schmidt, M.K.; Baan, F.H. van der; Spurdle, A.B.; Walker, L.C.; Lose, F.; Maia, A.T.; Montagna, M.; Matricardi, L.; Lubinski, J.; Jakubowska, A.; Garcia, E.B.; Olopade, O.I.; Nussbaum, R.L.; Nathanson, K.L.; Domchek, S.M.; Rebbeck, T.R.; Arun, B.K.; Karlan, B.Y.; Orsulic, S.; Lester, J.; Chung, W.K.; Miron, A.; Southey, M.C.; Goldgar, D.E.; Buys, S.S.; Janavicius, R.; Dorfling, C.M.; Rensburg, E.J. van; Ding, Y.C.; Neuhausen, S.L.; Hansen, T.V.; Gerdes, A.M.; Ejlertsen, B.; Jonson, L.; Osorio, A.; Martinez-Bouzas, C.; Benitez, J.; Conway, E.E.; Blazer, K.R.; Weitzel, J.N.; Manoukian, S.; Peissel, B.; Zaffaroni, D.; Scuvera, G.; Barile, M.; Ficarazzi, F.; Mariette, F.; Fortuzzi, S.; Viel, A.; Giannini, G.; Papi, L.; Martayan, A.; Tibiletti, M.G.; Radice, P.; Vratimos, A.; Fostira, F.; Garber, J.E.; Donaldson, A.; Brewer, C.; Foo, C.; Evans, D.G.; Frost, D.; Eccles, D.; Brady, A.; Cook, J.; Tischkowitz, M.; Adlard, J.; Barwell, J.; Izatt, L.; Side, L.E.; Kennedy, M.J.; Rogers, M.T.; Porteous, M.E.; Morrison, P.J.; Platte, R.; Davidson, R.; Hodgson, S.V.; Ellis, S.; Cole, T.; Godwin, A.K.; Claes, K.; Maerken, T. Van; Meindl, A.; Gehrig, A.; Sutter, C.; Engel, C.; Hoogerbrugge, N.; et al.,

2015-01-01

BACKGROUND: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In
Mumps Parotitis and Ovarian Cancer: Modern Significance of an Historic Association

Science.gov (United States)

2009-10-01

ligation or a breast mastitis , found to protect against ovarian cancer, might do so by causing overexpression of the hypoglycosylated form of MUC1...negative plates were incubated overnight and washed three times with PBS before addition of 100 μl of 2.5% bovine serum albumin in PBS. Serially...a breast mastitis which have been shown to protect against ovarian cancer(10), might confer protection because of injury to the tissue causing
Familial risks and estrogen receptor-positive breast cancer in Hong Kong Chinese women.

Science.gov (United States)

Tse, Lap Ah; Li, Mengjie; Chan, Wing-cheong; Kwok, Chi-hei; Leung, Siu-lan; Wu, Cherry; Yu, Ignatius Tak-sun; Yu, Wai-cho; Lao, Xiangqian; Wang, Xiaorong; Wong, Carmen Ka-man; Lee, Priscilla Ming-yi; Wang, Feng; Yang, Xiaohong Rose

2015-01-01

The role of family history to the risk of breast cancer was analyzed by incorporating menopausal status in Hong Kong Chinese women, with a particular respect to the estrogen receptor-positive (ER+) type. Seven hundred and forty seven breast cancer incident cases and 781 hospital controls who had completed information on family cancer history in first-degree relatives (nature father, mother, and siblings) were recruited. Odds ratio for breast cancer were calculated by unconditional multiple logistic regression, stratified by menopausal status (a surrogate of endogenous female sex hormone level and age) and type of relative affected with the disease. Further subgroup analysis by tumor type according to ER status was investigated. Altogether 52 (6.96%) breast cancer cases and 23 (2.95%) controls was found that the patients' one or more first-degree relatives had a history of breast cancer, showing an adjusted odds ratio (OR) of 2.41 (95%CI: 1.45-4.02). An excess risk of breast cancer was restricted to the ER+ tumor (OR = 2.43, 95% CI: 1.38-4.28), with a relatively higher risk associated with an affected mother (OR = 3.97, 95%CI: 1.46-10.79) than an affected sister (OR = 2.06, 95%CI: 1.07-3.97), while the relative risk was more prominent in the subgroup of pre-menopausal women. Compared with the breast cancer overall, the familial risks to the ER+ tumor increased progressively with the number of affected first-degree relatives. This study provides new insights on a relationship between family breast cancer history, menopausal status, and the ER+ breast cancer. A separate risk prediction model for ER+ tumor in Asian population is desired.
Age and Geographical Distribution in Families with BRCA1/BRCA2 Mutations in the Slovak Republic

Directory of Open Access Journals (Sweden)

Ciernikova Sona

2006-12-01

Full Text Available Abstract Molecular diagnostics of hereditary breast and/or ovarian cancer is mainly based on detection of BRCA1 and BRCA2 germline mutations in suspected families. The aim of the study was to determine the frequency, age and geographical distribution in 130 Slovak hereditary breast and ovarian cancer (HBOC families diagnosed within the years 2000-2004. Mutation screening was performed by single-strand conformation polymorphism (SSCP, heteroduplex analysis (HDA and sequencing of PCR products showing an abnormal migration pattern. Twenty of 130 (15.6% HBOC suspected families were found to carry mutations in BRCA1 or BRCA2 genes. The glossary data from the National Cancer Registry of Slovakia (NCRS were compared with the results from HBOC suspected kindreds. Age distribution of breast cancer onset in our study group showed the highest proportion of onset in HBC families within the 5th decade of life, while NCRS reports at least a ten year later onset. These findings confirmed that cases of breast cancer under 50 years of age can be used as one of the principal criteria to assign a family as a hereditary breast and/or ovarian cancer kindred. In contrast with unselected ovarian cancer cases, about 75% of all HOC index cases were diagnosed between 40 and 49 years of age. To study the geographical distribution of hereditary breast and/or ovarian cancer, Slovakia was divided into three parts. The distribution of HBOC suspected families approximately follows this division, with an increasing number in the western area of the country.
Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

DEFF Research Database (Denmark)

Bojesen, Stig Egil; Pooley, Karen A; Johnatty, Sharon E

2013-01-01

TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ∼480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases...
Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers

NARCIS (Netherlands)

Peterlongo, Paolo; Chang-Claude, Jenny; Moysich, Kirsten B.; Rudolph, Anja; Schmutzler, Rita K.; Simard, Jacques; Soucy, Penny; Eeles, Rosalind A.; Easton, Douglas F.; Hamann, Ute; Wilkening, Stefan; Chen, Bowang; Rookus, Matti A.; Schmidt, Marjanka K.; van der Baan, Frederieke H.; Spurdle, Amanda B.; Walker, Logan C.; Lose, Felicity; Maia, Ana-Teresa; Montagna, Marco; Matricardi, Laura; Lubinski, Jan; Jakubowska, Anna; Gómez Garcia, Encarna B.; Olopade, Olufunmilayo I.; Nussbaum, Robert L.; Nathanson, Katherine L.; Domchek, Susan M.; Rebbeck, Timothy R.; Arun, Banu K.; Karlan, Beth Y.; Orsulic, Sandra; Lester, Jenny; Chung, Wendy K.; Miron, Alex; Southey, Melissa C.; Goldgar, David E.; Buys, Saundra S.; Janavicius, Ramunas; Dorfling, Cecilia M.; van Rensburg, Elizabeth J.; Ding, Yuan Chun; Neuhausen, Susan L.; Hansen, Thomas V. O.; Gerdes, Anne-Marie; Ejlertsen, Bent; Jønson, Lars; Osorio, Ana; Martínez-Bouzas, Cristina; Benitez, Javier; Conway, Edye E.; Blazer, Kathleen R.; Weitzel, Jeffrey N.; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Scuvera, Giulietta; Barile, Monica; Ficarazzi, Filomena; Mariette, Frederique; Fortuzzi, Stefano; Viel, Alessandra; Giannini, Giuseppe; Papi, Laura; Martayan, Aline; Tibiletti, Maria Grazia; Radice, Paolo; Vratimos, Athanassios; Fostira, Florentia; Garber, Judy E.; Donaldson, Alan; Brewer, Carole; Foo, Claire; Evans, D. Gareth R.; Frost, Debra; Eccles, Diana; Brady, Angela; Cook, Jackie; Tischkowitz, Marc; Adlard, Julian; Barwell, Julian; Walker, Lisa; Izatt, Louise; Side, Lucy E.; Kennedy, M. John; Rogers, Mark T.; Porteous, Mary E.; Morrison, Patrick J.; Platte, Radka; Davidson, Rosemarie; Hodgson, Shirley V.; Ellis, Steve; Cole, Trevor; Godwin, Andrew K.; Claes, Kathleen; van Maerken, Tom; Meindl, Alfons; Gehrig, Andrea; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Plendl, Hansjoerg; Kast, Karin; Rhiem, Kerstin; Ditsch, Nina; Arnold, Norbert; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Wang-Gohrke, Shan; Bressac-de Paillerets, Brigitte; Buecher, Bruno; Delnatte, Capucine; Houdayer, Claude; Stoppa-Lyonnet, Dominique; Damiola, Francesca; Coupier, Isabelle; Barjhoux, Laure; Venat-Bouvet, Laurence; Golmard, Lisa; Boutry-Kryza, Nadia; Sinilnikova, Olga M.; Caron, Olivier; Pujol, Pascal; Mazoyer, Sylvie; Belotti, Muriel; Piedmonte, Marion; Friedlander, Michael L.; Rodriguez, Gustavo C.; Copeland, Larry J.; de la Hoya, Miguel; Segura, Pedro Perez; Nevanlinna, Heli; Aittomäki, Kristiina; van Os, Theo A. M.; Meijers-Heijboer, Hanne E. J.; van der Hout, Annemarie H.; Vreeswijk, Maaike P. G.; Hoogerbrugge, Nicoline; Ausems, Margreet G. E. M.; van Doorn, Helena C.; Collée, J. Margriet; Olah, Edith; Diez, Orland; Blanco, Ignacio; Lazaro, Conxi; Brunet, Joan; Feliubadalo, Lidia; Cybulski, Cezary; Gronwald, Jacek; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Sukiennicki, Grzegorz; Arason, Adalgeir; Chiquette, Jocelyne; Teixeira, Manuel R.; Olswold, Curtis; Couch, Fergus J.; Lindor, Noralane M.; Wang, Xianshu; Szabo, Csilla I.; Offit, Kenneth; Corines, Marina; Jacobs, Lauren; Robson, Mark E.; Zhang, Liying; Joseph, Vijai; Berger, Andreas; Singer, Christian F.; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; tea, Muy-Kheng M.; Phelan, Catherine M.; Greene, Mark H.; Mai, Phuong L.; Rennert, Gad; Mulligan, Anna Marie; Glendon, Gord; Tchatchou, Sandrine; Andrulis, Irene L.; Toland, Amanda Ewart; Bojesen, Anders; Pedersen, Inge Sokilde; Thomassen, Mads; Jensen, Uffe Birk; Laitman, Yael; Rantala, Johanna; von Wachenfeldt, Anna; Ehrencrona, Hans; Askmalm, Marie Stenmark; Borg, Åke; Kuchenbaecker, Karoline B.; McGuffog, Lesley; Barrowdale, Daniel; Healey, Sue; Lee, Andrew; Pharoah, Paul D. P.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Friedman, Eitan

2015-01-01

BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we
BRCA Mutation Frequency and Patterns of Treatment Response in BRCA Mutation–Positive Women With Ovarian Cancer: A Report From the Australian Ovarian Cancer Study Group

Science.gov (United States)

Alsop, Kathryn; Fereday, Sian; Meldrum, Cliff; deFazio, Anna; Emmanuel, Catherine; George, Joshy; Dobrovic, Alexander; Birrer, Michael J.; Webb, Penelope M.; Stewart, Colin; Friedlander, Michael; Fox, Stephen; Bowtell, David; Mitchell, Gillian

2012-01-01

Purpose The frequency of BRCA1 and BRCA2 germ-line mutations in women with ovarian cancer is unclear; reports vary from 3% to 27%. The impact of germ-line mutation on response requires further investigation to understand its impact on treatment planning and clinical trial design. Patients and Methods Women with nonmucinous ovarian carcinoma (n = 1,001) enrolled onto a population-based, case-control study were screened for point mutations and large deletions in both genes. Survival outcomes and responses to multiple lines of chemotherapy were assessed. Results Germ-line mutations were found in 14.1% of patients overall, including 16.6% of serous cancer patients (high-grade serous, 22.6%); 44% had no reported family history of breast or ovarian cancer. Patients carrying germ-line mutations had improved rates of progression-free and overall survival. In the relapse setting, patients carrying mutations more frequently responded to both platin- and nonplatin-based regimens than mutation-negative patients, even in patients with early relapse after primary treatment. Mutation-negative patients who responded to multiple cycles of platin-based treatment were more likely to carry somatic BRCA1/2 mutations. Conclusion BRCA mutation status has a major influence on survival in ovarian cancer patients and should be an additional stratification factor in clinical trials. Treatment outcomes in BRCA1/2 carriers challenge conventional definitions of platin resistance, and mutation status may be able to contribute to decision making and systemic therapy selection in the relapse setting. Our data, together with the advent of poly(ADP-ribose) polymerase inhibitor trials, supports the recommendation that germ-line BRCA1/2 testing should be offered to all women diagnosed with nonmucinous, ovarian carcinoma, regardless of family history. PMID:22711857

Parity and the risk of breast and ovarian cancer in and mutation carriers

OpenAIRE

Milne , Roger L.; Osorio , Ana; Ramón Y Cajal , Teresa; Baiget , Montserrat; Lasa , Adriana; Diaz-Rubio , Eduardo; Hoya , Miguel; Caldés , Trinidad; Teulé , Alex; Lázaro , Conxi; Blanco , Ignacio; Balmaña , Judith; Sánchez-Ollé , Gessamí; Vega , Ana; Blanco , Ana

2009-01-01

Abstract Environmental or lifestyle factors are likely to explain part of the heterogeneity in breast and ovarian cancer risk among BRCA1 and BRCA2 mutation carriers. We assessed parity as a risk modifier in 515 and 503 Spanish female carriers of mutations in BRCA1 and BRCA2, respectively. Hazard ratios (HR) and their corresponding 95% confidence intervals (CI) were estimated using weighted Cox proportional hazards regression, adjusted for year of birth and study centre. The result...
Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

NARCIS (Netherlands)

Bojesen, Stig E.; Pooley, Karen A.; Johnatty, Sharon E.; Beesley, Jonathan; Michailidou, Kyriaki; Tyrer, Jonathan P.; Edwards, Stacey L.; Pickett, Hilda A.; Shen, Howard C.; Smart, Chanel E.; Hillman, Kristine M.; Mai, Phuong L.; Lawrenson, Kate; Stutz, Michael D.; Lu, Yi; Karevan, Rod; Woods, Nicholas; Johnston, Rebecca L.; French, Juliet D.; Chen, Xiaoqing; Weischer, Maren; Nielsen, Sune F.; Maranian, Melanie J.; Ghoussaini, Maya; Ahmed, Shahana; Baynes, Caroline; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Healey, Sue; Lush, Michael; Tessier, Daniel C.; Vincent, Daniel; Bacot, Françis; Vergote, Ignace; Lambrechts, Sandrina; Despierre, Evelyn; Risch, Harvey A.; González-Neira, Anna; Rossing, Mary Anne; Pita, Guillermo; Doherty, Jennifer A.; Alvarez, Nuria; Larson, Melissa C.; Fridley, Brooke L.; Schoof, Nils; Chang-Claude, Jenny; Cicek, Mine S.; Peto, Julian; Kalli, Kimberly R.; Broeks, Annegien; Armasu, Sebastian M.; Schmidt, Marjanka K.; Braaf, Linde M.; Winterhoff, Boris; Nevanlinna, Heli; Konecny, Gottfried E.; Lambrechts, Diether; Rogmann, Lisa; Guénel, Pascal; Teoman, Attila; Milne, Roger L.; Garcia, Joaquin J.; Cox, Angela; Shridhar, Vijayalakshmi; Burwinkel, Barbara; Marme, Frederik; Hein, Rebecca; Sawyer, Elinor J.; Haiman, Christopher A.; Wang-Gohrke, Shan; Andrulis, Irene L.; Moysich, Kirsten B.; Hopper, John L.; Odunsi, Kunle; Lindblom, Annika; Giles, Graham G.; Brenner, Hermann; Simard, Jacques; Lurie, Galina; Fasching, Peter A.; Carney, Michael E.; Radice, Paolo; Wilkens, Lynne R.; Swerdlow, Anthony; Goodman, Marc T.; Brauch, Hiltrud; Garcia-Closas, Montserrat; Hillemanns, Peter; Winqvist, Robert; Dürst, Matthias; Devilee, Peter; Runnebaum, Ingo; Jakubowska, Anna; Lubinski, Jan; Mannermaa, Arto; Butzow, Ralf; Bogdanova, Natalia V.; Dörk, Thilo; Pelttari, Liisa M.; Zheng, Wei; Leminen, Arto; Anton-Culver, Hoda; Bunker, Clareann H.; Kristensen, Vessela; Ness, Roberta B.; Muir, Kenneth; Edwards, Robert; Meindl, Alfons; Heitz, Florian; Matsuo, Keitaro; du Bois, Andreas; Wu, Anna H.; Harter, Philipp; teo, Soo-Hwang; Schwaab, Ira; Shu, Xiao-Ou; Blot, William; Hosono, Satoyo; Kang, Daehee; Nakanishi, Toru; Hartman, Mikael; Yatabe, Yasushi; Hamann, Ute; Karlan, Beth Y.; Sangrajrang, Suleeporn; Kjaer, Susanne Krüger; Gaborieau, Valerie; Jensen, Allan; Eccles, Diana; Høgdall, Estrid; Shen, Chen-Yang; Brown, Judith; Woo, Yin Ling; Shah, Mitul; Azmi, Mat Adenan Noor; Luben, Robert; Omar, Siti Zawiah; Czene, Kamila; Vierkant, Robert A.; Nordestgaard, Børge G.; Flyger, Henrik; Vachon, Celine; Olson, Janet E.; Wang, Xianshu; Levine, Douglas A.; Rudolph, Anja; Weber, Rachel Palmieri; Flesch-Janys, Dieter; Iversen, Edwin; Nickels, Stefan; Schildkraut, Joellen M.; Silva, Isabel Dos Santos; Cramer, Daniel W.; Gibson, Lorna; Terry, Kathryn L.; Fletcher, Olivia; Vitonis, Allison F.; van der Schoot, C. Ellen; Poole, Elizabeth M.; Hogervorst, Frans B. L.; Tworoger, Shelley S.; Liu, Jianjun; Bandera, Elisa V.; Li, Jingmei; Olson, Sara H.; Humphreys, Keith; Orlow, Irene; Blomqvist, Carl; Rodriguez-Rodriguez, Lorna; Aittomäki, Kristiina; Salvesen, Helga B.; Muranen, Taru A.; Wik, Elisabeth; Brouwers, Barbara; Krakstad, Camilla; Wauters, Els; Halle, Mari K.; Wildiers, Hans; Kiemeney, Lambertus A.; Mulot, Claire; Aben, Katja K.; Laurent-Puig, Pierre; Altena, Anne Mvan; Truong, Thérèse; Massuger, Leon F. A. G.; Benitez, Javier; Pejovic, Tanja; Perez, Jose Ignacio Arias; Hoatlin, Maureen; Zamora, M. Pilar; Cook, Linda S.; Balasubramanian, Sabapathy P.; Kelemen, Linda E.; Schneeweiss, Andreas; Le, Nhu D.; Sohn, Christof; Brooks-Wilson, Angela; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Cybulski, Cezary; Henderson, Brian E.; Menkiszak, Janusz; Schumacher, Fredrick; Wentzensen, Nicolas; Le Marchand, Loic; Yang, Hannah P.; Mulligan, Anna Marie; Glendon, Gord; Engelholm, Svend Aage; Knight, Julia A.; Høgdall, Claus K.; Apicella, Carmel; Gore, Martin; Tsimiklis, Helen; Song, Honglin; Southey, Melissa C.; Jager, Agnes; den Ouweland, Ans M. Wvan; Brown, Robert; Martens, John W. M.; Flanagan, James M.; Kriege, Mieke; Paul, James; Margolin, Sara; Siddiqui, Nadeem; Severi, Gianluca; Whittemore, Alice S.; Baglietto, Laura; McGuire, Valerie; Stegmaier, Christa; Sieh, Weiva; Müller, Heiko; Arndt, Volker; Labrèche, France; Gao, Yu-Tang; Goldberg, Mark S.; Yang, Gong; Dumont, Martine; McLaughlin, John R.; Hartmann, Arndt; Ekici, Arif B.; Beckmann, Matthias W.; Phelan, Catherine M.; Lux, Michael P.; Permuth-Wey, Jenny; Peissel, Bernard; Sellers, Thomas A.; Ficarazzi, Filomena; Barile, Monica; Ziogas, Argyrios; Ashworth, Alan; Gentry-Maharaj, Aleksandra; Jones, Michael; Ramus, Susan J.; Orr, Nick; Menon, Usha; Pearce, Celeste L.; Brüning, Thomas; Pike, Malcolm C.; Ko, Yon-Dschun; Lissowska, Jolanta; Figueroa, Jonine; Kupryjanczyk, Jolanta; Chanock, Stephen J.; Dansonka-Mieszkowska, Agnieszka; Jukkola-Vuorinen, Arja; Rzepecka, Iwona K.; Pylkäs, Katri; Bidzinski, Mariusz; Kauppila, Saila; Hollestelle, Antoinette; Seynaeve, Caroline; Tollenaar, Rob A. E. M.; Durda, Katarzyna; Jaworska, Katarzyna; Hartikainen, Jaana M.; Kosma, Veli-Matti; Kataja, Vesa; Antonenkova, Natalia N.; Long, Jirong; Shrubsole, Martha; Deming-Halverson, Sandra; Lophatananon, Artitaya; Siriwanarangsan, Pornthep; Stewart-Brown, Sarah; Ditsch, Nina; Lichtner, Peter; Schmutzler, Rita K.; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Tseng, Chiu-Chen; Stram, Daniel O.; van den Berg, David; Yip, Cheng Har; Ikram, M. Kamran; teh, Yew-Ching; Cai, Hui; Lu, Wei; Signorello, Lisa B.; Cai, Qiuyin; Noh, Dong-Young; Yoo, Keun-Young; Miao, Hui; Iau, Philip Tsau-Choong; teo, Yik Ying; McKay, James; Shapiro, Charles; Ademuyiwa, Foluso; Fountzilas, George; Hsiung, Chia-Ni; Yu, Jyh-Cherng; Hou, Ming-Feng; Healey, Catherine S.; Luccarini, Craig; Peock, Susan; Stoppa-Lyonnet, Dominique; Peterlongo, Paolo; Rebbeck, Timothy R.; Piedmonte, Marion; Singer, Christian F.; Friedman, Eitan; Thomassen, Mads; Offit, Kenneth; Hansen, Thomas V. O.; Neuhausen, Susan L.; Szabo, Csilla I.; Blanco, Ignacio; Garber, Judy; Narod, Steven A.; Weitzel, Jeffrey N.; Montagna, Marco; Olah, Edith; Godwin, Andrew K.; Yannoukakos, Drakoulis; Goldgar, David E.; Caldes, Trinidad; Imyanitov, Evgeny N.; Tihomirova, Laima; Arun, Banu K.; Campbell, Ian; Mensenkamp, Arjen R.; van Asperen, Christi J.; van Roozendaal, Kees E. P.; Meijers-Heijboer, Hanne; Collée, J. Margriet; Oosterwijk, Jan C.; Hooning, Maartje J.; Rookus, Matti A.; van der Luijt, Rob B.; Os, Theo A. Mvan; Evans, D. Gareth; Frost, Debra; Fineberg, Elena; Barwell, Julian; Walker, Lisa; Kennedy, M. John; Platte, Radka; Davidson, Rosemarie; Ellis, Steve D.; Cole, Trevor; Bressac-de Paillerets, Brigitte; Buecher, Bruno; Damiola, Francesca; Faivre, Laurence; Frenay, Marc; Sinilnikova, Olga M.; Caron, Olivier; Giraud, Sophie; Mazoyer, Sylvie; Bonadona, Valérie; Caux-Moncoutier, Virginie; Toloczko-Grabarek, Aleksandra; Gronwald, Jacek; Byrski, Tomasz; Spurdle, Amanda B.; Bonanni, Bernardo; Zaffaroni, Daniela; Giannini, Giuseppe; Bernard, Loris; Dolcetti, Riccardo; Manoukian, Siranoush; Arnold, Norbert; Engel, Christoph; Deissler, Helmut; Rhiem, Kerstin; Niederacher, Dieter; Plendl, Hansjoerg; Sutter, Christian; Wappenschmidt, Barbara; Borg, Ake; Melin, Beatrice; Rantala, Johanna; Soller, Maria; Nathanson, Katherine L.; Domchek, Susan M.; Rodriguez, Gustavo C.; Salani, Ritu; Kaulich, Daphne Gschwantler; tea, Muy-Kheng; Paluch, Shani Shimon; Laitman, Yael; Skytte, Anne-Bine; Kruse, Torben A.; Jensen, Uffe Birk; Robson, Mark; Gerdes, Anne-Marie; Ejlertsen, Bent; Foretova, Lenka; Savage, Sharon A.; Lester, Jenny; Soucy, Penny; Kuchenbaecker, Karoline B.; Olswold, Curtis; Cunningham, Julie M.; Slager, Susan; Pankratz, Vernon S.; Dicks, Ed; Lakhani, Sunil R.; Couch, Fergus J.; Hall, Per; Monteiro, Alvaro N. A.; Gayther, Simon A.; Pharoah, Paul D. P.; Reddel, Roger R.; Goode, Ellen L.; Greene, Mark H.; Easton, Douglas F.; Berchuck, Andrew; Antoniou, Antonis C.; Chenevix-Trench, Georgia; Dunning, Alison M.

2013-01-01

TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ∼480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and
Hereditary breast and ovarian cancer and reproduction: an observational study on the suitability of preimplantation genetic diagnosis for both asymptomatic carriers and breast cancer survivors.

Science.gov (United States)

Derks-Smeets, Inge A P; de Die-Smulders, Christine E M; Mackens, Shari; van Golde, Ron; Paulussen, Aimee D; Dreesen, Jos; Tournaye, Herman; Verdyck, Pieter; Tjan-Heijnen, Vivianne C G; Meijer-Hoogeveen, Madelon; De Greve, Jacques; Geraedts, Joep; De Rycke, Martine; Bonduelle, Maryse; Verpoest, Willem M

2014-06-01

Preimplantation genetic diagnosis (PGD) is a reproductive option for BRCA1/2 mutation carriers wishing to avoid transmission of the predisposition for hereditary breast and ovarian cancer (HBOC) to their offspring. Embryos obtained by in vitro fertilisation (IVF/ICSI) are tested for the presence of the mutation. Only BRCA-negative embryos are transferred into the uterus. The suitability and outcome of PGD for HBOC are evaluated in an observational cohort study on treatments carried out in two of Western-Europe's largest PGD centres from 2006 until 2012. Male carriers, asymptomatic female carriers and breast cancer survivors were eligible. If available, PGD on embryos cryopreserved before chemotherapy was possible. Generic PGD-PCR tests were developed based on haplotyping, if necessary combined with mutation detection. 70 Couples underwent PGD for BRCA1/2. 42/71 carriers (59.2 %) were female, six (14.3 %) of whom have had breast cancer prior to PGD. In total, 145 PGD cycles were performed. 720 embryos were tested, identifying 294 (40.8 %) as BRCA-negative. Of fresh IVF/PGD cycles, 23.9 % resulted in a clinical pregnancy. Three cycles involved PGD on embryos cryopreserved before chemotherapy; two of these women delivered a healthy child. Overall, 38 children were liveborn. Two BRCA1 carriers were diagnosed with breast cancer shortly after PGD treatment, despite negative screening prior to PGD. PGD for HBOC proved to be suitable, yielding good pregnancy rates for asymptomatic carriers as well as breast cancer survivors. Because of two cases of breast cancer shortly after treatment, maternal safety of IVF(PGD) in female carriers needs further evaluation.
Familial risks and estrogen receptor-positive breast cancer in Hong Kong Chinese women.

Directory of Open Access Journals (Sweden)

Lap Ah Tse

Full Text Available The role of family history to the risk of breast cancer was analyzed by incorporating menopausal status in Hong Kong Chinese women, with a particular respect to the estrogen receptor-positive (ER+ type.Seven hundred and forty seven breast cancer incident cases and 781 hospital controls who had completed information on family cancer history in first-degree relatives (nature father, mother, and siblings were recruited. Odds ratio for breast cancer were calculated by unconditional multiple logistic regression, stratified by menopausal status (a surrogate of endogenous female sex hormone level and age and type of relative affected with the disease. Further subgroup analysis by tumor type according to ER status was investigated.Altogether 52 (6.96% breast cancer cases and 23 (2.95% controls was found that the patients' one or more first-degree relatives had a history of breast cancer, showing an adjusted odds ratio (OR of 2.41 (95%CI: 1.45-4.02. An excess risk of breast cancer was restricted to the ER+ tumor (OR = 2.43, 95% CI: 1.38-4.28, with a relatively higher risk associated with an affected mother (OR = 3.97, 95%CI: 1.46-10.79 than an affected sister (OR = 2.06, 95%CI: 1.07-3.97, while the relative risk was more prominent in the subgroup of pre-menopausal women. Compared with the breast cancer overall, the familial risks to the ER+ tumor increased progressively with the number of affected first-degree relatives.This study provides new insights on a relationship between family breast cancer history, menopausal status, and the ER+ breast cancer. A separate risk prediction model for ER+ tumor in Asian population is desired.
Common variants at the 19p13.1 and ZNF365 loci are associated with ER subtypes of breast cancer and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers

NARCIS (Netherlands)

F.J. Couch (Fergus); M.M. Gaudet (Mia); A.C. Antoniou (Antonis); S.J. Ramus (Susan); K.B. Kuchenbaecker (Karoline); P. Soucy (Penny); J. Beesley (Jonathan); X. Chen (Xiaoqing); X. Wang (Xing); T. Kircchoff (Tomas); L. McGuffog (Lesley); D. Barrowdale (Daniel); A. Lee (Andrew); S. Healey (Sue); O. Sinilnikova (Olga); I.L. Andrulis (Irene); H. Ozcelik (Hilmi); A.M. Mulligan (Anna Marie); M. Thomassen (Mads); A-M. Gerdes (Anne-Marie); U.B. Jensen; A.-B. Skytte (Anne-Bine); T.A. Kruse (Torben); M.A. Caligo (Maria); A. von Wachenfeldt (Anna); G. Barbany-Bustinza (Gisela); N. Loman (Niklas); M. Soller (Maria); H. Ehrencrona (Hans); P. Karlsson (Per); K.L. Nathanson (Katherine); R. Rebbeck (Timothy); S.M. Domchek (Susan); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska (Katarzyna); K. Durda (Katarzyna); E. Zołwocka (Elzbieta); T. Huzarski (Tomasz); T. Byrski (Tomasz); J. Gronwald (Jacek); C. Cybulski (Cezary); B. Górski (Bohdan); A. Osorio (Ana); M. Durán (Mercedes); M.I. Tejada; J. Benítez (Javier); U. Hamann (Ute); F.B.L. Hogervorst (Frans); T.A.M. van Os (Theo); F.E. van Leeuwen (Flora); E.J. Meijers-Heijboer (Hanne); J.T. Wijnen (Juul); M.J. Blok (Marinus); C.M. Kets; M.J. Hooning (Maartje); R.A. Oldenburg (Rogier); M.G.E.M. Ausems (Margreet); S. Peock (Susan); D. Frost (Debra); S.D. Ellis (Steve); R. Platte (Radka); E. Fineberg (Elena); D.G. Evans (Gareth); C. Jacobs (Chris); R. Eeles (Rosalind); J.W. Adlard (Julian); R. Davidson (Rosemarie); D. Eccles (Diana); T.J. Cole (Trevor); J. Cook (Jackie); J. Paterson (Joan); C. Brewer (Carole); F. Douglas (Fiona); S.V. Hodgson (Shirley); P.J. Morrison (Patrick); L.J. Walker (Lisa); M.E. Porteous (Mary); M.J. Kennedy (John); L. Side (Lucy); B. Bove (B.); A.K. Godwin (Andrew); D. Stoppa-Lyonnet (Dominique); M. Fassy-Colcombet (Marion); L. Castera (Laurent); F. Cornelis (Franco̧is); S. Mazoyer (Sylvie); M. Léone (Mélanie); N. Boutry-Kryza (N.); B. Bressac-de Paillerets (Brigitte); O. Caron (Olivier); P. Pujol (Pascal); I. Coupier (Isabelle); C.D. Delnatte (Capucine); L. Akloul (Linda); H. Lynch (Henry); C.L. Snyder (Carrie); S.S. Buys (Saundra); M.B. Daly (Mary); M.-B. Terry (Mary-Beth); W. Chung (Wendy); E.M. John (Esther); A. Miron (Alexander); M.C. Southey (Melissa); J.L. Hopper (John); D. Goldgar (David); C.F. Singer (Christian); C. Rappaport (Christine); M.-K. Tea; A. Fink-Retter (Anneliese); T.V.O. Hansen (Thomas); F.C. Nielsen (Finn); A. Arason (Adalgeir); J. Vijai (Joseph); S. Shah (Sonia); K. Sarrel (Kara); M. Robson (Mark); M. Piedmonte (Marion); K. Phillips (Kelly); J. Basil (Jack); W.S. Rubinstein (Wendy); J.F. Boggess (John); K. Wakeley (Katie); A. Ewart-Toland (Amanda); M. Montagna (Marco); S. Agata (Simona); E.N. Imyanitov (Evgeny); C. Isaacs (Claudine); R. Janavicius (Ramunas); C. Lazaro (Conxi); I. Blanco (Ignacio); L. Feliubadaló (L.); J. Brunet (Joan); S.A. Gayther (Simon); P.D.P. Pharoah (Paul); K. Odunsi (Kunle); B.Y. Karlan (Beth); C.S. Walsh (Christine); E. Olah; S.-H. Teo (Soo-Hwang); P.A. Ganz (Patricia); M.S. Beattie (Mary); E.J. van Rensburg (Elizabeth); C.M. Dorfling (Cecelia); O. Diez (Orland); A. Kwong (Ava); R.K. Schmutzler (Rita); B. Wapenschmidt (Barbara); C.W. Engel (Christoph); A. Meindl (Alfons); N. Ditsch (Nina); N. Arnold (Norbert); S. Heidemann (Simone); D. Niederacher (Dieter); S. Preisler-Adams (Sabine); D. Gadzicki (Dorothea); R. Varon-Mateeva (Raymonda); H. Deissler (Helmut); P.A. Gehrig (Paola A.); C. Sutter (Christian); K. Kast (Karin); B. Fiebig (Britta); W. Heinritz (Wolfram); T. Caldes (Trinidad); M. de La Hoya (Miguel); T.A. Muranen (Taru); H. Nevanlinna (Heli); M. Tischkowitz (Marc); A.B. Spurdle (Amanda); S.L. Neuhausen (Susan); Y.C. Ding (Yuan); N.M. Lindor (Noralane); Z. Fredericksen (Zachary); V.S. Pankratz (Shane); P. Peterlongo (Paolo); S. Manoukian (Siranoush); B. Peissel (Bernard); D. Zaffaroni (D.); M. Barile (Monica); L. Bernard (Loris); A. Viel (Alessandra); G. Giannini (Giuseppe); L. Varesco (Liliana); P. Radice (Paolo); M.H. Greene (Mark); P.L. Mai (Phuong); D.F. Easton (Douglas); G. Chenevix-Trench (Georgia); K. Offit (Kenneth); J. Simard (Jacques)

2012-01-01

textabstractBackground: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for
Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

NARCIS (Netherlands)

Couch, Fergus J.; Gaudet, Mia M.; Antoniou, Antonis C.; Ramus, Susan J.; Kuchenbaecker, Karoline B.; Soucy, Penny; Beesley, Jonathan; Chen, Xiaoqing; Wang, Xianshu; Kirchhoff, Tomas; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Healey, Sue; Sinilnikova, Olga M.; Andrulis, Irene L.; Ozcelik, Hilmi; Mulligan, Anna Marie; Thomassen, Mads; Gerdes, Anne-Marie; Jensen, Uffe Birk; Skytte, Anne-Bine; Kruse, Torben A.; Caligo, Maria A.; von Wachenfeldt, Anna; Barbany-Bustinza, Gisela; Loman, Niklas; Soller, Maria; Ehrencrona, Hans; Karlsson, Per; Nathanson, Katherine L.; Rebbeck, Timothy R.; Domchek, Susan M.; Jakubowska, Ania; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Zlowocka, Elzbieta; Huzarski, Tomasz; Byrski, Tomasz; Gronwald, Jacek; Cybulski, Cezary; Górski, Bohdan; Osorio, Ana; Durán, Mercedes; Tejada, María Isabel; Benitez, Javier; Hamann, Ute; Hogervorst, Frans B. L.; van Os, Theo A.; van Leeuwen, Flora E.; Meijers-Heijboer, Hanne E. J.; Wijnen, Juul; Blok, Marinus J.; Kets, Marleen; Hooning, Maartje J.; Oldenburg, Rogier A.; Ausems, Margreet G. E. M.; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Evans, D. Gareth; Jacobs, Chris; Eeles, Rosalind A.; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana M.; Cole, Trevor; Cook, Jackie; Paterson, Joan; Brewer, Carole; Douglas, Fiona; Hodgson, Shirley V.; Morrison, Patrick J.; Walker, Lisa; Porteous, Mary E.; Kennedy, M. John; Side, Lucy E.; Bove, Betsy; Godwin, Andrew K.; Stoppa-Lyonnet, Dominique; Fassy-Colcombet, Marion; Castera, Laurent; Cornelis, François; Mazoyer, Sylvie; Léoné, Mélanie; Boutry-Kryza, Nadia; Bressac-de Paillerets, Brigitte; Caron, Olivier; Pujol, Pascal; Coupier, Isabelle; Delnatte, Capucine; Akloul, Linda; Lynch, Henry T.; Snyder, Carrie L.; Buys, Saundra S.; Daly, Mary B.; Terry, Marybeth; Chung, Wendy K.; John, Esther M.; Miron, Alexander; Southey, Melissa C.; Hopper, John L.; Goldgar, David E.; Singer, Christian F.; Rappaport, Christine; tea, Muy-Kheng M.; Fink-Retter, Anneliese; Hansen, Thomas V. O.; Nielsen, Finn C.; Arason, Aðalgeir; Vijai, Joseph; Shah, Sohela; Sarrel, Kara; Robson, Mark E.; Piedmonte, Marion; Phillips, Kelly; Basil, Jack; Rubinstein, Wendy S.; Boggess, John; Wakeley, Katie; Ewart-Toland, Amanda; Montagna, Marco; Agata, Simona; Imyanitov, Evgeny N.; Isaacs, Claudine; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Ignacio; Feliubadalo, Lidia; Brunet, Joan; Gayther, Simon A.; Pharoah, Paul P. D.; Odunsi, Kunle O.; Karlan, Beth Y.; Walsh, Christine S.; Olah, Edith; teo, Soo Hwang; Ganz, Patricia A.; Beattie, Mary S.; van Rensburg, Elizabeth J.; Dorfling, Cecelia M.; Diez, Orland; Kwong, Ava; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Heidemann, Simone; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorothea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Fiebig, Britta; Heinritz, Wolfram; Caldes, Trinidad; de la Hoya, Miguel; Muranen, Taru A.; Nevanlinna, Heli; Tischkowitz, Marc D.; Spurdle, Amanda B.; Neuhausen, Susan L.; Ding, Yuan Chun; Lindor, Noralane M.; Fredericksen, Zachary; Pankratz, V. Shane; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Barile, Monica; Bernard, Loris; Viel, Alessandra; Giannini, Giuseppe; Varesco, Liliana; Radice, Paolo; Greene, Mark H.; Mai, Phuong L.; Easton, Douglas F.; Chenevix-Trench, Georgia; Offit, Kenneth; Simard, Jacques

2012-01-01

Background: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these
Family aggregation study for breast cancer in Cienfuegos province

International Nuclear Information System (INIS)

Sosa Aguila, Leydi Maria; Marcheco Teruel, Beatriz; Ocanna Gil, Maria Antonia

2009-01-01

Breast cancer is one of the most frequent causes of death in developed countries and it is the second cause of female mortality for malignant tumor in Cuba. We conducted an observational, analytic, transversal study of cases and controls for the purpose of evaluating the clinical, epidemiologic and genealogical behavior of breast cancer in Cienfuegos province, in a period of 6 years. The universe of the study was made up of 304 women distributed in 152 cases and 152 controls; they were surveyed after they gave their informed consent. Collected data were processed by means of methods of inferential statistics. It was observed that most of the cases were diagnosed in patients aged 50 to 59 years, with 24.34%, the most frequent type was infiltrating duct carcinoma, with 43.42%. We found statistical association with the personal history of benign breast pathology and the family history of cancer of any type. Presence of familial aggregation was observed for breast cancer in the first-degree relatives and the non-genetic risk factors; they did not show significant association with the occurrence of the disease in the studied population
Excess breast cancer risk in first degree relatives of CHEK2∗1100delC positive familial breast cancer cases

NARCIS (Netherlands)

Adank, Muriel A.; Verhoef, Senno; Oldenburg, Rogier A.; Schmidt, Marjanka K.; Hooning, Maartje J.; Martens, John W. M.; Broeks, Annegien; Rookus, Matti; Waisfisz, Quinten; Witte, Birgit I.; Jonker, Marianne A.; Meijers-Heijboer, Hanne

2013-01-01

The CHEK2∗1100delC mutation confers a relative risk of two for breast cancer (BC) in the general population. This study aims to explore the excess cancer risk due to the CHEK2∗1100delC mutation within a familial non-BRCA1/2 breast cancer setting. Cancer incidences were compared between first degree
Breast and gynecological cancers in Croatia, 1988-2008

Science.gov (United States)

Kelava, Iva; Tomičić, Karlo; Kokić, Marina; Ćorušić, Ante; Planinić, Pavao; Kirac, Iva; Murgić, Jure; Kuliš, Tomislav; Znaor, Ariana

2012-01-01

Aim To analyze and interpret incidence and mortality trends of breast and ovarian cancers and incidence trends of cervical and endometrial cancers in Croatia for the period 1988-2008. Methods Incidence data were obtained from the Croatian National Cancer Registry. The mortality data were obtained from the World Health Organization (WHO) mortality database. Trends of incidence and mortality were analyzed by joinpoint regression analysis. Results Joinpoint analysis showed an increase in the incidence of breast cancer with estimated annual percent of change (EAPC) of 2.6% (95% confidence interval [CI], 1.9 to 3.4). The mortality rate was stable, with the EAPC of 0.3% (95% CI, -0.6 to 0.0). Endometrial cancer showed an increasing incidence trend, with EAPC of 0.8% (95% CI, 0.2 to 1.4), while cervical cancer showed a decreasing incidence trend, with EAPC of -1.0 (95% CI, -1.6 to -0.4). Ovarian cancer incidence showed three trends, but the average annual percent change (AAPC) for the overall period was not significant, with a stable trend of 0.1%. Ovarian cancer mortality was increasing since 1992, with EAPC of 1.2% (95% CI, 0.4 to 1.9), while the trend for overall period was stable with AAPC 0.1%. Conclusion Incidence trends of breast, endometrial, and ovarian cancers in Croatia 1988-2008 are similar to the trends observed in most of the European countries, while the modest decline in cervical cancer incidence and lack of decline in breast cancer mortality suggest suboptimal cancer prevention and control. PMID:22522987
Psychological distress in women at risk for hereditary breast cancer: the role of family communication and perceived social support.

Science.gov (United States)

den Heijer, Mariska; Seynaeve, Caroline; Vanheusden, Kathleen; Duivenvoorden, Hugo J; Bartels, Carina C M; Menke-Pluymers, Marian B E; Tibben, Aad

2011-12-01

Hereditary breast cancer has a profound impact on individual family members and on their mutual communication and interactions. The way at-risk women cope with the threat of hereditary breast cancer may depend on the quality of family communication about hereditary breast cancer and on the perceived social support from family and friends. To examine the associations of family communication and social support with long-term psychological distress in a group of women at risk for hereditary breast cancer, who opted either for regular breast surveillance or prophylactic surgery. The study cohort consisted of 222 women at risk for hereditary breast cancer, who previously participated in a study on the psychological consequences of either regular breast cancer surveillance or prophylactic surgery. General and breast cancer specific distress, hereditary cancer-related family communication, perceived social support, and demographics were assessed. Using structural equation modelling, we found that open communication about hereditary cancer within the family was associated with less general and breast cancer specific distress. In addition, perceived support from family and friends was indirectly associated with less general and breast cancer-specific distress through open communication within the family. These findings indicate that family communication and perceived social support from friends and family are of paramount importance in the long-term adaptation to being at risk for hereditary breast cancer. Attention for these issues needs to be incorporated in the care of women at risk for hereditary breast cancer. Copyright © 2010 John Wiley & Sons, Ltd.
Ovarian Cancer Susceptibility Alleles and Risk of Ovarian Cancer in BRCA1 and BRCA2 Mutation Carriers

Science.gov (United States)

Ramus, Susan J.; Antoniou, Antonis C; Kuchenbaecker, Karoline B.; Soucy, Penny; Beesley, Jonathan; Chen, Xiaoqing; McGuffog, Lesley; Sinilnikova, Olga M.; Healey, Sue; Barrowdale, Daniel; Lee, Andrew; Thomassen, Mads; Gerdes, Anne-Marie; Kruse, Torben A.; Jensen, Uffe Birk; Skytte, Anne-Bine; Caligo, Maria A.; Liljegren, Annelie; Lindblom, Annika; Olsson, Håkan; Kristoffersson, Ulf; Stenmark-Askmalm, Marie; Melin, Beatrice; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Złowocka, Elżbieta; Gronwald, Jacek; Huzarski, Tomasz; Byrski, Tomasz; Cybulski, Cezary; Toloczko-Grabarek, Aleksandra; Osorio, Ana; Benitez, Javier; Duran, Mercedes; Tejada, Maria-Isabel; Hamann, Ute; Rookus, Matti; van Leeuwen, Flora E.; Aalfs, Cora M.; Meijers-Heijboer, Hanne E.J.; van Asperen, Christi J.; van Roozendaal, K.E.P.; Hoogerbrugge, Nicoline; Collée, J. Margriet; Kriege, Mieke; van der Luijt, Rob B.; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Evans, D. Gareth; Lalloo, Fiona; Jacobs, Chris; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Paterson, Joan; Douglas, Fiona; Brewer, Carole; Hodgson, Shirley; Morrison, Patrick J.; Walker, Lisa; Porteous, Mary E.; Kennedy, M. John; Pathak, Harsh; Godwin, Andrew K.; Stoppa-Lyonnet, Dominique; Caux-Moncoutier, Virginie; de Pauw, Antoine; Gauthier-Villars, Marion; Mazoyer, Sylvie; Léoné, Mélanie; Calender, Alain; Lasset, Christine; Bonadona, Valérie; Hardouin, Agnès; Berthet, Pascaline; Bignon, Yves-Jean; Uhrhammer, Nancy; Faivre, Laurence; Loustalot, Catherine; Buys, Saundra; Daly, Mary; Miron, Alex; Terry, Mary Beth; Chung, Wendy K.; John, Esther M; Southey, Melissa; Goldgar, David; Singer, Christian F; Tea, Muy-Kheng; Pfeiler, Georg; Fink-Retter, Anneliese; Hansen, Thomas v. O.; Ejlertsen, Bent; Johannsson, Oskar Th.; Offit, Kenneth; Kirchhoff, Tomas; Gaudet, Mia M.; Vijai, Joseph; Robson, Mark; Piedmonte, Marion; Phillips, Kelly-Anne; Van Le, Linda; Hoffman, James S; Toland, Amanda Ewart; Montagna, Marco; Tognazzo, Silvia; Imyanitov, Evgeny; Isaacs, Claudine; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Ignacio; Tornero, Eva; Navarro, Matilde; Moysich, Kirsten B.; Karlan, Beth Y.; Gross, Jenny; Olah, Edith; Vaszko, Tibor; Teo, Soo-Hwang; Ganz, Patricia A.; Beattie, Mary S.; Dorfling, Cecelia M; van Rensburg, Elizabeth J; Diez, Orland; Kwong, Ava; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Heidemann, Simone; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorotehea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Fiebig, Britta; Schäfer, Dieter; Caldes, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomäki, Kristiina; Plante, Marie; Spurdle, Amanda B.; Neuhausen, Susan L.; Ding, Yuan Chun; Wang, Xianshu; Lindor, Noralane; Fredericksen, Zachary; Pankratz, V. Shane; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Bonanni, Bernardo; Bernard, Loris; Dolcetti, Riccardo; Papi, Laura; Ottini, Laura; Radice, Paolo; Greene, Mark H.; Mai, Phuong L.; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Pharoah, Paul D.P.; Gayther, Simon A.; Simard, Jacques; Easton, Douglas F.; Couch, Fergus J.; Chenevix-Trench, Georgia

2012-01-01

Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67–0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21–1.83) P-trend = 1.8 × 10−4, rs717852 HR = 1.25 (95% CI: 1.10–1.42) P-trend = 6.6 × 10−4, rs9303542 HR = 1.16 (95% CI: 1.02–1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81–0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10–1.42) P-trend = 6.1 × 10−4. The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer. PMID:22253144
Common variants at the 19p13.1 and ZNF365 loci are associated with ER subtypes of breast cancer and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers

DEFF Research Database (Denmark)

Couch, Fergus J; Gaudet, Mia M; Antoniou, Antonis C

2012-01-01

Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mut...
Gene-expression patterns in peripheral blood classify familial breast cancer susceptibility.

Science.gov (United States)

Piccolo, Stephen R; Andrulis, Irene L; Cohen, Adam L; Conner, Thomas; Moos, Philip J; Spira, Avrum E; Buys, Saundra S; Johnson, W Evan; Bild, Andrea H

2015-11-04

Women with a family history of breast cancer face considerable uncertainty about whether to pursue standard screening, intensive screening, or prophylactic surgery. Accurate and individualized risk-estimation approaches may help these women make more informed decisions. Although highly penetrant genetic variants have been associated with familial breast cancer (FBC) risk, many individuals do not carry these variants, and many carriers never develop breast cancer. Common risk variants have a relatively modest effect on risk and show limited potential for predicting FBC development. As an alternative, we hypothesized that additional genomic data types, such as gene-expression levels, which can reflect genetic and epigenetic variation, could contribute to classifying a person's risk status. Specifically, we aimed to identify common patterns in gene-expression levels across individuals who develop FBC. We profiled peripheral blood mononuclear cells from women with a family history of breast cancer (with or without a germline BRCA1/2 variant) and from controls. We used the support vector machines algorithm to differentiate between patients who developed FBC and those who did not. Our study used two independent datasets, a training set of 124 women from Utah (USA) and an external validation (test) set from Ontario (Canada) of 73 women (197 total). We controlled for expression variation associated with clinical, demographic, and treatment variables as well as lymphocyte markers. Our multigene biomarker provided accurate, individual-level estimates of FBC occurrence for the Utah cohort (AUC = 0.76 [0.67-84]) . Even at their lower confidence bounds, these accuracy estimates meet or exceed estimates from alternative approaches. Our Ontario cohort resulted in similarly high levels of accuracy (AUC = 0.73 [0.59-0.86]), thus providing external validation of our findings. Individuals deemed to have "high" risk by our model would have an estimated 2.4 times greater odds of
New treatment option for women with hormone-sensitive breast cancer

Science.gov (United States)

A drug used for treating breast cancer, known as exemestane, is more effective than a common breast cancer prevention drug, tamoxifen, in preventing breast cancer recurrence in young women who also receive post-surgical treatment to suppress ovarian funct
Hereditary breast and ovarian cancer: successful systematic implementation of a group approach to genetic counselling.

Science.gov (United States)

Benusiglio, Patrick R; Di Maria, Marina; Dorling, Leila; Jouinot, Anne; Poli, Antoine; Villebasse, Sophie; Le Mentec, Marine; Claret, Béatrice; Boinon, Diane; Caron, Olivier

2017-01-01

The increase in referrals to cancer genetics clinics, partially associated with the "Angelina Jolie effect", presents a challenge to existing services, many are already running at full capacity. More efficient ways to deliver genetic counselling are therefore urgently needed. We now systematically offer group instead of standard individual counselling to patients with suspected Hereditary Breast and Ovarian Cancer. Group sessions last 30 min. The first twenty consist of a presentation by the genetic counsellor, the next ten of a discussion involving a cancer geneticist and a psychologist. A short individual consultation ensues, where personal and family issues are addressed and consent obtained. Blood is drawn afterwards. Satisfaction and knowledge are evaluated. We report data for the Oct-2014-Aug-2015 period. 210 patients attended group counselling, up to eight simultaneously. We always fitted them within a 4-h time frame. Mean satisfaction score was 41/43. Knowledge scores increased from 3.1/6 to 4.9/6 post-counselling (p value group counselling, we have withstood increases in referrals without compromising care. The "Angelina Jolie effect" and rapid developments in personalized medicine threaten to overwhelm cancer genetics clinics. In this context, our innovative approach should ensure that all patients have access to approved services.
Latent class joint model of ovarian function suppression and DFS for premenopausal breast cancer patients.

Science.gov (United States)

Zhang, Jenny J; Wang, Molin

2010-09-30

Breast cancer is the leading cancer in women of reproductive age; more than a quarter of women diagnosed with breast cancer in the US are premenopausal. A common adjuvant treatment for this patient population is chemotherapy, which has been shown to cause premature menopause and infertility with serious consequences to quality of life. Luteinizing-hormone-releasing hormone (LHRH) agonists, which induce temporary ovarian function suppression (OFS), has been shown to be a useful alternative to chemotherapy in the adjuvant setting for estrogen-receptor-positive breast cancer patients. LHRH agonists have the potential to preserve fertility after treatment, thus, reducing the negative effects on a patient's reproductive health. However, little is known about the association between a patient's underlying degree of OFS and disease-free survival (DFS) after receiving LHRH agonists. Specifically, we are interested in whether patients with lower underlying degrees of OFS (i.e. higher estrogen production) after taking LHRH agonists are at a higher risk for late breast cancer events. In this paper, we propose a latent class joint model (LCJM) to analyze a data set from International Breast Cancer Study Group (IBCSG) Trial VIII to investigate the association between OFS and DFS. Analysis of this data set is challenging due to the fact that the main outcome of interest, OFS, is unobservable and the available surrogates for this latent variable involve masked event and cured proportions. We employ a likelihood approach and the EM algorithm to obtain parameter estimates and present results from the IBCSG data analysis.
Genetics of Breast and Gynecologic Cancers (PDQ®)—Health Professional Version

Science.gov (United States)

Genetics of Breast and Gynecologic Cancers includes information on BRCA1 and BRCA2 variants (breast and ovarian cancer) and Lynch syndrome (endometrial cancer). Get more information about hereditary breast and gynecologic cancer syndromes in this clinician summary.
Genetic variation at 9p22.2 and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers

DEFF Research Database (Denmark)

Ramus, Susan J; Kartsonaki, Christiana; Gayther, Simon A

2011-01-01

Background Germline mutations in the BRCA1 and BRCA2 genes are associated with increased risks of breast and ovarian cancers. Although several common variants have been associated with breast cancer susceptibility in mutation carriers, none have been associated with ovarian cancer susceptibility....
Familial transmission of prostate, breast and colorectal cancer in adoptees is related to cancer in biological but not in adoptive parents: a nationwide family study.

Science.gov (United States)

Zöller, Bengt; Li, Xinjun; Sundquist, Jan; Sundquist, Kristina

2014-09-01

Familial clustering of prostate, breast and colorectal cancer is well established, but the familial risk of these cancers has not been determined among adoptees. The aim was to disentangle the contributions of genetic and environmental factors to the familial transmission of prostate, breast and colorectal cancer. The Swedish Multi-Generation Register was used to follow all adoptees born between 1932 and 1969 (n=70,965) for prostate, breast and colorectal cancer from January 1958 up to December 2010. The risk of prostate, breast and colorectal cancer was estimated in adoptees with at least one biological parent with the same cancer type compared with adoptees without a biological parent with the same cancer type. The risk of cancer was also determined in adoptees with at least one adoptive parent with cancer compared with adoptees with an adoptive parent without cancer. Adoptees with at least one biological parent with prostate, breast or colorectal cancer were more likely to have cancer of the same type than adoptees with biological parents not affected by these respective cancer types (standardised incidence ratio=SIR: 1.8 [95% confidence interval 1.2-2.7], 2.0 [1.6-2.5] and 1.9 [1.2-2.9], respectively). In contrast, adoptees with at least one adoptive parent with prostate, breast or colorectal cancer were not at an increased risk of these respective cancer types (SIR=1.2 [0.94-1.6], 0.97 [0.71-1.3], and 1.1 [0.71-1.5], respectively). The findings of the study support the importance of genetic/biological factors in the familial transmission of prostate, breast and colorectal cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.
[A survey of willingness about genetic counseling and tests in patients of epithelial ovarian cancer].

Science.gov (United States)

Li, L; Qiu, L; Wu, M

2017-11-21

Objective: To analyze patients' tendency towards genetics counseling and tests based on a prospective cohort study on hereditary ovarian cancer. Methods: From February 2017 to June 2017, among 220 cases of epithelial ovarian cancer in Peking Union Medical College Hospital, we collected epidemiological, pathological and tendency towards genetics counseling and tests via medical records and questionnaire.All patients would get education about hereditary ovarian cancer by pamphlets and WeChat.If they would receive further counseling, a face to face interview and tests will be given. Results: Among all 220 patients, 10 (4.5%) denied further counseling.For 210 patients receiving genetic counseling, 170 (81%) accepted genetic tests.In multivariate analysis, risk factors relevant to acceptance of genetic tests included: being charged by physicians of gynecologic oncology for diagnosis and treatment, receiving counseling in genetic counseling clinics, and having family history of breast cancer.For patients denying genetic tests, there were many subjective reasons, among which, "still not understanding genetic tests" (25%) and "unable bear following expensive targeting medicine" . Conclusions: High proportion patients of epithelial ovarian cancer would accept genetic counseling and tests.Genetic counseling clinics for gynecologic oncology would further improve genetic tests for patients.

Outcomes of Incidental Fallopian Tube High-Grade Serous Carcinoma and Serous Tubal Intraepithelial Carcinoma in Women at Low Risk of Hereditary Breast and Ovarian Cancer.

Science.gov (United States)

Chay, Wen Yee; McCluggage, W Glenn; Lee, Cheng-Han; Köbel, Martin; Irving, Julie; Millar, Joanne; Gilks, C Blake; Tinker, Anna V

2016-03-01

The natural history and optimal management of serous tubal intraepithelial carcinoma (STIC), regardless of BRCA status, is unknown. We report the follow-up findings of a series of incidental fallopian tube high-grade serous carcinomas (HGSCs) and STICs identified in women at low risk for hereditary breast and ovarian cancer (HBOC), undergoing surgery for other indications. Cases of incidental STIC and HGSC were identified from 2008. Patients with known BRCA1 or BRCA2 mutations, or a family history of ovarian or breast cancer before the diagnosis of STIC or HGSC were excluded. A retrospective chart review was conducted to obtain clinical data. Eighteen cases were identified with a median follow-up of 25 months (range, 4-88 months). Twelve of 18 patients had a diagnosis of STIC with no associated invasive HGSC and 6 had STIC associated with other invasive malignancies. Completion staging surgery was performed on 7 of the 18 patients, including 5 of 12 in which there was STIC only identified on primary surgery; 3 cases were upstaged from STIC only to HGSC based on the staging surgery. Recurrence of HGSC occurred in 2 of the 18 patients. BRCA testing was performed on 3 patients, 1 of whom tested positive for a pathogenic BRCA1 mutation. Our study suggests that completion staging surgery for incidental STICs in non-BRCA patients may be considered. These patients should be offered hereditary testing. The Pelvic-Ovarian cancer INTerception (POINT) Project is an international registry set up to add to our understanding of STICs.
Family history suggestive of an inherited susceptibility to breast cancer and treatment outcome in young women after breast-conserving therapy

International Nuclear Information System (INIS)

Chabner, E.; Nixon, A.J.; Garber, J.; Gelman, R.; Bornstein, B.; Connolly, J.; Hetelekidis, S.; Recht, A.; Schnitt, S.; Silver, B.; Harris, J.R.

1997-01-01

PURPOSE: To determine whether outcome after conservative surgery and radiation therapy for young women is affected by having a family history (FH) suggestive of an inherited susceptibility to breast cancer. MATERIALS AND METHODS: Between 1968 and 1986, 205 patients 36 years of age or younger at diagnosis were treated with breast-conserving surgery and radiation therapy for clinical stage I or II invasive breast cancer. Three patients were not evaluable for FH; the remainder constitute the study population. At the time of diagnosis, 34 patients (17%; 95% CI 12-29%) had a mother or sister who had breast cancer diagnosed before age 50 years or who had ovarian cancer (2 cases) and were recorded as having a positive FH. This definition was chosen for clinical utility and to maximize the probability of inherited breast cancer within this sub-group (average 40-50%). Without genetic testing, the possibility of misclassification exists in both groups. The median age at diagnosis of the 34 patients with a positive FH was 33 years and was the same as the median age of the 168 patients in whom the FH was negative. All but 2 patients (99%) had a potential follow-up time of at least 5 years; 173 patients (86%) had a potential follow-up time of at least 10 years. RESULTS: Distributions of tumor size, pathologic nodal involvement, histologic type, histologic grade, the presence of an extensive intraductal component or lymphatic vascular invasion, volume of tissue excised, and use of adjuvant chemotherapy did not differ significantly by FH. The distribution of the sites of first failure within the first 5 years of follow-up is shown. The overall pattern of failure was significantly different (p=0.03) between patients with a positive FH and those with a negative FH; however, there was no statistically significant difference (Fisher Exact Test) in percentage of patients with no evidence of disease or local failure. At 5 years follow-up, the development of an opposite breast cancer
Genetic variation at 9p22.2 and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers

DEFF Research Database (Denmark)

Ramus, Susan J; Kartsonaki, Christiana; Gayther, Simon A

2011-01-01

Germline mutations in the BRCA1 and BRCA2 genes are associated with increased risks of breast and ovarian cancers. Although several common variants have been associated with breast cancer susceptibility in mutation carriers, none have been associated with ovarian cancer susceptibility. A genome-w...
Detection of high frequency of mutations in a breast and/or ovarian cancer cohort: implications of embracing a multi-gene panel in molecular diagnosis in India.

Science.gov (United States)

Mannan, Ashraf U; Singh, Jaya; Lakshmikeshava, Ravikiran; Thota, Nishita; Singh, Suhasini; Sowmya, T S; Mishra, Avshesh; Sinha, Aditi; Deshwal, Shivani; Soni, Megha R; Chandrasekar, Anbukayalvizhi; Ramesh, Bhargavi; Ramamurthy, Bharat; Padhi, Shila; Manek, Payal; Ramalingam, Ravi; Kapoor, Suman; Ghosh, Mithua; Sankaran, Satish; Ghosh, Arunabha; Veeramachaneni, Vamsi; Ramamoorthy, Preveen; Hariharan, Ramesh; Subramanian, Kalyanasundaram

2016-06-01

Breast and/or ovarian cancer (BOC) are among the most frequently diagnosed forms of hereditary cancers and leading cause of death in India. This emphasizes on the need for a cost-effective method for early detection of these cancers. We sequenced 141 unrelated patients and families with BOC using the TruSight Cancer panel, which includes 13 genes strongly associated with risk of inherited BOC. Multi-gene sequencing was done on the Illumina MiSeq platform. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform. We were able to detect pathogenic mutations in 51 (36.2%) cases, out of which 19 were novel mutations. When we considered familial breast cancer cases only, the detection rate increased to 52%. When cases were stratified based on age of diagnosis into three categories, ⩽40 years, 40-50 years and >50 years, the detection rates were higher in the first two categories (44.4% and 53.4%, respectively) as compared with the third category, in which it was 26.9%. Our study suggests that next-generation sequencing-based multi-gene panels increase the sensitivity of mutation detection and help in identifying patients with a high risk of developing cancer as compared with sequential tests of individual genes.
relationship between family history of breast cancer

African Journals Online (AJOL)

User

2013-07-02

Jul 2, 2013 ... features of familial and sporadic breast cancer in Moroccan patients. METHODS: A ... 1Genetics and Molecular Pathology Laboratory, Medical School of Casablanca, Morocco. 2Department of ... prognosis (9, 10), whereas others have found no significant ..... slightly higher rate of this histological subtype.
Breast cancer screening, outside the population-screening program, of women from breast cancer families without proven BRCA1/BRCA2 mutations : a simulation study

NARCIS (Netherlands)

Jacobi, C.E.; Nagelkerke, N.J.D.; van Houwelingen, J.C.; de Bock, G.H.

Purpose: We assessed the cost-effectiveness of mammography screening for women under the age of 50, from breast cancer families without proven BRCA1./BRCA2 mutations, because current criteria for screening healthy women from breast cancer families are not evidence-based. Methods: We did simulation
Breast cancer screening, outside the population-screening program, of women from breast cancer families without proven BRCA1/BRCA2 mutations: a simulation study

NARCIS (Netherlands)

Jacobi, C.E.; Nagelkerke, N.J.D.; van Houwelingen, J.C.; de Bock, Truuske

2006-01-01

Purpose: We assessed the cost-effectiveness of mammography screening for women under the age of 50, from breast cancer families without proven BRCA1./BRCA2 mutations, because current criteria for screening healthy women from breast cancer families are not evidence-based. Methods: We did simulation
Short-term effects of night shift work on breast cancer risk; a cohort study of payroll data

DEFF Research Database (Denmark)

Vistisen, Helene Tilma; Garde, Anne Helene; Frydenberg, Morten

2017-01-01

were followed from 2007-2012. Day-to-day work-hour information was available from payroll registers and 1245 incident cases of breast cancer were identified in national cancer registries together with receptor subtype information. Results: A rate ratio (RR) of 0.90 [95% confidence interval (95% CI) 0......Objectives: The objective was to examine if night shift work is a short-term risk factor for breast cancer, including combined estrogen receptor (ER) and human epidermal growth factor 2 (HER2) breast cancer subtypes. Methods: The cohort comprised 155 540 public sector female workers in Denmark who.......80-1.01] was observed for workers ever working night shifts during the follow-up period compared with workers only working day shifts after adjustment for age, age at first child, parity, family history of breast or ovarian cancer, sex hormones, medications related to alcoholism, family educational level, mammography...
Risk-reducing Salpingo-Oophorectomy in Women at Higher Risk of Ovarian and Breast Cancer: A Single Institution Prospective Series.

Science.gov (United States)

Ricciardi, Enzo; Tomao, Federica; Aletti, Giovanni; Bazzurini, Luca; Bocciolone, Luca; Boveri, Sara; Landoni, Fabio; Lapresa, Maria Teresa; Maruccio, Matteo; Parma, Gabriella; Peccatori, Fedro; Petrella, Maria Cristina; Zanagnolo, Vanna; Colombo, Nicoletta; Maggioni, Angelo

2017-09-01

Occult cancers' reported rates vary from 2-12% and serous tubal intraepithelial carcinomas (STICs) have been identified in 3-12% of the prophylactically removed tubes of women carrying a BRCA mutation. The aim of this study was to evaluate the incidence of tubal minor epithelial atypia (STIL), STIC, and occult invasive cancer and to evaluate the cancer-specific mortality in a prospective series of women at higher risk of ovarian and breast cancer undergoing risk-reducing salpingo-oophorectomy (RRSO) n a tertiary cancer center. A series of RRSO specimens (including endometrial biopsy) from women carrying a BRCA mutation, BRCA-unknown and BRCA-negative were collected between January 1998 and April 2016 at the Division of Gynecology at the European Institute of Oncology. Inclusion criteria were: asymptomatic women who had a negative gynecologic screening within 3 months prior to RRSO. Exclusion criteria were: women with ovarian/tubal cancer prior to RRSO. A total of 411 women underwent RRSO. Median age at RRSO was 47.0 years (range=32-70 years); 75.2% had a history of breast cancer. Fifteen women were diagnosed with an occult cancer (7 STIC, 4 invasive cancers, 2 breast cancers metastatic to the adnexa, 2 endometrial cancer) (3.6%). Sixteen showed a STIL (3.9%). When excluding cases with preoperative positive markers, the occult invasive cancer rate drops to 1.5%. Our study, covering an 18-year period, shows a substantial low risk of occult cancer among a high-risk population of women undergoing RRSO. Our data still support the indication for RRSO in higher-risk patients. An endometrial biopsy should also be routinely obtained as it raises the chances of detecting occult endometrial cancers that may be otherwise missed. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
A case-control study of risk factors for epithelial ovarian cancer

Directory of Open Access Journals (Sweden)

Ghaem Maghami Noori F

2001-09-01

Full Text Available Ovarian cancer is second prevalent cancer among gynecologic malignancies and the most common type of ovarian cancer is epithelial form (85-90 percent. To detect the risk factors for the epithelial ovarian cancer, a case-control study was conducted in Valieasr hospital in 1988. In this study, 118 cases with epithelial ovarian cancer (according histological records and 240 controls without any gynecological cancer in gynecologic clinic had been interviewed. For data analysis, T-test, Chi2 test and logistic regression have been used at a =0.05 as level of significance. The mean age in cases was 50±13 and in controls was 49.9±12 years, without significant different. The mean number of pregnancies and parity in cases was less than controls, significantly (P<0.03. The mean months of breast feeding in cases was less than controls (54.9±71.2 versus 82.4±62.7 (P<0.001. The cases had a lower mean age of menarch than controls (P=0.03. 58 percent of cases and 21.3 percent of controls hadn't used any contraception methods (P=0.00001. The mean years of contraception was significantly less in cases versus controls (P<0.001. The odds ratio for epithelial ovarian cancer was 0.24 (95 percent CI: 0.13-0.48 in OCP users, 0.47 (95 percent CI: 0.005-0.43 in TL method, and was 0.41 (95 percent CI: 0.22-0.76 in other contraception methods, relative to women who hadn't used any contraception methods. This study reveals that epithelial ovarian cancer risk increases significantly with earlier menarch, decreasing number of pregnancy, deliveries duration of breast feeding and use of contraception methods. Use of contraception pill and tubal ligation method decreases risk of epithelial ovarian cancer.
Functional polymorphisms in the TERT promoter are associated with risk of serous epithelial ovarian and breast cancers.

Directory of Open Access Journals (Sweden)

Jonathan Beesley

Full Text Available Genetic variation at the TERT-CLPTM1L locus at 5p15.33 is associated with susceptibility to several cancers, including epithelial ovarian cancer (EOC. We have carried out fine-mapping of this region in EOC which implicates an association with a single nucleotide polymorphism (SNP within the TERT promoter. We demonstrate that the minor alleles at rs2736109, and at an additional TERT promoter SNP, rs2736108, are associated with decreased breast cancer risk, and that the combination of both SNPs substantially reduces TERT promoter activity.
Associations of child adjustment with parent and family functioning: comparison of families of women with and without breast cancer.

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Vannatta, Kathryn; Ramsey, Rachelle R; Noll, Robert B; Gerhardt, Cynthia A

2010-01-01

To examine the impact of maternal breast cancer on the emotional and behavioral functioning of school-age children; evaluate whether child adjustment is associated with variations in distress, marital satisfaction, and parenting behavior evidenced by mothers and fathers; and determine whether these associations differ from families that are not contending with cancer. Participants included 40 children (age 8-16 years) of mothers with breast cancer along with their parents as well as 40 families of comparison classmates not affected by parental illness. Questionnaires assessing the domains of interest were administered in families' homes. Mothers with breast cancer and their spouses reported higher levels of distress than comparison parents; child internalizing problems were inversely associated with parental adjustment in both groups. No group differences were found in any indicators of family functioning, including parent-child relationships. Warm and supportive parenting by both mothers and fathers were associated with lower levels of child internalizing behavior, but only in families affected by breast cancer. These results suggest that children of mothers with breast cancer, such as most children, may be at risk for internalizing behavior when parents are distressed. These children may particularly benefit from interactions with mothers and fathers who are warm and supportive, and maintenance of positive parenting may partially account for the apparent resilience of these youth.
Impact of preventive therapy on the risk of breast cancer among women with benign breast disease.

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Cuzick, Jack; Sestak, Ivana; Thorat, Mangesh A

2015-11-01

There are three main ways in which women can be identified as being at high risk of breast cancer i) family history of breast and/or ovarian cancer, which includes genetic factors ii) mammographically identified high breast density, and iii) certain types of benign breast disease. The last category is the least common, but in some ways the easiest one for which treatment can be offered, because these women have already entered into the treatment system. The highest risk is seen in women with lobular carcinoma in situ (LCIS), but this is very rare. More common is atypical hyperplasia (AH), which carries a 4-5-fold risk of breast cancer as compared to general population. Even more common is hyperplasia of the usual type and carries a roughly two-fold increased risk. Women with aspirated cysts are also at increased risk of subsequent breast cancer. Tamoxifen has been shown to be particularly effective in preventing subsequent breast cancer in women with AH, with a more than 70% reduction in the P1 trial and a 60% reduction in IBIS-I. The aromatase inhibitors (AIs) also are highly effective for AH and LCIS. There are no published data on the effectiveness of tamoxifen or the AIs for breast cancer prevention in women with hyperplasia of the usual type, or for women with aspirated cysts. Improving diagnostic consistency, breast cancer risk prediction and education of physicians and patients regarding therapeutic prevention in women with benign breast disease may strengthen breast cancer prevention efforts. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
The contribution of reproductive factors and family history towards premenopausal breast cancer risk in Kuala Lumpur, Malaysia.

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Razif, S Mohd; Sulaiman, S; Hanie, S Soraya; Aina, E Nor; Rohaizak, M; Fuad, I; Nurismah, M I; Sharifah, N A

2011-08-01

Breast cancer is the most common cancer among Malaysian women. This study aimed to determine the reproductive for premenopausal breast cancer risk in Kuala Lumpur, Malaysia. A case-control study was conducted in 216 histopathologically confirmed cases of premenopausal breast cancer and 216 community-based controls that were matched by age within a 5-year period and ethnicity. The results of this study showed that premenopausal breast cancer risks were strongly related to parity, number of live births and family history of breast cancer. Premenopausal women with these known reproductive and family history risk factors should take extra measures to undergo appropriate screening method for early detection of breast cancer.
Anxiety and depression symptoms among women attending group-based patient education courses for hereditary breast and ovarian cancer.

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Listøl, Wenche; Høberg-Vetti, Hildegunn; Eide, Geir Egil; Bjorvatn, Cathrine

2017-01-01

Women carrying BRCA -mutations are facing significant challenges, including decision making regarding surveillance and risk-reducing surgery. They often report that they are left alone with these important decisions. In order to enhance the genetic counselling session we organized a group-based patient education (GPE) course for women with BRCA -mutations. The study aims were to characterize women attending a group-based patient education (GPE) course for hereditary breast and ovarian cancer, consider the usefulness of the course, evaluate symptoms of anxiety and depression among the participants, and finally investigate whether their levels of anxiety and depression changed from before to after the course session. A prospective study was conducted. Two weeks before (T1) and 2 weeks after (T2) attending the GPE-course the participants received questionnaires by mail. We collected information on demographic- and medical variables, anxiety and depression using Hospital Anxiety and Depression Scale (HADS), self-efficacy using The Bergen Genetic Counseling Self-Efficacy scale (BGCSES) and coping style using the Threatening Medical Situations Inventory (TMSI). A total of N = 100 (77% response rate) women participated at baseline and 75 (58% response rate) also completed post-course assessment. The mean level of anxiety symptoms was elevated among participants but decreased significantly during follow-up. Lower anxiety symptom levels were associated with "longer time since disclosure of gene test result", "higher levels of self-efficacy" and having experienced "loss of a close relative due to breast or ovarian cancer". Lower depression symptom levels were associated with "higher levels of education" and "loss of a close relative due to breast or ovarian cancer". The women in this study seemed to benefit from the GPE course. Women newly diagnosed with a BRCA mutation who reported lower levels of self-efficacy and lower levels of education were more vulnerable. These
A Phase 1 trial of the PARP inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer

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Liu, Joyce F.; Tolaney, Sara M.; Birrer, Michael; Fleming, Gini F.; Buss, Mary K.; Dahlberg, Suzanne E.; Lee, Hang; Whalen, Christin; Tyburski, Karin; Winer, Eric; Ivy, Percy; Matulonis, Ursula A.

2014-01-01

Background PARP-inhibitors and anti-angiogenics have activity in recurrent ovarian and breast cancer; however, the effect of combined therapy against PARP and angiogenesis in this population has not been reported. We investigated the toxicities and recommended phase 2 dosing (RP2D) of the combination of cediranib, a multitargeted inhibitor of VEGFR-1/2/3, and olaparib, a PARP-inhibitor (NCT01116648). Methods Cediranib tablets once daily and olaparib capsules twice daily were administered orally in a standard 3+3 dose escalation design. Patients with recurrent ovarian or metastatic triple-negative breast cancer were eligible. Patients had measurable disease by RECIST 1.1 or met GCIG CA125 criteria. No prior PARP-inhibitors or anti-angiogenics in the recurrent setting were allowed. Results 28 patients (20 ovarian, 8 breast) enrolled to 4 dose levels. 2 DLTs (1 grade 4 neutropenia ≥4 days; 1 grade 4 thrombocytopenia) occurred at the highest dose level (cediranib 30mg daily; olaparib 400mg BID). The RP2D was cediranib 30mg daily and olaparib 200mg BID. Grade 3 or higher toxicities occurred in 75% of patients, and included grade 3 hypertension (25%) and grade 3 fatigue (18%). One grade 3 bowel obstruction occurred. The overall response rate (ORR) in the 18 RECIST-evaluable ovarian cancer patients was 44%, with a clinical benefit rate (ORR plus SD >24 weeks) of 61%. None of the 7 evaluable breast cancer patients achieved clinical response; 2 patients had stable disease for >24 weeks. Interpretation The combination of cediranib and olaparib has hematologic DLTs and anticipated class toxicities, with promising evidence of activity in ovarian cancer patients. PMID:23810467
Accuracy of Self-Reported Breast Cancer Information among Women from the Ontario Site of the Breast Cancer Family Registry

International Nuclear Information System (INIS)

Barisic, A.; Glendon, G.; Andrulis, I. L.; Knight, J. A.; Barisic, A.; Knight, J. A.; Glendon, G.; Weerasooriya, N.; Andrulis, I. L.

2012-01-01

Obtaining complete medical record information can be challenging and expensive in breast cancer studies. The current literature is limited with respect to the accuracy of self-report and factors that may influence this. We assessed the agreement between self-reported and medical record breast cancer information among women from the Ontario site of the Breast Cancer Family Registry. Women aged 20-69 years diagnosed with incident breast cancer 1996-1998 were identified from the Ontario Cancer Registry, sampled on age and family history. We calculated kappa statistics, proportion correct, sensitivity, specificity, and positive and negative predictive values and conducted unconditional logistic regression to examine whether characteristics of the women influenced agreement. The proportions of women who correctly reported having received a broad category of therapy (hormone therapy, chemotherapy, radiation, or surgery) as well as sensitivity and specificity were above 90%, and the kappa statistics were above 0.80. The specific type of hormonal or chemotherapy was reported with low-to-moderate agreement. Aside from recurrence, no factors were consistently associated with agreement. Thus, most women were able to accurately report broad categories of treatment but not necessarily specific treatment types. The finding of this study can aid researchers in the use and design of self-administered treatment questionnaires
Managing the impact of posttreatment fatigue on the family: breast cancer survivors share their experiences.

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Oktay, Julianne S; Bellin, Melissa H; Scarvalone, Susan; Appling, Sue; Helzlsouer, Kathy J

2011-06-01

With improvements in both early detection and treatments for breast cancer, the number of survivors has increased dramatically in recent decades. One of the most common lingering symptoms posttreatment for cancer survivors is chronic fatigue. Based on family stress theory and Rolland's typology of illness, this qualitative study extends our understanding of the impact of persistent posttreatment fatigue on families and how breast cancer survivors manage the family issues that arise because of this chronic stressor. Participants included 35 female survivors of breast cancer (mean age = 54 years) who experienced fatigue after the completion of active cancer treatment, with the exception of long-term hormonal therapy. Data were generated from (a) observations of group sessions from a randomized controlled fatigue intervention designed to reduce fatigue in breast cancer survivors, (b) individual in-depth interviews, and (c) family sessions. Qualitative analysis revealed two broad themes that illustrate how the survivors manage the impact of fatigue on their families: Interpreting the meaning of the fatigue and Dealing with the inability to perform family roles. Study findings describe the difficulties in family adaptation when the family is not able to assign a clear meaning to a chronic symptom posttreatment and build upon family stress theory by highlighting interrelationships among communication patterns and role shifts in the family system. ©2011 APA
Stress Reduction in Improving Quality of Life in Patients With Recurrent Gynecologic or Breast Cancer

Science.gov (United States)

2015-10-08

Anxiety Disorder; Depression; Fatigue; Leydig Cell Tumor; Ovarian Sarcoma; Ovarian Stromal Cancer; Pain; Peritoneal Carcinomatosis; Pseudomyxoma Peritonei; Recurrent Breast Cancer; Recurrent Cervical Cancer; Recurrent Endometrial Carcinoma; Recurrent Fallopian Tube Cancer; Recurrent Gestational Trophoblastic Tumor; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Cavity Cancer; Recurrent Uterine Sarcoma; Recurrent Vaginal Cancer; Recurrent Vulvar Cancer
Relationships between family resilience and posttraumatic growth in breast cancer survivors and caregiver burden.

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Liu, Ye; Li, Yuli; Chen, Lijun; Li, Yurong; Qi, Weiye; Yu, Li

2018-04-01

To examine the relationships between family resilience and posttraumatic growth (PTG) of breast cancer survivors and caregiver burden among principal caregivers in China. Participants in this cross-sectional study comprised 108 women aged 26 to 74 years (M = 49, SD = 9) with early-stage breast cancer and 108 principal caregivers. Participants were recruited from a comprehensive cancer center of a public hospital in Shandong Province, China. The principal caregivers completed the Shortened Chinese Version of the Family Resilience Assessment Scale and the Chinese Version of the Zarit Caregiver Burden Interview; patients completed the Short Form of the Posttraumatic Growth Inventory and questions designed to obtain sociodemographic information. Hierarchical regression analysis was conducted to assess the adjusted association between family resilience and PTG and caregiver burden, while controlling for sociodemographics. Families showed a slightly elevated level of family resilience since the cancer experience, and patients showed a moderate degree of PTG. Principal caregivers reported moderate burden. The Shortened Chinese Version of the Family Resilience Assessment Scale total score was positively related to the Short Form of the Posttraumatic Growth Inventory total score (β = .28, P Caregiver Burden Interview total score (β = -.28, P resilience impacts PTG of breast cancer survivors and caregiver burden. Our findings indicated the necessity of interventions to facilitate family resilience, promote PTG among breast cancer survivors, and decrease family members' caregiver burden. Copyright © 2018 John Wiley & Sons, Ltd.

The Effect of Breast Cancer Fatalism on Breast Cancer Awareness Among Turkish Women.

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Altintas, Hulya Kulakci; Ayyildiz, Tulay Kuzlu; Veren, Funda; Topan, Aysel Kose

2017-10-01

The aim of this study was to evaluate the effect of breast cancer fatalism and other factors on breast cancer awareness among Turkish women. This cross-sectional and comparative descriptive study was conducted with 894 women. Data were collected by Personal Information Form, Powe Fatalism Inventory and Champion's Health Belief Model Scale. Seriousness, health motivation, BSE benefits and BSE self-efficacy perceptions of the women were moderate, and susceptibility and BSE barriers perceptions were low. It was determined that awareness of breast cancer of the women was affected by breast cancer fatalism, age, education level, employment status, marital status, family type, economic status, social assurance, menopause status, family history of cancer, family history of breast cancer, knowledge on BSE, source of information on BSE, performing of BSE, frequency of BSE performing, having a problem with breast, having a breast examination in hospital, feeling during breast examination by healthcare professional, sex of healthcare professional for breast examination and their health beliefs (p breast cancer of the women was affected by breast cancer fatalism. In providing breast cancer early diagnosis behaviors, it is recommended to evaluate fatalism perceptions and health beliefs of the women and to arrange educational programs for this purpose.
Targeting HOX and PBX transcription factors in ovarian cancer

International Nuclear Information System (INIS)

Morgan, Richard; Plowright, Lynn; Harrington, Kevin J; Michael, Agnieszka; Pandha, Hardev S

2010-01-01

Ovarian cancer still has a relatively poor prognosis due to the frequent occurrence of drug resistance, making the identification of new therapeutic targets an important goal. We have studied the role of HOX genes in the survival and proliferation of ovarian cancer cells. These are a family of homeodomain-containing transcription factors that determine cell and tissue identity in the early embryo, and have an anti-apoptotic role in a number of malignancies including lung and renal cancer. We used QPCR to determine HOX gene expression in normal ovary and in the ovarian cancer cell lines SK-OV3 and OV-90. We used a short peptide, HXR9, to disrupt the formation of HOX/PBX dimers and alter transcriptional regulation by HOX proteins. In this study we show that the ovarian cancer derived line SK-OV3, but not OV-90, exhibits highly dysregulated expression of members of the HOX gene family. Disrupting the interaction between HOX proteins and their co-factor PBX induces apoptosis in SK-OV3 cells and retards tumour growth in vivo. HOX/PBX binding is a potential target in ovarian cancer
Ovarian cancer at young age: the contribution of mismatch-repair defects in a population-based series of epithelial ovarian

DEFF Research Database (Denmark)

Domanska, K; Malander, S; Måsbäck, A

2007-01-01

age is a hallmark of heredity, and ovarian cancers associated with HNPCC have been demonstrated to develop at a particularly early age. We used the Swedish Cancer Registry to identify a population-based series of 98 invasive epithelial ovarian cancers that developed before 40 years. Mucinous......At least one of ten patients with ovarian cancer is estimated to develop their tumor because of heredity with the breast and ovarian cancer syndrome due to mutations in the BRCA1 and BRCA2 genes and hereditary nonpolyposis colorectal cancer (HNPCC) being the major genetic causes. Cancer at young...... and endometrioid cancers were overrepresented and were diagnosed in 27% and 16% of the tumors, respectively. Immunostaining using antibodies against MLH1, PMS2, MSH2, and MSH6 was used to assess the mismatch-repair status and revealed loss of expression of MLH1/PMS2 in two cases, loss of MSH2/MSH6 in one case...
Legal termination of a pregnancy resulting from transplanted cryopreserved ovarian tissue due to cancer recurrence

DEFF Research Database (Denmark)

Ernst, Emil Hagen; Offersen, Birgitte Vrou; Andersen, Claus Yding

2013-01-01

To report on a woman who conceived naturally and had a normal intrauterine pregnancy following transplantation of frozen/thawed ovarian tissue but decided to have an early abortion due to recurrence of breast cancer.......To report on a woman who conceived naturally and had a normal intrauterine pregnancy following transplantation of frozen/thawed ovarian tissue but decided to have an early abortion due to recurrence of breast cancer....
Evaluation of Polygenic Risk Scores for Breast and Ovarian Cancer Risk Prediction in BRCA1 and BRCA2 Mutation Carriers

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Kuchenbaecker, Karoline B; McGuffog, Lesley; Barrowdale, Daniel

2017-01-01

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic ...... risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management....
Identification of BRCA1-deficient ovarian cancers

DEFF Research Database (Denmark)

Skytte, Anne-Bine; Waldstrøm, Marianne; Rasmussen, Anders Aamann

2011-01-01

of offering genetic counseling and due to beneficial effects of PARP inhibitor treatment in this group. Since DNA sequencing is expensive and time-consuming efforts have been devoted to develop more indirect methods for BRCA screening that can improve the selection of patients for sequence-based BRCA testing....... Design. BRCA1-immunohistochemistry (IHC), fluorescence in-situ hybridization (FISH) and methylation analyses were performed on formalin-fixed, paraffin-embedded ovarian cancer tissue. Sample: 54 ovarian cancers; 15 BRCA1 cancers, 4 BRCA2 cancers, 10 cancers from patients with a family history...
Methylation of Breast Cancer Predisposition Genes in Early-Onset Breast Cancer: Australian Breast Cancer Family Registry.

Directory of Open Access Journals (Sweden)

Cameron M Scott

Full Text Available DNA methylation can mimic the effects of both germline and somatic mutations for cancer predisposition genes such as BRCA1 and p16INK4a. Constitutional DNA methylation of the BRCA1 promoter has been well described and is associated with an increased risk of early-onset breast cancers that have BRCA1-mutation associated histological features. The role of methylation in the context of other breast cancer predisposition genes has been less well studied and often with conflicting or ambiguous outcomes. We examined the role of methylation in known breast cancer susceptibility genes in breast cancer predisposition and tumor development. We applied the Infinium HumanMethylation450 Beadchip (HM450K array to blood and tumor-derived DNA from 43 women diagnosed with breast cancer before the age of 40 years and measured the methylation profiles across promoter regions of BRCA1, BRCA2, ATM, PALB2, CDH1, TP53, FANCM, CHEK2, MLH1, MSH2, MSH6 and PMS2. Prior genetic testing had demonstrated that these women did not carry a germline mutation in BRCA1, ATM, CHEK2, PALB2, TP53, BRCA2, CDH1 or FANCM. In addition to the BRCA1 promoter region, this work identified regions with variable methylation at multiple breast cancer susceptibility genes including PALB2 and MLH1. Methylation at the region of MLH1 in these breast cancers was not associated with microsatellite instability. This work informs future studies of the role of methylation in breast cancer susceptibility gene silencing.
Levels of Distress in Women at Risk for Ovarian Cancer

National Research Council Canada - National Science Library

Kash, Kathryn M

2008-01-01

The overall goal of this study was to determine the levels of distress in women with a family history of ovarian cancer and to identify the mediating factors between risk of developing ovarian cancer and distress...
Screening for germline BRCA1, BRCA2, TP53 and CHEK2 mutations in families at-risk for hereditary breast cancer identified in a population-based study from Southern Brazil

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Edenir Inêz Palmero

2016-01-01

Full Text Available Abstract In Brazil, breast cancer is a public health care problem due to its high incidence and mortality rates. In this study, we investigated the prevalence of hereditary breast cancer syndromes (HBCS in a population-based cohort in Brazils southernmost capital, Porto Alegre. All participants answered a questionnaire about family history (FH of breast, ovarian and colorectal cancer and those with a positive FH were invited for genetic cancer risk assessment (GCRA. If pedigree analysis was suggestive of HBCS, genetic testing of the BRCA1, BRCA2, TP53, and CHEK2 genes was offered. Of 902 women submitted to GCRA, 214 had pedigrees suggestive of HBCS. Fifty of them underwent genetic testing: 18 and 40 for BRCA1/BRCA2 and TP53 mutation screening, respectively, and 7 for CHEK2 1100delC testing. A deleterious BRCA2 mutation was identified in one of the HBOC probands and the CHEK2 1100delC mutation occurred in one of the HBCC families. No deleterious germline alterations were identified in BRCA1 or TP53. Although strict inclusion criteria and a comprehensive testing approach were used, the suspected genetic risk in these families remains unexplained. Further studies in a larger cohort are necessary to better understand the genetic component of hereditary breast cancer in Southern Brazil.
Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

DEFF Research Database (Denmark)

Kar, Siddhartha P; Beesley, Jonathan; Amin Al Olama, Ali

2016-01-01

UNLABELLED: Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112...... (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell......-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P cancer meta-analysis. SIGNIFICANCE...
Enhancer of the rudimentary gene homologue (ERH expression pattern in sporadic human breast cancer and normal breast tissue

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Knüchel Ruth

2008-05-01

Full Text Available Abstract Background The human gene ERH (Enhancer of the Rudimentary gene Homologue has previously been identified by in silico analysis of four million ESTs as a gene differentially expressed in breast cancer. The biological function of ERH protein has not been fully elucidated, however functions in cell cycle progression, pyrimidine metabolism a possible interaction with p21(Cip1/Waf1 via the Ciz1 zinc finger protein have been suggested. The aim of the present study was a systematic characterization of ERH expression in human breast cancer in order to evaluate possible clinical applications of this molecule. Methods The expression pattern of ERH was analyzed using multiple tissue northern blots (MTN on a panel of 16 normal human tissues and two sets of malignant/normal breast and ovarian tissue samples. ERH expression was further analyzed in breast cancer and normal breast tissues and in tumorigenic as well as non-tumorigenic breast cancer cell lines, using quantitative RT-PCR and non-radioisotopic in situ hybridization (ISH. Results Among normal human tissues, ERH expression was most abundant in testis, heart, ovary, prostate, and liver. In the two MTN sets of malignant/normal breast and ovarian tissue,ERH was clearly more abundantly expressed in all tumours than in normal tissue samples. Quantitative RT-PCR analyses showed that ERH expression was significantly more abundant in tumorigenic than in non-tumorigenic breast cancer cell lines (4.5-fold; p = 0.05, two-tailed Mann-Whitney U-test; the same trend was noted in a set of 25 primary invasive breast cancers and 16 normal breast tissue samples (2.5-fold; p = 0.1. These findings were further confirmed by non-radioisotopic ISH in human breast cancer and normal breast tissue. Conclusion ERH expression is clearly up-regulated in malignant as compared with benign breast cells both in primary human breast cancer and in cell models of breast cancer. Since similar results were obtained for ovarian
Pre-test genetic counseling services for hereditary breast and ovarian cancer delivered by non-genetics professionals in the state of Florida.

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Vadaparampil, S T; Scherr, C L; Cragun, D; Malo, T L; Pal, T

2015-05-01

Genetic counseling and testing for hereditary breast and ovarian cancer now includes practitioners from multiple healthcare professions, specialties, and settings. This study examined whether non-genetics professionals (NGPs) perform guideline-based patient intake and informed consent before genetic testing. NGPs offering BRCA testing services in Florida (n = 386) were surveyed about clinical practices. Among 81 respondents (response rate = 22%), approximately half reported: sometimes scheduling a separate session for pre-test counseling lasting 11-30 min prior to testing, discussing familial implications of testing, benefits and limitations of risk management options, and discussing the potential psychological impact and insurance-related issues. Few constructed a three-generation pedigree, discussed alternative hereditary cancer syndromes, or the meaning of a variant result. This lack of adherence to guideline-based practice may result in direct harm to patients and their family members. NGPs who are unable to deliver guideline adherent cancer genetics services should focus on identification and referral of at-risk patients to in person or telephone services provided by genetics professionals. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
A primary care audit of familial risk in patients with a personal history of breast cancer.

Science.gov (United States)

Nathan, Paul; Ahluwalia, Aneeta; Chorley, Wendy

2014-12-01

Breast cancer is the most common cancer diagnosed in women, both in the UK and worldwide. A small proportion of women are at very high risk of breast cancer, having a particularly strong family history. The National Institute for Health and Clinical Excellence (NICE) has advised that practitioners should not, in most instances, actively seek to identify women with a family history of breast cancer. An audit was undertaken at an urban primary care practice of 15,000 patients, using a paper-based, self-administered questionnaire sent to patients identified with a personal history of breast cancer. The aim of this audit was to determine whether using targeted screening of relatives of patients with breast cancer to identify familial cancer risk is worthwhile in primary care. Since these patients might already expected to have been risk assessed following their initial diagnosis, this audit acts as a quality improvement exercise. The audit used a validated family history questionnaire and risk assessment tool as a screening approach for identifying and grading familial risk in line with the NICE guidelines, to guide referral to the familial cancer screening service. The response rate to family history questionnaires was 54 % and the majority of patients responded positively to their practitioner seeking to identify familial cancer risks in their family. Of the 57 returned questionnaires, over a half (54 %) contained pedigrees with individuals eligible for referral. Patients and their relatives who are often registered with the practice welcome the discussion. An appropriate referral can therefore be made. The findings suggest a role for primary care practitioners in the identification of those at higher familial risk. However integrated systems and processes need designing to facilitate this work.
Screening for large genomic rearrangements in the FANCA gene reveals extensive deletion in a Finnish breast cancer family.

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Solyom, Szilvia; Winqvist, Robert; Nikkilä, Jenni; Rapakko, Katrin; Hirvikoski, Pasi; Kokkonen, Hannaleena; Pylkäs, Katri

2011-03-28

A portion of familial breast cancer cases are caused by mutations in the same genes that are inactivated in the downstream part of Fanconi anemia (FA) signaling pathway. Here we have assessed the FANCA gene for breast cancer susceptibility by examining blood DNA for aberrations from 100 Northern Finnish breast cancer families using the MLPA method. We identified a novel heterozygous deletion, removing the promoter and 12 exons of the gene in one family. This allele was absent from 124 controls. We conclude that FANCA deletions might contribute to breast cancer susceptibility, potentially in combination with other germline mutations. To our knowledge, this is the first study reporting a large deletion in an upstream FA gene in familial breast cancer. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Ovarian Suppression With Triptorelin During Adjuvant Breast Cancer Chemotherapy and Long-term Ovarian Function, Pregnancies, and Disease-Free Survival: A Randomized Clinical Trial.

Science.gov (United States)

Lambertini, Matteo; Boni, Luca; Michelotti, Andrea; Gamucci, Teresa; Scotto, Tiziana; Gori, Stefania; Giordano, Monica; Garrone, Ornella; Levaggi, Alessia; Poggio, Francesca; Giraudi, Sara; Bighin, Claudia; Vecchio, Carlo; Sertoli, Mario Roberto; Pronzato, Paolo; Del Mastro, Lucia

Whether the administration of luteinizing hormone-releasing hormone analogues (LHRHa) during chemotherapy is a reliable strategy to preserve ovarian function is controversial owing to both the lack of data on long-term ovarian function and pregnancies and the safety concerns about the potential negative interactions between endocrine therapy and chemotherapy. To evaluate long-term results of LHRHa-induced ovarian suppression during breast cancer chemotherapy. Parallel, randomized, open-label, phase 3 superiority trial conducted at 16 Italian sites. Between October 2003 and January 2008, 281 premenopausal women with stage I to III hormone receptor-positive or hormone receptor-negative breast cancer were enrolled. Last annual follow-up was June 3, 2014. Patients were randomized to receive adjuvant or neoadjuvant chemotherapy alone (control group) or chemotherapy plus triptorelin (LHRHa group). The primary planned end point was incidence of chemotherapy-induced early menopause. Post hoc end points were long-term ovarian function (evaluated by yearly assessment of menstrual activity and defined as resumed by the occurrence of at least 1 menstrual cycle), pregnancies, and disease-free survival (DFS). A total of 281 women (median age, 39 [range, 24-45] years) were randomized. Median follow-up was 7.3 years (interquartile range, 6.3-8.2 years). The 5-year cumulative incidence estimate of menstrual resumption was 72.6% (95% CI, 65.7%-80.3%) among the 148 patients in the LHRHa group and 64.0% (95% CI, 56.2%-72.8%) among the 133 patients in the control group (hazard ratio [HR], 1.28 [95% CI, 0.98-1.68]; P = .07; age-adjusted HR, 1.48 [95% CI, 1.12-1.95]; P = .006). Eight pregnancies (5-year cumulative incidence estimate of pregnancy, 2.1% [95% CI, 0.7%-6.3%]) occurred in the LHRHa group and 3 (5-year cumulative incidence estimate of pregnancy, 1.6% [95% CI, 0.4%-6.2%]) in the control group (HR, 2.56 [95% CI, 0.68-9.60]; P = .14; age-adjusted HR, 2.40 [95% CI, 0
[Latest international guidelines for screening, prevention and treatment of familial breast cancer - implications for the relevant practice in Hungary].

Science.gov (United States)

Romics, László; Kocsis, Judit; Ormándi, Katalin; Molnár, Béla Ákos

2016-07-01

Screening, prevention and treatment of familial breast cancer require a multidisciplinary approach. New guidelines were published in the United Kingdom for the management of familial breast cancer. The authors summarise these new guidelines and analyse the relevant practice in Hungary. Relevant guidelines of the National Institute for Health and Care Excellence and Familial Breast Cancer Report (NHS Scotland) are described. New guidelines will increase the number of genetic tests as well as genetic counselling. An increase in the number of breast magnetic resonance imaging is expected, too. Chemoprevention can be offered for individuals with medium risk and above. Promising trials are underway with platinum based chemotherapy and polyADP-ribose polimerase inhibitors for the systemic treatment of familial breast cancer. The increase in the number of genetic tests, counselling, and breast magnetic resonance imaging may have a significant impact on health care budget. These guidelines will change some aspects of the current management of familial breast cancer. Orv. Hetil., 2016, 157(28), 1117-1125.
Exploration of the family's role and strengths after a young woman is diagnosed with breast cancer: views of women and their families.

Science.gov (United States)

Coyne, Elisabeth; Wollin, Judy; Creedy, Debra K

2012-04-01

This exploratory descriptive study examined the role and strengths of the family when supporting the younger woman (<50 years) after a diagnosis of breast cancer. The perspectives of women and family members were sought. Participants were recruited from oncology outpatient units in Australia. Semi-structured interviews guided by the Family Resiliency Framework were undertaken with 14 young women with breast cancer and 11 family members who reflected on the roles of family. Transcripts were analysed individually and in family groupings. Women with breast cancer and their family members experienced a range of emotions during the treatment period. Roles within the family changed as members responded to their circumstances. Analysis of interview transcripts identified the following primary themes; 'just being there', 'paradox of help' and 'buffer from society'. A secondary theme related to support, specifically 'the changing role of support for family members', highlighting the strengths and experiences of family. Recognition needs to be given to the complexity of changing roles experienced by young women with breast cancer and their families. Young women with breast cancer require unique forms of support because of the nature of their experience. Family roles were shaped through a shared sense of commitment and open communication amongst members. Families may demonstrate a range of strengths but are also vulnerable during this stressful period. Health professionals need to be aware of the possible needs of families, assess their adaptation to changing circumstances, and intervene through the provision of information, and counselling to enhance coping. Copyright Â© 2011 Elsevier Ltd. All rights reserved.
[Histopathological characteristics of genital and breast cancer included in epidemiologic study cohort].

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Matei, Mioara; Azoicăi, Doina

2009-01-01

The correct management of genitals and breast cancers and the improving of the preventional and therapeutical successes ratio involve the knowledge of the histopathological features of these nosological entities which have different origins, different risk factors, different simptomatology and also different prognosis. The descriptive evaluation of the histopathological features of the genitals and breast cancers to women from North-Eastern region of Romania. We have been included in the study 96 women (age range 23-77 years, mean 54,49) diagnosed with breast cancer, ovarian cancer, endometrial cancer and cervical cancer at the hospital admission, residency in the Obstetrics and Gynecology Clinics within 23 months. The following main parameters were assessed: histological types, stage at diagnosis, Pap test. After data collection, these have been codified and included in a MS Excel Database, in order to be processed with SPSS 16 and EpiInfo 3.5.1. (2008) Softwares. The following cases' repartition on diagnostic types was observed: breast cancer (44 cases), cervical cancer (24 cases), endometrial cancer (16 cases) and ovarian cancer (12 cases). In our study, the most affected range of age was 40-69 years for breast cancer, 30-59 years for cervical cancer, over 6 years for endometrial cancer and 50-59 years for ovarian cancer. For the cervical neoplasia, 40% of analyzed cases were in incipient stages (in situ to IB stage lessions). More than 50% of breast cancer cases have been diagnosed in advances stages (IIB to IIIC stages). For the endometrium carcinoma, 45% of cases have been identified in incipient stages (in situ to IC). The ovarian neoplasia cases have been detected, most frequently, in advanced stages (III and IV). 25% of women which participated in our study had showed cervical changes. From a histopathological point of view, for cervical neoplasia, squamous carcinoma was the most frequent type (87%), for breast neoplasia--invasive ductal carcinoma (80
Variants in estrogen-biosynthesis genes CYP17 and CYP19 and breast cancer risk: a family-based genetic association study

International Nuclear Information System (INIS)

Ahsan, Habibul; Whittemore, Alice S; Chen, Yu; Senie, Ruby T; Hamilton, Steven P; Wang, Qiao; Gurvich, Irina; Santella, Regina M

2005-01-01

Case-control studies have reported inconsistent results concerning breast cancer risk and polymorphisms in genes that control endogenous estrogen biosynthesis. We report findings from the first family-based association study examining associations between female breast cancer risk and polymorphisms in two key estrogen-biosynthesis genes CYP17 (T→C promoter polymorphism) and CYP19 (TTTA repeat polymorphism). We conducted the study among 278 nuclear families containing one or more daughters with breast cancer, with a total of 1123 family members (702 with available constitutional DNA and questionnaire data and 421 without them). These nuclear families were selected from breast cancer families participating in the Metropolitan New York Registry, one of the six centers of the National Cancer Institute's Breast Cancer Family Registry. We used likelihood-based statistical methods to examine allelic associations. We found the CYP19 allele with 11 TTTA repeats to be associated with breast cancer risk in these families. We also found that maternal (but not paternal) carrier status of CYP19 alleles with 11 repeats tended to be associated with breast cancer risk in daughters (independently of the daughters' own genotype), suggesting a possible in utero effect of CYP19. We found no association of a woman's breast cancer risk either with her own or with her mother's CYP17 genotype. This family-based study indicates that a woman's personal and maternal carrier status of CYP19 11 TTTA repeat allele might be related to increased breast cancer risk. However, because this is the first study to report an association between CYP19 11 TTTA repeat allele and breast cancer, and because multiple comparisons have been made, the associations should be interpreted with caution and need confirmation in future family-based studies
High frequency of the recurrent c.1310_1313delAAGA BRCA2 mutation in the North-East of Morocco and implication for hereditary breast-ovarian cancer prevention and control.

Science.gov (United States)

Laarabi, Fatima-Zahra; Ratbi, Ilham; Elalaoui, Siham Chafai; Mezzouar, Loubna; Doubaj, Yassamine; Bouguenouch, Laila; Ouldim, Karim; Benjaafar, Noureddine; Sefiani, Abdelaziz

2017-06-02

To date, a limited number of BRCA1/2 germline mutations have been reported in hereditary breast and/or ovarian cancer in the Moroccan population. Less than 20 different mutations of these two genes have been identified in Moroccan patients, and recently we reported a further BRCA2 mutation (c.1310_1313delAAGA; p.Lys437IlefsX22) in three unrelated patients, all from the North-East of the country. We aimed in this study to evaluate the frequency and geographic distribution of this BRCA2 frameshift mutation, in order to access its use as the first-line BRCA genetic testing strategy for Moroccan patients. We enrolled in this study 122 patients from different regions of Morocco, with suggestive inherited predisposition to breast and ovarian cancers. All subjects gave written informed consent to BRCA1/2 genetic testing. According to available resources of our lab and enrolled families, 51 patients were analyzed by the conventional individual exon-by-exon Sanger sequencing, 23 patients were able to benefit from a BRCA next generation sequencing and a target screening for exon 10 of BRCA2 gene was performed in 48 patients. Overall, and among the 122 patients analyzed for at least the exon 10 of the BRCA2 gene, the c.1310_1313delAAGA frameshift mutation was found in 14 patients. Genealogic investigation revealed that all carriers of this mutation shared the same geographic origin and were descendants of the North-East of Morocco. In this study, we highlighted that c.1310_1313delAAGA mutation of BRCA2 gene is recurrent with high frequency in patients from the North-East region of Morocco. Therefore, we propose to use, in public health strategies, the detection of this mutation as the first-line screening tests in patients with breast and ovarian cancer originated from this region.

Relationships between Family Levels of Socioeconomic Status and Distribution of Breast Cancer Risk Factors.

Science.gov (United States)

Mohaghegh, Pegah; Yavari, Parvin; Akbari, Mohammad Esmaeil; Abadi, Alireza; Ahmadi, Farzaneh; Shormeij, Zeinab

2015-01-01

Not only the expand development of knowledge for reducing risk factors, but also the improvement in early diagnosis and treatment of cancer, and socioeconomic inequalities could affect cancer incidence, diagnosis stage, and mortality. The aim of this study was investigation the relationships between family levels of socioeconomic status and distribution of breast cancer risk factors. This descriptive cross-sectional study has conducted on 526 patients who were suffering from breast cancer, and have registered in Cancer Research Center of Shahid Beheshti University of Medical Sciences from March 2008 to December 2013. A reliable and valid questionnaire about family levels of socioeconomic status has filled by interviewing the patients via phone. For analyzing the data, Multinomial logistic regression, Kendal tau-b correlation coefficient and Contingency Coefficient tests have executed by SPSS19. The mean age of the patients was 48.30 (SD=11.41). According to the results of this study, there was a significant relationship between family socioeconomic status and patient's age at diagnosis of breast cancer (p valuesocioeconomic status and number of pregnancies, and duration of breast feeding were significant (p value> 0.001). In the multiple logistic regressions, the relationship between excellent socioeconomic status and number of abortions was significant (p value> 0.007). Furthermore, the relationships between moderate and good socioeconomic statuses and smoking were significant (p value=0.05 and p value=0.02, respectively). The results have indicated that among those patients having better socioeconomic status, age at cancer diagnosis, number of pregnancies and duration of breast feeding was lower, and then number of abortions was more than the others. According to the results of this study, it was really important to focus on family socioeconomic status as a critical and effective variable on breast cancer risk factors among the Iranian women.
Recent trends in incidence of and mortality from breast, ovarian and endometrial cancers in England and Wales and their relation to changing fertility and oral contraceptive use.

OpenAIRE

dos Santos Silva, I.; Swerdlow, A. J.

1995-01-01

Reproductive-related factors play a major role in the aetiology of cancers of the breast, ovary and endometrium. Pregnancy history influences the risk of each of these cancers, and oral contraceptive use modifies the risks of ovarian and endometrial cancers, although its effect on breast cancer risk is less certain. We analysed recent time trends in the incidence and mortality of these cancers in England and Wales and assessed whether they can be explained by changes in fertility and oral con...
Ovarian reserve in breast cancer: assessment with anti-Müllerian hormone.

Science.gov (United States)

Hamy, Anne-Sophie; Porcher, Raphaël; Cuvier, Caroline; Giacchetti, Sylvie; Schlageter, Marie-Hélène; Coussieu, Christiane; Gronier, Héloise; Feugeas, Jean-Paul; Adoui, Nadir; Lacorte, Jean-Marc; Poirot, Catherine; Habdous, Mohamed; Espié, Marc

2014-11-01

Anti-Müllerian hormone (AMH) levels fall during chemotherapy. Treatment-induced amenorrhoea is a reversible phenomenon, but few data are available on long-term AMH changes in breast cancer. The aim of the study was to describe serum AMH levels before, during and in the long term after chemotherapy, and to show a potential AMH recovery. Between May 2010 and June 2011, we selected 134 women aged 18-43 years at the time of breast cancer diagnosis who received chemotherapy between 2005 and 2011, and had not undergone an oophorectomy or had previous cytotoxic treatment. The AMH levels were assessed before, during and 4 months to 5.5 years after the end of chemotherapy. During chemotherapy, AMH was undetectable in 69% of women. After chemotherapy, a significant increase in AMH was found, with an average magnitude of +1.2% per month (95% credibility interval: 0.7 to 1.6). Older age and 12 months of amenorrhoea were found to be associated with a lower AMH recovery rate, whereas baseline AMH and number of chemotherapy cycles were not. The process of AMH changes during and after chemotherapy is dynamic, and shows recovery after ovarian injury. Caution should be exercised in interpreting individual AMH assessment in this context. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
Hereditary forms of breast cancer

International Nuclear Information System (INIS)

Bella, V.

2009-01-01

Breast cancer is the most common oncologic disease in the female population. Besides the sporadic occurrence it occurs in the familial and hereditary form. Persons with the occurrence of positive family anamnesis of breast cancer should be actively investigated. In the indicated cases it is necessary to send the woman to genetic examination. In case that the hereditary form of breast cancer is affirmed it is necessary to examine her family relatives. Women with the hereditary form of breast cancer occur in about 5 – 10 % portion from all women diagnosed with breast cancer. Nowadays we already know that 80 % of hereditary breast cancers are due to germ mutations in BRCA 1 and BRCA 2 gene. Persons with detected gene mutations must be dispensarized in the centres intended for it. (author)
Subtypes of Ovarian Cancer and Ovarian Cancer Screening

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Masafumi Koshiyama

2017-03-01

Full Text Available Ovarian cancer is the foremost cause of gynecological cancer death in the developed world, as it is usually diagnosed at an advanced stage. In this paper we discuss current issues, the efficacy and problems associated with ovarian cancer screening, and compare the characteristics of ovarian cancer subtypes. There are two types of ovarian cancer: Type I carcinomas, which are slow-growing, indolent neoplasms thought to arise from a precursor lesion, which are relatively common in Asia; and Type II carcinomas, which are clinically aggressive neoplasms that can develop de novo from serous tubal intraepithelial carcinomas (STIC and/or ovarian surface epithelium and are common in Europe and the USA. One of the most famous studies on the subject reported that annual screening using CA125/transvaginal sonography (TVS did not reduce the ovarian cancer mortality rate in the USA. In contrast, a recent study in the UK showed an overall average mortality reduction of 20% in the screening group. Another two studies further reported that the screening was associated with decreased stage at detection. Theoretically, annual screening using CA125/TVS could easily detect precursor lesions and could be more effective in Asia than in Europe and the USA. The detection of Type II ovarian carcinoma at an early stage remains an unresolved issue. The resolving power of CA125 or TVS screening alone is unlikely to be successful at resolving STICs. Biomarkers for the early detection of Type II carcinomas such as STICs need to be developed.
Subtypes of Ovarian Cancer and Ovarian Cancer Screening.

Science.gov (United States)

Koshiyama, Masafumi; Matsumura, Noriomi; Konishi, Ikuo

2017-03-02

Ovarian cancer is the foremost cause of gynecological cancer death in the developed world, as it is usually diagnosed at an advanced stage. In this paper we discuss current issues, the efficacy and problems associated with ovarian cancer screening, and compare the characteristics of ovarian cancer subtypes. There are two types of ovarian cancer: Type I carcinomas, which are slow-growing, indolent neoplasms thought to arise from a precursor lesion, which are relatively common in Asia; and Type II carcinomas, which are clinically aggressive neoplasms that can develop de novo from serous tubal intraepithelial carcinomas (STIC) and/or ovarian surface epithelium and are common in Europe and the USA. One of the most famous studies on the subject reported that annual screening using CA125/transvaginal sonography (TVS) did not reduce the ovarian cancer mortality rate in the USA. In contrast, a recent study in the UK showed an overall average mortality reduction of 20% in the screening group. Another two studies further reported that the screening was associated with decreased stage at detection. Theoretically, annual screening using CA125/TVS could easily detect precursor lesions and could be more effective in Asia than in Europe and the USA. The detection of Type II ovarian carcinoma at an early stage remains an unresolved issue. The resolving power of CA125 or TVS screening alone is unlikely to be successful at resolving STICs. Biomarkers for the early detection of Type II carcinomas such as STICs need to be developed.
Familial Breast Cancer in Costa Rica: An Initial Approach

Directory of Open Access Journals (Sweden)

Adriana Ramírez Monge

2004-09-01

Full Text Available Cancer is a worldwide problem because of its high rates of incidence and associated mortality. By 2000, more than 6.2 million people died from this illness worldwide. Among all types of cancer, breast cancer is one of the most studied. Each year, one million new cases are diagnosed around the world. We can classify breast cancer into two main kinds: sporadic cases and those which are a product of inherited genetic alterations. Approximately 5-10% of breast cancer cases are the result of inherited mutations, or alterations in breast cancer susceptibility genes, BRCA1 and BRCA2. Like other countries, Costa Rica possesses high rates of incidence and mortality for breast cancer. According to the "Registro Nacional de Tumores" (National Office of Tumor Records, in 2000 breast cancer had the highest rate of incidence and in 2002 it had the highest rate of mortality in comparison to other types of cancer. For this reason and the generalized lack of knowledge in the field we conducted an epidemiological research on breast cancer patients from Hospital San Juan de Dios, San José, Costa Rica, to find families with a history of breast cancer, and to determine the occurrence of familial cases within the population studied. So far, we have found 23 families, within which we discovered very informative cases that have rendered the identification of a pattern of inheritance. These findings allow us to announce that in Costa Rica there are several cases of inherited breast cancer and that we need more research is needed to improve the prevention, control, and treatment of this disease. Rev. Biol. Trop. 52(3: 531-536. Epub 2004 Dic 15.El cáncer es un problema a nivel mundial porque posee altas tasas de incidencia y mortalidad. Para el año 2000 más de 6.2 millones de personas murieron a causa de esta enfermedad. El cáncer de mama es uno de los tipos de cáncer más estudiados en el mundo por las mismas razones. Cada año, se diagnostican más de un mill
Cost-effectiveness analysis of a low-fat diet in the prevention of breast and ovarian cancer.

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Bós, Antônio M; Howard, Barbara V; Beresford, Shirley A A; Urban, Nicole; Tinker, Lesley F; Waters, Hugh; Bós, Angelo J; Chlebowski, Rowan; Ennis, Jacqueline M

2011-01-01

Results of the Women's Health Initiative Randomized Controlled Dietary Modification Trial (WHI-DM) suggest that a low-fat diet may be associated with beneficial health outcomes for specific groups of women. The objective is to assess how cost-effective the WHI-DM would be if implemented as a public health intervention and under the sponsorship of private health insurers and Medicare. Breast and ovarian cancers are the health outcomes of interest. Two groups of WHI-DM participants form the target population for this analysis: participants consuming >36.8% of energy from fat at baseline, and participants at high risk for breast cancer with 32% or more of energy from fat at baseline. This study uses Markov cohort modeling, following societal and health care payer perspectives, with Monte Carlo simulations and one-way sensitivity analyses. WHI-DM records, nationally representative prices, and published estimates of medical care costs were the sources of cost information. Simulations were performed for hypothetical cohorts of women aged 50, 55, 60, 65, or 70 years at the beginning of the intervention. Effectiveness was estimated by quality-adjusted life years (QALYs) and the main outcome measure was the incremental cost-effectiveness ratio (ICER). Following the societal perspective, the ICERs for the 50-year old cohort are $13,773/QALY (95% confidence interval $7,482 to $20,916) for women consuming >36.8% of energy from fat at baseline and $10,544/QALY ($2,096 to $23,673) for women at high risk for breast cancer. The comparable ICER from a private health care payer perspective is $66,059/QALY ($30,155 to $121,087) and from a Medicare perspective, it is $15,051/QALY ($6,565 to $25,105). The WHI-DM is a cost-effective strategy for the prevention of breast and ovarian cancers in the target population, from both societal and Medicare perspectives. Private health care payers have a relative short timeframe to realize a return on investment, since after age 65 years the
Frequency of CHEK2 mutations in a population based, case–control study of breast cancer in young women

International Nuclear Information System (INIS)

Friedrichsen, Danielle M; Malone, Kathleen E; Doody, David R; Daling, Janet R; Ostrander, Elaine A

2004-01-01

The cell-cycle checkpoint kinase (CHEK)2 protein truncating mutation 1100delC has been associated with increased risk for breast or prostate cancer. Multiple studies have found an elevated frequency of the 1100delC variant in specific stratifications of breast cancer patients with a family history of the disease, including BRCA1/BRCA2 negative families and families with a history of bilateral disease or male breast cancer. However, the 1100delC mutation has only been investigated in a few population-based studies and none from North America. We report here on the frequency of three CHEK2 variants that alter protein function – 1100delC, R145W, and I175T – in 506 cases and 459 controls from a population based, case–control study of breast cancer conducted in young women from western Washington. There was a suggestive enrichment in the 1100delC variant in the cases (1.2%) as compared with the controls (0.4%), but this was based on small numbers of carriers and the differences were not statistically significant. The 1100delC variant was more frequent in cases with a first-degree family history of breast cancer (4.3%; P = 0.02) and slightly enriched in cases with a family history of ovarian cancer (4.4%; P = 0.09). The CHEK2 variants are rare in the western Washington population and, based on accumulated evidence across studies, are unlikely to be major breast cancer susceptibility genes. Thus, screening for the 1100delC variant may have limited usefulness in breast cancer prevention programs in the USA
Expression and function of androgen receptor coactivator p44/Mep50/WDR77 in ovarian cancer.

Directory of Open Access Journals (Sweden)

Martin Ligr

Full Text Available Hormones, including estrogen and progesterone, and their receptors play an important role in the development and progression of ovarian carcinoma. Androgen, its receptor and coactivators have also been implicated in these processes. p44/Mep50/WDR77 was identified as a subunit of the methylosome complex and lately characterized as a steroid receptor coactivator that enhances androgen receptor as well as estrogen receptor-mediated transcriptional activity in a ligand-dependent manner. We previously described distinct expression and function of p44 in prostate, testis, and breast cancers. In this report, we examined the expression and function of p44 in ovarian cancer. In contrast to findings in prostate and testicular cancer and similar to breast cancer, p44 shows strong cytoplasmic localization in morphologically normal ovarian surface and fallopian tube epithelia, while nuclear p44 is observed in invasive ovarian carcinoma. We observed that p44 can serve as a coactivator of both androgen receptor (AR and estrogen receptor (ER in ovarian cells. Further, overexpression of nuclear-localized p44 stimulates proliferation and invasion in ovarian cancer cells in the presence of estrogen or androgen. These findings strongly suggest that p44 plays a role in mediating the effects of hormones during ovarian tumorigenesis.
Levels of Distress in Women With a Family History of Ovarian Cancer

National Research Council Canada - National Science Library

Kash, Kathryn

2005-01-01

... (mothers sisters or daughters). Women will be queried about their objective and subjective risk status their knowledge of ovarian cancer and risk factors their uncertainty about ovarian cancer levels of anxiety and depress...
CpG methylation of APC promoter 1A in sporadic and familial breast cancer patients.

Science.gov (United States)

Debouki-Joudi, Saoussen; Trifa, Fatma; Khabir, Abdelmajid; Sellami-Boudawara, Tahia; Frikha, Mounir; Daoud, Jamel; Mokdad-Gargouri, Raja

2017-01-01

Tumour suppressor gene (TSG) silencing through promoter hypermethylation plays an important role in cancer initiation. The aim of this study was to assess the extent of methylation of APC gene promoter in 91 sporadic and 44 familial cases of Tunisian patients with breast cancer (BC) in. The frequency of APC promoter methylation is somewhat similar for sporadic and familial breast cancer cases, (52.1%, and 54.5% respectively). For sporadic breast cancer patients, there was a significant correlation of APC promoter hypermethylation with TNM stage (p = 0.024) and 3-year survival (p = 0.025). Regarding the hormonal status (HR), we found significant association between negativity to PR and unmethylated APC (p= 0.005) while ER and Her2/neu are not correlated. Moreover, unmethylated APC promoter is more frequent in tumours expressing at least one out the 3 proteins compared to triple negative cases (p= 0.053). On the other hand, aberrant methylation of APC was associated with tumour size (p = 0.036), lymph node (p = 0.028), distant metastasis (p = 0.031), and 3-year survival (p = 0.046) in the group of patients with familial breast cancer. Moreover, patients with sporadic breast cancer displaying the unmethylated profile have a significant prolonged overall survival compared to those with the methylated pattern of APC promoter (p log rank = 0.008). Epigenetic change at the CpG islands in the APC promoter was associated with the silence of its transcript and the loss of protein expression suggesting that this event is the main mechanism regulating the APC expression in breast cancer. In conclusion, our data showed that the loss of APC through aberrant methylation is associated with the aggressive behavior of both sporadic and familial breast cancer in Tunisian patients.
Somatic mutations in breast and serous ovarian cancer young patients: a systematic review and meta-analysis

Directory of Open Access Journals (Sweden)

Giselly Encinas

2015-10-01

Full Text Available Summary Objective: our aim was to evaluate whether somatic mutations in five genes were associated with an early age at presentation of breast cancer (BC or serous ovarian cancer (SOC. Methods: COSMIC database was searched for the five most frequent somatic mutations in BC and SOC. A systematic review of PubMed was performed. Young age for BC and SOC patients was set at ≤35 and ≤40 years, respectively. Age groups were also classified in <30years and every 10 years thereafter. Results: twenty six (1,980 patients, 111 younger and 16 studies (598, 41 younger, were analyzed for BC and SOC, respectively. In BC, PIK3CA wild type tumor was associated with early onset, not confirmed in binary regression with estrogen receptor (ER status. In HER2-negative tumors, there was increased frequency of PIK3CA somatic mutation in older age groups; in ER-positive tumors, there was a trend towards an increased frequency of PIK3CA somatic mutation in older age groups. TP53 somatic mutation was described in 20% of tumors from both younger and older patients; PTEN, CDH1 and GATA3 somatic mutation was investigated only in 16 patients and PTEN mutation was detected in one of them. In SOC, TP53 somatic mutation was rather common, detected in more than 50% of tumors, however, more frequently in older patients. Conclusion: frequency of somatic mutations in specific genes was not associated with early-onset breast cancer. Although very common in patients with serous ovarian cancer diagnosed at all ages, TP53 mutation was more frequently detected in older women.
A Phase 1 trial of the poly(ADP-ribose) polymerase inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer.

Science.gov (United States)

Liu, Joyce F; Tolaney, Sara M; Birrer, Michael; Fleming, Gini F; Buss, Mary K; Dahlberg, Suzanne E; Lee, Hang; Whalen, Christin; Tyburski, Karin; Winer, Eric; Ivy, Percy; Matulonis, Ursula A

2013-09-01

Poly(ADP-ribose) polymerase (PARP)-inhibitors and anti-angiogenics have activity in recurrent ovarian and breast cancer; however, the effect of combined therapy against PARP and angiogenesis in this population has not been reported. We investigated the toxicities and recommended phase 2 dosing (RP2D) of the combination of cediranib, a multitargeted inhibitor of vascular endothelial growth factor receptor (VEGFR)-1/2/3 and olaparib, a PARP-inhibitor (NCT01116648). Cediranib tablets once daily and olaparib capsules twice daily were administered orally in a standard 3+3 dose escalation design. Patients with recurrent ovarian or metastatic triple-negative breast cancer were eligible. Patients had measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or met Gynecologic Cancer InterGroup (GCIG) CA125 criteria. No prior PARP-inhibitors or anti-angiogenics in the recurrent setting were allowed. 28 patients (20 ovarian, 8 breast) enrolled to 4 dose levels. 2 dose limiting toxicities (DLTs) (1 grade 4 neutropenia ≥ 4 days; 1 grade 4 thrombocytopenia) occurred at the highest dose level (cediranib 30 mg daily; olaparib 400 mg twice daily [BID]). The RP2D was cediranib 30 mg daily and olaparib 200 mg BID. Grade 3 or higher toxicities occurred in 75% of patients, and included grade 3 hypertension (25%) and grade 3 fatigue (18%). One grade 3 bowel obstruction occurred. The overall response rate (ORR) in the 18 RECIST-evaluable ovarian cancer patients was 44%, with a clinical benefit rate (ORR plus stable disease (SD) > 24 weeks) of 61%. None of the seven evaluable breast cancer patients achieved clinical response; two patients had stable disease for > 24 weeks. The combination of cediranib and olaparib has haematologic DLTs and anticipated class toxicities, with promising evidence of activity in ovarian cancer patients. Copyright © 2013 Elsevier Ltd. All rights reserved.
A nationwide population-based retrospective cohort study of the risk of uterine, ovarian and breast cancer in women with polycystic ovary syndrome.

Science.gov (United States)

Shen, Cheng-Che; Yang, Albert C; Hung, Jeng-Hsiu; Hu, Li-Yu; Tsai, Shih-Jen

2015-01-01

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. We used a nationwide population-based retrospective cohort study to explore the relationship between PCOS and the subsequent development of gynecological cancers including uterine, breast, or ovarian cancer. We identified subjects who were diagnosed with PCOS between January 1, 2000, and December 31, 2004, in the Taiwan National Health Insurance (NHI) Research Database. A comparison cohort was constructed for patients without known PCOS who were also matched according to age. All PCOS and control patients were observed until diagnosed with breast cancer, ovarian cancer, or uterine cancer or until death, withdrawal from the NHI system, or December 31, 2009. The PCOS cohort consisted of 3,566 patients, and the comparison cohort consisted of 14,264 matched control patients without PCOS. The adjusted hazard ratio (HR) of uterine cancer and breast cancer in subjects with PCOS were higher (HR: 8.42 [95% confidence interval: 1.62-43.89] and HR: 1.99 [95% confidence interval: 1.05-3.77], respectively) than that of the controls during the follow-up. With the Monte Carlo method, only the mean adjusted HR of 1,000 comparisons for developing uterine cancer during the follow-up period was greater for the PCOS group than for the control groups (HR: 4.71, 95% confidence interval: 1.57-14.11). PCOS might increase the risk of subsequent newly diagnosed uterine cancer. It is critical that further large-scale, well-designed studies be conducted to confirm the association between PCOS and gynecological cancer risk. ©AlphaMed Press.
Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

OpenAIRE

Bojesen, Stig E; Pooley, Karen A; Johnatty, Sharon E; Beesley, Jonathan; Michailidou, Kyriaki; Tyrer, Jonathan P; Edwards, Stacey L; Pickett, Hilda A; Shen, Howard C; Smart, Chanel E; Hillman, Kristine M; Mai, Phuong L; Lawrenson, Kate; Stutz, Michael D; Lu, Yi

2013-01-01

TERT-locus single nucleotide polymorphisms (SNPs) and leucocyte telomere measures are reportedly associated with risks of multiple cancers. Using the iCOGs chip, we analysed ~480 TERT-locus SNPs in breast (n=103,991), ovarian (n=39,774) and BRCA1 mutation carrier (11,705) cancer cases and controls. 53,724 participants have leucocyte telomere measures. Most associations cluster into three independent peaks. Peak 1 SNP rs2736108 minor allele associates with longer telomeres (P=5.8×10−7), reduce...
Immunophenotyping of hereditary breast cancer

NARCIS (Netherlands)

van der Groep, P.

2009-01-01

Hereditary breast cancer runs in families where several family members in different generations are affected. Most of these breast cancers are caused by mutations in the high penetrance genes BRCA1 and BRCA2 which account for about 5% of all breast cancers. However, mutations in BRCA1 and BRCA2 may
Levels of Distress in Women With a Family History of Ovarian Cancer

National Research Council Canada - National Science Library

Kash, Kathryn

2005-01-01

... and distress The proposed study will use 180 first-degree relatives (FDR) of women diagnosed with ovarian cancer in a cross-sectional design Information the ovarian cancer index case provides will be used to identify maternal relatives...
Cytotoxic activity of erypogein d from erythrina poeppigiana (leguminosae) against cervical cancer (HeLa), breast cancer (MCF-7) and ovarian cancer (SKOV-3) cells

Science.gov (United States)

Herlina, T.; Gaffar, S.; Widowati, W.

2018-05-01

Cancer is the uncontrolled growth of abnormal cells and continues to divide rapidly in the body. Current anticancer treatment usually causes many side effects. Natural products are then explored to be new alternatives for cancer treatment. Flavonoids have been known to possess medicinal properties, including anticancer. This study was performed to observe the cytotoxic activity of isoflavanone compound, erypogein D from Erythrina poeppigiana, toward cervical cancer (HeLa), breast cancer (MCF-7) and ovarian cancer (SKOV-3) cells. The cytotoxic activity of erypogein D was tested using MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3- carboxyme-thoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. The percentage of cell mortality was calculated and the IC50 was analyzed using probit analysis. The result showed that cytotoxic activity of the erypogein D against HeLa, SKOV-3, and MCF-7 cells had an IC50 value 225, 70.74, and 30.12 μM, respectively. Based on IC50 value can be concluded that erypogein D is the most cytotoxic to breast cancer MCF-7 cell. However the cytotoxic activity of erypogein D toward MCF7 is moderate.
Influence of race/ethnicity on genetic counseling and testing for hereditary breast and ovarian cancer.

Science.gov (United States)

Forman, Andrea D; Hall, Michael J

2009-01-01

Risk assessment coupled with genetic counseling and testing for the cancer predisposition genes BRCA1 and BRCA2 (BRCA1/2) has become an integral element of comprehensive patient evaluation and cancer risk management in the United States for individuals meeting high-risk criteria for hereditary breast and ovarian cancer (HBOC). For mutation carriers, several options for risk modification have achieved substantial reductions in future cancer risk. However, several recent studies have shown lower rates of BRCA1/2 counseling and testing among minority populations. Here, we explore the role of race/ethnicity in cancer risk assessment, genetic counseling and genetic testing for HBOC and the BRCA1/2 cancer predisposition genes. Barriers to genetic services related to race/ethnicity and underserved populations, including socioeconomic barriers (e.g., time, access, geographic, language/cultural, awareness, cost) and psychosocial barriers (e.g., medical mistrust, perceived disadvantages to genetic services), as well as additional barriers to care once mutation carriers are identified, will be reviewed.

Psychological distress in women at risk of hereditary breast/ovarian or HNPCC cancers in the absence of demonstrated mutations.

Science.gov (United States)

Geirdal, Amy Østertun; Reichelt, Jon G; Dahl, Alv A; Heimdal, Ketil; Maehle, Lovise; Stormorken, Astrid; Møller, Pål

2005-01-01

To examine psychological distress in women at risk of familial breast-ovarian cancer (FBOC) or hereditary non-polyposis colorectal cancer (HNPCC) with absence of demonstrated mutations in the family (unknown mutation). Two-hundred and fifty three consecutive women at risk of FBOC and 77 at risk of HNPCC and with no present or past history of cancer. They were aware of their risk and had received genetic counseling. Comparisons were made between these two groups, normal controls, and women who were identified to be BRCA1 mutation carriers. The questionnaires Beck Hopelessness Scale (BHS), General Health Questionnaire (GHQ-28), Hospital Anxiety and Depression Scale (HADS) and Impact of Event Scale (IES) were employed to assess psychological distress. No significant differences concerning psychological distress were observed between women with FBOC and women with HNPCC. Compared to mutation carriers for BRCA1, the level of anxiety and depression was significantly higher in the FBOC group with absence of demonstrated mutation. Compared to normal controls, the level of anxiety was higher, while the level of depression was lower in the groups with unknown mutation. Women in the absence of demonstrated mutations have higher anxiety and depression levels than women with known mutation-carrier status. Access to genetic testing may be of psychologically benefit to women at risk for FBOC or HNPCC.
Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis.

Science.gov (United States)

Barry, John A; Azizia, Mallika M; Hardiman, Paul J

2014-01-01

Polycystic ovary syndrome (PCOS) is a common condition affecting ∼8% of women. The objective of the present study was to quantify separately the risk of endometrial cancer, ovarian cancer and breast cancer in women with PCOS compared with non-PCOS controls, and quantify separately the risk to women of all ages as well as the risk to premenopausal women. We conducted a systematic review and meta-analysis of observational studies. Studies were eligible for inclusion if they compared women with PCOS to non-PCOS groups for fatal or non-fatal gynaecological cancers. Studies listed in MEDLINE and EMBASE published up to 7 October 2013 in any language were identified, and relevant papers were also searched by hand. Relevant data (for example, study design, source of control data, diagnostic criteria) were extracted and tabulated. From 698 references, 11 studies (5 of endometrial cancer and 3 each of ovarian and breast cancer) met the inclusion criteria for the meta-analysis (919 women with PCOS and 72054 non-PCOS controls). Using the Mantel-Haenszel method, with fixed or random effects model as appropriate, women with PCOS were at a significantly increased risk of endometrial cancer (odds ratio (OR), 2.79; 95% confidence interval (CI), 1.31-5.95, P cancers was not significantly increased (OR, 1.41; 95% CI, 0.93-2.15, P cancer (OR, 4.05; 95% CI, 2.42-6.76, P cancer (OR, 2.52; 95% CI, 1.08-5.89, P cancer (OR, 0.78; 95% CI, 0.46-1.32, P cancers in women with PCOS younger than 54 years of age compared with controls of similar age. Current data suggest that women of all ages with PCOS are at an increased risk of endometrial cancer but the risk of ovarian and breast cancer was not significantly increased overall. These results highlight the potential risk of gynaecological cancer morbidities associated with PCOS. However, the available evidence is far from robust and variation in diagnostic criteria for PCOS, associated risk factors (particularly obesity), and selection bias
First-in-man application of a novel therapeutic cancer vaccine formulation with the capacity to induce multi-functional T cell responses in ovarian, breast and prostate cancer patients

Directory of Open Access Journals (Sweden)

Berinstein Neil L

2012-08-01

Full Text Available Abstract Background DepoVaxTM is a novel non-emulsion depot-forming vaccine platform with the capacity to significantly enhance the immunogenicity of peptide cancer antigens. Naturally processed HLA-A2 restricted peptides presented by breast, ovarian and prostate cancer cells were used as antigens to create a therapeutic cancer vaccine, DPX-0907. Methods A phase I clinical study was designed to examine the safety and immune activating potential of DPX-0907 in advanced stage breast, ovarian and prostate cancer patients. A total of 23 late stage cancer patients were recruited and were divided into two dose/volume cohorts in a three immunization protocol. Results DPX-0907 was shown to be safe with injection site reactions being the most commonly reported adverse event. All breast cancer patients (3/3, most of ovarian (5/6 and one third of prostate (3/9 cancer patients exhibited detectable immune responses, resulting in a 61% immunological response rate. Immune responses were generally observed in patients with better disease control after their last prior treatment. Antigen-specific responses were detected in 73% of immune responders (44% of evaluable patients after the first vaccination. In 83% of immune responders (50% of evaluable patients, peptide-specific T cell responses were detected at ≥2 time points post vaccination with 64% of the responders (39% of evaluable patients showing evidence of immune persistence. Immune monitoring also demonstrated the generation of antigen-specific T cell memory with the ability to secrete multiple Type 1 cytokines. Conclusions The novel DepoVax formulation promotes multifunctional effector memory responses to peptide-based tumor associated antigens. The data supports the capacity of DPX-0907 to elicit Type-1 biased immune responses, warranting further clinical development of the vaccine. This study underscores the importance of applying vaccines in clinical settings in which patients are more likely to be
Emotional, Biological, and Cognitive Impact of a Brief Expressive Writing Intervention for Women at Familial Breast Cancer Risk

National Research Council Canada - National Science Library

Valdimarsdottir, Heiddis

2006-01-01

...) than women without familial breast cancer risk. The proposed study will examine the impact of an expressive writing intervention on emotional biological and cognitive processes among women at familial breast cancer risk...
Modifiers of the Efficacy of Risk-Reducing Salpingo-Oophorectomy for the Prevention of Breast and Ovarian Cancer in Carriers of BRCA1 and BRCA2

National Research Council Canada - National Science Library

Kauff, Noah D

2006-01-01

.... This plan included 1) conduct of a prospective study examining modifiers of the efficacy of risk-reducing salpingo-oophorectomy for the prevention of breast and ovarian cancer in carriers of BRCA mutations; and 2...
Histopathological features of breast tumours in BRCA1, BRCA2 and mutation-negative breast cancer families

International Nuclear Information System (INIS)

Eerola, Hannaleena; Heikkilä, Päivi; Tamminen, Anitta; Aittomäki, Kristiina; Blomqvist, Carl; Nevanlinna, Heli

2005-01-01

Histopathological features of BRCA1 and BRCA2 tumours have previously been characterised and compared with unselected breast tumours; however, familial non-BRCA1/2 tumours are less well known. The aim of this study was to characterise familial non-BRCA1/2 tumours and to evaluate routine immunohistochemical and pathological markers that could help us to further distinguish families carrying BRCA1/2 mutations from other breast cancer families. Breast cancer tissue specimens (n = 262) from 25 BRCA1, 20 BRCA2 and 74 non-BRCA1/2 families were studied on a tumour tissue microarray. Immunohistochemical staining of oestrogen receptor (ER), progesterone receptor (PgR) and p53 as well as the histology and grade of these three groups were compared with each other and with the respective information on 862 unselected control patients from the archives of the Pathology Department of Helsinki University Central Hospital. Immunohistochemical staining of erbB2 was also performed among familial cases. BRCA1-associated cancers were diagnosed younger and were more ER-negative and PgR-negative, p53-positive and of higher grade than the other tumours. However, in multivariate analysis the independent factors compared with non-BRCA1/2 tumours were age, grade and PgR negativity. BRCA2 cases did not have such distinctive features compared with non-BRCA1/2 tumours or with unselected control tumours. Familial cases without BRCA1/2 mutations had tumours of lower grade than the other groups. BRCA1 families differed from mutation-negative families by age, grade and PgR status, whereas ER status was not an independent marker
The Activities and Impact of State Programs to Address Hereditary Breast and Ovarian Cancer, 2011–2014

Directory of Open Access Journals (Sweden)

Katrina F. Trivers

2015-10-01

Full Text Available In 2011, the Division of Cancer Prevention and Control (DCPC, at the United States Centers for Disease Control and Prevention (CDC, released a three-year funding opportunity announcement (FOA for a competitive, non-research cooperative agreement. The agreement enhanced the capacities of state health departments to promote the application of best practices for evidence-based breast cancer genomics through education, surveillance, and policy activities. The FOA required that applicants focus on activities related to hereditary breast and ovarian cancer (HBOC. The DCPC funded three states: Georgia, Michigan, and Oregon. Georgia was a first-time recipient of cancer genomics funding, whereas Michigan and Oregon had long standing activities in cancer genomics and had received CDC funding in the past. By the end of the funding period, each state had well-functioning and impactful state-based programs in breast cancer genomics. This article highlights the impact of a few key state activities by using CDC’s Science Impact Framework. There were challenges to implementing public health genomics programs, including the need to develop relevant partnerships, the highly technical nature of the subject matter, a lack of genetic services in certain areas, and the difficulty in funding genetic services. Georgia, Michigan, and Oregon have served as models for others interested in initiating or expanding cancer genomics programs, and they helped to determine what works well for promoting and integrating public health genomics into existing systems.
Facilitators and Challenges in Psychosocial Adaptation to Being at Increased Familial Risk of Breast Cancer.

Science.gov (United States)

Heiniger, Louise; Price, Melanie A; Charles, Margaret; Butow, Phyllis N

2015-12-01

Little is known about the process of psychosocial adaptation to familial risk in tested and untested individuals at increased familial risk of cancer. This paper presents findings from a qualitative study of 36 women participating in the Kathleen Cuningham Consortium for Research into Familial Breast cancer (kConFab) Psychosocial study. Facilitators and challenges in psychosocial adaptation were identified through semi-structured interviews. The women, who were either tested (carriers or non-carriers of breast cancer susceptibility mutations) or untested (ineligible for testing or eligible but delayed or declined testing), described personal, support network and healthcare characteristics that impacted on the adaptation process. Challenges in one domain could be overcome by facilitators in other domains and key differences relating to whether women had undergone testing, or not, were identified. Tested and untested women with an increased familial risk of breast cancer may benefit from support tailored to their mutation testing status in order to enhance adaptation.
Hierarchical clustering of breast cancer methylomes revealed differentially methylated and expressed breast cancer genes.

Directory of Open Access Journals (Sweden)

I-Hsuan Lin

Full Text Available Oncogenic transformation of normal cells often involves epigenetic alterations, including histone modification and DNA methylation. We conducted whole-genome bisulfite sequencing to determine the DNA methylomes of normal breast, fibroadenoma, invasive ductal carcinomas and MCF7. The emergence, disappearance, expansion and contraction of kilobase-sized hypomethylated regions (HMRs and the hypomethylation of the megabase-sized partially methylated domains (PMDs are the major forms of methylation changes observed in breast tumor samples. Hierarchical clustering of HMR revealed tumor-specific hypermethylated clusters and differential methylated enhancers specific to normal or breast cancer cell lines. Joint analysis of gene expression and DNA methylation data of normal breast and breast cancer cells identified differentially methylated and expressed genes associated with breast and/or ovarian cancers in cancer-specific HMR clusters. Furthermore, aberrant patterns of X-chromosome inactivation (XCI was found in breast cancer cell lines as well as breast tumor samples in the TCGA BRCA (breast invasive carcinoma dataset. They were characterized with differentially hypermethylated XIST promoter, reduced expression of XIST, and over-expression of hypomethylated X-linked genes. High expressions of these genes were significantly associated with lower survival rates in breast cancer patients. Comprehensive analysis of the normal and breast tumor methylomes suggests selective targeting of DNA methylation changes during breast cancer progression. The weak causal relationship between DNA methylation and gene expression observed in this study is evident of more complex role of DNA methylation in the regulation of gene expression in human epigenetics that deserves further investigation.
Targeted next generation sequencing identifies functionally deleterious germline mutations in novel genes in early-onset/familial prostate cancer.

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Paula Paulo

2018-04-01

Full Text Available Considering that mutations in known prostate cancer (PrCa predisposition genes, including those responsible for hereditary breast/ovarian cancer and Lynch syndromes, explain less than 5% of early-onset/familial PrCa, we have sequenced 94 genes associated with cancer predisposition using next generation sequencing (NGS in a series of 121 PrCa patients. We found monoallelic truncating/functionally deleterious mutations in seven genes, including ATM and CHEK2, which have previously been associated with PrCa predisposition, and five new candidate PrCa associated genes involved in cancer predisposing recessive disorders, namely RAD51C, FANCD2, FANCI, CEP57 and RECQL4. Furthermore, using in silico pathogenicity prediction of missense variants among 18 genes associated with breast/ovarian cancer and/or Lynch syndrome, followed by KASP genotyping in 710 healthy controls, we identified "likely pathogenic" missense variants in ATM, BRIP1, CHEK2 and TP53. In conclusion, this study has identified putative PrCa predisposing germline mutations in 14.9% of early-onset/familial PrCa patients. Further data will be necessary to confirm the genetic heterogeneity of inherited PrCa predisposition hinted in this study.
Effects of irradiation for cervical cancer on subsequent breast cancer

International Nuclear Information System (INIS)

Harlan, L.C.M.

1985-01-01

Previous research suggests that cervical cancer patients have a lower risk of breast cancer than women in the general population. Possible explanations include opposing risk factors for cervical cancer and breast cancer, the effect of irradiation used to treat cervical cancer, or both. The purpose of this study was to explore the relationship between irradiation for cervical cancer and the subsequent development of breast cancer. There was no statistically significant relationship between radiation to the ovarian area and the risk of breast cancer in this study. However, the results were consistent with a 19% reduction in risk for women irradiated for cervical cancer when compared to nonirradiated women. In a dose-response analysis, there was a nonsignificant trend of decreased risk of breast cancer with increased radiation up to 1800 rad. There was no consistent pattern for higher doses. The trend, although nonsignificant, differed by age. Women <60 years of age at irradiation were generally at a lower risk of breast cancer than nonirradiated women. Women over 59 years were at an increased risk. There are some potentially important findings from this study which might influence medical care. These should be examined in the larger International Radiation Study
The Importance of Family History in Breast Cancer Patients in Primary Care Setting: a Cross-sectional Study.

Science.gov (United States)

Kartal, Mehtap; Ozcakar, Nilgun; Hatipoglu, Sehnaz; Tan, Makbule Neslisah; Guldal, Azize Dilek

2018-06-01

Screening recommendations of physicians are important for women to raise awareness about their risk factors and to promote appropriate screening behaviors. However, it seems challenging for primary care physicians (PCPs) to balance disease prevention and diagnosis, treatment. The objective of this study was to describe physicians' breast cancer consultancy practice including family history, cancer prevention issues for the women they care. This cross-sectional study included 577 women aged above 45 years, free of breast cancer, during their visits to their PCPs. Nearly half of the women reported their visit to PCPs for an annual examination during the year. Among them, 36.1% had first-degree relatives with cancer and 7.3% with breast cancer. But they reported to be asked about family history of cancer and informed about cancer prevention issues 35.1 and 26.4%, respectively. Cancer still seems to be a hard issue to be discussed, even with women visiting PCPs for annual examination. Asking first-degree relative with breast cancer can give PCPs the chance of determining women with increased risk and support women's appropriate understanding of their own risk in relation to their family history. This routine can make shared-decision making for developing person-centered approach for breast cancer screening possible. Further studies are needed for better understanding of loss of consultancy leadership of physicians for breast cancer.
Breast cancer after bilateral risk-reducing mastectomy

DEFF Research Database (Denmark)

Skytte, A-B; Crüger, Dorthe Gylling; Gerster, M

2011-01-01

This study aims to evaluate the incidence of breast cancer after risk-reducing mastectomy (RRM) in healthy BRCA mutation carriers. This study is a long-term follow-up of 307 BRCA mutation carriers of whom 96 chose RRM. None of the study participants had a previous history of breast or ovarian...... cancer nor had they undergone RRM or risk-reducing bilateral salpingo-oophorectomy (BSO) prior to the time of BRCA testing. The annual incidence of post-mastectomy breast cancer was 0.8% compared with 1.7% in the non-operated group. Implications of these findings in relation to genetic counseling...
Polycystic ovarian syndrome (PCOS), related symptoms/sequelae, and breast cancer risk in a population-based case-control study.

Science.gov (United States)

Kim, Jayeon; Mersereau, Jennifer E; Khankari, Nikhil; Bradshaw, Patrick T; McCullough, Lauren E; Cleveland, Rebecca; Shantakumar, Sumitra; Teitelbuam, Susan L; Neugut, Alfred I; Senie, Ruby T; Gammon, Marilie D

2016-03-01

Despite the overlap between the clinical symptoms/sequelae of polycystic ovarian syndrome (PCOS) and many known reproductive risk factors for breast cancer, the relationship between PCOS and breast cancer remains unclear, possibly because of the complex heterogeneity and challenges in diagnosing PCOS over time. We hypothesized that PCOS, specific PCOS-related symptoms/sequelae, or clusters of PCOS-related symptoms/sequelae may be differentially associated with pre- versus postmenopausal breast cancer risk. Cases were 1,508 women newly diagnosed with a first primary in situ or invasive breast, and the 1,556 population-based controls were frequency-matched by age. History of physician-diagnosed PCOS was reported by 2.2 % (n = 67), among whom oral contraceptive (OC) use, irregular menstruation, and infertility due to ovulatory dysfunction were common. Using unconditional logistic regression, adjusted odds ratios (95 % CI) for PCOS were increased for premenopausal [2.74 (1.13, 6.63)], but not postmenopausal breast cancer [0.87 (0.44, 1.71)]. We used cluster analysis to investigate whether risk among all women varied by PCOS-related symptoms/sequelae, such as reproductive irregularities, OC use, and components of insulin resistance. In the cluster analysis, odds ratios were elevated among premenopausal women who had a history of OC use and no ovulatory dysfunction [1.39 (1.03, 1.88)], compared to those with fewer number of PCOS-related symptoms/sequelae. PCOS and associated PCOS-related symptoms/sequelae including OC use may play a role in the development of premenopausal breast cancer. Our findings require confirmation in studies with a larger number of premenopausal women with systematically applied diagnostic criteria for PCOS.
Polycystic ovarian syndrome (PCOS), related symptoms/sequelae, and breast cancer risk in a population-based case-control study

Science.gov (United States)

Kim, Jayeon; Mersereau, Jennifer E.; Khankari, Nikhil; Bradshaw, Patrick T.; McCullough, Lauren E.; Cleveland, Rebecca; Shantakumar, Sumitra; Teitelbuam, Susan L.; Neugut, Alfred I.; Senie, Ruby T.; Gammon, Marilie D.

2016-01-01

Purpose Despite the overlap between the clinical symptoms/sequelae of polycystic ovarian syndrome (PCOS) and many known reproductive risk factors for breast cancer, the relationship between PCOS and breast cancer remains unclear, possibly because of the complex heterogeneity and challenges in diagnosing PCOS over time. We hypothesized that PCOS, specific PCOS-related symptoms/sequelae, or clusters of PCOS-related symptoms/sequelae, may be differentially associated with pre- vs. postmenopausal breast cancer risk. Materials and Methods Cases were 1,508 women newly diagnosed with a first primary in situ or invasive breast, and the 1,556 population-based controls were frequency-matched by age. Results History of physician-diagnosed PCOS was reported by 2.2% (n=67), among whom oral contraceptive (OC) use, irregular menstruation, and infertility due to ovulatory dysfunction were common. Using unconditional logistic regression, adjusted odds ratios (95% confidence intervals) for PCOS were increased for premenopausal [2.74 (1.13, 6.63)], but not post-menopausal breast cancer [0.87 (0.44, 1.71)]. We used cluster analysis to investigate whether risk among all women varied by PCOS-related symptoms/sequelae, such as reproductive irregularities, OC use, and components of insulin resistance. In the cluster analysis, odds ratios were elevated among premenopausal women who had a history of OC use and no ovulatory dysfunction [1.39 (1.03, 1.88)], compared to those with fewer number of PCOS-related symptoms/sequelae. Conclusion PCOS, and associated PCOS-related symptoms/sequelae including OC use, may play a role in the development of premenopausal breast cancer. Our findings require confirmation in studies with a larger number of premenopausal women with systematically applied diagnostic criteria for PCOS. PMID:26797454
BRCA2 Mutations in 154 Finnish Male Breast Cancer Patients

Directory of Open Access Journals (Sweden)

Kirsi Syrjäkoski

2004-09-01

Full Text Available The etiology and pathogenesis of male breast cancer (MBC are poorly known. This is due to the fact that the disease is rare, and large-scale genetic epidemiologic studies have been difficult to carry out. Here, we studied the frequency of eight recurrent Finnish BRCA2 founder mutations in a large cohort of 154 MBC patients (65% diagnosed in Finland from 1967 to 1996. Founder mutations were detected in 10 patients (6.5%, eight of whom carried the 9346(-2 A>G mutation. Two novel mutations (4075 delGT and 5808 del5 were discovered in a screening of the entire BRCA2 coding region in 34 samples. However, these mutations were not found in the rest of the 120 patients studied. Patients with positive family history of breast and/or ovarian cancer were often BRCA2 mutation carriers (44%, whereas those with no family history showed a low frequency of involvement (3.6%; P < .0001. Finally, we found only one Finnish MBC patient with 999 dell, the most common founder mutation in Finnish female breast cancer (FBC patients, and one that explains most of the hereditary FBC and MBC cases in Iceland. The variation in BRCA2 mutation spectrum between Finnish MBC patients and FBC patients in Finland and breast cancer patients in Iceland suggests that modifying genetic and environmental factors may significantly influence the penetrance of MBC and FBC in individuals carrying germline BRCA2 mutations in some populations.
Short-term effects of night shift work on breast cancer risk: a cohort study of payroll data.

Science.gov (United States)

Vistisen, Helene Tilma; Garde, Anne Helene; Frydenberg, Morten; Christiansen, Peer; Hansen, Åse Marie; Andersen, Johnni; Bonde, Jens Peter E; Kolstad, Henrik A

2017-01-01

Objectives The objective was to examine if night shift work is a short-term risk factor for breast cancer, including combined estrogen receptor (ER) and human epidermal growth factor 2 (HER2) breast cancer subtypes. Methods The cohort comprised 155 540 public sector female workers in Denmark who were followed from 2007-2012. Day-to-day work-hour information was available from payroll registers and 1245 incident cases of breast cancer were identified in national cancer registries together with receptor subtype information. Results A rate ratio (RR) of 0.90 [95% confidence interval (95% CI) 0.80-1.01] was observed for workers ever working night shifts during the follow-up period compared with workers only working day shifts after adjustment for age, age at first child, parity, family history of breast or ovarian cancer, sex hormones, medications related to alcoholism, family educational level, mammography screening, and other potential confounders. Comparable results were seen for the inception population of employees with first recorded employment after 2007. Modestly increased RR were suggested for breast cancer subtypes characterized by a positive HER2 status irrespective of ER status. Conclusions These findings do not support an overall short-term effect of night shift work on breast cancer risk. Future studies should explore further the impact of HER2 status.
Fertility concerns and preservation in younger women with breast cancer.

Science.gov (United States)

Anchan, Raymond Manohar; Ginsburg, Elizabeth Sarah

2010-06-01

Nearly 30% of breast cancer cases present in women younger than 50 years old. While newer treatment regimens employed are less gonadotoxic, regimens still consist of combination medications that include cyclophosphamide, known to deplete the number of primordial follicles, thereby potentially leading to infertility. For common regimens such as adriamycin/cytoxan (AC), the risk of premature ovarian failure was thought to be largely dependent on patient age, with the risk of complete ovarian failure women women >40 (Hortobagyi et al. (1986) [1]); however recent studies indicate that AC is considered to have intermediate risk for gonadotoxicity in women >40 years age. This review examines major strides in the field of reproductive medicine over the past 20 years including the use of leuprolide acetate, embryo cryopreservation, oocyte cryopreservation and ovarian tissue banking. We also discuss the role of gestational carriers and adoption in establishing families as a viable option for many of these cancer patients who may be unable to avail themselves of other alternatives to fertility preservation. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.
Familial risks of breast and prostate cancers: does the definition of the at risk period matter?

Science.gov (United States)

Brandt, Andreas; Bermejo, Justo Lorenzo; Sundquist, Jan; Hemminki, Kari

2010-03-01

'Being at familial risk' may have different connotations in studies on familial risk of cancer. The register-based definition of a family history considers individuals with an affected relative at familial risk independently of the family member's diagnostic time. Alternatively, the individuals are classified to be at familial risk only after the diagnosis date of their relative, relevant to clinical counselling and screening situations. The aim of this study was to compare familial breast and prostate cancer risks according to the two definitions. The nationwide Swedish Family-Cancer Database with information on cancers from 1958 to 2006 was used to calculate the hazard ratio of breast and prostate cancers according to family history using Cox regression. Family history was defined considering the number and type of affected relatives and the relative's diagnostic age, respectively. Individuals were considered at familial risk from their entry to the study or, alternatively, from the diagnostic time of the relative. Hazard ratios were equal whether individuals were considered at risk independent of the relative's diagnostic date or only after the relative's diagnostic date. These results indicate that studies on familial breast or prostate cancer risk which do not take the relative's diagnosis date into account are applicable to screening and clinical counselling situations. The estimates according to the register-based definition are based on larger numbers of patients, which may be crucial for analysis of small groups such as families of multiple cases. Copyright 2009 Elsevier Ltd. All rights reserved.
Costs and Benefits of Diagnosing Familial Breast Cancer

Directory of Open Access Journals (Sweden)

Ketil Heimdal

1999-01-01

Full Text Available Based on results from our surveillance program for women at risk for inherited breast cancer, we have calculated cost per year earned. Norwegian National Insurance Service reimbursement fees were used in the calculations. The calculated costs are based on empirical figures for expanding already established medical genetic departments and diagnostic outpatient clinics to undertake the work described. Cost per year earned was estimated at Euro 753 using our current practice of identifying the high-risk women through a traditional cancer family clinic.

The pathology of familial breast cancer: Immunohistochemistry and molecular analysis

International Nuclear Information System (INIS)

Osin, Pinchas P; Lakhani, Sunil R

1999-01-01

Extensive studies of BRCA1- and BRCA2-associated breast tumours have been carried out in the few years since the identification of these familial breast cancer predisposing genes. The morphological studies suggest that BRCA1 tumours differ from BRCA2 tumours and from sporadic breast cancers. Recent progress in immunohistochemistry and molecular biology techniques has enabled in-depth investigation of molecular pathology of these tumours. Studies to date have investigated issues such as steroid hormone receptor expression, mutation status of tumour suppressor genes TP53 and c-erbB2, and expression profiles of cell cycle proteins p21, p27 and cyclin D 1 . Despite relative paucity of data, strong evidence of unique biological characteristics of BRCA1-associated breast cancer is accumulating. BRCA1-associated tumours appear to show an increased frequency of TP53 mutations, frequent p53 protein stabilization and absence of imunoreactivity for steroid hormone receptors. Further studies of larger number of samples of both BRCA1- and BRCA2-associated tumours are necessary to clarify and confirm these observations
Modifiers of the Efficacy of Risk-Reducing Salpingo-Oophorectomy for the Prevention of Breast and Ovarian Cancer in Carriers of BRCA1 and BRCA2 Mutations

National Research Council Canada - National Science Library

Kauff, Noah

2004-01-01

.... This plan included 1) conduct of a prospective study examining modifiers of the efficacy of risk-reducing salpingo-oophorectomy for the prevention of breast and ovarian cancer in carriers of BRCA mutations; and 2...
African American women's limited knowledge and experiences with genetic counseling for hereditary breast cancer.

Science.gov (United States)

Sheppard, Vanessa B; Graves, Kristi D; Christopher, Juleen; Hurtado-de-Mendoza, Alejandra; Talley, Costellia; Williams, Karen Patricia

2014-06-01

Genetic counseling and testing for hereditary breast cancer have the potential benefit of early detection and early interventions in African American women. However, African American women have low use of these services compared to White women. We conducted two focus groups with African American women diagnosed with breast cancer (affected group, n = 13) and women with at least one first-degree relative with breast/ovarian cancer (unaffected group, n = 8). A content analysis approach was employed to analyze interview data. Breast cancer survivors had more knowledge about genetic counseling and testing than participants who were unaffected with cancer. However, knowledge about genetic counseling was limited in both groups. Barriers to pursuing genetic counseling and testing included poor understanding of the genetic counseling and testing process, fear of carrying the mutation, concerns about discrimination, and cost. Motivators to participate in genetic counseling and testing included desire to help family members, insurance coverage, and potential of benefiting the larger African American community. Education efforts are needed to increase genetic counseling and testing awareness in the African American community.
Mutation and Methylation Analysis of the Chromodomain-Helicase-DNA Binding 5 Gene in Ovarian Cancer

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Kylie L. Gorringe

2008-11-01

Full Text Available Chromodomain, helicase, DNA binding 5 (CHD5 is a member of a subclass of the chromatin remodeling Swi/Snf proteins and has recently been proposed as a tumor suppressor in a diverse range of human cancers. We analyzed all 41 coding exons of CHD5 for somatic mutations in 123 primary ovarian cancers as well as 60 primary breast cancers using high-resolution melt analysis. We also examined methylation of the CHD5 promoter in 48 ovarian cancer samples by methylation-specific single-stranded conformation polymorphism and bisulfite sequencing. In contrast to previous studies, no mutations were identified in the breast cancers, but somatic heterozygous missense mutations were identified in 3 of 123 ovarian cancers. We identified promoter methylation in 3 of 45 samples with normal CHD5 and in 2 of 3 samples with CHD5 mutation, suggesting these tumors may have biallelic inactivation of CHD5. Hemizygous copy number loss at CHD5 occurred in 6 of 85 samples as assessed by single nucleotide polymorphism array. Tumors with CHD5 mutation or methylation were more likely to have mutation of KRAS or BRAF (P = .04. The aggregate frequency of CHD5 haploinsufficiency or inactivation is 16.2% in ovarian cancer. Thus, CHD5 may play a role as a tumor suppressor gene in ovarian cancer; however, it is likely that there is another target of the frequent copy number neutral loss of heterozygosity observed at 1p36.
Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

OpenAIRE

Lawrenson, Kate; Kar, Siddhartha; McCue, Karen; Kuchenbaeker, Karoline; Michailidou, Kyriaki; Tyrer, Jonathan; Beesley, Jonathan; Ramus, Susan J.; Li, Qiyuan; Delgado, Melissa K.; Lee, Janet M.; Aittomaki, Kristiina; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker

2016-01-01

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10−20), ER-negative BC (P=1.1 × 10−13), BRCA1-associated BC (P=7.7 × 10−16) and triple negative BC (P-diff=2 × 10−5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10...
Presymptomatic breast cancer in Egypt: role of BRCA1 and BRCA2 tumor suppressor genes mutations detection

Directory of Open Access Journals (Sweden)

Hashishe Mervat M

2010-06-01

Full Text Available Abstract Background Breast cancer is one of the most common diseases affecting women. Inherited susceptibility genes, BRCA1 and BRCA2, are considered in breast, ovarian and other common cancers etiology. BRCA1 and BRCA2 genes have been identified that confer a high degree of breast cancer risk. Objective Our study was performed to identify germline mutations in some exons of BRCA1 and BRCA2 genes for the early detection of presymptomatic breast cancer in females. Methods This study was applied on Egyptian healthy females who first degree relatives to those, with or without a family history, infected with breast cancer. Sixty breast cancer patients, derived from 60 families, were selected for molecular genetic testing of BRCA1 and BRCA2 genes. The study also included 120 healthy first degree female relatives of the patients, either sisters and/or daughters, for early detection of presymptomatic breast cancer mutation carriers. Genomic DNA was extracted from peripheral blood lymphocytes of all the studied subjects. Universal primers were used to amplify four regions of the BRCA1 gene (exons 2,8,13 and 22 and one region (exon 9 of BRCA2 gene using specific PCR. The polymerase chain reaction was carried out. Single strand conformation polymorphism assay and heteroduplex analysis were used to screen for mutations in the studied exons. In addition, DNA sequencing of the normal and mutated exons were performed. Results Mutations in both BRCA1 and BRCA2 genes were detected in 86.7% of the families. Current study indicates that 60% of these families were attributable to BRCA1 mutations, while 26.7% of them were attributable to BRCA2 mutations. Results showed that four mutations were detected in the BRCA1 gene, while one mutation was detected in the BRCA2 gene. Asymptomatic relatives, 80(67% out of total 120, were mutation carriers. Conclusions BRCA1 and BRCA2 genes mutations are responsible for a significant proportion of breast cancer. BRCA mutations
Emotional, Biological, and Cognitive Impact of a Brief Expressive Writing Intervention for African American Women at Familial Breast Cancer

National Research Council Canada - National Science Library

Valdimarsdottir, Heiddis

2007-01-01

...) than women without familial breast cancer risk. The proposed study will examine the impact of an expressive writing intervention on emotional biological, and cognitive processes among women at familial breast cancer risk...
ATM variants and cancer risk in breast cancer patients from Southern Finland

Directory of Open Access Journals (Sweden)

Aittomäki Kristiina

2006-08-01

Full Text Available Abstract Background Individuals heterozygous for germline ATM mutations have been reported to have an increased risk for breast cancer but the role for ATM genetic variants for breast cancer risk has remained unclear. Recently, a common ATM variant, ATMivs38 -8T>C in cis with the ATMex39 5557G>A (D1853N variant, was suggested to associate with bilateral breast cancer among familial breast cancer patients from Northern Finland. We have here evaluated the 5557G>A and ivs38-8T>C variants in an extensive case-control association analysis. We also aimed to investigate whether there are other ATM mutations or variants contributing to breast cancer risk in our population. Methods Two common ATM variants, 5557G>A and ivs38-8T>C, previously suggested to associate with bilateral breast cancer, were genotyped in an extensive set of 786 familial and 884 unselected breast cancer cases as well as 708 healthy controls. We also screened the entire coding region and exon-intron boundaries of the ATM gene in 47 familial breast cancer patients and constructed haplotypes of the patients. The identified variants were also evaluated for increased breast cancer risk among additional breast cancer cases and controls. Results Neither of the two common variants, 5557G>A and ivs38-8T>C, nor any haplotype containing them, was significantly associated with breast cancer risk, bilateral breast cancer or multiple primary cancers in any of the patient groups or subgoups. Three rare missense alterations and one intronic change were each found in only one patient of over 250 familial patients studied and not among controls. The fourth missense alteration studied further was found with closely similar frequencies in over 600 familial cases and controls. Conclusion Altogether, our results suggest very minor effect, if any, of ATM genetic variants on familial breast cancer in Southern Finland. Our results do not support association of the 5557G>A or ivs38-8T>C variant with
Is there an association between invasive lobular carcinoma of the breast and a family history of gastric cancer?

Science.gov (United States)

Chikman, Bar; Davidson, Tima; Kais, Hasan; Jeroukhimov, Igor; Leshno, Ari; Sandbank, Judith; Halevy, Ariel; Lavy, Ron

2016-01-01

CDH1 gene mutations have been found to be associated with diffuse type gastric cancer and invasive lobular carcinoma (ILC) of the breast. To the best of our knowledge, this is the only study relating a family history of gastric cancer to ILC of the breast. We conducted a retrospective study comparing the family history of malignancies in patients with invasive ductal carcinoma (IDC) of the breast and ILC treated in our Medical Center. The comparison was evaluated in both types of breast cancer groups, dividing the patients into two age groups, cancer was reported in 7.2 % in the ILC group as compared to 2.3 % in the IDC group, P cancer was more common in the ILC group as opposed to the IDC group, 18 versus 8.1 % respectively, P = 0.002 and persisted in both age groups. We conclude that a family history of malignancies in first degree relatives is more common in patients with ILC than IDC and that there is a significant association between a family history of gastric cancer and ILC.
Combinatorial effect of non-steroidal anti-inflammatory drugs and NF-κB inhibitors in ovarian cancer therapy.

Directory of Open Access Journals (Sweden)

Luiz F Zerbini

Full Text Available Several epidemiological studies have correlated the use of non-steroidal anti-inflammatory drugs (NSAID with reduced risk of ovarian cancer, the most lethal gynecological cancer, diagnosed usually in late stages of the disease. We have previously established that the pro-apoptotic cytokine melanoma differentiation associated gene-7/Interleukin-24 (mda-7/IL-24 is a crucial mediator of NSAID-induced apoptosis in prostate, breast, renal and stomach cancer cells. In this report we evaluated various structurally different NSAIDs for their efficacies to induce apoptosis and mda-7/IL-24 expression in ovarian cancer cells. While several NSAIDs induced apoptosis, Sulindac Sulfide and Diclofenac most potently induced apoptosis and reduced tumor growth. A combination of these agents results in a synergistic effect. Furthermore, mda-7/IL-24 induction by NSAIDs is essential for programmed cell death, since inhibition of mda-7/IL-24 by small interfering RNA abrogates apoptosis. mda-7/IL-24 activation leads to upregulation of growth arrest and DNA damage inducible (GADD 45 α and γ and JNK activation. The NF-κB family of transcription factors has been implicated in ovarian cancer development. We previously established NF-κB/IκB signaling as an essential step for cell survival in cancer cells and hypothesized that targeting NF-κB could potentiate NSAID-mediated apoptosis induction in ovarian cancer cells. Indeed, combining NSAID treatment with NF-κB inhibitors led to enhanced apoptosis induction. Our results indicate that inhibition of NF-κB in combination with activation of mda-7/IL-24 expression may lead to a new combinatorial therapy for ovarian cancer.
Sequencing analysis of SLX4/FANCP gene in Italian familial breast cancer cases.

Directory of Open Access Journals (Sweden)

Irene Catucci

Full Text Available Breast cancer can be caused by germline mutations in several genes that are responsible for different hereditary cancer syndromes. Some of the genes causing the Fanconi anemia (FA syndrome, such as BRCA2, BRIP1, PALB2, and RAD51C, are associated with high or moderate risk of developing breast cancer. Very recently, SLX4 has been established as a new FA gene raising the question of its implication in breast cancer risk. This study aimed at answering this question sequencing the entire coding region of SLX4 in 526 familial breast cancer cases from Italy. We found 81 different germline variants and none of these were clearly pathogenic. The statistical power of our sample size allows concluding that in Italy the frequency of carriers of truncating mutations of SLX4 may not exceed 0.6%. Our results indicate that testing for SLX4 germline mutations is unlikely to be relevant for the identification of individuals at risk of breast cancer, at least in the Italian population.
Crowdsourcing awareness: exploration of the ovarian cancer knowledge gap through Amazon Mechanical Turk.

Science.gov (United States)

Carter, Rebecca R; DiFeo, Analisa; Bogie, Kath; Zhang, Guo-Qiang; Sun, Jiayang

2014-01-01

Ovarian cancer is the most lethal gynecologic disease in the United States, with more women dying from this cancer than all gynecological cancers combined. Ovarian cancer has been termed the "silent killer" because some patients do not show clear symptoms at an early stage. Currently, there is a lack of approved and effective early diagnostic tools for ovarian cancer. There is also an apparent severe knowledge gap of ovarian cancer in general and of its indicative symptoms among both public and many health professionals. These factors have significantly contributed to the late stage diagnosis of most ovarian cancer patients (63% are diagnosed at Stage III or above), where the 5-year survival rate is less than 30%. The paucity of knowledge concerning ovarian cancer in the United States is unknown. The present investigation examined current public awareness and knowledge about ovarian cancer. The study implemented design strategies to develop an unbiased survey with quality control measures, including the modern application of multiple statistical analyses. The survey assessed a reasonable proxy of the US population by crowdsourcing participants through the online task marketplace Amazon Mechanical Turk, at a highly condensed rate of cost and time compared to traditional recruitment methods. Knowledge of ovarian cancer was compared to that of breast cancer using repeated measures, bias control and other quality control measures in the survey design. Analyses included multinomial logistic regression and categorical data analysis procedures such as correspondence analysis, among other statistics. We confirmed the relatively poor public knowledge of ovarian cancer among the US population. The simple, yet novel design should set an example for designing surveys to obtain quality data via Amazon Mechanical Turk with the associated analyses.
Amplification of PVT1 contributes to the pathophysiology ofovarian and breast cancer

Energy Technology Data Exchange (ETDEWEB)

Guan, Yinghui; Kuo, Wen-Lin; Stilwell, Jackie; Takano, Hirokuni; Lapuk, Anna; Fridlyand, Jane; Mao, Jian-Hua; Yu, Mami; Ginzinger, David; Gray, Joe W.

2007-10-09

Purpose. This study was designed to elucidate the role of amplification at 8q24 in the pathophysiology of ovarian and breast cancer since increased copy number at this locus is one of the most frequent genomic abnormalities in these cancers. Experimental Design. To accomplish this, we assessed the association of amplification at 8q24 with outcome in ovarian cancers using FISH to tissue microarrays and measured responses of ovarian and breast cancer cell lines to specific small interfering RNAs (siRNA) against the oncogene, MYC, and a putative noncoding RNA, PVT1, both of which map to 8q24. Results. Amplification of 8q24 was associated with significantly reduced survival duration. In addition, siRNA-mediated reduction in either PVT1 or MYC expression inhibited proliferation in breast and ovarian cancer cell lines in which they were both amplified and over expressed but not in lines in which they were not amplified/over expressed. Inhibition of PVT1 expression also induced a strong apoptotic response in cell lines in which it was over expressed but not in lines in which it was not amplified/over expressed. Inhibition of MYC, on the other hand, did not induce an apoptotic response in cell lines in which MYC was amplified and over expressed. Conclusions. These results suggest that MYC and PVT1 contribute independently to ovarian and breast pathogenesis when over expressed because of genomic abnormalities. They also suggest that PVT1 mediated inhibition of apoptosis may explain why amplification of 8q24 is associated with reduced survival duration in patients treated with agents that act through apoptotic mechanisms.
Cross-Ethnicity Measurement Equivalence of Family Coping for Breast Cancer Survivors

Science.gov (United States)

Lim, Jung-won; Townsend, Aloen

2012-01-01

Objective: The current study examines the equivalence of a measure of family coping, the Family Crisis Oriented Personal Evaluation scales (F-COPES), in Chinese American and Korean American breast cancer survivors (BCS). Methods: Factor structure and cross-ethnicity equivalence of the F-COPES were tested using structural equation modeling with 157…
A dyadic analysis of stress processes in Latinas with breast cancer and their family caregivers.

Science.gov (United States)

Segrin, Chris; Badger, Terry A; Sikorskii, Alla; Crane, Tracy E; Pace, Thaddeus W W

2018-03-01

Breast cancer diagnosis and treatment negatively affect quality of life for survivors and their family caregivers. The stress process model has been useful for describing the cascade of social and psychological experiences that culminate in degraded quality of life for both survivors and their family caregivers. This study is designed to test theoretically specified predictors of negative psychosocial outcomes in a dyadic context. Participants were 230 dyads composed of Latinas recently diagnosed with breast cancer and their primary family caregiver, who completed measures of socioeconomic status, stress, family conflict, depression, and anxiety. Data were analyzed following the Actor-Partner Interdependence Mediation Model in structural equation modeling. For both survivors and caregivers, there were significant direct and indirect actor effects (through family conflict) of perceived stress on depression and anxiety. Several indirect partner effects were also evident in this sample. Specifically, caregivers' stress was predictive of survivors' depression and anxiety through survivors' increased perceptions of family conflict. As predicted by the stress process model, stress and family conflict were predictive of psychological distress in breast cancer survivors and their family caregivers. Significant partner effects in the Actor-Partner Interdependence Mediation Model suggest that there are some dyadic influences, particularly from caregivers' stress to survivors' perceptions of exacerbated family conflict. These findings show how strained family relationships can aggravate the well-being of cancer survivors and their family caregivers through this challenging experience. Copyright © 2017 John Wiley & Sons, Ltd.
BRCA1 status in Pakistani breast cancer patients with moderate family history

International Nuclear Information System (INIS)

Moatter, T.; Pervez, S.; Khan, S.; Azam, I.

2011-01-01

Objective: To determine BRCA1 status in breast carcinoma patients of Pakistani origin. Study Design: Observational study. Place and Duration of Study: The Oncology Clinics of the Aga Khan University Hospital, Karachi, between May 2005 and December 2009. Methodology: Fifty three breast cancer patients based on clinical and laboratory diagnosis were recruited for this study. Moderate family history was defined as having a close relative (mother, daughter, sister) diagnosed with breast cancer under 45 years. Peripheral blood samples were collected from each patient in a 5 ml tube containing EDTA as anticoagulant. Subsequent to DNA extraction, mutational analysis of BRCA1 exons 2, 5, 6, 16, 20 and 22 was carried out using single strand conformation polymorphism (SSCP) assay while protein truncation test (PTT) was used to examine mutations in exon 11. All BRCA1 sequence variants were confirmed by DNA sequencing. Results: Twenty-three patients were diagnosed with early onset breast cancer, 30 patients had moderate family history. At the time of diagnosis, the median age of enrolled patients was 39 years (range 24-65 years). Out of 53 patients, analyzed by SSCP assay, mobility shift was detected in exon 6, 16 and 20 of three patients, whereas one patient was tested positive for mutation in exon 11 by PTT assays. All patients with BRCA1 mutations were further confirmed by DNA sequencing analysis. In exon 16 c.4837A > G was confirmed, which is a common polymorphism reported in several populations including Asians. Moreover, mutations in exon 6 (c.271T > G), exon 20 (c.5231 del G) and exon 11 (c.1123 T > G) were reported first time in the Pakistani population. Several BRCA1 mutations were observed in Pakistani breast cancer patients with moderate family history. Therefore, mutation-based genetic counselling for patients with moderate family history can facilitate management, if one first or second degree relative or early onset disease is apparent. (author)
Ovarian cancer and smoking

DEFF Research Database (Denmark)

Beral, V; Gaitskell, K; Hermon, C

2012-01-01

Smoking has been linked to mucinous ovarian cancer, but its effects on other ovarian cancer subtypes and on overall ovarian cancer risk are unclear, and the findings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence....
Screening for breast cancer with MRI: recent experience from the Australian Capital Territory

International Nuclear Information System (INIS)

Price, J.; Chen, S. W.

2009-01-01

Full text: The American Cancer Society now recommends annual MRI screening for women at 20-25% or greater lifetime risk of breast cancer. The role of MRI screening in other risk subgroups is unproved because of insufficient data. Our study comprised 209 breast MRI scans carried out in 171 asymptomatic patients (age range 22-67 years, mean 46 years), referred between January 2005 and June 2008. Targeted ultrasound was carried out in 32 episodes (15%) and biopsies were taken in 23 patients (13%). In four patients, MR-guided procedures were required to establish a diagnosis, two using hook-wire localization and two by means of vacuum-assisted biopsy. Seven cancers were detected by MRI in the 171 patients, with a yield of 4.1%. Only one of the seven cancers was also shown by x-ray mammography. Four patients had invasive ductal cancer (all axillary node negative) and three had high-grade ductal carcinoma in situ or pleomorphic lobular carcinoma in situ. The three women with in situ disease were all potentially high risk, based on the National Breast and Ovarian Cancer Centre (NBOCC) criteria. Three women with invasive breast cancer were at only average risk based on NBOCC criteria, but two of these had extremely dense breasts. A fourth patient, found to have multifocal invasive cancer, had a personal history of contralateral breast cancer, but no relevant family history. Our findings suggest that breast MRI could be used to screen a larger Australian population at increased risk of developing breast cancer.
African American Women’s Limited Knowledge and Experiences with Genetic Counseling for Hereditary Breast Cancer

Science.gov (United States)

Sheppard, Vanessa B.; Graves, Kristi D.; Christopher, Juleen; Hurtado-de-Mendoza, Alejandra; Talley, Costellia; Williams, Karen Patricia

2014-01-01

Genetic counseling and testing for hereditary breast cancer have the potential benefit of early detection and early interventions in African American women. However, African American women have low use of these services compared to White women. We conducted two focus groups with African American women diagnosed with breast cancer (affected group, n=13) and women with at least one first-degree relative with breast/ovarian cancer (unaffected group, n= 8). A content analysis approach was employed to analyze interview data. Breast cancer survivors had more knowledge about genetic counseling and testing than participants who were unaffected with cancer. However, knowledge about genetic counseling was limited in both groups. Barriers to pursuing genetic counseling and testing included poor understanding of the genetic counseling and testing process, fear of carrying the mutation, concerns about discrimination, and cost. Motivators to participate in genetic counseling and testing included desire to help family members, insurance coverage, and potential of benefiting the larger African American community. Education efforts are needed to increase genetic counseling and testing awareness in the African American community. PMID:24186304
Prevalence of BRCA1 and BRCA2 mutations in unselected breast cancer patients from Peru.

Science.gov (United States)

Abugattas, J; Llacuachaqui, M; Allende, Y Sullcahuaman; Velásquez, A Arias; Velarde, R; Cotrina, J; Garcés, M; León, M; Calderón, G; de la Cruz, M; Mora, P; Royer, R; Herzog, J; Weitzel, J N; Narod, S A

2015-10-01

The prevalence of BRCA1 and BRCA2 mutations among breast cancer patients in Peru has not yet been explored. We enrolled 266 women with breast cancer from a National cancer hospital in Lima, Peru, unselected for age or family history. DNA was screened with a panel of 114 recurrent Hispanic BRCA mutations (HISPANEL). Among the 266 cases, 13 deleterious mutations were identified (11 in BRCA1 and 2 in BRCA2), representing 5% of the total. The average age of breast cancer in the mutation-positive cases was 44 years. BRCA1 185delAG represented 7 of 11 mutations in BRCA1. Other mutations detected in BRCA1 included: two 2080delA, one 943ins10, and one 3878delTA. The BRCA2 3036del4 mutation was seen in two patients. Given the relatively low cost of the HISPANEL test, one should consider offering this test to all Peruvian women with breast or ovarian cancer. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acceptance of, inclination for, and barriers in genetic testing for gene mutations that increase the risk of breast and ovarian cancers among female residents of Warsaw

Science.gov (United States)

Dera, Paulina; Religioni, Urszula; Duda-Zalewska, Aneta; Deptała, Andrzej

2016-01-01

Aim of the study To check the degree of acceptance of, inclination for, and barriers in genetic testing for gene mutations that increase the risk of breast and ovarian cancers among female residents of Warsaw Material and methods This study involved 562 women between 20 and 77 years of age, all of whom were patients visiting gynaecologists practising in clinics in the City of Warsaw. The studied population was divided into six age categories. The study method was a diagnostic poll conducted with the use of an original questionnaire containing 10 multiple-choice questions. Results Nearly 70% of the women showed an interest in taking a test to detect predispositions to develop breast and ovarian cancer. More than 10% did not want to take such a test, while every fifth women was undecided. No statistically significant differences between the respondents’ willingness to pay and education were found (p = 0.05). The most frequent answer given by women in all groups was that the amount to pay was too high. Such an answer was given by 52.17% of women with primary education, 65.22% of women with vocational education, 58.61% of women with secondary education, and 41.62% of women with higher education. Conclusions Women with a confirmed increased risk of developing breast and/or ovarian cancer due to inter alia the presence of BRCA1 and BRCA2 gene mutations should pay particular attention to 1st and 2nd level prophylaxis. PMID:27095945
Acceptance of, inclination for, and barriers in genetic testing for gene mutations that increase the risk of breast and ovarian cancers among female residents of Warsaw

Directory of Open Access Journals (Sweden)

Dominik Olejniczak

2016-03-01

Full Text Available Aim of the study : To check the degree of acceptance of, inclination for, and barriers in genetic testing for gene mutations that increase the risk of breast and ovarian cancers among female residents of Warsaw Material and methods : This study involved 562 women between 20 and 77 years of age, all of whom were patients visiting gynaecologists practising in clinics in the City of Warsaw. The studied population was divided into six age categories. The study method was a diagnostic poll conducted with the use of an original questionnaire containing 10 multiple-choice questions. Results: Nearly 70% of the women showed an interest in taking a test to detect predispositions to develop breast and ovarian cancer. More than 10% did not want to take such a test, while every fifth women was undecided. No statistically significant differences between the respondents’ willingness to pay and education were found (p = 0.05. The most frequent answer given by women in all groups was that the amount to pay was too high. Such an answer was given by 52.17% of women with primary education, 65.22% of women with vocational education, 58.61% of women with secondary education, and 41.62% of women with higher education. Conclusions : Women with a confirmed increased risk of developing breast and/or ovarian cancer due to inter alia the presence of BRCA1 and BRCA2 gene mutations should pay particular attention to 1 st and 2 nd level prophylaxis.
Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer

DEFF Research Database (Denmark)

Andersson, Ulrika; Wibom, Carl; Cederquist, Kristina

2014-01-01

-dependent probe amplification. These families all had at least 2 verified glioma cases and a third reported or verified glioma case in the same family or 2 glioma cases in the family with at least one family member affected with melanoma, colon, or breast cancer.The genomic areas covering TP53, CDKN2A, MLH1...
Risk factors related to female breast cancer in regions of Northeast China: a 1:3 matched case-control population-based study.

Science.gov (United States)

Yu, Zhi-gang; Jia, Cun-xian; Geng, Cui-zhi; Tang, Jin-hai; Zhang, Jin; Liu, Li-yuan

2012-03-01

There has been an increase in the incidence of breast cancer in China, but no definite risk and protective factors for breast cancer have been identified in Chinese females. This study was designed to identify the risk factors for female breast cancer in North and East China. A 1:3 matched, case-control study was conducted. All of the subjects in the case and control groups were selected from a previous epidemiological survey of 122 058 females aged 25 to 70 years. Single and multiple Logistic regression analyses were used to study potential factors in the development of breast cancer. Significant differences at the level of α=0.20 between case and control groups were observed for the following factors: economic status, social status, family annual income, bean product consumption, body mass index (BMI), family history of breast cancer in the first or second degree, number of miscarriages, menstrual pattern, benign breast disease history, nipple leakage, inverted nipple, history of diabetes mellitus, history of hypertension, history of ovarian cyst, physical exercise, current and global quality of life satisfaction, healthy behavior and prevention, and scores of breast cancer-related knowledge. After Cox-regression model analysis (α=0.10), six factors were found to be significantly related to breast cancer, of which the ORs and 95%CIs were: BMI, 1.696 (1.169-2.460, P=0.005); benign breast disease history, 2.672 (0.848-8.416, P=0.093); family history of breast cancer, 7.080 (1.758-28.551, P=0.006); number of miscarriages, 1.738 (1.014-2.978, P=0.044); global quality of life satisfaction, 3.044 (1.804-5.136, P=0.000); healthy behavior and prevention, 3.294 (1.692-6.412, P=0.000). A comprehensive range of factors related to breast cancer was identified. Women should be educated about a healthy lifestyle, especially those with a family history of breast cancer or a personal history of benign breast disease.
Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium

DEFF Research Database (Denmark)

Pearce, C L; Near, A M; Van Den Berg, D J

2009-01-01

The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had...... been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P... and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted....
Survival in common cancers defined by risk and survival of family members

Directory of Open Access Journals (Sweden)

Jianguang Ji

2011-10-01

Full Text Available Studies on survival between familial and sporadic cancers have been inconclusive and only recent data on a limited number of cancers are available on the concordance of survival between family members. In this review, we address these questions by evaluating the published and unpublished data from the nation-wide Swedish Family-Cancer Database and a total of 13 cancer sites were assessed. Using sporadic cancer as reference, HRs were close to 1.0 for most of the familial cancers in both the offspring and parental generations, which suggested that survival in patients with familial and sporadic cancers was equal, with an exception for ovarian cancer with a worse prognosis. Compared to offspring whose parents had a poor survival, those with a good parental survival had a decreased risk of death for most cancers and HR was significantly decreased for cancers in the breast, prostate, bladder, and kidney. For colorectal and nervous system cancers, favorable survival between the generations showed a borderline significance. These data are consistent in showing that both good and poor survival in certain cancers aggregate in families. Genetic factors are likely to contribute to the results. These observations call for intensified efforts to consider heritability in survival as one mechanism regulating prognosis in cancer patients.
Crowdsourcing awareness: exploration of the ovarian cancer knowledge gap through Amazon Mechanical Turk.

Directory of Open Access Journals (Sweden)

Rebecca R Carter

Full Text Available BACKGROUND: Ovarian cancer is the most lethal gynecologic disease in the United States, with more women dying from this cancer than all gynecological cancers combined. Ovarian cancer has been termed the "silent killer" because some patients do not show clear symptoms at an early stage. Currently, there is a lack of approved and effective early diagnostic tools for ovarian cancer. There is also an apparent severe knowledge gap of ovarian cancer in general and of its indicative symptoms among both public and many health professionals. These factors have significantly contributed to the late stage diagnosis of most ovarian cancer patients (63% are diagnosed at Stage III or above, where the 5-year survival rate is less than 30%. The paucity of knowledge concerning ovarian cancer in the United States is unknown. METHODS: The present investigation examined current public awareness and knowledge about ovarian cancer. The study implemented design strategies to develop an unbiased survey with quality control measures, including the modern application of multiple statistical analyses. The survey assessed a reasonable proxy of the US population by crowdsourcing participants through the online task marketplace Amazon Mechanical Turk, at a highly condensed rate of cost and time compared to traditional recruitment methods. CONCLUSION: Knowledge of ovarian cancer was compared to that of breast cancer using repeated measures, bias control and other quality control measures in the survey design. Analyses included multinomial logistic regression and categorical data analysis procedures such as correspondence analysis, among other statistics. We confirmed the relatively poor public knowledge of ovarian cancer among the US population. The simple, yet novel design should set an example for designing surveys to obtain quality data via Amazon Mechanical Turk with the associated analyses.
Assessment of SLX4 Mutations in Hereditary Breast Cancers.

Directory of Open Access Journals (Sweden)

Sohela Shah

Full Text Available SLX4 encodes a DNA repair protein that regulates three structure-specific endonucleases and is necessary for resistance to DNA crosslinking agents, topoisomerase I and poly (ADP-ribose polymerase (PARP inhibitors. Recent studies have reported mutations in SLX4 in a new subtype of Fanconi anemia (FA, FA-P. Monoallelic defects in several FA genes are known to confer susceptibility to breast and ovarian cancers.To determine if SLX4 is involved in breast cancer susceptibility, we sequenced the entire SLX4 coding region in 738 (270 Jewish and 468 non-Jewish breast cancer patients with 2 or more family members affected by breast cancer and no known BRCA1 or BRCA2 mutations. We found a novel nonsense (c.2469G>A, p.W823* mutation in one patient. In addition, we also found 51 missense variants [13 novel, 23 rare (MAF1%], of which 22 (5 novel and 17 rare were predicted to be damaging by Polyphen2 (score = 0.65-1. We performed functional complementation studies using p.W823* and 5 SLX4 variants (4 novel and 1 rare cDNAs in a human SLX4-null fibroblast cell line, RA3331. While wild type SLX4 and all the other variants fully rescued the sensitivity to mitomycin C (MMC, campthothecin (CPT, and PARP inhibitor (Olaparib the p.W823* SLX4 mutant failed to do so.Loss-of-function mutations in SLX4 may contribute to the development of breast cancer in very rare cases.
Menarche menopause breast cancer risk individual

NARCIS (Netherlands)

Collaborative Group on Hormonal Factors in Breast Cancer; Bausch-Goldbohm, R.A.

2012-01-01

BACKGROUND:Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected
BRCA1 and TP53 Gene-Mutations: Family Predisposition and Radioecological Risk of Developing Breast Cancer.

Science.gov (United States)

Apsalikov, Bakytbek; Manambaeva, Zukhra; Ospanov, Erlan; Massabayeva, Meruyert; Zhabagin, Kuantkan; Zhagiparova, Zhanar; Maximov, Vladymir; Voropaeva, Elena; Apsalikov, Kazbek; Belikhina, Tatiana; Abdrahmanov, Ramil; Cherepkova, Elena; Tanatarov, Sayat; Massadykov, Adilzhan; Urazalina, Naylia

2016-01-01

Frequencies of polymorphisms of genes BRCA1 and TP53 in breast cancer (BC) patients with a BC family history and radiation history were assessed and compared in the Semey region of Kazakhstan. The study included 60 women directly irradiated by the activities of the Semipalatinsk test site with a calculated effective equivalent dose of 500 mSv and their first generation descendants (group BC+Her+Exp); 65 women with family BC and absence of radiological history - the effective equivalent dose due to anthropogenic sources not exceeding 50 mSv (group BC+Her-Exp). The comparison group consisted of 65 women patients with breast cancer without family and radiological history (BC-Her-Exp). The control group comprised 60 women without breast cancer and without family and radiological history (nonBC). We carried out the genotyping of the polymorphisms c.2311T>C, c.4308T>C and 5382insC of the BRCA1 gene and rs1042522 of the TP53 gene. The frequency of the polymorphism c.2311T>C was significantly higher in patients of the group BC+Her+Exp than in healthy women, and of the polymorphism 5382insC in BC+Her+Exp compared to all other groups. The frequency of the rs1042522 polymorphism of TP53 was significantly higher in all groups of patients with breast cancer compared with the control group. Differences between groups of women with breast cancer were significant only in BC+Her+Exp vs. BC+Her-Exp. Combinations of polymorphisms of the genes BRCA1 and TP53 predominated in women with a family and radiological history.
Ovarian Cancer and Comorbidity

DEFF Research Database (Denmark)

Noer, Mette Calundann; Sperling, Cecilie Dyg; Ottesen, Bent

2017-01-01

OBJECTIVES: Comorbidity influences survival in ovarian cancer, but the causal relations between prognosis and comorbidity are not well characterized. The aim of this study was to investigate the associations between comorbidity, system delay, the choice of primary treatment, and survival in Danish...... ovarian cancer patients. METHODS: This population-based study was conducted on data from 5317 ovarian cancer patients registered in the Danish Gynecological Cancer Database. Comorbidity was classified according to the Charlson Comorbidity Index and the Ovarian Cancer Comorbidity Index. Pearson χ test...... and multivariate logistic regression analyses were used to investigate the association between comorbidity and primary outcome measures: primary treatment ("primary debulking surgery" vs "no primary surgery") and system delay (more vs less than required by the National Cancer Patient Pathways [NCPPs]). Cox...
Metastasis of breast cancer rectum

International Nuclear Information System (INIS)

Suárez, L.; Santander, G.

2004-01-01

Introduction: Metastases to the breast are rare, corresponding approximately to 3% of breast cancers. Primary tumors that spread more commonly are own breast, often following them in melanomas, neuroendocrine, ovarian and lymphoma. Medical history: A 59-year consultation rectoragias repeated and thinning. It is studied and finally intervenes (low anterior resection) diagnosed with rectal cancer whose Histopathology revealed a poorly differentiated adenocarcinoma stage III. Concomitantly the patient has a left breast lump that was studied with mammography, which revealed a dense mass of larger diameter 4 cm in topografiada 3 hour left breast with well defined contours and ultrasonographic structure solid. MI lumpectomy is performed whose pathology reports a poorly differentiated adenocarcinoma with cytoarchitectural features matching the lesion of rectum. Hormone receptors were negative. The patient is treated as a rectal cancer with RT spread over QT (5FU i /c). Died 7 months after diagnosis. Discusion: In literature are reported only 3 cases of breast metastases secondary to rectal cancer; how unusual this presentation justify this report.In this event they occurred in patients with a previous diagnosis of rectal cancer and in the context of systemic lesion progression. In our case clinician early diagnosis of rectal and breast metastases was synchronous. The mammographic image consistent with those described for these cases in the literature.The development of metastases in breast tissue is associated with a poor prognosis as which correlates with the survival of the patient
Hereditary breast cancer

DEFF Research Database (Denmark)

Larsen, Martin J; Thomassen, Mads; Gerdes, Anne-Marie

2014-01-01

Pathogenic mutations in BRCA1 or BRCA2 are only detected in 25% of families with a strong history of breast cancer, though hereditary factors are expected to be involved in the remaining families with no recognized mutation. Molecular characterization is expected to provide new insight...... into the tumor biology to guide the search of new high-risk alleles and provide better classification of the growing number of BRCA1/2 variants of unknown significance (VUS). In this review, we provide an overview of hereditary breast cancer, its genetic background, and clinical implications, before focusing...... on the pathologically and molecular features associated with the disease. Recent transcriptome and genome profiling studies of tumor series from BRCA1/2 mutation carriers as well as familial non-BRCA1/2 will be discussed. Special attention is paid to its association with molecular breast cancer subtypes as well...
Exosomal microRNA Signatures in the Diagnosis and Prognosis of Ovarian Cancer

Science.gov (United States)

2013-10-01

including CLL ,41 breast cancer,42 glioblastoma,43 thyroid papillary carcinoma,44 hepatocellular carcinoma,45 ovarian cancer,46 colon...modify cancer cell gene expression. Extracellular vesicles derived from cancer stem cells were shown to contain pro-angiogenic RNAs able to induce a pre...content differs. Extracellular vesicles from cancer stem cells contained miR29a, miR650, and miR151, all associated with tumor invasion and
Pre-counseling education for low literacy women at risk of Hereditary Breast and Ovarian Cancer (HBOC): patient experiences using the Cancer Risk Education Intervention Tool (CREdIT).

Science.gov (United States)

Joseph, Galen; Beattie, Mary S; Lee, Robin; Braithwaite, Dejana; Wilcox, Carolina; Metrikin, Maya; Lamvik, Kate; Luce, Judith

2010-10-01

The Cancer Risk Education Intervention Tool (CREdIT) is a computer-based (non-interactive) slide presentation designed to educate low-literacy, and ethnically and racially diverse public hospital patients at risk of Hereditary Breast and Ovarian Cancer (HBOC) about genetics. To qualitatively evaluate participants' experience with and perceptions of a genetic education program as an adjunct to genetic counseling, we conducted direct observations of the intervention, semi-structured in person interviews with 11 women who viewed CREdIT, and post-counseling questionnaires with the two participating genetic counselors. Five themes emerged from the analysis of interviews: (1) genetic counseling and testing for breast/ovarian cancer was a new concept; (2) CREdIT's story format was particularly appealing; (3) changes in participants' perceived risk for breast cancer varied; (4) some misunderstandings about individual risk and heredity persisted after CREdIT and counseling; (5) the context for viewing CREdIT shaped responses to the presentation. Observations demonstrated ways to make the information provided in CREdIT and by genetic counselors more consistent. In a post-session counselor questionnaire, counselors' rating of the patient's preparedness before the session was significantly higher for patients who viewed CREdIT prior to their appointments than for other patients. This novel educational tool fills a gap in HBOC education by tailoring information to women of lower literacy and diverse ethnic/racial backgrounds. The tool was well received by interview participants and counselors alike. Further study is needed to examine the varied effects of CREdIT on risk perception. In addition, the implementation of CREdIT in diverse clinical settings and the cultural adaptation of CREdIT to specific populations reflect important areas for future work.
CHEK2 1100delC and polygenic susceptibility to breast cancer and colorectal cancer

NARCIS (Netherlands)

M. Wasielewski (Marijke)

2009-01-01

textabstractApproximately 15-25% of breast cancers are identified in women with a family history of breast cancer. Yet, germline mutations in the currently known breast cancer susceptibility genes account for only one-third of familial breast cancer cases. In 2002, our research group had identified
[Association between obesity and ovarian cancer].

Science.gov (United States)

Valladares, Macarena; Corsini, Gino; Romero, Carmen

2014-05-01

Obesity is a risk factor for cancer. Epidemiological evidences associate ovarian cancer with obesity. Epithelial ovarian cancer (EOC) is the most common type of ovarian cancer and accounts for a high rate of mortality. The association between ovarian cancer and obesity could be explained by molecular factors secreted by adipose tissue such as leptin. In EOC, leptin increases cell proliferation and inhibits apoptosis. Additionally, adipose tissue synthesizes endogenous estrogens, which increase cell proliferation of epithelial ovarian cells. Also, obesity associated hyperinsulinism could increase ovarian estrogen secretion.
A breast cancer case-control study in Girona, Spain. Endocrine, familial and lifestyle factors.

Science.gov (United States)

Viladiu, P; Izquierdo, A; de Sanjosé, S; Bosch, F X

1996-10-01

This study was designed to explore risk factors for breast cancer with emphasis on the detection of clinical markers of the hormonal imbalance during the perimenarche. Three hundred and thirty women diagnosed with breast cancer and 346 population controls were identified and interviewed in Girona, Spain between 1986 and 89. Cases were more likely than controls to have had long menstrual periods in the first 5 years after menarche [odds ratio (OR) = 3.0], to experience menopause at a late age (OR = 1.5) and to report acne during adolescence (OR = 1.6). Family history of breast cancer was associated with an increased risk (OR = 2.3). Cases reported a lower use of drug treatments for anxiety and sleep disorders than controls. Moderate alcohol drinkers and smokers were at lower risk for breast cancer. No statistically significant association with breast cancer was observed for number of children, age at last pregnancy, oral contraceptive use, hormonal treatment after menopause and weight perception during the teenage years. Hormonal changes in the years following menarche may be relevant to breast cancer risk. The roles of menstrual period length and acne during adolescence should be further explored.
Fertility Preservation and Pregnancy in Women With and Without BRCA Mutation–Positive Breast Cancer

Science.gov (United States)

Rodriguez-Wallberg, Kenny A.

2012-01-01

Women with breast cancer face many challenges when considering fertility preservation. Delayed referral results in the limitation of fertility preservation options because most established methods, such as embryo and oocyte cryopreservation, require several weeks to complete. Women with BRCA mutations, on the other hand, may be more aware of fertility issues and motivated to see fertility preservation specialists earlier. Fear of exposure to estrogen limits access to fertility preservation via embryo or oocyte cryopreservation; however, the use of aromatase inhibitors as ovarian stimulants reduces such concern. Ovarian cryopreservation can be used when there is insufficient time to perform ovarian stimulation because this technique does not require hormonal stimulation, but there are safety concerns both in women with BRCA mutations and in patients with hormone receptor–positive disease as well. There does not seem to be a proven ovarian suppression strategy to preserve fertility in women with breast cancer. Pregnancy appears to be safe for breast cancer survivors but studies specific for women with BRCA mutations are lacking. Women with BRCA mutations may elect to use preimplantation genetic diagnosis during in vitro fertilization to avoid transmitting the mutation, but there may be psychosocial difficulties in entertaining this option. Overall, the last decade has brought many options for women with breast cancer considering fertility preservation, but numerous challenges remain. The presence of BRCA mutations further contributes to these challenges. PMID:23006497
Higher occurrence of childhood cancer in families with germline mutations in BRCA2, MMR and CDKN2A genes

DEFF Research Database (Denmark)

Magnusson, S.; Borg, A.; Kristoffersson, U.

2008-01-01

The contribution of hereditary factors for development of childhood tumors is limited to some few known syndromes associated with predominance of tumors in childhood. Occurrence of childhood tumors in hereditary cancer syndromes such as BRCA1/2 associated breast and ovarian cancer, DNA-mismatch r......-mismatch repair (MMR) genes associated hereditary non polyposis colorectal cancer and CDKN2A associated familial malignant melanoma are very little studied. Herein we report the prevalence of childhood tumors (diagnosed...

The influence of family history of cancer, irradiation and anticancer medication (mitomycin C), on the occurrence of multiple primary neoplasms with breast cancer

International Nuclear Information System (INIS)

Yoshimoto, Masataka; Kasumi, Fujio; Fukami, Atsuo; Nishi, Mitsumasa; Kajitani, Tamaki; Sakamoto, Goi

1985-01-01

The influence of family history of cancer, radiation therapy and anticancer drug therapy (mitomycin C) on the occurrence of multiple primary neoplasms, following treatment of a first primary cancer of the breast, was analyzed by the person-year method in 1,359 patients, in Japan. During 14,371.8 person-years of observation, 111 multiple primary neoplasms including bilateral breast cancers were found in 109 patients. The incidence rate of multiple primary neoplasms were 0.00772 per person-year. The incidence in patients with a family history of cancer was 1.29 times greater than that in patients without such a family history, and the incidence in patients with a family history of breast cancer was about three times greater than that in those without it (p < 0.01). Radiation therapy raised the occurrence of subsequent primary neoplasms 1.28-fold (or 1.62 fold after 5 years), and mitomycin C (a total dose of 0.8 mg/kg) therapy caused no increase in the occurrence of subsequent primary cancers, after an observation of 10 years or so. (author)
Factors associated with quality of life of outpatients with breast cancer and gynecologic cancers and their family caregivers: a controlled study

Directory of Open Access Journals (Sweden)

Hamad Hussein MA

2007-06-01

Full Text Available Abstract Background Quality of life (QOL issues are of interest in cancer because effective methods of treatment and detection have led to an increase in the number of long-term survivors. The objectives of the study were: to assess the subjective QOL of stable Sudanese women cancer outpatients and their family caregivers, using the WHO 26-item QOL Instrument; compare with matched general population groups, as well as diabetic and psychiatric patient groups; examine patient-caregiver concordance in ratings; and assess the variables associated with their QOL, with a view to identifying factors that can enhance quality of care. Methods Responses of oncology outpatients with breast cancer (117, cervical cancer (46 and ovarian cancer (18 (aged 44.6, SD 11.5 were compared with those of their family caregivers and matched general population groups. Data were analyzed by univariate and multivariate statistics. Results The cancer groups had similar QOL domain scores, which were significantly lower than those of their caregivers, but higher than the control group as well as those of psychiatric and diabetic patients studied previously. Patients who were married, with higher education, better employment, and with longer duration of illness had higher QOL. Patients on radiotherapy and their caregivers had higher QOL scores. Correlations between patient's ratings and caregiver impression of patient's QOL were high. Caregiver impression was a significant predictor of patient's and caregiver's QOL. Other predictors for the patient were: currently feeling sick and duration of illness; for the caregiver: feeling sick, relationship to patient, and age. Conclusion Cancer patients in stable condition and with psychosocial support can hope to enjoy good QOL with treatment. The findings constitute an evidence base for the country's cancer care program, to boost national health education about prognosis in cancer. Families living with women cancer patients are
Emotional, Biological, and Cognitive Impact of a Brief Expressive Writing Intervention for African American Women at Familial Breast Cancer Risk

National Research Council Canada - National Science Library

Valdimarsdottir, Heiddie; Bovbjerg, Dana

2005-01-01

...) than women without familial breast cancer risk. To date, little research has been done on women of African descent with family histories of breast cancer, despite the fact that they may be at particularly high risk for chronic distress due...
BAG3-mediated Mcl-1 stabilization contributes to drug resistance via interaction with USP9X in ovarian cancer.

Science.gov (United States)

Habata, Shutaro; Iwasaki, Masahiro; Sugio, Asuka; Suzuki, Miwa; Tamate, Masato; Satohisa, Seiro; Tanaka, Ryoichi; Saito, Tsuyoshi

2016-07-01

Paclitaxel in combination with carboplatin improves survival among patients with susceptible ovarian cancers, but no strategy has been established against resistant ovarian cancers. BAG3 (Bcl-2-associated athanogene 3) is one of six BAG family proteins, which are involved in such cellular processes as proliferation, migration and apoptosis. In addition, expression of BAG3 with Mcl-1, a Bcl-2 family protein, reportedly associates with resistance to chemotherapy. Our aim in this study was to evaluate the functional role of BAG3 and Mcl-1 in ovarian cancer chemoresistance and explore possible new targets for treatment. We found that combined expression of BAG3 and Mcl-1 was significantly associated with a poor prognosis in ovarian cancer patients. In vitro, BAG3 knockdown in ES2 clear ovarian cancer cells significantly increased the efficacy of paclitaxel in combination with the Mcl-1 antagonist MIM1, with or without the Bcl-2 family antagonist ABT737. Moreover, BAG3 was found to positively regulate Mcl-1 levels by binding to and inhibiting USP9X. Our data show that BAG3 and Mcl-1 are key mediators of resistance to chemotherapy in ovarian cancer. In BAG3 knockdown ES2 clear ovarian cancer cells, combination with ABT737 and MIM1 enhanced the efficacy of paclitaxel. These results suggest that inhibiting BAG3 in addition to anti-apoptotic Bcl-2 family proteins may be a useful therapeutic strategy for the treatment of chemoresistant ovarian cancers.
A rare FANCA gene variation as a breast cancer susceptibility allele in an Iranian population.

Science.gov (United States)

Abbasi, Sakineh; Rasouli, Mina

2017-06-01

Fanconi Anemia (FA) is an autosomal recessive syndrome characterized by congenital abnormalities, progressive bone marrow failure and Fanconi anemia complementation group A (FANCA) is also a potential breast and ovarian cancer susceptibility gene. A novel allele with tandem duplication of 13 base pair sequence in promoter region was identified. To investigate whether the 13 base pair sequence of tandem duplication in promoter region of the FANCA gene is of high penetrance in patients with breast cancer and to determine if the presence of the duplicated allele was associated with an altered risk of breast cancer, the present study screened DNA in blood samples from 304 breast cancer patients and 295 normal individuals as controls. The duplication allele had a frequency of 35.4 and 21.2% in patients with breast cancer and normal controls, respectively. There was a significant increase in the frequency of the duplication allele in patients with familial breast cancer compared with controls (45.1%, P=0.001). Furthermore, the estimated risk of breast cancer in individuals with a homozygote [odds ratio (OR), 4.093; 95% confidence intervals (CI), 1.957‑8.561] or heterozygote duplicated genotype (OR, 3.315; 95% CI, 1.996‑5.506) was higher compared with the corresponding normal homozygote genotype. In conclusion, the present study indicated that the higher the frequency of the duplicated allele, the higher the risk of breast cancer. To the best of our knowledge, the present study is the first to report FANCA gene duplication in patients with breast cancer.
Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer

Science.gov (United States)

Andersson, Ulrika; Wibom, Carl; Cederquist, Kristina; Aradottir, Steina; Borg, Åke; Armstrong, Georgina N.; Shete, Sanjay; Lau, Ching C.; Bainbridge, Matthew N.; Claus, Elizabeth B.; Barnholtz-Sloan, Jill; Lai, Rose; Il'yasova, Dora; Houlston, Richard S.; Schildkraut, Joellen; Bernstein, Jonine L.; Olson, Sara H.; Jenkins, Robert B.; Lachance, Daniel H.; Wrensch, Margaret; Davis, Faith G.; Merrell, Ryan; Johansen, Christoffer; Sadetzki, Siegal; Bondy, Melissa L.; Melin, Beatrice S.; Adatto, Phyllis; Morice, Fabian; Payen, Sam; McQuinn, Lacey; McGaha, Rebecca; Guerra, Sandra; Paith, Leslie; Roth, Katherine; Zeng, Dong; Zhang, Hui; Yung, Alfred; Aldape, Kenneth; Gilbert, Mark; Weinberger, Jeffrey; Colman, Howard; Conrad, Charles; de Groot, John; Forman, Arthur; Groves, Morris; Levin, Victor; Loghin, Monica; Puduvalli, Vinay; Sawaya, Raymond; Heimberger, Amy; Lang, Frederick; Levine, Nicholas; Tolentino, Lori; Saunders, Kate; Thach, Thu-Trang; Iacono, Donna Dello; Sloan, Andrew; Gerson, Stanton; Selman, Warren; Bambakidis, Nicholas; Hart, David; Miller, Jonathan; Hoffer, Alan; Cohen, Mark; Rogers, Lisa; Nock, Charles J; Wolinsky, Yingli; Devine, Karen; Fulop, Jordonna; Barrett, Wendi; Shimmel, Kristen; Ostrom, Quinn; Barnett, Gene; Rosenfeld, Steven; Vogelbaum, Michael; Weil, Robert; Ahluwalia, Manmeet; Peereboom, David; Staugaitis, Susan; Schilero, Cathy; Brewer, Cathy; Smolenski, Kathy; McGraw, Mary; Naska, Theresa; Rosenfeld, Steven; Ram, Zvi; Blumenthal, Deborah T.; Bokstein, Felix; Umansky, Felix; Zaaroor, Menashe; Cohen, Avi; Tzuk-Shina, Tzeela; Voldby, Bo; Laursen, René; Andersen, Claus; Brennum, Jannick; Henriksen, Matilde Bille; Marzouk, Maya; Davis, Mary Elizabeth; Boland, Eamon; Smith, Marcel; Eze, Ogechukwu; Way, Mahalia; Lada, Pat; Miedzianowski, Nancy; Frechette, Michelle; Paleologos, Nina; Byström, Gudrun; Svedberg, Eva; Huggert, Sara; Kimdal, Mikael; Sandström, Monica; Brännström, Nikolina; Hayat, Amina; Tihan, Tarik; Zheng, Shichun; Berger, Mitchel; Butowski, Nicholas; Chang, Susan; Clarke, Jennifer; Prados, Michael; Rice, Terri; Sison, Jeannette; Kivett, Valerie; Duo, Xiaoqin; Hansen, Helen; Hsuang, George; Lamela, Rosito; Ramos, Christian; Patoka, Joe; Wagenman, Katherine; Zhou, Mi; Klein, Adam; McGee, Nora; Pfefferle, Jon; Wilson, Callie; Morris, Pagan; Hughes, Mary; Britt-Williams, Marlin; Foft, Jessica; Madsen, Julia; Polony, Csaba; McCarthy, Bridget; Zahora, Candice; Villano, John; Engelhard, Herbert; Borg, Ake; Chanock, Stephen K; Collins, Peter; Elston, Robert; Kleihues, Paul; Kruchko, Carol; Petersen, Gloria; Plon, Sharon; Thompson, Patricia; Johansen, C.; Sadetzki, S.; Melin, B.; Bondy, Melissa L.; Lau, Ching C.; Scheurer, Michael E.; Armstrong, Georgina N.; Liu, Yanhong; Shete, Sanjay; Yu, Robert K.; Aldape, Kenneth D.; Gilbert, Mark R.; Weinberg, Jeffrey; Houlston, Richard S.; Hosking, Fay J.; Robertson, Lindsay; Papaemmanuil, Elli; Claus, Elizabeth B.; Claus, Elizabeth B.; Barnholtz-Sloan, Jill; Sloan, Andrew E.; Barnett, Gene; Devine, Karen; Wolinsky, Yingli; Lai, Rose; McKean-Cowdin, Roberta; Il'yasova, Dora; Schildkraut, Joellen; Sadetzki, Siegal; Yechezkel, Galit Hirsh; Bruchim, Revital Bar-Sade; Aslanov, Lili; Sadetzki, Siegal; Johansen, Christoffer; Kosteljanetz, Michael; Broholm, Helle; Bernstein, Jonine L.; Olson, Sara H.; Schubert, Erica; DeAngelis, Lisa; Jenkins, Robert B.; Yang, Ping; Rynearson, Amanda; Andersson, Ulrika; Wibom, Carl; Henriksson, Roger; Melin, Beatrice S.; Cederquist, Kristina; Aradottir, Steina; Borg, Åke; Merrell, Ryan; Lada, Patricia; Wrensch, Margaret; Wiencke, John; Wiemels, Joe; McCoy, Lucie; McCarthy, Bridget J.; Davis, Faith G.

2014-01-01

Background Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several cancer phenotypes, to determine whether common chromosomal modifications might account for the familial aggregation of glioma and other cancers. Methods Germline rearrangements in 146 glioma families (from the Gliogene Consortium; http://www.gliogene.org/) were examined using multiplex ligation-dependent probe amplification. These families all had at least 2 verified glioma cases and a third reported or verified glioma case in the same family or 2 glioma cases in the family with at least one family member affected with melanoma, colon, or breast cancer.The genomic areas covering TP53, CDKN2A, MLH1, and MSH2 were selected because these genes have been previously reported to be associated with cancer pedigrees known to include glioma. Results We detected a single structural rearrangement, a deletion of exons 1-6 in MSH2, in the proband of one family with 3 cases with glioma and one relative with colon cancer. Conclusions Large deletions and duplications are rare events in familial glioma cases, even in families with a strong family history of cancers that may be involved in known cancer syndromes. PMID:24723567
Role of KCNMA1 in breast cancer.

Directory of Open Access Journals (Sweden)

Martin Oeggerli

Full Text Available KCNMA1 encodes the α-subunit of the large conductance, voltage and Ca(2+-activated (BK potassium channel and has been reported as a target gene of genomic amplification at 10q22 in prostate cancer. To investigate the prevalence of the amplification in other human cancers, the copy number of KCNMA1 was analyzed by fluorescence-in-situ-hybridization (FISH in 2,445 tumors across 118 different tumor types. Amplification of KCNMA1 was restricted to a small but distinct fraction of breast, ovarian and endometrial cancer with the highest prevalence in invasive ductal breast cancers and serous carcinoma of ovary and endometrium (3-7%. We performed an extensive analysis on breast cancer tissue microarrays (TMA of 1,200 tumors linked to prognosis. KCNMA1 amplification was significantly associated with high tumor stage, high grade, high tumor cell proliferation, and poor prognosis. Immunofluorescence revealed moderate or strong KCNMA1 protein expression in 8 out of 9 human breast cancers and in the breast cancer cell line MFM223. KCNMA1-function in breast cancer cell lines was confirmed by whole-cell patch clamp recordings and proliferation assays, using siRNA-knockdown, BK channel activators such as 17ß-estradiol and the BK-channel blocker paxilline. Our findings revealed that enhanced expression of KCNMA1 correlates with and contributes to high proliferation rate and malignancy of breast cancer.
Long-term effects of first degree family history of breast cancer in young women: Recurrences and bilateral breast cancer

NARCIS (Netherlands)

Jobsen, Jan J.; van der Palen, Jacobus Adrianus Maria; Brinkhuis, Mariël; Ong, Francisca; Struikmans, Henk

2016-01-01

Background. The aim of this study is to analyze the impact of first degree relative (FDR) of young breast cancer patients. Methods. Data were used from our prospective population-based cohort study which started in 1983. The family history (FH) was registered with regard to FDR: the presence or
Tumor characteristics and family history in relation to mammographic density and breast cancer: The French E3N cohort.

Science.gov (United States)

Maskarinec, Gertraud; Dartois, Laureen; Delaloge, Suzette; Hopper, John; Clavel-Chapelon, Françoise; Baglietto, Laura

2017-08-01

Mammographic density is a known heritable risk factor for breast cancer, but reports how tumor characteristics and family history may modify this association are inconsistent. Dense and total breast areas were assessed using Cumulus™ from pre-diagnostic mammograms for 820 invasive breast cancer cases and 820 matched controls nested within the French E3N cohort study. To allow comparisons across models, percent mammographic density (PMD) was standardized to the distribution of the controls. Odds ratios (OR) and 95% confidence intervals (CI) of breast cancer risk for mammographic density were estimated by conditional logistic regression while adjusting for age and body mass index. Heterogeneity according to tumor characteristic and family history was assessed using stratified analyses. Overall, the OR per 1 SD for PMD was 1.50 (95% CI, 1.33-1.69). No evidence for significant heterogeneity by tumor size, lymph node status, grade, and hormone receptor status (estrogen, progesterone, and HER2) was detected. However, the association of PMD was stronger for women reporting a family history of breast cancer (OR 1SD =2.25; 95% CI, 1.67-3.04) than in women reporting none (OR 1SD =1.41; 95% CI, 1.24-1.60; p heterogeneity =0.002). Similarly, effect modification by FHBC was observed using categories of PMD (p heterogeneity =0.02) with respective ORs of 15.16 (95% CI, 4.23-54.28) vs. 3.14 (95% CI, 1.89-5.22) for ≥50% vs. breast cancer risk with a family history supports the hypothesis of shared genetic factors responsible for familial aggregation of breast cancer and the heritable component of mammographic density. Copyright © 2017 Elsevier Ltd. All rights reserved.
Building Family Capacity for Native Hawaiian Women with Breast Cancer

Science.gov (United States)

Mokuau, Noreen; Braun, Kathryn L.; Daniggelis, Ephrosine

2012-01-01

Native Hawaiian women have the highest breast cancer incidence and mortality rates when compared with other large ethnic groups in Hawai'i. Like other women, they rely on the support of their families as co-survivors. This project explored the feasibility and effects of a culturally tailored educational intervention designed to build family…
Ovarian Cancer

Science.gov (United States)

... I find more information about ovarian and other gynecologic cancers? Centers for Disease Control and Prevention: 800-CDC-INFO or www. cdc. gov/ cancer/ gynecologic National Cancer Institute: 800-4-CANCER or www. ...
Tamoxifen or letrozole versus standard methods for women with estrogen-receptor positive breast cancer undergoing oocyte or embryo cryopreservation in assisted reproduction

NARCIS (Netherlands)

Dahhan, Taghride; Balkenende, Eva; van Wely, Madelon; Linn, Sabine; Goddijn, Mariette

2013-01-01

Cryopreservation of oocytes or embryos preceded by controlled ovarian stimulation (COS) can increase the chance of future pregnancy in women with breast cancer who risk therapy-induced ovarian failure. In women with estrogen-receptor (ER) positive breast cancer, alternative COS protocols with
Mammography Screening Among African-American Women with a Family History of Breast Cancer

National Research Council Canada - National Science Library

Lipkus, Issac

1997-01-01

Comparisons were made between African-American women with and without a family history of breast cancer with respect to mammography screening, attitudes towards mammography screening and perceptions...
Occupational exposure and ovarian cancer risk.

Science.gov (United States)

Le, Nhu D; Leung, Andy; Brooks-Wilson, Angela; Gallagher, Richard P; Swenerton, Kenneth D; Demers, Paul A; Cook, Linda S

2014-07-01

Relatively little work has been done concerning occupational risk factors in ovarian cancer. Although studies conducted in occupational settings have reported positive associations, their usefulness is generally limited by the lack of information on important confounders. In a population-based case-control study, we assessed risk for developing epithelial ovarian cancer (EOC) associated with occupational exposure while accounting for important confounders. Participants were identified through provincial population-based registries. Lifetime occupational history and information on potential confounding factors were obtained through a self-administered questionnaire. Unconditional logistic regression and the likelihood ratio test were used to assess EOC risk with each occupation (or industry), relative to all other occupations (or industries), adjusting for potential confounders including body mass index, oral contraceptive use, menopausal hormone therapy, parity, age at first childbirth, age at menarche, age at menopause, family history of breast and ovarian cancer in mother and sister(s), tubal ligation, partial oophorectomy, and hysterectomy. Occupations and industries were coded according to the Canadian Standard Occupational Classification (SOC) and Standard Industrial Classification (SIC). Significant excess risk was observed for several groups of teaching occupations, including SOC 27, teaching and related (adjusted OR 1.77, 95% CI 1.15-2.81) and SOC 279, other teaching and related (adjusted OR 3.11, 95% CI 1.35-8.49). Significant excess was also seen for a four-digit occupational group SOC 4131, bookkeepers and accounting clerks (adjusted OR 2.80, 95% CI 1.30-6.80). Industrial sub-groups showing significant excess risk included SIC 65, other retail stores (adjusted OR 2.19, 95 % CI 1.16-4.38); SIC 85, educational service (adjusted OR 1.45, 95% CI 1.00-2.13); and SIC 863, non-institutional health services (adjusted OR 2.54, 95% CI 1.13-6.52). Our study found
Screening for Lynch syndrome using risk assessment criteria in patients with ovarian cancer.

Science.gov (United States)

Takeda, Takashi; Tsuji, Kosuke; Banno, Kouji; Yanokura, Megumi; Kobayashi, Yusuke; Tominaga, Eiichiro; Aoki, Daisuke

2018-05-01

Lynch syndrome is a cancer predisposition syndrome caused by germline mutation of DNA mismatch repair (MMR) genes. Lynch syndrome only causes about 0.4% of cases of ovarian cancer, which suggests that universal screening may not be cost-efficient. However, the frequency of Lynch syndrome in ovarian cancer is unclear in the Asian population. The goal of the study was to investigate a screening strategy using family history. The subjects were 129 patients with ovarian cancer. Clinical and family history were collected using a self-administered questionnaire, and Society of Gynecologic Oncology (SGO) criteria 2007 and PREMM₅ were used for risk assessment. Microsatellite instability, immunohistochemistry, and methylation of MMR genes were analyzed. Of the 129 cases, 25 (19.4%) met the SGO criteria, and 4 of these 25 had MSI-high and MMR deficiency. Two cases had loss of MSH2 and MSH6, indicating MSH2 mutation, and the other two had loss of MLH1 and PMS2, including one without MLH1 methylation indicating MLH1 mutation. These results show that screening using family history can detect Lynch syndrome in 12.0% (3/25) of ovarian cancer cases. The 3 cases were positive for PREMM₅, but negative for Amsterdam II criteria and revised Bethesda guidelines. Genetic testing in one case with MSH2 and MSH6 deficiency confirmed the diagnosis of Lynch syndrome with MSH2 mutation. This is the first study of screening for Lynch syndrome in ovarian cancer using clinical and family history in an Asian population. This approach may be effective for diagnosis in these patients. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.
Hormone therapy and ovarian cancer

DEFF Research Database (Denmark)

Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms

2009-01-01

CONTEXT: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE: To assess risk of ovarian cancer in perimenopausal and postmenopau......CONTEXT: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE: To assess risk of ovarian cancer in perimenopausal...... and postmenopausal women receiving different hormone therapies. DESIGN AND SETTING: Nationwide prospective cohort study including all Danish women aged 50 through 79 years from 1995 through 2005 through individual linkage to Danish national registers. Redeemed prescription data from the National Register...... bands included hormone exposures as time-dependent covariates. PARTICIPANTS: A total of 909,946 women without hormone-sensitive cancer or bilateral oophorectomy. MAIN OUTCOME MEASURE: Ovarian cancer. RESULTS: In an average of 8.0 years of follow-up (7.3 million women-years), 3068 incident ovarian...
Systematic Analysis of Gene Expression Alterations and Clinical Outcomes for Long-Chain Acyl-Coenzyme A Synthetase Family in Cancer.

Directory of Open Access Journals (Sweden)

Wei-Ching Chen

Full Text Available Dysregulated lipid metabolism contributes to cancer progression. Our previous study indicates that long-chain fatty acyl-Co A synthetase (ACSL 3 is essential for lipid upregulation induced by endoplasmic reticulum stress. In this report, we aimed to identify the role of ACSL family in cancer with systematic analysis and in vitro experiment. We explored the ACSL expression using Oncomine database to determine the gene alteration during carcinogenesis and identified the association between ACSL expression and the survival of cancer patient using PrognoScan database. ACSL1 may play a potential oncogenic role in colorectal and breast cancer and play a potential tumor suppressor role in lung cancer. Co-expression analysis revealed that ACSL1 was coexpressed with MYBPH, PTPRE, PFKFB3, SOCS3 in colon cancer and with LRRFIP1, TSC22D1 in lung cancer. In accordance with PrognoScan analysis, downregulation of ACSL1 in colon and breast cancer cell line inhibited proliferation, migration, and anchorage-independent growth. In contrast, increase of oncogenic property was observed in lung cancer cell line by attenuating ACSL1. High ACSL3 expression predicted a better prognosis in ovarian cancer; in contrast, high ACSL3 predicted a worse prognosis in melanoma. ACSL3 was coexpressed with SNUPN, TRIP13, and SEMA5A in melanoma. High expression of ACSL4 predicted a worse prognosis in colorectal cancer, but predicted better prognosis in breast, brain and lung cancer. ACSL4 was coexpressed with SERPIN2, HNRNPCL1, ITIH2, PROCR, LRRFIP1. High expression of ACSL5 predicted good prognosis in breast, ovarian, and lung cancers. ACSL5 was coexpressed with TMEM140, TAPBPL, BIRC3, PTPRE, and SERPINB1. Low ACSL6 predicted a worse prognosis in acute myeloid leukemia. ACSL6 was coexpressed with SOX6 and DARC. Altogether, different members of ACSLs are implicated in diverse types of cancer development. ACSL-coexpressed molecules may be used to further investigate the role of ACSL
Pre-diagnosis insulin-like growth factor-I and risk of epithelial invasive ovarian cancer by histological subtypes : A collaborative re-analysis from the Ovarian Cancer Cohort Consortium

NARCIS (Netherlands)

Ose, Jennifer; Schock, Helena; Poole, Elizabeth M; Lehtinen, Matti; Visvanathan, Kala; Helzlsouer, Kathy; Buring, Julie E; Lee, I-Min; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Trichopoulou, Antonia; Mattiello, Amalia; Onland-Moret, N Charlotte; Weiderpass, Elisabete; Sánchez, María-José; Idahl, Annika; Travis, Ruth C; Rinaldi, Sabina; Merritt, Melissa A; Wentzensen, Nicolas; Tworoger, Shelley S; Kaaks, Rudolf; Fortner, Renée T

PURPOSE: Biologic evidence suggests that the Insulin-like growth factor (IGF)-family may be involved in the etiology of epithelial invasive ovarian cancer (EOC). However, prospective studies investigating the role of IGF-I in ovarian carcinogenesis have yielded conflicting results. METHODS: We
Family support in cancer survivorship.

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Muhamad, Mazanah; Afshari, Mojgan; Kazilan, Fitrisehara

2011-01-01

This paper raises issues about the role of family members in providing support for breast cancer survivors. Data were collected from 400 breast cancer survivors in Peninsular Malaysia through a custom-designed questionnaire fielded at hospitals and support group meetings. The data were analyzed using descriptive statistics. The analyses show that all family members could be supportive, especially in decision making and help with emotional issues. The spouse was the main support provider among the family members (others were children, parents, siblings and more distant relatives). The results also indicated that a significant percentage practiced collaborative decision-making. Breast cancer survivors needed their family members' support for information on survivorship strategies such as managing emotions, health, life style and dietary practice. The family members' supportive role may be linked to the Malaysian strong family relationship culture. For family members to contribute more adequately to cancer survivorship, it is suggested that appropriate educational intervention also be provided to them.
The role of the addition of ovarian suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or regain menstruation after chemotherapy (ASTRRA): study protocol for a randomized controlled trial and progress

International Nuclear Information System (INIS)

Kim, Hyun-Ah; Ahn, Sei Hyun; Nam, Seok Jin; Park, Seho; Ro, Jungsil

2016-01-01

Ovarian function suppression (OFS) has been shown to be effective as adjuvant endocrine therapy in premenopausal women with hormone receptor-positive breast cancer. However, it is currently unclear if addition of OFS to standard tamoxifen therapy after completion of adjuvant chemotherapy results in a survival benefit. In 2008, the Korean Breast Cancer Society Study Group initiated the ASTRRA randomized phase III trial to evaluate the efficacy of OFS in addition to standard tamoxifen treatment in hormone receptor-positive breast cancer patients who remain or regain premenopausal status after chemotherapy. Premenopausal women with estrogen receptor-positive breast cancer treated with definitive surgery were enrolled after completion of neoadjuvant or adjuvant chemotherapy. Ovarian function was assessed at the time of enrollment and every 6 months for 2 years by follicular-stimulating hormone levels and bleeding history. If ovarian function was confirmed as premenopausal status, the patient was randomized to receive 2 years of goserelin plus 5 years of tamoxifen treatment or 5 years of tamoxifen alone. The primary end point will be the comparison of the 5-year disease-free survival rates between the OFS and tamoxifen alone groups. Patient recruitment was finished on March 2014 with the inclusion of a total of 1483 patients. The interim analysis will be performed at the time of the observation of the 187th event. This study will provide evidence of the benefit of OFS plus tamoxifen compared with tamoxifen only in premenopausal patients with estrogen receptor-positive breast cancer treated with chemotherapy

Cancerous leptomeningitis and familial congenital hypopituitarism.

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Vujovic, S; Vujosevic, S; Kavaric, S; Sopta, J; Ivovic, M; Saveanu, A; Brue, T; Korbonits, M; Popovic, V

2016-05-01

People are at higher risk of cancer as they get older or have a strong family history of cancer. The potential influence of environmental and behavioral factors remains poorly understood. Earlier population and case control studies reported that upper quartile of circulating IGF-I is associated with a higher risk of developing cancer suggesting possible involvement of the growth hormone (GH)/IGF system in initiation or progression of cancer. Since GH therapy increases IGF-1 levels, there have been concerns that GH therapy in hypopituitarism might increase the risk of cancer. We report a 42-year-old female patient who presented with subacute onset of symptoms of meningitis and with the absence of fever which resulted in death 70 days after the onset of symptoms. The patient together with her younger brother was diagnosed at the age of 5 years with familial congenital hypopituitarism, due to homozygous mutation c.150delA in PROP1 gene. Due to evolving hypopituitarism, she was replaced with thyroxine (from age 5), hydrocortisone (from age 13), GH (from age 13 until 17), and sex steroids in adolescence and adulthood. Her consanguineous family has a prominent history of malignant diseases. Six close relatives had malignant disease including her late maternal aunt with breast cancer. BRCA 1 and BRCA 2 mutational analysis in the patient's mother was negative. Histology after autopsy disclosed advanced ovarian cancer with multiple metastases to the brain, leptomeninges, lungs, heart, and adrenals. Low circulating IGF-1 did not seem to protect this patient from cancer initiation and progression in the context of strong family history of malignancies.
Decision aids for familial breast cancer: exploring women's views using focus groups.

NARCIS (Netherlands)

Rapport, F.; Iredale, R.; Jones, W.; Sivell, S.; Edwards, A.; Gray, J.; Elwyn, G.

2006-01-01

BACKGROUND: There is increasing need for accessible information about familial breast cancer for those facing complex decisions around genetic testing, screening and treatment. Information currently includes leaflets and computerized decision aids, offering interactive interfaces to clarify complex
Perceived risk, anxiety, mammogram uptake and breast self examination of women with a family history of breast cancer: The role of knowing to be at increased risk

NARCIS (Netherlands)

Drossaert, Constance H.C.; Boer, Hendrik; Seydel, E.R.

1996-01-01

Since women with a first-degree relative with breast cancer are at increased risk for breast cancer, it is of special importance that they adhere to early detection programs. In this study, women with (389) and without (3295) a family history of breast cancer were compared with respect to risk
RELATIONSHIP BETWEEN TYPE C BEHAVIOR AND BREAST CANCER

Directory of Open Access Journals (Sweden)

ÁNGELA MARÍA TORRES MARIÑO

2006-10-01

Full Text Available The main objective of this study was to investigate deeply the relationship between Type C behavior pattern andbreast cancer through an analytical observation design of cases and controls. Three groups of variables were established:demographical, medical and risk factors, including in the last one the Type C behavior, for three groups: a women withbreast cancer, b women with cervix cancer, and c healthy women. The changing answer for ‘having breast cancer’ isdetermined by the family history of sickness, having hormone replace therapy, the history of the ovarian and endometrialcancer, and the age of the participants. One concludes that the behavior pattern, so and as is raised until the moment,is related more to the way the disease is faced, than a type of premorbid personality. New factors are proposed in baseof the Five Factor Model, the Temperament and Character set out.
Ovarian and tubal cancer in Denmark

DEFF Research Database (Denmark)

Gottschau, Mathilde; Mellemkjaer, Lene; Hannibal, Charlotte G

2016-01-01

INTRODUCTION: The Nordic countries are areas with a high-incidence of ovarian cancer; however, differences between the countries exist. MATERIAL AND METHODS: We used the Danish Cancer Registry to identify 11 264 cases of ovarian cancer and 363 cases of tubal cancer during 1993-2013. We calculated...... age-standardized (world standard population) incidence rates for overall and subtype-specific ovarian cancer, and for tubal cancer. We compared age-standardized incidence rates, and 1- and 5-year age-standardized relative survival rates, respectively, for ovarian and tubal cancer combined in four...... Nordic countries using the NORDCAN database. RESULTS: The incidence rate of ovarian cancer overall in Denmark decreased statistically significantly by approximately 2.3% per year among women aged
Breast cancer in systemic lupus

DEFF Research Database (Denmark)

Bernatsky, S.; Ramsey-Goldman, R.; Petri, M.

2017-01-01

Objective There is a decreased breast cancer risk in systemic lupus erythematosus (SLE) versus the general population. We assessed a large sample of SLE patients, evaluating demographic and clinical characteristics and breast cancer risk. Methods We performed case-cohort analyses within a multi......-center international SLE sample. We calculated the breast cancer hazard ratio (HR) in female SLE patients, relative to demographics, reproductive history, family history of breast cancer, and time-dependent measures of anti-dsDNA positivity, cumulative disease activity, and drugs, adjusted for SLE duration. Results...... There were 86 SLE breast cancers and 4498 female SLE cancer-free controls. Patients were followed on average for 7.6 years. Versus controls, SLE breast cancer cases tended to be white and older. Breast cancer cases were similar to controls regarding anti-dsDNA positivity, disease activity, and most drug...
Influence of family history, irradiation and anti-cancer drug (mitomycin C) on the occurrence of multiple primary neoplasms in breast carcinoma patients

International Nuclear Information System (INIS)

Yoshimoto, Masataka; Sakamoto, Goi; Sugano, Haruo; Kasumi, Fujio; Fukami, Atsuo; Kuno, Keijiro.

1984-01-01

The influence of family history, irradiation and anti-cancer drug (Mitomycin C) on the occurrence of multiple primary neoplasms was analysed using the person-year method in 1359 Japanese breast carcinoma patients. There were 111 multiple primary neoplasms, including bilaterl breast cancer, in 109 patients; the incidence rate was 0.0072 per person-year. The incidence rate in patients with a family history of cancer was 1.29 times higher than in those without. In the bilateral breast cancer group there was about a 3 times higher frequency of family history of breast cancer. Irradiation therapy raised the occurrence of multiple primary neoplasms 1.28 fold, and Mitomycin C (40 mg) had no effect on the occurrence of neoplasms during a 10-year observation period. (author)
Hornerin, an S100 family protein, is functional in breast cells and aberrantly expressed in breast cancer

International Nuclear Information System (INIS)

Fleming, Jodie M; Ginsburg, Erika; Oliver, Shannon D; Goldsmith, Paul; Vonderhaar, Barbara K

2012-01-01

Recent evidence suggests an emerging role for S100 protein in breast cancer and tumor progression. These ubiquitous proteins are involved in numerous normal and pathological cell functions including inflammatory and immune responses, Ca 2+ homeostasis, the dynamics of cytoskeleton constituents, as well as cell proliferation, differentiation, and death. Our previous proteomic analysis demonstrated the presence of hornerin, an S100 family member, in breast tissue and extracellular matrix. Hornerin has been reported in healthy skin as well as psoriatic and regenerating skin after wound healing, suggesting a role in inflammatory/immune response or proliferation. In the present study we investigated hornerin’s potential role in normal breast cells and breast cancer. The expression levels and localization of hornerin in human breast tissue, breast tumor biopsies, primary breast cells and breast cancer cell lines, as well as murine mammary tissue were measured via immunohistochemistry, western blot analysis and PCR. Antibodies were developed against the N- and C-terminus of the protein for detection of proteolytic fragments and their specific subcellular localization via fluorescent immunocytochemisty. Lastly, cells were treated with H 2 O 2 to detect changes in hornerin expression during induction of apoptosis/necrosis. Breast epithelial cells and stromal fibroblasts and macrophages express hornerin and show unique regulation of expression during distinct phases of mammary development. Furthermore, hornerin expression is decreased in invasive ductal carcinomas compared to invasive lobular carcinomas and less aggressive breast carcinoma phenotypes, and cellular expression of hornerin is altered during induction of apoptosis. Finally, we demonstrate the presence of post-translational fragments that display differential subcellular localization. Our data opens new possibilities for hornerin and its proteolytic fragments in the control of mammary cell function and breast
Hornerin, an S100 family protein, is functional in breast cells and aberrantly expressed in breast cancer

Directory of Open Access Journals (Sweden)

Fleming Jodie M

2012-06-01

Full Text Available Abstract Background Recent evidence suggests an emerging role for S100 protein in breast cancer and tumor progression. These ubiquitous proteins are involved in numerous normal and pathological cell functions including inflammatory and immune responses, Ca2+ homeostasis, the dynamics of cytoskeleton constituents, as well as cell proliferation, differentiation, and death. Our previous proteomic analysis demonstrated the presence of hornerin, an S100 family member, in breast tissue and extracellular matrix. Hornerin has been reported in healthy skin as well as psoriatic and regenerating skin after wound healing, suggesting a role in inflammatory/immune response or proliferation. In the present study we investigated hornerin’s potential role in normal breast cells and breast cancer. Methods The expression levels and localization of hornerin in human breast tissue, breast tumor biopsies, primary breast cells and breast cancer cell lines, as well as murine mammary tissue were measured via immunohistochemistry, western blot analysis and PCR. Antibodies were developed against the N- and C-terminus of the protein for detection of proteolytic fragments and their specific subcellular localization via fluorescent immunocytochemisty. Lastly, cells were treated with H2O2 to detect changes in hornerin expression during induction of apoptosis/necrosis. Results Breast epithelial cells and stromal fibroblasts and macrophages express hornerin and show unique regulation of expression during distinct phases of mammary development. Furthermore, hornerin expression is decreased in invasive ductal carcinomas compared to invasive lobular carcinomas and less aggressive breast carcinoma phenotypes, and cellular expression of hornerin is altered during induction of apoptosis. Finally, we demonstrate the presence of post-translational fragments that display differential subcellular localization. Conclusions Our data opens new possibilities for hornerin and its
Fertility drugs and ovarian cancer.

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Ali, Aus Tariq

2017-06-20

The aetiology of ovarian cancer is multifactorial with both endogenous and exogenous risk factors playing an important role. The exact pathogenesis of ovarian cancer is still not well understood, despite the number of hypotheses published. Due to an increase in the number of women using fertility drugs, much attention has been focused on the long-term health effects of such drugs. Although fertility drugs facilitate the ovulation process, it is however associated with a significant increase in hormone concentrations, placing exposed women at increased risk of gynaecological cancer. Many clinical and epidemiological studies have examined the association between fertility drugs and ovarian cancer risk. Results from these studies have been contradictory, as some studies have reported an increased risk of ovarian cancer while others reported no increased risk. Nevertheless, recent studies have shown that women who used fertility drugs and did not conceive had a higher risk of developing ovarian cancer, compared to women who used fertility drugs and conceived and delivered successfully. This review discusses the effect of fertility drugs on the risk of developing ovarian cancer, providing details on four possible scenarios associated with fertility treatment. In addition, the limitations of previous studies and their impact on our understanding of the association between fertility drugs and ovarian cancer also have been highlighted. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Novel mutations in the BRCA1 and BRCA2 genes in Iranian women with early-onset breast cancer

International Nuclear Information System (INIS)

Yassaee, Vahid R; Zeinali, Sirous; Harirchi, Iraj; Jarvandi, Soghra; Mohagheghi, Mohammad A; Hornby, David P; Dalton, Ann

2002-01-01

Breast cancer is the most common female malignancy and a major cause of death in middle-aged women. So far, germline mutations in the BRCA1 and BRCA2 genes in patients with early-onset breast and/or ovarian cancer have not been identified within the Iranian population. With the collaboration of two main centres for cancer in Iran, we obtained clinical information, family history and peripheral blood from 83 women under the age of 45 with early-onset breast cancer for scanning of germline mutations in the BRCA1 and BRCA2 genes. We analysed BRCA1 exons 11 and BRCA2 exons 10 and 11 by the protein truncation test, and BRCA1 exons 2, 3, 5, 13 and 20 and BRCA2 exons 9, 17, 18 and 23 with the single-strand conformation polymorphism assay on genomic DNA amplified by polymerase chain reaction. Ten sequence variants were identified: five frameshifts (putative mutations – four novel); three missense changes of unknown significance and two polymorphisms, one seen commonly in both Iranian and British populations. Identification of these novel mutations suggests that any given population should develop a mutation database for its programme of breast cancer screening. The pattern of mutations seen in the BRCA genes seems not to differ from other populations studied. Early-onset breast cancer (less than 45 years) and a limited family history is sufficient to justify mutation screening with a detection rate of over 25% in this group, whereas sporadic early-onset breast cancer (detection rate less than 5%) is unlikely to be cost-effective
19p13.1 is a triple-negative-specific breast cancer susceptibility locus

DEFF Research Database (Denmark)

Stevens, Kristen N; Fredericksen, Zachary; Vachon, Celine M

2012-01-01

(PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly......The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor...... associated with ER-negative breast cancer risk [rs8170 OR, 1.10; 95% confidence interval (CI), 1.05-1.15; P = 3.49 × 10(-5)] and triple-negative (ER-, PR-, and HER2-negative) breast cancer (rs8170: OR, 1.22; 95% CI, 1.13-1.31; P = 2.22 × 10(-7)). However, rs8170 was no longer associated with ER...
Retrospective study of the impact of pharmacogenetic variants on paclitaxel toxicity and survival in patients with ovarian cancer

DEFF Research Database (Denmark)

Bergmann, Troels K; Gréen, Henrik; Andersen, Charlotte Brasch

2011-01-01

Paclitaxel has a broad spectrum of anti-tumor activity and is useful in the treatment of ovarian, breast, and lung cancer. Paclitaxel is metabolized in the liver by CYP2C8 and CYP3A4 and transported by P-glycoprotein. The dose-limiting toxicities are neuropathy and neutropenia, but the interindiv......Paclitaxel has a broad spectrum of anti-tumor activity and is useful in the treatment of ovarian, breast, and lung cancer. Paclitaxel is metabolized in the liver by CYP2C8 and CYP3A4 and transported by P-glycoprotein. The dose-limiting toxicities are neuropathy and neutropenia...
Breast density as indicator for the use of mammography or MRI to screen women with familial risk for breast cancer (FaMRIsc: a multicentre randomized controlled trial

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Saadatmand Sepideh

2012-10-01

Full Text Available Abstract Background To reduce mortality, women with a family history of breast cancer often start mammography screening at a younger age than the general population. Breast density is high in over 50% of women younger than 50 years. With high breast density, breast cancer incidence increases, but sensitivity of mammography decreases. Therefore, mammography might not be the optimal method for breast cancer screening in young women. Adding MRI increases sensitivity, but also the risk of false-positive results. The limitation of all previous MRI screening studies is that they do not contain a comparison group; all participants received both MRI and mammography. Therefore, we cannot empirically assess in which stage tumours would have been detected by either test. The aim of the Familial MRI Screening Study (FaMRIsc is to compare the efficacy of MRI screening to mammography for women with a familial risk. Furthermore, we will assess the influence of breast density. Methods/Design This Dutch multicentre, randomized controlled trial, with balanced randomisation (1:1 has a parallel grouped design. Women with a cumulative lifetime risk for breast cancer due to their family history of ≥20%, aged 30–55 years are eligible. Identified BRCA1/2 mutation carriers or women with 50% risk of carrying a mutation are excluded. Group 1 receives yearly mammography and clinical breast examination (n = 1000, and group 2 yearly MRI and clinical breast examination, and mammography biennially (n = 1000. Primary endpoints are the number and stage of the detected breast cancers in each arm. Secondary endpoints are the number of false-positive results in both screening arms. Furthermore, sensitivity and positive predictive value of both screening strategies will be assessed. Cost-effectiveness of both strategies will be assessed. Analyses will also be performed with mammographic density as stratification factor. Discussion Personalized breast cancer screening
The Complex Interaction of Matrix Metalloproteinases in the Migration of Cancer Cells through Breast Tissue Stroma

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Kerry J. Davies

2014-01-01

Full Text Available Breast cancer mortality is directly linked to metastatic spread. The metastatic cell must exhibit a complex phenotype that includes the capacity to escape from the primary tumour mass, invade the surrounding normal tissue, and penetrate into the circulation before proliferating in the parenchyma of distant organs to produce a metastasis. In the normal breast, cellular structures change cyclically in response to ovarian hormones leading to regulated cell proliferation and apoptosis. Matrix metalloproteinases (MMPs are a family of zinc dependent endopeptidases. Their primary function is degradation of proteins in the extracellular matrix to allow ductal progression through the basement membrane. A complex balance between matrix metalloproteinases and their inhibitors regulate these changes. These proteinases interact with cytokines, growth factors, and tumour necrosis factors to stimulate branching morphologies in normal breast tissues. In breast cancer this process is disrupted facilitating tumour progression and metastasis and inhibiting apoptosis increasing the life of the metastatic cells. This paper highlights the role of matrix metalloproteinases in cell progression through the breast stroma and reviews the complex relationships between the different proteinases and their inhibitors in relation to breast cancer cells as they metastasise.
Inhibin as a tumor marker of ovarian cancer in postmenopausal women

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Modarres Gilani M

2010-05-01

Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Inhibin is a dimeric glycoprotein that has a depressive effect on the anterior hypophys secretion. The level of this tumor marker is undetectable in menopause women. In patients with gynecological cancer, especially granulosa and epidermal-type (mucinous, ovarian cancers considerable increase in the serum level of inhibin has been reported. The increased level of inhibin has been reported in patients with recurrent ovarian cancer."n"nMethods: We measured total serum inhibin and CA125 tumor marker level in 38 postmenopausal women with pathologically confirmed ovarian cancer before and after surgery out of 51 suspected women. Our control group were postmenopausal women that attended to our clinic for routine gynecologic check up. Both tumor markers were measured in these patients too."n"nResults: Among 38 women with ovarian cancer, 13(34.2% had elevated serum levels of total inhibin. Among the 16 women with serous adenocarcinoma, 3 patients (18.8% had elevated serum levels of inhibin. All the three women with granulosa cell tumor had elevated serum levels of inhibin (100% and 3 of 4(75% women with mucinous ovarian cancer had the same result. three out of 38 women in control group had elevated serum levels of
Comprehensive analysis of NuMA variation in breast cancer

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Aittomäki Kristiina

2008-03-01

Full Text Available Abstract Background A recent genome wide case-control association study identified NuMA region on 11q13 as a candidate locus for breast cancer susceptibility. Specifically, the variant Ala794Gly was suggested to be associated with increased risk of breast cancer. Methods In order to evaluate the NuMa gene for breast cancer susceptibility, we have here screened the entire coding region and exon-intron boundaries of NuMa in 92 familial breast cancer patients and constructed haplotypes of the identified variants. Five missense variants were further screened in 341 breast cancer cases with a positive family history and 368 controls. We examined the frequency of Ala794Gly in an extensive series of familial (n = 910 and unselected (n = 884 breast cancer cases and controls (n = 906, with a high power to detect the suggested breast cancer risk. We also tested if the variant is associated with histopathologic features of breast tumors. Results Screening of NuMA resulted in identification of 11 exonic variants and 12 variants in introns or untranslated regions. Five missense variants that were further screened in breast cancer cases with a positive family history and controls, were each carried on a unique haplotype. None of the variants, or the haplotypes represented by them, was associated with breast cancer risk although due to low power in this analysis, very low risk alleles may go unrecognized. The NuMA Ala794Gly showed no difference in frequency in the unselected breast cancer case series or familial case series compared to control cases. Furthermore, Ala794Gly did not show any significant association with histopathologic characteristics of the tumors, though Ala794Gly was slightly more frequent among unselected cases with lymph node involvement. Conclusion Our results do not support the role of NuMA variants as breast cancer susceptibility alleles.
Comprehensive analysis of NuMA variation in breast cancer

International Nuclear Information System (INIS)

Kilpivaara, Outi; Rantanen, Matias; Tamminen, Anitta; Aittomäki, Kristiina; Blomqvist, Carl; Nevanlinna, Heli

2008-01-01

A recent genome wide case-control association study identified NuMA region on 11q13 as a candidate locus for breast cancer susceptibility. Specifically, the variant Ala794Gly was suggested to be associated with increased risk of breast cancer. In order to evaluate the NuMa gene for breast cancer susceptibility, we have here screened the entire coding region and exon-intron boundaries of NuMa in 92 familial breast cancer patients and constructed haplotypes of the identified variants. Five missense variants were further screened in 341 breast cancer cases with a positive family history and 368 controls. We examined the frequency of Ala794Gly in an extensive series of familial (n = 910) and unselected (n = 884) breast cancer cases and controls (n = 906), with a high power to detect the suggested breast cancer risk. We also tested if the variant is associated with histopathologic features of breast tumors. Screening of NuMA resulted in identification of 11 exonic variants and 12 variants in introns or untranslated regions. Five missense variants that were further screened in breast cancer cases with a positive family history and controls, were each carried on a unique haplotype. None of the variants, or the haplotypes represented by them, was associated with breast cancer risk although due to low power in this analysis, very low risk alleles may go unrecognized. The NuMA Ala794Gly showed no difference in frequency in the unselected breast cancer case series or familial case series compared to control cases. Furthermore, Ala794Gly did not show any significant association with histopathologic characteristics of the tumors, though Ala794Gly was slightly more frequent among unselected cases with lymph node involvement. Our results do not support the role of NuMA variants as breast cancer susceptibility alleles
Management of menopause in women with breast cancer.

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Vincent, A J

2015-10-01

Increasing breast cancer incidence and decreasing mortality have highlighted the importance of survivorship issues related to breast cancer. A consideration of the issues related to menopause is therefore of great importance to both women and clinicians. Menopause/menopausal symptoms, with significant negative effects on quality of life and potential long-term health impacts, may in women with breast cancer be associated with: (1) natural menopause occurring concurrently with a breast cancer diagnosis; (2) recurrence of menopausal symptoms following cessation of hormone replacement therapy; (3) treatment-induced menopause (chemotherapy, ovarian ablation/suppression) and adjuvant endocrine therapy. A variety of non-hormonal pharmacological and non-pharmacological therapies have been investigated as therapeutic options for menopausal symptoms with mixed results, and ongoing research is required. This review presents a summary of the causes, common problematic symptoms of menopause (vasomotor, genitourinary and sexual dysfunction), and longer-term consequences (cardiovascular disease and osteoporosis) related to menopause. It proposes an evidenced-based multidisciplinary approach to the management of menopause/menopausal symptoms in women with breast cancer.
Why do women not return family history forms when referred to breast cancer genetics services? A mixed-method study.

Science.gov (United States)

Hanning, Kirstie A; Steel, Michael; Goudie, David; McLeish, Lorna; Dunlop, Jackie; Myring, Jessica; Sullivan, Frank; Berg, Jonathan; Humphris, Gerry; Ozakinci, Gozde

2015-10-01

Personal and family data forms, completed by women referred to breast cancer genetics clinics, are valuable tools for verification and extension of family history, crucial steps in accurate risk evaluation. A significant minority of women do not complete and return these forms, despite reminders, even when completion is a pre-requisite for a clinic appointment. To facilitate access of women at increased familial risk of breast cancer to screening and counselling services by investigating reasons for non-return of the forms. Based on a single regional 'breast cancer family' service in the UK, Analysis of quantitative data comparing women who did not return forms (n = 55) with those who had done so (n = 59), together with qualitative evaluation of potential barriers to form-completion through semi-structured telephone interviews with a random subset of 'non-returners' (n = 23). Non-returners have higher proportions of the very young (below the age at which surveillance could be offered) and of women from lower social deprivation categories. Interviews revealed that the majority of non-returners are anxious, rather than unconcerned about their breast cancer risk and circumstances and attitudes contributed to non-compliance. Twenty-one participants confirmed that they would welcome an appointment at a 'breast cancer family' clinic, but nine did not attend for the appointment. They were significantly younger than those who attend, but were not at lower familial risk. Many women who fail to complete and return a family history form would benefit from risk assessment and genetic counselling. Several steps are suggested that might help them access the relevant services. © 2014 John Wiley & Sons Ltd.

Measurement of psychological factors associated with genetic testing for hereditary breast, ovarian and colon cancers.

Science.gov (United States)

Vadaparampil, Susan T; Ropka, Mary; Stefanek, Michael E

2005-01-01

Despite numerous individual studies of psychological factors (depression, anxiety, distress) related to genetic testing for inherited cancer syndromes (CGT), there has been no systematic review of the psychological factors are measured among individuals at increased risk for hereditary breast, ovarian, or colon cancer. Our review provides an analysis of psychological factors in studies of CGT and discusses the instruments most commonly used to measure them. We performed a literature search using three major OVID databases from 1993 to January 2003. In the 19 studies that met our inclusion criteria, the most commonly assessed psychological factors were distress, anxiety, and depression. These factors were most often measured by the impact of event scale (IES), the state-trait anxiety inventory (STAI), and the Centers for Epidemiologic Studies and Depression scale (CES-D), respectively. Our results show deficits in the existing body of literature on psychological factors associated with CGT including limited documentation of psychometrics and variability in instrumentation.
Breast cancer screening in BRCA1 and BRCA2 mutation carriers after risk reducing salpingo-oophorectomy

NARCIS (Netherlands)

Fakkert, I.E.; Jansen, L.; Meijer, K.; Kok, Theo; Oosterwijk, J.C.; Mourits, M.J.E.; de Bock, G.H.

Breast cancer screening is offered to BRCA1 and BRCA2 mutation carriers from the age of 25 years because of their increased risk of breast cancer. As ovarian cancer screening is not effective, risk-reducing salpingho-oophorectomy (RRSO) is offered after child bearing age. RRSO before menopause
Asymmetry in family history implicates nonstandard genetic mechanisms: application to the genetics of breast cancer.

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Clarice R Weinberg

2014-03-01

Full Text Available Genome-wide association studies typically target inherited autosomal variants, but less studied genetic mechanisms can play a role in complex disease. Sex-linked variants aside, three genetic phenomena can induce differential risk in maternal versus paternal lineages of affected individuals: 1. maternal effects, reflecting the maternal genome's influence on prenatal development; 2. mitochondrial variants, which are inherited maternally; 3. autosomal genes, whose effects depend on parent of origin. We algebraically show that small asymmetries in family histories of affected individuals may reflect much larger genetic risks acting via those mechanisms. We apply these ideas to a study of sisters of women with breast cancer. Among 5,091 distinct families of women reporting that exactly one grandmother had breast cancer, risk was skewed toward maternal grandmothers (p<0.0001, especially if the granddaughter was diagnosed between age 45 and 54. Maternal genetic effects, mitochondrial variants, or variant genes with parent-of-origin effects may influence risk of perimenopausal breast cancer.
Internet-based physical activity intervention for women with a family history of breast cancer.

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Hartman, Sheri J; Dunsiger, Shira I; Marinac, Catherine R; Marcus, Bess H; Rosen, Rochelle K; Gans, Kim M

2015-12-01

Physical inactivity is a modifiable risk factor for breast cancer. Physical activity interventions that can be delivered through the Internet have the potential to increase participant reach. The efficacy of an Internet-based physical activity intervention was tested in a sample of women at an elevated risk for breast cancer. A total of 55 women with at least 1 first-degree relative with breast cancer (but no personal history of breast cancer) were randomized to a 3-month theoretically grounded Internet-based physical activity intervention or an active control arm. Minutes of moderate to vigorous physical activity, psychosocial mediators of physical activity adoption and maintenance, as well as worry and perceived risk of developing breast cancer were assessed at baseline, 3-month, and 5-month follow up. Participants were on average 46.2 (SD = 11.4) years old with a body mass index of 27.3 (SD = 4.8) kg/m2. The intervention arm significantly increased minutes of moderate to vigorous physical activity compared to the active control arm at 3 months (213 vs. 129 min/week) and 5 months (208 vs. 119 min/week; both ps Internet-based physical activity intervention may substantially increase physical activity in women with a family history of breast cancer. (PsycINFO Database Record (c) 2015 APA, all rights reserved).
Nedd4L expression is decreased in ovarian epithelial cancer tissues compared to ovarian non-cancer tissue.

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Yang, Qiuyun; Zhao, Jinghe; Cui, Manhua; Gi, Shuting; Wang, Wei; Han, Xiaole

2015-12-01

Recent studies have demonstrated that the neural precursor cell expressed, developmentally downregulated 4-like (Nedd4L) gene plays a role in the progression of various cancers. However, reports describing Nedd4L expression in ovarian cancer tissues are limited. A cohort (n = 117) of archival formalin-fixed, paraffin embedded resected normal ovarian epithelial tissues (n = 10), benign ovarian epithelial tumor tissues (n = 10), serous borderline ovarian epithelial tumor tissues (n = 14), mucous borderline ovarian epithelial tumor tissues (n = 11), and invasive ovarian epithelial cancer tissues (n = 72) were assessed for Nedd4L protein expression using immunohistochemistry. Nedd4L protein expression was significantly decreased in invasive ovarian epithelial cancer tissues compared to non-cancer tissues (P < 0.05). Decreased Nedd4L protein expression correlated with clinical stage, pathological grade, lymph node metastasis and survival (P < 0.05). Nedd4L protein expression may be an independent prognostic marker of ovarian cancer development. © 2015 Japan Society of Obstetrics and Gynecology.
Two different BRCA2 mutations found in a multigenerational family with a history of breast, prostate, and lung cancers

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Caporale DA

2014-06-01

Full Text Available Diane A Caporale, Erica E SwensonDepartment of Biology, University of Wisconsin – Stevens Point, Stevens Point, WI, USAAbstract: Breast and lung cancer are two of the most common malignancies in the United States, causing approximately 40,000 and 160,000 deaths each year, respectively. Over 80% of hereditary breast cancer cases are due to mutations in two breast cancer predisposition genes, BRCA1 and BRCA2. These are tumor-suppressor genes associated with DNA repair. Since the discovery of these two genes in the mid-1990s, several other breast cancer predisposition genes have been identified, such as the CHEK2 gene encoding a regulator of BRCA1. Recently, studies have begun investigating the roles of BRCA1 and BRCA2 gene expression in lung cancer. We conducted a family-based case study that included a bloodline of Italian heritage with several cases of breast cancer and associated cancers (prostate and stomach through multiple generations and on a nonblood relative of Scottish/Irish descent who was consecutively diagnosed with breast and lung cancer. Cancer history and environmental risk factors were recorded for each family member. To investigate possible genetic risks, we screened for mutations in specific hypervariable regions of the BRCA1, BRCA2, and CHEK2 genes. DNA was extracted and isolated from the individuals' hair follicles and cheek cells. Polymerase chain reaction (PCR, allele-specific PCR, and DNA sequencing were performed to identify and verify the presence or absence of mutations in these regions. Genotypes of several family members were determined and carriers of mutations were identified. Here we report for the first time the occurrence of two different BRCA2 frameshift mutations within the same family. Specifically, three Italian family members were found to be carriers of the BRCA2-c.2808_2811delACAA (3036delACAA mutation, a 4-nucleotide deletion in exon 11, which is a truncated mutation that causes deleterious function of
Case Report: Mammary and rectal metastases from an ovarian cancer: report of two cases and review of literature [v2; ref status: indexed, http://f1000r.es/4wh

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Mounia Amzerin

2014-12-01

Full Text Available In this paper we report two interesting cases of metastatic ovarian cancer. The first case is a patient who developed rectal and breast metastases mimicking an inflammatory breast cancer. In the second case, subclinical breast and axillary lymph node metastases were revealed by PET/CT. Metastases in the breast originating from solid tumors are extremely rare. The ovarian primitive is the fourth most common origin. The occurrence of breast metastasis is associated with an advanced disease and a poor prognosis. Their incidence is increasing since they are found more often due to better imaging techniques and to better treatment that, accordingly, improve patients’ survival. Thus, unusual sites of metastases are more and more reported. Indeed, some authors reported the occurrence of colorectal metastases from ovarian cancer. However, they remain much less frequent.
Case Report: Mammary and rectal metastases from an ovarian cancer: report of two cases and review of literature [v1; ref status: indexed, http://f1000r.es/27k

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Mounia Amzerin

2014-10-01

Full Text Available In this paper we report two interesting cases of metastatic ovarian cancer. The first case is a patient who developed rectal and breast metastases mimicking an inflammatory breast cancer. In the second case, subclinical breast and axillary lymph node metastases were revealed by PET/CT. Metastases in the breast originating from solid tumors are extremely rare. The ovarian primitive is the fourth most common origin. The occurrence of breast metastasis is associated with an advanced disease and a poor prognosis. Their incidence is increasing since they are found more often due to better imaging techniques and to better treatment that, accordingly, improve patients’ survival. Thus, unusual sites of metastases are more and more reported. Indeed, some authors reported the occurrence of colorectal metastases from ovarian cancer. However, they remain much less frequent.
Analysis of 30 putative BRCA1 splicing mutations in hereditary breast and ovarian cancer families identifies exonic splice site mutations that escape in silico prediction.

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Barbara Wappenschmidt

Full Text Available Screening for pathogenic mutations in breast and ovarian cancer genes such as BRCA1/2, CHEK2 and RAD51C is common practice for individuals from high-risk families. However, test results may be ambiguous due to the presence of unclassified variants (UCV in the concurrent absence of clearly cancer-predisposing mutations. Especially the presence of intronic or exonic variants within these genes that possibly affect proper pre-mRNA processing poses a challenge as their functional implications are not immediately apparent. Therefore, it appears necessary to characterize potential splicing UCV and to develop appropriate classification tools. We investigated 30 distinct BRCA1 variants, both intronic and exonic, regarding their spliceogenic potential by commonly used in silico prediction algorithms (HSF, MaxEntScan along with in vitro transcript analyses. A total of 25 variants were identified spliceogenic, either causing/enhancing exon skipping or activation of cryptic splice sites, or both. Except from a single intronic variant causing minor effects on BRCA1 pre-mRNA processing in our analyses, 23 out of 24 intronic variants were correctly predicted by MaxEntScan, while HSF was less accurate in this cohort. Among the 6 exonic variants analyzed, 4 severely impair correct pre-mRNA processing, while the remaining two have partial effects. In contrast to the intronic alterations investigated, only half of the spliceogenic exonic variants were correctly predicted by HSF and/or MaxEntScan. These data support the idea that exonic splicing mutations are commonly disease-causing and concurrently prone to escape in silico prediction, hence necessitating experimental in vitro splicing analysis.
Metabolic Syndrome and Breast Cancer Risk.

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Wani, Burhan; Aziz, Shiekh Aejaz; Ganaie, Mohammad Ashraf; Mir, Mohammad Hussain

2017-01-01

The study was meant to estimate the prevalence of metabolic syndrome in patients with breast cancer and to establish its role as an independent risk factor on occurrence of breast cancer. Fifty women aged between 40 and 80 years with breast cancer and fifty controls of similar age were assessed for metabolic syndrome prevalence and breast cancer risk factors, including age at menarche, reproductive status, live births, breastfeeding, and family history of breast cancer, age at diagnosis of breast cancer, body mass index, and metabolic syndrome parameters. Metabolic syndrome prevalence was found in 40.0% of breast cancer patients, and 18.0% of those in control group ( P = 0.02). An independent and positive association was seen between metabolic syndrome and breast cancer risk (odds ratio = 3.037; 95% confidence interval 1.214-7.597). Metabolic syndrome is more prevalent in breast cancer patients and is an independent risk factor for breast cancer.
76 FR 55209 - National Ovarian Cancer Awareness Month, 2011

Science.gov (United States)

2011-09-07

... month, we remember the mothers, sisters, and daughters we have lost to ovarian cancer, and we extend our... the women, families, and professionals working to end this disease. The Centers for Disease Control...
Breast cancer correlates in a cohort of breast screening program participants in Riyadh, KSA

International Nuclear Information System (INIS)

Al-Amri, F.; Saeedi, M.Y.; Al-Tahan, F.M.; Alomary, S.A.; Kassim, K.A.; Ali, A.M.; Mostafa Arafa, M.; Ibrahim, A.K.; Ali, A.M.

2015-01-01

Background: Breast cancer is the first cancer among females in the Kingdom of Saudi Arabia, accounting for 27.4% of all newly diagnosed female cancers in 2010. There are several risk factors affecting the incidence of breast cancer where some factors influence the risk more than the others. Aim: We aimed to identify the different risk factors related to breast cancer among females participating in the breast-screening program in Riyadh, KSA. Methods: Based on data from phase-I of the breast-screening program, a case-control study was conducted on women living in Riyadh, KSA. A sample of 349 women (58 cases and 290 controls) was recruited to examine the different breast cancer correlates. Multivariate regression model was built to investigate the most important risk factors. Results: The mean age of cases was 48.5 ± 7.1 years. Age at marriage, number of pregnancy, age at menopause, oral contraceptive pills, breast feeding and family history of breast cancer in first-degree relative were identified as the most important correlates among the studied cohort. Conclusions: The findings of the current work suggested that age at marriage, age at menopause ≥50 years, and 1st degree family history of breast cancer were risk factors for breast cancer, while, age at menopause<50 years, number of pregnancies and practicing breast feeding were protective factors against breast cancer. There was no effect of body mass index or physical inactivity. Further studies are needed to explore the hereditary, familial and genetic background risk factors in Saudi population.
Risk of Breast Cancer in Families with Cleft Lip and Palate

DEFF Research Database (Denmark)

Dietz, Alexander; Pedersen, Dorthe Almind; Jacobsen, Rune

2012-01-01

PURPOSE: To test whether female subjects in families with cleft lip and/or palate (CL/P) have an increased risk of breast cancer. METHODS: By using the Danish Facial Cleft Registry, we identified female subjects with CL/P, mothers of children with CL/P, and sisters to CL/P cases for the Danish...
Hypoxia-Activated Alkylating Agents in BRCA1-Mutant Ovarian Serous Carcinoma.

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Conroy, Michael; Borad, Mitesh J; Bryce, Alan H

2017-07-26

Breast cancer 1 antigen (BRCA 1) and breast cancer 2 antigen (BRCA2) genes play a significant role in deoxyribonucleic acid (DNA) repair by means of interstrand crosslink repair, and deleterious germline mutations of these are responsible for most hereditary breast and ovarian cancers. Therapeutic strategies which specifically target interstrand crosslink repair can therefore be helpful in patients with harmful mutations. We describe two patients with advanced ovarian cancer and deleterious BRCA1 mutations who were treated with TH-302, a hypoxia-activated alkylating agent.
Genetic polymorphisms of the GNRH1 and GNRHR genes and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3

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Lund Eiliv

2009-07-01

Full Text Available Abstract Background Gonadotropin releasing hormone (GNRH1 triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3. Methods We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms (SNPs were genotyped and used to identify haplotype-tagging SNPs (htSNPS in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II, European Prospective Investigation on Cancer and Nutrition (EPIC, Multiethnic Cohort (MEC, Nurses' Health Study (NHS, and Women's Health Study (WHS. Circulating levels of sex steroids (androstenedione, estradiol, estrone and testosterone were also measured in 4713 study subjects. Results Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels. Conclusion Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians.
Genetic polymorphisms of the GNRH1 and GNRHR genes and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3)

International Nuclear Information System (INIS)

Canzian, Federico; Calle, Eugenia E; Chanock, Stephen; Clavel-Chapelon, Francoise; Dossus, Laure; Feigelson, Heather Spencer; Haiman, Christopher A; Hankinson, Susan E; Hoover, Robert; Hunter, David J; Isaacs, Claudine; Kaaks, Rudolf; Lenner, Per; Lund, Eiliv; Overvad, Kim; Palli, Domenico; Pearce, Celeste Leigh; Quiros, Jose R; Riboli, Elio; Stram, Daniel O; Thomas, Gilles; Thun, Michael J; Cox, David G; Trichopoulos, Dimitrios; Gils, Carla H van; Ziegler, Regina G; Henderson, Katherine D; Henderson, Brian E; Berg, Christine; Bingham, Sheila; Boeing, Heiner; Buring, Julie

2009-01-01

Gonadotropin releasing hormone (GNRH1) triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR) in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3). We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms (SNPs) were genotyped and used to identify haplotype-tagging SNPs (htSNPS) in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II), European Prospective Investigation on Cancer and Nutrition (EPIC), Multiethnic Cohort (MEC), Nurses' Health Study (NHS), and Women's Health Study (WHS). Circulating levels of sex steroids (androstenedione, estradiol, estrone and testosterone) were also measured in 4713 study subjects. Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels. Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians
Targeting Stromal-Cancer Cell Crosstalk Networks in Ovarian Cancer Treatment

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Tsz-Lun Yeung

2016-01-01

Full Text Available Ovarian cancer is a histologically, clinically, and molecularly diverse disease with a five-year survival rate of less than 30%. It has been estimated that approximately 21,980 new cases of epithelial ovarian cancer will be diagnosed and 14,270 deaths will occur in the United States in 2015, making it the most lethal gynecologic malignancy. Ovarian tumor tissue is composed of cancer cells and a collection of different stromal cells. There is increasing evidence that demonstrates that stromal involvement is important in ovarian cancer pathogenesis. Therefore, stroma-specific signaling pathways, stroma-derived factors, and genetic changes in the tumor stroma present unique opportunities for improving the diagnosis and treatment of ovarian cancer. Cancer-associated fibroblasts (CAFs are one of the major components of the tumor stroma that have demonstrated supportive roles in tumor progression. In this review, we highlight various types of signaling crosstalk between ovarian cancer cells and stromal cells, particularly with CAFs. In addition to evaluating the importance of signaling crosstalk in ovarian cancer progression, we discuss approaches that can be used to target tumor-promoting signaling crosstalk and how these approaches can be translated into potential ovarian cancer treatment.
The BRCA1 c. 5096G > A p.Arg1699Gln (R1699Q) intermediate risk variant : Breast and ovarian cancer risk estimation and recommendations for clinical management from the ENIGMA consortium

NARCIS (Netherlands)

Moghadasi, Setareh; Meeks, Huong D.; Vreeswijk, Maaike P. G.; Janssen, Linda A. M.; Borg, Ake; Ehrencrona, Hans; Paulsson-Karlsson, Ylva; Wappenschmidt, Barbara; Engel, Christoph; Gehrig, Andrea; Arnold, Norbert; Hansen, Thomas Van Overeem; Thomassen, Mads; Jensen, Uffe Birk; Kruse, Torben A.; Ejlertsen, Bent; Gerdes, Anne-Marie; Pedersen, Inge Sokilde; Caputo, Sandrine M.; Couch, Fergus; Hallberg, Emily J.; van den Ouweland, Ans M. W.; Collee, Margriet J.; Teugels, Erik; Adank, Muriel A.; van der Luijt, Rob B.; Mensenkamp, Arjen R.; Oosterwijk, Jan C.; Blok, Marinus J.; Janin, Nicolas; Claes, Kathleen B. M.; Tucker, Kathy; Viassolo, Valeria; Toland, Amanda Ewart; Eccles, Diana E.; Devilee, Peter; Van Asperen, Christie J.; Spurdle, Amanda B.; Goldgar, David E.; Garcia, Encarna Gomez

2018-01-01

Background: We previously showed that the BRCA1 variant c. 5096G> A p.Arg1699Gln (R1699Q) was associated with an intermediate risk of breast cancer (BC) and ovarian cancer (OC). This study aimed to assess these cancer risks for R1699Q carriers in a larger cohort, including follow-up of previously
Risk Perception and Psychological Distress in Genetic Counselling for Hereditary Breast and/or Ovarian Cancer.

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Cicero, G; De Luca, R; Dorangricchia, P; Lo Coco, G; Guarnaccia, C; Fanale, D; Calò, V; Russo, A

2017-10-01

Oncological Genetic Counselling (CGO) allows the identification of a genetic component that increases the risk of developing a cancer. Individuals' psychological reactions are influenced by both the content of the received information and the subjective perception of their own risk of becoming ill or being a carrier of a genetic mutation. This study included 120 participants who underwent genetic counselling for breast and/or ovarian cancer. The aim of the study was to examine the relation between their cancer risk perception and the genetic risk during CGO before receiving genetic test results, considering the influence of some psychological variables, in particular distress, anxiety and depression. Participants completed the following tools during a psychological interview: a socio-demographic form, Cancer Risk Perception (CRP) and Genetic Risk Perception (GRP), Hospital Anxiety and Depression Scale (HADS) and Distress Thermometer (DT). The data seem to confirm our hypothesis. Positive and significant correlations were found between the observed variables. Moreover, genetic risk perception determined an increase in depressive symptomatology and cancer risk perception led to an increase in anxious symptomatology, specifically in participants during cancer treatment. The present results suggest the importance of assessing genetic and cancer risk perception in individuals who undergo CGO, to identify those who are at risk of a decrease in psychological well-being and of developing greater psychological distress.
History of Comorbidities and Survival of Ovarian Cancer Patients, Results from the Ovarian Cancer Association Consortium

DEFF Research Database (Denmark)

Minlikeeva, Albina N; Freudenheim, Jo L; Eng, Kevin H

2017-01-01

carcinoma who participated in 23 studies included in the Ovarian Cancer Association Consortium, we explored associations between histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, and neurological diseases and overall and progression-free survival...... with ovarian cancer outcome in the overall sample nor in strata defined by histologic subtype, weight status, age at diagnosis, or stage of disease (local/regional vs. advanced).Conclusions: Histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, or neurologic......Background: Comorbidities can affect survival of ovarian cancer patients by influencing treatment efficacy. However, little evidence exists on the association between individual concurrent comorbidities and prognosis in ovarian cancer patients.Methods: Among patients diagnosed with invasive ovarian...

Increased oxidative stress mediates the antitumor effect of PARP inhibition in ovarian cancer

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Dong Hou

2018-07-01

Full Text Available PARP inhibitors have been widely tested in clinical trials, especially for the treatment of breast cancer and ovarian cancer, and were shown to be highly successful. Because PARP primarily functions in sensing and repairing DNA strand breaks, the therapeutic effect of PARP inhibition is generally believed to be attributed to impaired DNA repair. We here report that oxidative stress is also increased by PARP inhibition and mediates the antitumor effect. We showed that PARP1 is highly expressed in specimens of high grade serous ovarian carcinoma and its activity is required for unperturbed proliferation of ovarian cancer cells. Inhibition or depletion of PARP leads to not only an increase in DNA damage, but also an elevation in the levels of reactive oxygen species (ROS. Importantly, antioxidant N-acetylcysteine (NAC significantly attenuated the induction of DNA damage and the perturbation of proliferation by PARP inhibition or depletion. We further showed that NADPH oxidases 1 and 4 were significantly upregulated by PARP inhibition and were partially responsible for the induction of oxidative stress. Depletion of NOX1 and NOX4 partially rescued the growth inhibition of PARP1-deficient tumor xenografts. Our findings suggest that in addition to compromising the repair of DNA damage, PARP inhibition or depletion may exert extra antitumor effect by elevating oxidative stress in ovarian cancer cells. Keywords: PARP1, Oxidative stress, NADPH oxidases, Ovarian cancer
Psychological distress and breast self-examination frequency in women at increased risk for hereditary or familial breast cancer

NARCIS (Netherlands)

van Dooren, S.; Rijnsburger, A. J.; Seynaeve, C.; Kriege, A.; Duivenvoorden, H. J.; Bartels, C. C. M.; Essink-Bot, M. L.; de Koning, H. J.; Tibben, A.

2003-01-01

BACKGROUND: The Magnetic Resonance Imaging Screening study evaluates the efficacy and psychological impact of a surveillance program for women at increased risk for hereditary or familial breast cancer in the Netherlands. Surveillance consists of biannual physical examination, annual mammography,
[Informing the family: emotions and attitudes of oncogenetic counselees for familial breast/ovarian and/or colon cancer risk].

Science.gov (United States)

Kwiatkowski, Fabrice; Laquet, Claire; Dessenne, Pascal; Bignon, Yves-Jean

2015-02-01

Transmission of oncogenetic information (TOI) by probands to their families is of major importance to organize medical prevention in his family. Little is known about the difficulties that the proband faces when he tries to endorse his "duty to warn". To characterize the barriers to TOI, a survey was performed, previously to the bioethic law of 2011, on a representative sample of 337 counselees seen in the last 10 years at the Centre Jean-Perrin Oncogenetics Department. A questionnaire comprising 97 items was prepared by experts and validated by a group of patients and health professionals. Nineteen Lickert-scale questions specially concerned TOI. Analysis found two dimensions, one of emotions and one concerning communication attitudes. Both dimensions were negatively correlated (r=-0.34, Pemotional levels limited communication attitudes. The probands' history of cancer was the main factor impacting TOI. TOI was more difficult for cancer patients than for healthy counselees (P=0.025). Delay since consultation and type of cancer risk had no bearing on TOI. Cancer and its treatments seem to deeply affect patient's relatives and limit his capacity to involve his family into the oncogenetic inquiry. Measures are suggested to help ex-patients improve TOI. Copyright © 2014 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.
Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies

DEFF Research Database (Denmark)

Beral, V.; Bull, D.; Pirie, K.

2012-01-01

Background Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected w...
Breast cancer correlates in a cohort of breast screening program participants in Riyadh, KSA

Directory of Open Access Journals (Sweden)

Fahad A. Al-Amri

2015-06-01

Conclusions: The findings of the current work suggested that age at marriage, age at menopause ⩾50 years and 1st degree family history of breast cancer were risk factors for breast cancer, while, age at menopause <50 years, number of pregnancies and practicing breast feeding were protective factors against breast cancer. There was no effect of body mass index or physical inactivity. Further studies are needed to explore the hereditary, familial and genetic background risk factors in Saudi population.
Ovarian Cancer Stroma: Pathophysiology and the Roles in Cancer Development

International Nuclear Information System (INIS)

Furuya, Mitsuko

2012-01-01

Ovarian cancer represents one of the cancers with the worst prognostic in adult women. More than half of the patients who present with clinical signs such as abdominal bloating and a feeling of fullness already show advanced stages. The majority of ovarian cancers grow as cystic masses, and cancer cells easily spread into the pelvic cavity once the cysts rupture or leak. When the ovarian cancer cells disseminate into the peritoneal cavity, metastatic nests may grow in the cul-de-sac, and in more advanced stages, the peritoneal surfaces of the upper abdomen become the next largest soil for cancer progression. Ascites is also produced frequently in ovarian cancers, which facilitates distant metastasis. Clinicopathologic, epidemiologic and molecular studies on ovarian cancers have improved our understanding and therapeutic approaches, but still further efforts are required to reduce the risks in the patients who are predisposed to this lethal disease and the mortality of the patients in advanced stages. Among various molecules involved in ovarian carcinogenesis, special genes such as TP53, BRCA1 and BRCA2 have been well investigated. These genes are widely accepted as the predisposing factors that trigger malignant transformation of the epithelial cells of the ovary. In addition, adnexal inflammatory conditions such as chronic salpingitis and ovarian endometriosis have been great research interests in the context of carcinogenic background of ovarian cancers. In this review, I discuss the roles of stromal cells and inflammatory factors in the carcinogenesis and progression of ovarian cancers
Ovarian Cancer Stroma: Pathophysiology and the Roles in Cancer Development

Energy Technology Data Exchange (ETDEWEB)

Furuya, Mitsuko [Department of Pathology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004 (Japan)

2012-07-18

Ovarian cancer represents one of the cancers with the worst prognostic in adult women. More than half of the patients who present with clinical signs such as abdominal bloating and a feeling of fullness already show advanced stages. The majority of ovarian cancers grow as cystic masses, and cancer cells easily spread into the pelvic cavity once the cysts rupture or leak. When the ovarian cancer cells disseminate into the peritoneal cavity, metastatic nests may grow in the cul-de-sac, and in more advanced stages, the peritoneal surfaces of the upper abdomen become the next largest soil for cancer progression. Ascites is also produced frequently in ovarian cancers, which facilitates distant metastasis. Clinicopathologic, epidemiologic and molecular studies on ovarian cancers have improved our understanding and therapeutic approaches, but still further efforts are required to reduce the risks in the patients who are predisposed to this lethal disease and the mortality of the patients in advanced stages. Among various molecules involved in ovarian carcinogenesis, special genes such as TP53, BRCA1 and BRCA2 have been well investigated. These genes are widely accepted as the predisposing factors that trigger malignant transformation of the epithelial cells of the ovary. In addition, adnexal inflammatory conditions such as chronic salpingitis and ovarian endometriosis have been great research interests in the context of carcinogenic background of ovarian cancers. In this review, I discuss the roles of stromal cells and inflammatory factors in the carcinogenesis and progression of ovarian cancers.
Analysis of SLX4/FANCP in non-BRCA1/2-mutated breast cancer families

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Fernández-Rodríguez Juana

2012-03-01

Full Text Available Abstract Background Genes that, when mutated, cause Fanconi anemia or greatly increase breast cancer risk encode for proteins that converge on a homology-directed DNA damage repair process. Mutations in the SLX4 gene, which encodes for a scaffold protein involved in the repair of interstrand cross-links, have recently been identified in unclassified Fanconi anemia patients. A mutation analysis of SLX4 in German or Byelorussian familial cases of breast cancer without detected mutations in BRCA1 or BRCA2 has been completed, with globally negative results. Methods The genomic region of SLX4, comprising all exons and exon-intron boundaries, was sequenced in 94 Spanish familial breast cancer cases that match a criterion indicating the potential presence of a highly-penetrant germline mutation, following exclusion of BRCA1 or BRCA2 mutations. Results This mutational analysis revealed extensive genetic variation of SLX4, with 21 novel single nucleotide variants; however, none could be linked to a clear alteration of the protein function. Nonetheless, genotyping 10 variants (nine novel, all missense amino acid changes in a set of controls (138 women and 146 men did not detect seven of them. Conclusions Overall, while the results of this study do not identify clearly pathogenic mutations of SLX4 contributing to breast cancer risk, further genetic analysis, combined with functional assays of the identified rare variants, may be warranted to conclusively assess the potential link with the disease.
Analysis of SLX4/FANCP in non-BRCA1/2-mutated breast cancer families

International Nuclear Information System (INIS)

Fernández-Rodríguez, Juana; Schindler, Detlev; Capellá, Gabriel; Brunet, Joan; Lázaro, Conxi; Pujana, Miguel Angel; Quiles, Francisco; Blanco, Ignacio; Teulé, Alex; Feliubadaló, Lídia; Valle, Jesús del; Salinas, Mónica; Izquierdo, Àngel; Darder, Esther

2012-01-01

Genes that, when mutated, cause Fanconi anemia or greatly increase breast cancer risk encode for proteins that converge on a homology-directed DNA damage repair process. Mutations in the SLX4 gene, which encodes for a scaffold protein involved in the repair of interstrand cross-links, have recently been identified in unclassified Fanconi anemia patients. A mutation analysis of SLX4 in German or Byelorussian familial cases of breast cancer without detected mutations in BRCA1 or BRCA2 has been completed, with globally negative results. The genomic region of SLX4, comprising all exons and exon-intron boundaries, was sequenced in 94 Spanish familial breast cancer cases that match a criterion indicating the potential presence of a highly-penetrant germline mutation, following exclusion of BRCA1 or BRCA2 mutations. This mutational analysis revealed extensive genetic variation of SLX4, with 21 novel single nucleotide variants; however, none could be linked to a clear alteration of the protein function. Nonetheless, genotyping 10 variants (nine novel, all missense amino acid changes) in a set of controls (138 women and 146 men) did not detect seven of them. Overall, while the results of this study do not identify clearly pathogenic mutations of SLX4 contributing to breast cancer risk, further genetic analysis, combined with functional assays of the identified rare variants, may be warranted to conclusively assess the potential link with the disease
Development and validation of a simple questionnaire for the identification of hereditary breast cancer in primary care

Directory of Open Access Journals (Sweden)

Palmero Edenir I

2009-08-01

Full Text Available Abstract Background Breast cancer is a significant public health problem worldwide and the development of tools to identify individuals at-risk for hereditary breast cancer syndromes, where specific interventions can be proposed to reduce risk, has become increasingly relevant. A previous study in Southern Brazil has shown that a family history suggestive of these syndromes may be prevalent at the primary care level. Development of a simple and sensitive instrument, easily applicable in primary care units, would be particularly helpful in underserved communities in which identification and referral of high-risk individuals is difficult. Methods A simple 7-question instrument about family history of breast, ovarian and colorectal cancer, FHS-7, was developed to screen for individuals with an increased risk for hereditary breast cancer syndromes. FHS-7 was applied to 9218 women during routine visits to primary care units in Southern Brazil. Two consecutive samples of 885 women and 910 women who answered positively to at least one question and negatively to all questions were included, respectively. The sensitivity, specificity and positive and negative predictive values were determined. Results Of the 885 women reporting a positive family history, 211 (23.8%; CI95%: 21.5–26.2 had a pedigree suggestive of a hereditary breast and/or breast and colorectal cancer syndrome. Using as cut point one positive answer, the sensitivity and specificity of the instrument were 87.6% and 56.4%, respectively. Concordance between answers in two different applications was given by a intra-class correlation (ICC of 0.84 for at least one positive answer. Temporal stability of the instrument was adequate (ICC = 0.65. Conclusion A simple instrument for the identification of the most common hereditary breast cancer syndrome phenotypes, showing good specificity and temporal stability was developed and could be used as a screening tool in primary care to refer at
Ovarian cancer mortality and industrial pollution

International Nuclear Information System (INIS)

García-Pérez, Javier; Lope, Virginia; López-Abente, Gonzalo; González-Sánchez, Mario

2015-01-01

We investigated whether there might be excess ovarian cancer mortality among women residing near Spanish industries, according to different categories of industrial groups and toxic substances. An ecologic study was designed to examine ovarian cancer mortality at a municipal level (period 1997–2006). Population exposure to pollution was estimated by means of distance from town to facility. Using Poisson regression models, we assessed the relative risk of dying from ovarian cancer in zones around installations, and analyzed the effect of industrial groups and pollutant substances. Excess ovarian cancer mortality was detected in the vicinity of all sectors combined, and, principally, near refineries, fertilizers plants, glass production, paper production, food/beverage sector, waste treatment plants, pharmaceutical industry and ceramic. Insofar as substances were concerned, statistically significant associations were observed for installations releasing metals and polycyclic aromatic chemicals. These results support that residing near industries could be a risk factor for ovarian cancer mortality. - Highlights: • We studied excess mortality due to ovarian cancer near Spanish industries. • Integrated nested Laplace approximations were used as a Bayesian inference tool. • We found excess ovarian cancer mortality near all industrial groups as a whole. • Risk also was found in towns near industries releasing carcinogens and metals. • Risk was associated with plants releasing polycyclic aromatic chemicals and POPs. - Our results support that residing in the vicinity of pollutant industries could be a risk factor for ovarian cancer mortality
Molecular Subtyping of Serous Ovarian Tumors Reveals Multiple Connections to Intrinsic Breast Cancer Subtypes

DEFF Research Database (Denmark)

Jönsson, Jenny-Maria; Johansson, Ida; Dominguez-Valentin, Mev

2014-01-01

expressed between benign and malignant serous ovarian tumors, with cell cycle processes enriched in the malignant subgroup. Borderline tumors were split between the two clusters. Significant correlations between the malignant serous tumors and the highly aggressive ovarian cancer signatures, and the basal...
Variations in the NBN/NBS1 gene and the risk of breast cancer in non-BRCA1/2 French Canadian families with high risk of breast cancer

International Nuclear Information System (INIS)

Desjardins, Sylvie; Beauparlant, Joly Charles; Labrie, Yvan; Ouellette, Geneviève; INHERIT BRCAs; Durocher, Francine

2009-01-01

The Nijmegen Breakage Syndrome is a chromosomal instability disorder characterized by microcephaly, growth retardation, immunodeficiency, and increased frequency of cancers. Familial studies on relatives of these patients indicated that they also appear to be at increased risk of cancer. In a candidate gene study aiming at identifying genetic determinants of breast cancer susceptibility, we undertook the full sequencing of the NBN gene in our cohort of 97 high-risk non-BRCA1 and -BRCA2 breast cancer families, along with 74 healthy unrelated controls, also from the French Canadian population. In silico programs (ESEfinder, NNSplice, Splice Site Finder and MatInspector) were used to assess the putative impact of the variants identified. The effect of the promoter variant was further studied by luciferase gene reporter assay in MCF-7, HEK293, HeLa and LNCaP cell lines. Twenty-four variants were identified in our case series and their frequency was further evaluated in healthy controls. The potentially deleterious p.Ile171Val variant was observed in one case only. The p.Arg215Trp variant, suggested to impair NBN binding to histone γ-H2AX, was observed in one breast cancer case and one healthy control. A promoter variant c.-242-110delAGTA displayed a significant variation in frequency between both sample sets. Luciferase reporter gene assay of the promoter construct bearing this variant did not suggest a variation of expression in the MCF-7 breast cancer cell line, but indicated a reduction of luciferase expression in both the HEK293 and LNCaP cell lines. Our analysis of NBN sequence variations indicated that potential NBN alterations are present, albeit at a low frequency, in our cohort of high-risk breast cancer cases. Further analyses will be needed to fully ascertain the exact impact of those variants on breast cancer susceptibility, in particular for variants located in NBN promoter region
New perspectives on targeted therapy in ovarian cancer

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Coward JIG

2015-02-01

Full Text Available Jermaine IG Coward,1–3 Kathryn Middleton,1 Felicity Murphy1 1Mater Health Services, Raymond Terrace, South Brisbane, QLD, Australia; 2Inflammtion and Cancer Therapeutics Group, Mater Research, University of Queensland, Translational Research Institute, Woolloongabba, Brisbane, QLD, Australia; 3School of Medicine, University of Queensland, Brisbane, QLD, Australia Abstract: Epithelial ovarian cancer remains the most lethal gynecologic malignancy. During the last 15 years, there has been only marginal improvement in 5 year overall survival. These daunting statistics are compounded by the fact that despite all subtypes exhibiting striking heterogeneity, their systemic management remains identical. Although changes to the scheduling and administration of chemotherapy have improved outcomes to a degree, a therapeutic ceiling is being reached with this approach, resulting in a number of trials investigating the efficacy of targeted therapies alongside standard treatment algorithms. Furthermore, there is an urge to develop subtype-specific studies in an attempt to improve outcomes, which currently remain poor. This review summarizes the key studies with antiangiogenic agents, poly(adenosine diphosphate [ADP]-ribose inhibitors, and epidermal growth factor receptor/human epidermal growth factor receptor family targeting, in addition to folate receptor antagonists and insulin growth factor receptor inhibitors. The efficacy of treatment paradigms used in non-ovarian malignancies for type I tumors is also highlighted, in addition to recent advances in appropriate patient stratification for targeted therapies in epithelial ovarian cancer. Keywords: antiangiogenic therapy, high-grade serous, low grade ovarian cancer, PARP inhibition, cancer-related inflammation
Breast cancer in high-risk Afrikaner families: Is BRCAfounder ...

African Journals Online (AJOL)

Breast cancer is the most common form of cancer in women worldwide. Altogether 6 224 cases were reported in South Africa (SA) in 2009.[1] Up to 10% of breast cancer cases are attributable to germline mutations in cancer susceptibility genes, leading to hereditary syndromes.[2] The most well described of these cancer.
Ovarian cancer surgery

DEFF Research Database (Denmark)

Seibaek, Lene; Blaakaer, Jan; Petersen, Lone Kjeld

2013-01-01

PURPOSE: The study objective was to survey general health and coping in women undergoing ovarian cancer surgery, and subsequently to develop and test a supportive care intervention. METHODS/MATERIALS: Women who underwent surgery on the suspicion of ovarian cancer participated in a follow...... standard levels. Concerning mental health, levels were below standard during the entire period, but did improve with time, also in women in whom the potential cancer diagnosis was refuted. The preoperative differences between these groups leveled out postoperatively in terms of physical health. At the end...
Polycystic Ovary Syndrome, Oligomenorrhea, and Risk of Ovarian Cancer Histotypes: Evidence from the Ovarian Cancer Association Consortium.

Science.gov (United States)

Harris, Holly R; Babic, Ana; Webb, Penelope M; Nagle, Christina M; Jordan, Susan J; Risch, Harvey A; Rossing, Mary Anne; Doherty, Jennifer A; Goodman, Marc T; Modugno, Francesmary; Ness, Roberta B; Moysich, Kirsten B; Kjær, Susanne K; Høgdall, Estrid; Jensen, Allan; Schildkraut, Joellen M; Berchuck, Andrew; Cramer, Daniel W; Bandera, Elisa V; Wentzensen, Nicolas; Kotsopoulos, Joanne; Narod, Steven A; Phelan, Catherine M; McLaughlin, John R; Anton-Culver, Hoda; Ziogas, Argyrios; Pearce, Celeste L; Wu, Anna H; Terry, Kathryn L

2018-02-01

Background: Polycystic ovary syndrome (PCOS), and one of its distinguishing characteristics, oligomenorrhea, have both been associated with ovarian cancer risk in some but not all studies. However, these associations have been rarely examined by ovarian cancer histotypes, which may explain the lack of clear associations reported in previous studies. Methods: We analyzed data from 14 case-control studies including 16,594 women with invasive ovarian cancer ( n = 13,719) or borderline ovarian disease ( n = 2,875) and 17,718 controls. Adjusted study-specific ORs were calculated using logistic regression and combined using random-effects meta-analysis. Pooled histotype-specific ORs were calculated using polytomous logistic regression. Results: Women reporting menstrual cycle length >35 days had decreased risk of invasive ovarian cancer compared with women reporting cycle length ≤35 days [OR = 0.70; 95% confidence interval (CI) = 0.58-0.84]. Decreased risk of invasive ovarian cancer was also observed among women who reported irregular menstrual cycles compared with women with regular cycles (OR = 0.83; 95% CI = 0.76-0.89). No significant association was observed between self-reported PCOS and invasive ovarian cancer risk (OR = 0.87; 95% CI = 0.65-1.15). There was a decreased risk of all individual invasive histotypes for women with menstrual cycle length >35 days, but no association with serous borderline tumors ( P heterogeneity = 0.006). Similarly, we observed decreased risks of most invasive histotypes among women with irregular cycles, but an increased risk of borderline serous and mucinous tumors ( P heterogeneity ovarian cancer risk differentially based on histotype. Impact: These results highlight the importance of examining ovarian cancer risk factors associations by histologic subtype. Cancer Epidemiol Biomarkers Prev; 27(2); 174-82. ©2017 AACR . ©2017 American Association for Cancer Research.
IL-8 expression and its possible relationship with estrogen-receptor-negative status of breast cancer cells

Science.gov (United States)

Freund, Ariane; Chauveau, Corine; Brouillet, Jean-Paul; Lucas, Annick; Lacroix, Matthieu; Licznar, Anne; Vignon, Françoise; Lazennec, Gwendal

2003-01-01

Estrogen receptor (ER) status is an important parameter in breast cancer management as ER-positive breast cancers have a better prognosis than ER-negative tumors. This difference comes essentially from the lower aggressiveness and invasiveness of ER-positive tumors. Here, we demonstrate, that IL-8 was clearly overexpressed in most ER-negative breast, ovary cell lines and breast tumor samples tested, whereas no significant IL-8 level could be detected in ER-positive breast or ovarian cell lines. We have also cloned human IL-8 from ER-negative MDA-MB-231 cells and we show that IL-8 produced by breast cancer cells is identical to monocyte-derived IL-8. Interestingly, the invasion potential of ER-negative breast cancer cells is associated at least in part with expression of interleukin-8 (IL-8), but not with IL-8 receptors levels. Moreover, IL-8 increases the invasiveness of ER-positive breast cancer cells by 2 fold, thus confirming the invasion-promoting role of IL-8. On the other hand, exogenous expression of estrogen receptors in ER-negative cells led to a decrease of IL-8 levels. In summary, our data show that IL-8 expression is negatively linked to ER-status of breast and ovarian cancer cells. We also support the idea that IL-8 expression is associated with a higher invasiveness potential of cancer cells in vitro, which suggests that IL-8 could be a novel marker of tumor aggressiveness. PMID:12527894
Understanding Endogenous c-Myc Function in Human Breast Cancer Development

National Research Council Canada - National Science Library

Xia, Bing

2003-01-01

My research is focused on BRCA2, whose mutation has been implicated in the development of breast, ovarian, prostate, pancreatic cancers and Fanconi anemia BRCA2 is an extremely large protein that is challenging% to study...
Breast cancer features in women under the age of 40 years

Directory of Open Access Journals (Sweden)

Deise Santiago Girão Eugênio

Full Text Available Summary Objective: To describe the clinical features, imaging findings and pathological aspects of breast cancer diagnosed in women under the age of 40 years. Method: A retrospective, descriptive study was performed through analysis of medical records between November 2008 and August 2012. One hundred and twenty (120 patients were included, of whom 112 underwent mammography, 113 underwent ultrasonography, and 105 underwent magnetic resonance imaging (MRI. The histopathological data was obtained in most cases from post-surgical analysis, which was available for 113 patients. Results: The mean age at diagnosis of primary breast cancer was 34 years. Only 11 patients (9.0% had a family history of breast or ovarian cancer in first-degree relative. Ninety-two (92 patients sought medical attention after showing breast symptoms, and the presence of a palpable nodule was the main complaint. One hundred and twenty-two (122 primary tumors were diagnosed, of which 112 were invasive (95%. The most common histological type was invasive ductal carcinoma (73.8%. Luminal B was the predominant molecular subtype (42.6%. Ultrasonography was positive in 94.5% of the cases and the most common finding were nodules (94.8%. At mammography, the malignancy was observed in 92.8% and the presence of suggestive calcifications was the dominant feature. The MRI was positive in 98% of patients, and mass lesions were the most common. Conclusion: Most cases of breast cancer diagnosed in patients under the age of 40 years, in our population, had symptoms at diagnosis and tumor with more aggressive biological behavior. Despite the ultrasound has been the most widely used method, we found improved characterization of breast lesions when also used mammography and MRI.

Emotional distress following genetic testing for hereditary breast and ovarian cancer: a meta-analytic review.

Science.gov (United States)

Hamilton, Jada G; Lobel, Marci; Moyer, Anne

2009-07-01

Meta-analysis was used to synthesize results of studies on emotional consequences of predictive genetic testing for BRCA1/2 mutations conferring increased risk of breast and ovarian cancer. Studies assessing anxiety or cancer-specific distress before and after provision of test results (k = 20) were analyzed using a random-effects model. Moderator variables included country of data collection and personal cancer history of study participants. Standardized mean gain effect sizes were calculated for mutation carriers, noncarriers, and those with inconclusive results over short (0-4 weeks), moderate (5-24 weeks), or long (25-52 weeks) periods of time after testing. Distress among carriers increased shortly after receiving results and returned to pretesting levels over time. Distress among noncarriers and those with inconclusive results decreased over time. Some distress patterns differed in studies conducted outside the United States and for individuals with varying cancer histories. Results underscore the importance of time; changes in distress observed shortly after test-result disclosure frequently differed from the pattern of distress seen subsequently. Although emotional consequences of this testing appear minimal, it remains possible that testing may affect cognitive and behavioral outcomes, which have rarely been examined through meta-analysis. Testing may also affect understudied subgroups differently.
Ovarian Cancer Stroma: Pathophysiology and the Roles in Cancer Development

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Mitsuko Furuya

2012-07-01

Full Text Available Ovarian cancer represents one of the cancers with the worst prognostic in adult women. More than half of the patients who present with clinical signs such as abdominal bloating and a feeling of fullness already show advanced stages. The majority of ovarian cancers grow as cystic masses, and cancer cells easily spread into the pelvic cavity once the cysts rupture or leak. When the ovarian cancer cells disseminate into the peritoneal cavity, metastatic nests may grow in the cul-de-sac, and in more advanced stages, the peritoneal surfaces of the upper abdomen become the next largest soil for cancer progression. Ascites is also produced frequently in ovarian cancers, which facilitates distant metastasis. Clinicopathologic, epidemiologic and molecular studies on ovarian cancers have improved our understanding and therapeutic approaches, but still further efforts are required to reduce the risks in the patients who are predisposed to this lethal disease and the mortality of the patients in advanced stages. Among various molecules involved in ovarian carcinogenesis, special genes such as TP53, BRCA1 and BRCA2 have been well investigated. These genes are widely accepted as the predisposing factors that trigger malignant transformation of the epithelial cells of the ovary. In addition, adnexal inflammatory conditions such as chronic salpingitis and ovarian endometriosis have been great research interests in the context of carcinogenic background of ovarian cancers. In this review, I discuss the roles of stromal cells and inflammatory factors in the carcinogenesis and progression of ovarian cancers.
Family beliefs about diet and traditional Chinese medicine for Hong Kong women with breast cancer.

Science.gov (United States)

Simpson, Peggy Burrows

2003-01-01

To explore beliefs about diet and traditional Chinese medicine related to the breast cancer experience of Hong Kong Chinese women and their families. Interpretive phenomenology. Hong Kong, China. A purposive sample of 20 Hong Kong Chinese women diagnosed with breast cancer at various stages of the illness trajectory and at least one other family member. A semistructured, three-hour interview was translated, transcribed, and back-translated. Many women and their family members believed that diet was responsible for their cancer and recurrence. They integrated their cultural beliefs about diet and traditional Chinese medicine to manage illness symptoms and prevent recurrence. Families were anxious and confused about conflicting messages from various sources about dietary practices to promote their health and prevent recurrence. Food and diet alternatives should be discussed with the understanding that beliefs about diet and traditional Chinese medicine are embedded in culture and that many Chinese women and their families seek a combination of Eastern Chinese medicine and Western medicine strategies to manage the illness trajectory. Many Chinese families have different beliefs about food and diet and the role that food plays in managing the cancer experience. Often, Chinese people will not seek clarification if they do not understand information. If information does not fit with their predominant belief systems, families may not implement it, nor will they discuss a situation if they think the conversation will result in a relationship of conflict with healthcare providers.
Claudins Overexpression in Ovarian Cancer: Potential Targets for Clostridium Perfringens Enterotoxin (CPE Based Diagnosis and Therapy

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Diana P. English

2013-05-01

Full Text Available Claudins are a family of tight junction proteins regulating paracellular permeability and cell polarity with different patterns of expression in benign and malignant human tissues. There are approximately 27 members of the claudin family identified to date with varying cell and tissue-specific expression. Claudins-3, -4 and -7 represent the most highly differentially expressed claudins in ovarian cancer. While their exact role in ovarian tumors is still being elucidated, these proteins are thought to be critical for ovarian cancer cell invasion/dissemination and resistance to chemotherapy. Claudin-3 and claudin-4 are the natural receptors for the Clostridium perfringens enterotoxin (CPE, a potent cytolytic toxin. These surface proteins may therefore represent attractive targets for the detection and treatment of chemotherapy-resistant ovarian cancer and other aggressive solid tumors overexpressing claudin-3 and -4 using CPE-based theranostic agents.
Subjective versus objective risk in genetic counseling for hereditary breast and/or ovarian cancers

Directory of Open Access Journals (Sweden)

Sperduti Isabella

2009-12-01

Full Text Available Abstract Background Despite the fact that genetic counseling in oncology provides information regarding objective risks, it can be found a contrast between the subjective and objective risk. The aims of this study were to evaluate the accuracy of the perceived risk compared to the objective risk estimated by the BRCApro computer model and to evaluate any associations between medical, demographic and psychological variables and the accuracy of risk perception. Methods 130 subjects were given medical-demographic file, Cancer and Genetic Risk Perception, Hospital Anxiety-Depression Scale. It was also computed an objective evaluation of the risk by the BRCApro model. Results The subjective risk was significantly higher than objective risk. The risk of tumour was overestimated by 56%, and the genetic risk by 67%. The subjects with less cancer affected relatives significantly overestimated their risk of being mutation carriers and made a more innacurate estimation than high risk subjects. Conclusion The description of this sample shows: general overestimation of the risk, inaccurate perception compared to BRCApro calculation and a more accurate estimation in those subjects with more cancer affected relatives (high risk subjects. No correlation was found between the levels of perception of risk and anxiety and depression. Based on our findings, it is worth pursuing improved communication strategies about the actual cancer and genetic risk, especially for subjects at "intermediate and slightly increased risk" of developing an hereditary breast and/or ovarian cancer or of being mutation carrier.
HER family kinase domain mutations promote tumor progression and can predict response to treatment in human breast cancer

KAUST Repository

Boulbes, Delphine R.; Arold, Stefan T.; Chauhan, Gaurav B.; Blachno, Korina V.; Deng, Nanfu; Chang, Wei-Chao; Jin, Quanri; Huang, Tzu-Hsuan; Hsu, Jung-Mao; Brady, Samuel W.; Bartholomeusz, Chandra; Ladbury, John E.; Stone, Steve; Yu, Dihua; Hung, Mien-Chie; Esteva, Francisco J.

2014-01-01

Resistance to HER2-targeted therapies remains a major obstacle in the treatment of HER2-overexpressing breast cancer. Understanding the molecular pathways that contribute to the development of drug resistance is needed to improve the clinical utility of novel agents, and to predict the success of targeted personalized therapy based on tumor-specific mutations. Little is known about the clinical significance of HER family mutations in breast cancer. Because mutations within HER1/EGFR are predictive of response to tyrosine kinase inhibitors (TKI) in lung cancer, we investigated whether mutations in HER family kinase domains are predictive of response to targeted therapy in HER2-overexpressing breast cancer. We sequenced the HER family kinase domains from 76 HER2-overexpressing invasive carcinomas and identified 12 missense variants. Patients whose tumors carried any of these mutations did not respond to HER2 directed therapy in the metastatic setting. We developed mutant cell lines and used structural analyses to determine whether changes in protein conformation could explain the lack of response to therapy. We also functionally studied all HER2 mutants and showed that they conferred an aggressive phenotype and altered effects of the TKI lapatinib. Our data demonstrate that mutations in the finely tuned HER kinase domains play a critical function in breast cancer progression and may serve as prognostic and predictive markers.
HER family kinase domain mutations promote tumor progression and can predict response to treatment in human breast cancer

KAUST Repository

Boulbes, Delphine R.

2014-11-11

Resistance to HER2-targeted therapies remains a major obstacle in the treatment of HER2-overexpressing breast cancer. Understanding the molecular pathways that contribute to the development of drug resistance is needed to improve the clinical utility of novel agents, and to predict the success of targeted personalized therapy based on tumor-specific mutations. Little is known about the clinical significance of HER family mutations in breast cancer. Because mutations within HER1/EGFR are predictive of response to tyrosine kinase inhibitors (TKI) in lung cancer, we investigated whether mutations in HER family kinase domains are predictive of response to targeted therapy in HER2-overexpressing breast cancer. We sequenced the HER family kinase domains from 76 HER2-overexpressing invasive carcinomas and identified 12 missense variants. Patients whose tumors carried any of these mutations did not respond to HER2 directed therapy in the metastatic setting. We developed mutant cell lines and used structural analyses to determine whether changes in protein conformation could explain the lack of response to therapy. We also functionally studied all HER2 mutants and showed that they conferred an aggressive phenotype and altered effects of the TKI lapatinib. Our data demonstrate that mutations in the finely tuned HER kinase domains play a critical function in breast cancer progression and may serve as prognostic and predictive markers.
Ovarian metastasis in colorectal cancer: retrospective review of 180 cases

Directory of Open Access Journals (Sweden)

Omranipour R

2009-12-01

Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Routine oophorectomy in women with colorectal cancer is under debate, the aim of this study is to determine incidence, clinicopathologic features and prognostic factors of ovarian involvement in primary colorectal cancer (CRC and to clear the role of prophylactic oophorectomy."n"nMethods: Data from primary CRC women treated between years 1990 and 2004 were retrieved and clinical and pathologic features of those who had undergone oophorectomy during CRC surgery were reviewed."n"nResults: One hundred eighty cases (mean age 47.5 years were included. In 120(66.6%, ovaries were preserved and 60(33.3% cases underwent bilateral oophorectomy in addition to primary CRC resection. Reasons for oophorectomy were prophylactic in 22(36.6%, abnormal morphology in 35(58.3%, and undetermined in 3(5% cases. There were five metastatic carcinomas, eight primary ovarian tumors and 47 normal ovaries in pathologic evaluation. No complication directly related to oophorectomy was noted. Patients with ovarian metastases had higher stages of tumor. Ovarian metastases were not related to menstrual status, CRC location, size, differentiation, and mucin production, as well as abnormal morphology of ovary. The global prevalence of
Ovarian failure due to cancer treatment and fertility preservation options

Directory of Open Access Journals (Sweden)

Soheila Aminimoghaddam

2016-04-01

Full Text Available Primary ovarian insufficiency (POI, commonly referred to premature ovarian failure, is defined as ovarian failure before the age of 40 years. It is the loss of ovarian function caused by a process directly affecting ovaries. Cancer therapy which includes surgery, radiotherapy, and chemotherapy influence ovarian function, leading to premature menopause and loss of fertility. POI is idiopathic in most cases (74-90%. The known causes, in addition to anticancer treatment, are other processes like chromosomal abnormalities, autoimmunity, and natural aging can result in secondary ovarian failure, which is detected by an increase in serum gonadotropin levels (FSH and LH. There are evident risks of POI in women treated for cancer. Those who receive anticancer treatments have an increased risk of developing POI. There by, anticancer drugs and radiation therapy are considered as the most common toxins of ovaries. Although cancer incidence rates in women less than 50 years old continue to increase during recent years, mortality rates are dramatically decreasing due to modern advances in treatment. Increasing numbers of survivors are now confronted with the long-term consequences of exposure to these treatments. The pool of primordial follicles in the ovary is fixed and any injury to the ovary can potentially reduce this ovarian reserve, effectively advancing the patient’s reproductive age, thus narrowing the window of reproductive opportunity. Ovarian failure occurs in a significant percentage of childhood cancer survivors and many of them will seek care for reproductive dysfunction. Nevertheless, Embryo cryopreservation, oocyte cryopreservation, ovary tissue cryopreservation, ovarian suppression and oophoro-pexy are some options to preserve fertility in these groups. As a result, having foreknowledge of potential treatment related ovarian failure will allow the physician to give a better counsel to patients and their family regarding the importance and
[Breast cancer and heredity: results of a population case-control study in Girona].

Science.gov (United States)

de Sanjosé, S; Viladiu, P; Cordón, F; Vilardell, L; Marcos, R; Izquìerdo, A

1998-03-21

To characterise the relationship between breast cancer and different aspects of the reproductive life, use of drugs and alcohol by family history of breast cancer. From the cancer registry of Girona, Spain, 330 women were identified with histologically confirmed breast cancer during 1986-1989. For each case, a control woman was selected from a random sample of the population living in the matched area to the case by age (+/- 5 yr.). The information was collected by a personal interview and included: family history of breast cancer, reproductive history, presence of acne during the teenage years, use of oral contraceptives and drugs for sleep and anxiety disorders, and alcohol consumption. 18.5% of breast cancer cases and 8.9% of all controls had a family history of breast cancer. Family history on a first degree relative (mother or sister) was present in 10.6% of the cases and 2.8% of controls, which represented an odds ratio for breast cancer of 3.7 (95% CI, 1.8-7.8) higher than the general population. Women with a first degree family history of breast cancer were at higher risk for breast cancer if they had a history of acne during the teenage period (OR = 2.4; 95% CI, 1.1-5.2) and if they referred long menstrual periods in the early years of menarche (OR = 3.1; 95% CI, 1.3-7.0). Women with no family history had a higher breast cancer risk if they had a late menarche, long menstrual periods, late first full term pregnancy, and history of acne during puberty. Alcohol consumption and use of drugs for anxiety and sleep disorders were associated with a decreased risk of breast cancer. First degree family history of breast cancer seems to be the best risk indicator for developing breast cancer. Long menstrual periods and presence of acne during puberty may indicate hormonal imbalance that act independently of the family history in breast cancer development.
The integrative role of leptin, oestrogen and the insulin family in obesity-associated breast cancer: potential effects of exercise.

Science.gov (United States)

Schmidt, S; Monk, J M; Robinson, L E; Mourtzakis, M

2015-06-01

Obesity is an established risk factor for postmenopausal breast cancer. The mechanisms through which obesity influences the development and progression of breast cancer are not fully elucidated; however, several factors such as increased oestrogen, concentrations of various members of the insulin family and inflammation that are associated with adiposity are purported to be important factors in this relationship. Emerging research has also begun to focus on the role of adipokines, (i.e. adipocyte secreted factors), in breast cancer. Leptin secretion is directly related to adiposity and is believed to promote breast cancer directly and independently, as well as through involvement with the oestrogen and insulin signalling pathways. As leptin is secreted from white adipose tissue, any intervention that reduces adiposity may be favourable. However, it is also important to consider that energy expenditure through exercise, independent of fat loss, may improve leptin regulation. The purpose of this narrative review was to explore the role of leptin in breast cancer development and progression, identify key interactions with oestrogen and the insulin family, and distinguish the potential effects of exercise on these interactions. © 2015 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity.
Culture, attitude and knowledge about breast cancer and preventive measures: a qualitative study of South Asian breast cancer patients in the UK.

Science.gov (United States)

Karbani, Gulshan; Lim, Jennifer N W; Hewison, Jenny; Atkin, Karl; Horgan, Kieran; Lansdown, Mark; Chu, Carol E

2011-01-01

Little is known about the influence of culture and beliefs about breast cancer, and its implications on preventive health behaviour among South Asian people in the UK. Using a qualitative approach, 24 South Asian breast cancer patients and their significant others were interviewed. Most patients were unfamiliar with the subject of cancer; they expressed lack of knowledge of cancer as a disease and its symptoms. They identified a painless lump in the breast as sign of abnormality, but not cancer. They also did not know any non-lump breast symptoms. Over half participated in breast screening after encouragement from daughters or relatives. Most did not practise breast self-examination. Perceptions of cancer and health behaviour were influenced by cultural beliefs. Common themes were cancer is a taboo subject and cancer is a stigma. Patients also expressed misunderstandings about the cause of cancer. Cancer in the family had ramifications on children' s marriage prospects and may cause marital breakdown. Terminology used also caused communication problems with healthcare professionals and within the family: the use of ' chest' to substitute ' breast' changed the meaning of the message conveyed. Cultural beliefs and practices accentuate difficulties in understanding breast cancer, breast screening and breast self-examination, and can prevent South Asian women from adopting preventive health practices.
CHARACTERISTICS OF CLINICAL COURSE OF METASTATIC AND PRIMARY OVARIAN TUMORS IN COLON CANCER

Directory of Open Access Journals (Sweden)

I. A. Dzhanyan

2015-01-01

Full Text Available The aim of this study was to investigate clinical pecuiliarities of ovarian tumors in colon cancer patients and determination of complex diagnostic methods.Subject and methods. Russian N.N. Blokhin Cancer Research Center archives were used for retrospective study, patients, who underwent treatment during 1989–2013 were included. Colon cancer patients with ovarian metastases and with synchronous or metachronous tumors were included.Results. 141 patients were included: 91 patients had colon cancer with ovarian metastases (group 1 and 50 patients had synchronous or metachronous ovarian tumours (group 2. Ovarian tumors were diagnosed during the 1 year in 74 (81.3 % patients in group 1 and in 23 (46 % in group 2. Patients in group 2 less frequently had children (9 (18.0 % vs 5 (5.5 + 2.3 %, р < 0.05, family history of cancer (3 (6 % vs 16 (17.6 %, р < 0.05 and concomitant diseases. Median CA 125 level in group 1 was 64.96 ng/ml and 180 ng/ml in group 2. Ovarian tumors had solid and cystic structure during US examination in 66 (73 % patients in group 1 and 31 (62 % patients in group 2 had solid ovarian tumors on US examination.Conclusions. The differential diagnostics of primary and metastatic ovarian tumors must include CEA, CA 19–9 and CA 125 serum levels and pelvic US.
Common Genetic Variation in Circadian Rhythm Genes and Risk of Epithelial Ovarian Cancer (EOC).

Science.gov (United States)

Jim, Heather S L; Lin, Hui-Yi; Tyrer, Jonathan P; Lawrenson, Kate; Dennis, Joe; Chornokur, Ganna; Chen, Zhihua; Chen, Ann Y; Permuth-Wey, Jennifer; Aben, Katja Kh; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V; Bean, Yukie T; Beckmann, Matthias W; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A; Brooks-Wilson, Angela; Bunker, Clareann H; Butzow, Ralf; Campbell, Ian G; Carty, Karen; Chang-Claude, Jenny; Cook, Linda S; Cramer, Daniel W; Cunningham, Julie M; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; du Bois, Andreas; Despierre, Evelyn; Sieh, Weiva; Doherty, Jennifer A; Dörk, Thilo; Dürst, Matthias; Easton, Douglas F; Eccles, Diana M; Edwards, Robert P; Ekici, Arif B; Fasching, Peter A; Fridley, Brooke L; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G; Glasspool, Rosalind; Goodman, Marc T; Gronwald, Jacek; Harter, Philipp; Hasmad, Hanis N; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A T; Hillemanns, Peter; Hogdall, Claus K; Hogdall, Estrid; Hosono, Satoyo; Iversen, Edwin S; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kellar, Melissa; Kiemeney, Lambertus A; Krakstad, Camilla; Kjaer, Susanne K; Kupryjanczyk, Jolanta; Vierkant, Robert A; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D; Lee, Alice W; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A; Liang, Dong; Lim, Boon Kiong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F A G; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; McNeish, Ian; Menon, Usha; Milne, Roger L; Modugno, Francesmary; Thomsen, Lotte; Moysich, Kirsten B; Ness, Roberta B; Nevanlinna, Heli; Eilber, Ursula; Odunsi, Kunle; Olson, Sara H; Orlow, Irene; Orsulic, Sandra; Palmieri Weber, Rachel; Paul, James; Pearce, Celeste L; Pejovic, Tanja; Pelttari, Liisa M; Pike, Malcolm C; Poole, Elizabeth M; Schernhammer, Eva; Risch, Harvey A; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H; Rudolph, Anja; Runnebaum, Ingo B; Rzepecka, Iwona K; Salvesen, Helga B; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Song, Honglin; Southey, Melissa C; Spiewankiewicz, Beata; Sucheston-Campbell, Lara; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Tangen, Ingvild L; Tworoger, Shelley S; van Altena, Anne M; Vergote, Ignace; Walsh, Christine S; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S; Wicklund, Kristine G; Wilkens, Lynne R; Wu, Anna H; Wu, Xifeng; Woo, Yin-Ling; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Amankwah, Ernest; Berchuck, Andrew; Schildkraut, Joellen M; Kelemen, Linda E; Ramus, Susan J; Monteiro, Alvaro N A; Goode, Ellen L; Narod, Steven A; Gayther, Simon A; Pharoah, Paul D P; Sellers, Thomas A; Phelan, Catherine M

Disruption in circadian gene expression, whether due to genetic variation or environmental factors (e.g., light at night, shiftwork), is associated with increased incidence of breast, prostate, gastrointestinal and hematologic cancers and gliomas. Circadian genes are highly expressed in the ovaries where they regulate ovulation; circadian disruption is associated with several ovarian cancer risk factors (e.g., endometriosis). However, no studies have examined variation in germline circadian genes as predictors of ovarian cancer risk and invasiveness. The goal of the current study was to examine single nucleotide polymorphisms (SNPs) in circadian genes BMAL1, CRY2, CSNK1E, NPAS2, PER3, REV1 and TIMELESS and downstream transcription factors KLF10 and SENP3 as predictors of risk of epithelial ovarian cancer (EOC) and histopathologic subtypes. The study included a test set of 3,761 EOC cases and 2,722 controls and a validation set of 44,308 samples including 18,174 (10,316 serous) cases and 26,134 controls from 43 studies participating in the Ovarian Cancer Association Consortium (OCAC). Analysis of genotype data from 36 genotyped SNPs and 4600 imputed SNPs indicated that the most significant association was rs117104877 in BMAL1 (OR = 0.79, 95% CI = 0.68-0.90, p = 5.59 × 10 -4 ]. Functional analysis revealed a significant down regulation of BMAL1 expression following cMYC overexpression and increasing transformation in ovarian surface epithelial (OSE) cells as well as alternative splicing of BMAL1 exons in ovarian and granulosa cells. These results suggest that variation in circadian genes, and specifically BMAL1 , may be associated with risk of ovarian cancer, likely through disruption of hormonal pathways.
Lead, selenium and nickel concentrations in epithelial ovarian cancer, borderline ovarian tumor and healthy ovarian tissues.

Science.gov (United States)

Canaz, Emel; Kilinc, Metin; Sayar, Hamide; Kiran, Gurkan; Ozyurek, Eser

2017-09-01

Wide variation exists in ovarian cancer incidence rates suggesting the importance of environmental factors. Due to increasing environmental pollution, trace elements and heavy metals have drawn attention in studies defining the etiology of cancer, but scant data is available for ovarian cancer. Our aim was to compare the tissue concentrations of lead, selenium and nickel in epithelial ovarian cancer, borderline tumor and healthy ovarian tissues. The levels of lead, selenium and nickel were estimated using atomic absorption spectrophotometry in formalin-fixed paraffin-embedded tissue samples. Tests were carried out in 20 malignant epithelial ovarian cancer, 15 epithelial borderline tumor and 20 non-neoplastic healthy ovaries. Two samples were collected for borderline tumors, one from papillary projection and one from the smooth surface of cyst wall. Pb and Ni concentrations were found to be higher both in malignant and borderline tissues than those in healthy ovaries. Concentrations of Pb and Ni in malignant tissues, borderline papillary projections and capsular tissue samples were not different. Comparison of Se concentrations of malignant, borderline and healthy ovarian tissues did not reveal statistical difference. Studied metal levels were not found to be different in either papillary projection or in cyst wall of the borderline tumors. This study revealed the accumulation of lead and nickel in ovarian tissue is associated with borderline and malignant proliferation of the surface epithelium. Accumulation of these metals in epithelial ovarian cancer and borderline ovarian tumor has not been demonstrated before. Copyright © 2017 Elsevier GmbH. All rights reserved.
Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response.

Science.gov (United States)

Heppner, K. J.; Matrisian, L. M.; Jensen, R. A.; Rodgers, W. H.

1996-01-01

Matrix metalloproteinase (MMP) family members have been associated with advanced-stage cancer and contribute to tumor progression, invasion, and metastasis as determined by inhibitor studies. In situ hybridization was performed to analyze the expression and localization of all known MMPs in a series of human breast cancer biopsy specimens. Most MMPs were localized to tumor stroma, and all MMPs had very distinct expression patterns. Matrilysin was expressed by morphologically normal epithelial ducts within tumors and in tissue from reduction mammoplasties, and by epithelial-derived tumor cells. Many family members, including stromelysin-3, gelatinase A, MT-MMP, interstitial collagenase, and stromelysin-1 were localized to fibroblasts of tumor stroma of invasive cancers but in quite distinct, and generally widespread, patterns. Gelatinase B, collagenase-3, and metalloelastase expression were more focal; gelatinase B was primarily localized to endothelial cells, collagenase-3 to isolated tumor cells, and metalloelastase to cytokeratin-negative, macrophage-like cells. The MMP inhibitor, TIMP-1, was expressed in both stromal and tumor components in most tumors, and neither stromelysin-2 nor neutrophil collagenase were detected in any of the tumors. These results indicate that there is very tight and complex regulation in the expression of MMP family members in breast cancer that generally represents a host response to the tumor and emphasize the need to further evaluate differential functions for MMP family members in breast tumor progression. Images Figure 1 Figure 2 Figure 3 PMID:8686751
Multiple metastases from ovarian cancer

African Journals Online (AJOL)

Ovarian cancer affects women in the age group >60 years much ... ovarian cancer presenting with liver and thoracic vertebral metastases 4 months after ... manifested by parenchymal liver or lung ... categorised as stage Ic as per International.
Cross Cancer Genomic Investigation of Inflammation Pathway for Five Common Cancers: Lung, Ovary, Prostate, Breast, and Colorectal Cancer.

Science.gov (United States)

Hung, Rayjean J; Ulrich, Cornelia M; Goode, Ellen L; Brhane, Yonathan; Muir, Kenneth; Chan, Andrew T; Marchand, Loic Le; Schildkraut, Joellen; Witte, John S; Eeles, Rosalind; Boffetta, Paolo; Spitz, Margaret R; Poirier, Julia G; Rider, David N; Fridley, Brooke L; Chen, Zhihua; Haiman, Christopher; Schumacher, Fredrick; Easton, Douglas F; Landi, Maria Teresa; Brennan, Paul; Houlston, Richard; Christiani, David C; Field, John K; Bickeböller, Heike; Risch, Angela; Kote-Jarai, Zsofia; Wiklund, Fredrik; Grönberg, Henrik; Chanock, Stephen; Berndt, Sonja I; Kraft, Peter; Lindström, Sara; Al Olama, Ali Amin; Song, Honglin; Phelan, Catherine; Wentzensen, Nicholas; Peters, Ulrike; Slattery, Martha L; Sellers, Thomas A; Casey, Graham; Gruber, Stephen B; Hunter, David J; Amos, Christopher I; Henderson, Brian

2015-11-01

Inflammation has been hypothesized to increase the risk of cancer development as an initiator or promoter, yet no large-scale study of inherited variation across cancer sites has been conducted. We conducted a cross-cancer genomic analysis for the inflammation pathway based on 48 genome-wide association studies within the National Cancer Institute GAME-ON Network across five common cancer sites, with a total of 64 591 cancer patients and 74 467 control patients. Subset-based meta-analysis was used to account for possible disease heterogeneity, and hierarchical modeling was employed to estimate the effect of the subcomponents within the inflammation pathway. The network was visualized by enrichment map. All statistical tests were two-sided. We identified three pleiotropic loci within the inflammation pathway, including one novel locus in Ch12q24 encoding SH2B3 (rs3184504), which reached GWAS significance with a P value of 1.78 x 10(-8), and it showed an association with lung cancer (P = 2.01 x 10(-6)), colorectal cancer (GECCO P = 6.72x10(-6); CORECT P = 3.32x10(-5)), and breast cancer (P = .009). We also identified five key subpathway components with genetic variants that are relevant for the risk of these five cancer sites: inflammatory response for colorectal cancer (P = .006), inflammation related cell cycle gene for lung cancer (P = 1.35x10(-6)), and activation of immune response for ovarian cancer (P = .009). In addition, sequence variations in immune system development played a role in breast cancer etiology (P = .001) and innate immune response was involved in the risk of both colorectal (P = .022) and ovarian cancer (P = .003). Genetic variations in inflammation and its related subpathway components are keys to the development of lung, colorectal, ovary, and breast cancer, including SH2B3, which is associated with lung, colorectal, and breast cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e
How should we discuss genetic testing with women newly diagnosed with breast cancer? Design and implementation of a randomized controlled trial of two models of delivering education about treatment-focused genetic testing to younger women newly diagnosed with breast cancer

Directory of Open Access Journals (Sweden)

Watts Kaaren J

2012-07-01

Full Text Available Abstract Background Germline BRCA1 and BRCA2 mutation testing offered shortly after a breast cancer diagnosis to inform women’s treatment choices - treatment-focused genetic testing ‘TFGT’ - has entered clinical practice in specialist centers and is likely to be soon commonplace in acute breast cancer management, especially for younger women. Yet the optimal way to deliver information about TFGT to younger women newly diagnosed with breast cancer is not known, particularly for those who were not suspected of having a hereditary breast cancer syndrome prior to their cancer diagnosis. Also, little is known about the behavioral and psychosocial impact or cost effectiveness of educating patients about TFGT. This trial aims to examine the impact and efficiency of two models of educating younger women newly diagnosed with breast cancer about genetic testing in order to provide evidence for a safe and effective future clinical pathway for this service. Design/methods In this non-inferiority randomized controlled trial, 140 women newly diagnosed with breast cancer (aged less than 50 years are being recruited from nine cancer centers in Australia. Eligible women with either a significant family history of breast and/or ovarian cancer or with other high risk features suggestive of a mutation detection rate of > 10% are invited by their surgeon prior to mastectomy or radiotherapy. After completing the first questionnaire, participants are randomized to receive either: (a an educational pamphlet about genetic testing (intervention or (b a genetic counseling appointment at a family cancer center (standard care. Each participant is offered genetic testing for germline BRCA mutations. Decision-related and psychosocial outcomes are assessed over 12 months and include decisional conflict (primary outcome;uptake of bilateral mastectomy and/or risk-reducing salpingo-oophorectomy; cancer-specific- and general distress; family involvement in decision
Australian clinicians and chemoprevention for women at high familial risk for breast cancer

Directory of Open Access Journals (Sweden)

Keogh Louise A

2009-05-01

Full Text Available Abstract Objectives Effective chemoprevention strategies exist for women at high risk for breast cancer, yet uptake is low. Physician recommendation is an important determinant of uptake, but little is known about clinicians' attitudes to chemoprevention. Methods Focus groups were conducted with clinicians at five Family Cancer Centers in three Australian states. Discussions were recorded, transcribed and analyzed thematically. Results Twenty three clinicians, including genetic counselors, clinical geneticists, medical oncologists, breast surgeons and gynaecologic oncologists, participated in six focus groups in 2007. The identified barriers to the discussion of the use of tamoxifen and raloxifene for chemoprevention pertained to issues of evidence (evidence for efficacy not strong enough, side-effects outweigh benefits, oophorectomy superior for mutation carriers, practice (drugs not approved for chemoprevention by regulatory authorities and not government subsidized, chemoprevention not endorsed in national guidelines and not many women ask about it, and perception (clinicians not knowledgeable about chemoprevention and women thought to be opposed to hormonal treatments. Conclusion The study demonstrated limited enthusiasm for discussing breast cancer chemoprevention as a management option for women at high familial risk. Several options for increasing the likelihood of clinicians discussing chemoprevention were identified; maintaining up to date national guidelines on management of these women and education of clinicians about the drugs themselves, the legality of "off-label" prescribing, and the actual costs of chemopreventive medications.

Ovarian cancer immunotherapy: opportunities, progresses and challenges

Directory of Open Access Journals (Sweden)

Stevens Richard

2010-02-01

Full Text Available Abstract Due to the low survival rates from invasive ovarian cancer, new effective treatment modalities are urgently needed. Compelling evidence indicates that the immune response against ovarian cancer may play an important role in controlling this disease. We herein summarize multiple immune-based strategies that have been proposed and tested for potential therapeutic benefit against advanced stage ovarian cancer. We will examine the evidence for the premise that an effective therapeutic vaccine against ovarian cancer is useful not only for inducing remission of the disease but also for preventing disease relapse. We will also highlight the questions and challenges in the development of ovarian cancer vaccines, and critically discuss the limitations of some of the existing immunotherapeutic strategies. Finally, we will summarize our own experience on the use of patient-specific tumor-derived heat shock protein-peptide complex for the treatment of advanced ovarian cancer.
Hormone therapy and different ovarian cancers

DEFF Research Database (Denmark)

Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms

2012-01-01

Postmenopausal hormone therapy use increases the risk of ovarian cancer. In the present study, the authors examined the risks of different histologic types of ovarian cancer associated with hormone therapy. Using Danish national registers, the authors identified 909,946 women who were followed from...... 1995-2005. The women were 50-79 years of age and had no prior hormone-sensitive cancers or bilateral oophorectomy. Hormone therapy prescription data were obtained from the National Register of Medicinal Product Statistics. The National Cancer and Pathology Register provided data on ovarian cancers......, including information about tumor histology. The authors performed Poisson regression analyses that included hormone exposures and confounders as time-dependent covariates. In an average of 8.0 years of follow up, 2,681 cases of epithelial ovarian cancer were detected. Compared with never users, women...
Type II diabetes mellitus and the incidence of epithelial ovarian cancer in the cancer prevention study-II nutrition cohort.

Science.gov (United States)

Gapstur, Susan M; Patel, Alpa V; Diver, W Ryan; Hildebrand, Janet S; Gaudet, Mia M; Jacobs, Eric J; Campbell, Peter T

2012-11-01

Despite consistent associations of type II diabetes mellitus with hormonally related cancers such as breast and endometrium, the relation between type II diabetes mellitus and ovarian cancer risk is unclear. Associations of type II diabetes mellitus status, duration, and insulin use with epithelial ovarian cancer overall, and with serous and nonserous histologic subtypes were examined in the Cancer Prevention Study-II Nutrition Cohort, a prospective study of U.S. men and women predominantly aged 50 years and older. Between 1992 and 2007, 524 incident epithelial ovarian cancer cases were identified among 63,440 postmenopausal women. Multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI) were computed using extended Cox regression to update diabetes status and bilateral oophorectomy status during follow-up. Type II diabetes mellitus status (RR = 1.05; 95% CI, 0.75-1.46) and duration were not associated with epithelial ovarian cancer risk. Although not statistically significantly different (P(difference) = 0.39), the RR was higher for type II diabetes mellitus with insulin use (RR = 1.28; 95% CI, 0.74-2.24) than for type II diabetes mellitus without insulin use (RR = 0.96; 95% CI, 0.64-1.43). Diabetes seemed to be more strongly associated with nonserous (RR = 1.41; 95% CI, 0.70-2.85) than serous (RR = 0.71; 95% CI, 0.41-1.23) histologic subtypes. Type II diabetes mellitus was not associated with risk of epithelial ovarian cancer, although higher risks with nonserous subtypes and among insulin users cannot be ruled out. Larger studies are needed to clarify associations of type II diabetes mellitus with or without insulin use with risk of ovarian cancer overall and by histologic subtypes. ©2012 AACR.
Epigenetic down-regulated DDX10 promotes cell proliferation through Akt/NF-κB pathway in ovarian cancer

International Nuclear Information System (INIS)

Gai, Muhuizi; Bo, Qifang; Qi, Lixia

2016-01-01

Ovarian cancer contributes to the majority of ovarian cancer, while the molecular mechanisms remain elusive. Recently, some DEAD box protein 1 has been reported play a tumor suppressor role in ovarian cancer progression. However, the functions of DEAD box protein (DDX) members in ovarian cancer development remain largely unknown. In current study, we retrieved GEO databases and surprisingly found that DDX10 is significantly down-regulated in ovarian cancer tissues compared with normal ovary. These findings suggest that DDX10 might also play a suppressive role in ovarian cancer. We then validated the down-regulated expression pattern of DDX10 in fresh ovarian cancer tissues. Furthermore, both loss- and gain-functions assays reveal that the down-regulated DDX10 could promote ovarian cancer proliferation in vitro and the xenograft subcutaneous tumor formation assays confirmed these findings in vivo. In addition, we found that DDX10 is epigenetic silenced by miR-155-5p in ovarian cancer. Moreover, we further preliminary illustrated that down-regulated DDX10 promotes ovarian cancer cell proliferation through Akt/NF-κB pathway. Taken together, in current study, we found a novel tumor suppressor, DDX10, is epigenetic silenced by miR-155-5p in ovarian cancer, and the down-regulated expression pattern of DDX10 promotes ovarian cancer proliferation through Akt/NF-κB pathway. Our findings shed the light that DDX families might be a novel for ovarian cancer treatment. - Highlights: • A novel DEAD box protein, DDX10 is significantly down-regulated in ovarian cancer tissues. • Down-regulated DDX10 promotes ovarian cancer cell proliferation and growth both in vitro and in vivo. • miR-155-5p is highly expressed in ovarian cancer tissues and epigenetically targets DDX10. • DDX10 and miR-155-5p regulates Akt/p65 axis in ovarian cancer cells.
Epigenetic down-regulated DDX10 promotes cell proliferation through Akt/NF-κB pathway in ovarian cancer

Energy Technology Data Exchange (ETDEWEB)

Gai, Muhuizi; Bo, Qifang; Qi, Lixia, E-mail: lixiaqi_dph@sina.com

2016-01-22

Ovarian cancer contributes to the majority of ovarian cancer, while the molecular mechanisms remain elusive. Recently, some DEAD box protein 1 has been reported play a tumor suppressor role in ovarian cancer progression. However, the functions of DEAD box protein (DDX) members in ovarian cancer development remain largely unknown. In current study, we retrieved GEO databases and surprisingly found that DDX10 is significantly down-regulated in ovarian cancer tissues compared with normal ovary. These findings suggest that DDX10 might also play a suppressive role in ovarian cancer. We then validated the down-regulated expression pattern of DDX10 in fresh ovarian cancer tissues. Furthermore, both loss- and gain-functions assays reveal that the down-regulated DDX10 could promote ovarian cancer proliferation in vitro and the xenograft subcutaneous tumor formation assays confirmed these findings in vivo. In addition, we found that DDX10 is epigenetic silenced by miR-155-5p in ovarian cancer. Moreover, we further preliminary illustrated that down-regulated DDX10 promotes ovarian cancer cell proliferation through Akt/NF-κB pathway. Taken together, in current study, we found a novel tumor suppressor, DDX10, is epigenetic silenced by miR-155-5p in ovarian cancer, and the down-regulated expression pattern of DDX10 promotes ovarian cancer proliferation through Akt/NF-κB pathway. Our findings shed the light that DDX families might be a novel for ovarian cancer treatment. - Highlights: • A novel DEAD box protein, DDX10 is significantly down-regulated in ovarian cancer tissues. • Down-regulated DDX10 promotes ovarian cancer cell proliferation and growth both in vitro and in vivo. • miR-155-5p is highly expressed in ovarian cancer tissues and epigenetically targets DDX10. • DDX10 and miR-155-5p regulates Akt/p65 axis in ovarian cancer cells.
[18F]fluorodeoxyglucose PET/computed tomography in breast cancer and gynecologic cancers

DEFF Research Database (Denmark)

Hildebrandt, Malene Grubbe; Kodahl, Annette Raskov; Teilmann-Jørgensen, Dorte

2015-01-01

In this literature review, an update is provided on the role of [(18)F]fluorodeoxyglucose PET/computed tomography in different clinical settings of the 4 most frequent female-specific cancer types: breast, endometrial, ovarian, and cervical cancer. The most recent knowledge regarding primary...... diagnosis, staging, response evaluation, prognostic and predictive values, recurrence detection, and radiotherapy planning is evaluated, including, when clinically relevant, considerations with respect to the epidemiology, treatment, and course of the diseases....
Estrogen and progesterone signalling in the normal breast and its implications for cancer development.

Science.gov (United States)

Hilton, Heidi N; Clarke, Christine L; Graham, J Dinny

2018-05-05

The ovarian hormones estrogen and progesterone are master regulators of the development and function of a broad spectrum of human tissues, including the breast, reproductive and cardiovascular systems, brain and bone. Acting through the nuclear estrogen (ER) and progesterone receptors (PR), both play complex and essential coordinated roles in the extensive development of the lobular alveolar epithelial structures of the normal breast during puberty, the normal menstrual cycle and pregnancy. The past decade has seen major advances in understanding the mechanisms of action of estrogen and progesterone in the normal breast and in the delineation of the complex hierarchy of cell types regulated by ovarian hormones in this tissue. There is evidence for a role for both ER and PR in driving breast cancer, and both are favourable prognostic markers with respect to outcome. In this review, we summarize current knowledge of the mechanisms of action of ER and PR in the normal breast, and implications for the development and management of breast cancer. Copyright © 2017 Elsevier B.V. All rights reserved.
Tubal ligation and salpingectomy and the risk of epithelial ovarian cancer and borderline ovarian tumors

DEFF Research Database (Denmark)

Madsen, C; Baandrup, Louise; Dehlendorff, Christian

2015-01-01

OBJECTIVE: According to the recent theories on the ovarian cancer origin, any protective effect of tubal ligation may vary with histologic subtype of ovarian cancer. Furthermore, bilateral salpingectomy may represent an opportunity for surgical prevention of serous ovarian cancer. DESIGN: Nationw......OBJECTIVE: According to the recent theories on the ovarian cancer origin, any protective effect of tubal ligation may vary with histologic subtype of ovarian cancer. Furthermore, bilateral salpingectomy may represent an opportunity for surgical prevention of serous ovarian cancer. DESIGN...... sampling. We required that cases and controls have no previous cancer and that controls have no previous bilateral oophorectomy. METHODS: Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals, adjusting for potential confounders. MAIN OUTCOME MEASURES: Epithelial...
Transition to the new role of caregiving for families of patients with breast cancer: a qualitative descriptive exploratory study.

Science.gov (United States)

Hashemi-Ghasemabadi, Masoumeh; Taleghani, Fariba; Yousefy, Alireza; Kohan, Shahnaz

2016-03-01

Families, especially in Eastern and Muslim countries, routinely accept the responsibility of caring for cancer patients. This study describes the transition to the new role of caregiving from the perspective of family caregivers in Iran as part of the current trend of recognizing the experiences of family members of breast cancer patients from different cultural perspectives. A descriptive exploratory qualitative research approach was used to investigate the experiences of family caregivers of patients with breast cancer in the transition to caregiving. The subjects were 23 family caregivers of breast cancer patients referred to cancer centers at Isfahan University hospitals who were selected by purposive sampling. Data was gathered through in-depth interviews. Interview transcripts were analyzed using conventional content analysis with an inductive approach. Data analysis identified the following categories: grasping a new situation without preparation, perceived inefficiency, infinite absence, and abandoned in the role. Caregivers believed that they were not prepared for their new circumstances and did not have the necessary competence and capabilities to meet the challenges of caregiving. They experienced negative consequences resulting from the difficult responsibility of caregiving. Moreover, they believed that they received limited support from relatives, health-care providers, and the community. The transition to the new role of caregiving is affected by experiences specific to the conditions of the caretakers. When these conditions can be understood and identified, it is possible to provide detailed information for policymaking and planning for family-centered care.
Ovarian cancer mortality and industrial pollution.

Science.gov (United States)

García-Pérez, Javier; Lope, Virginia; López-Abente, Gonzalo; González-Sánchez, Mario; Fernández-Navarro, Pablo

2015-10-01

We investigated whether there might be excess ovarian cancer mortality among women residing near Spanish industries, according to different categories of industrial groups and toxic substances. An ecologic study was designed to examine ovarian cancer mortality at a municipal level (period 1997-2006). Population exposure to pollution was estimated by means of distance from town to facility. Using Poisson regression models, we assessed the relative risk of dying from ovarian cancer in zones around installations, and analyzed the effect of industrial groups and pollutant substances. Excess ovarian cancer mortality was detected in the vicinity of all sectors combined, and, principally, near refineries, fertilizers plants, glass production, paper production, food/beverage sector, waste treatment plants, pharmaceutical industry and ceramic. Insofar as substances were concerned, statistically significant associations were observed for installations releasing metals and polycyclic aromatic chemicals. These results support that residing near industries could be a risk factor for ovarian cancer mortality. Copyright © 2015 Elsevier Ltd. All rights reserved.
Interleukin-19 in Breast Cancer

Directory of Open Access Journals (Sweden)

Ying-Yin Chen

2013-01-01

Full Text Available Inflammatory cytokines within the tumor microenvironment are linked to progression in breast cancer. Interleukin- (IL- 19, part of the IL-10 family, contributes to a range of diseases and disorders, such as asthma, endotoxic shock, uremia, psoriasis, and rheumatoid arthritis. IL-19 is expressed in several types of tumor cells, especially in squamous cell carcinoma of the skin, tongue, esophagus, and lung and invasive duct carcinoma of the breast. In breast cancer, IL-19 expression is correlated with increased mitotic figures, advanced tumor stage, higher metastasis, and poor survival. The mechanisms of IL-19 in breast cancer have recently been explored both in vitro and in vivo. IL-19 has an autocrine effect in breast cancer cells. It directly promotes proliferation and migration and indirectly provides a microenvironment for tumor progression, which suggests that IL-19 is a prognostic marker in breast cancer and that antagonizing IL-19 may have therapeutic potential.
Towards personalized screening: Cumulative risk of breast cancer screening outcomes in women with and without a first-degree relative with a history of breast cancer.

Science.gov (United States)

Ripping, Theodora Maria; Hubbard, Rebecca A; Otten, Johannes D M; den Heeten, Gerard J; Verbeek, André L M; Broeders, Mireille J M

2016-04-01

Several reviews have estimated the balance of benefits and harms of mammographic screening in the general population. The balance may, however, differ between individuals with and without family history. Therefore, our aim is to assess the cumulative risk of screening outcomes; screen-detected breast cancer, interval cancer, and false-positive results, in women screenees aged 50-75 and 40-75, with and without a first-degree relative with a history of breast cancer at the start of screening. Data on screening attendance, recall and breast cancer detection were collected for each woman living in Nijmegen (The Netherlands) since 1975. We used a discrete time survival model to calculate the cumulative probability of each major screening outcome over 19 screening rounds. Women with a family history of breast cancer had a higher risk of all screening outcomes. For women screened from age 50-75, the cumulative risk of screen-detected breast cancer, interval cancer and false-positive results were 9.0, 4.4 and 11.1% for women with a family history and 6.3, 2.7 and 7.3% for women without a family history, respectively. The results for women 40-75 followed the same pattern for women screened 50-75 for cancer outcomes, but were almost doubled for false-positive results. To conclude, women with a first-degree relative with a history of breast cancer are more likely to experience benefits and harms of screening than women without a family history. To complete the balance and provide risk-based screening recommendations, the breast cancer mortality reduction and overdiagnosis should be estimated for family history subgroups. © 2015 UICC.
Association between common germline genetic variation in 94 candidate genes or regions and risks of invasive epithelial ovarian cancer

DEFF Research Database (Denmark)

Quaye, Lydia; Tyrer, Jonathan; Ramus, Susan J

2009-01-01

BACKGROUND: Recent studies have identified several single nucleotide polymorphisms (SNPs) in the population that are associated with variations in the risks of many different diseases including cancers such as breast, prostate and colorectal. For ovarian cancer, the known highly penetrant suscept...
Psychometric testing of the Caregiver Quality of Life Index-Cancer scale in an Iranian sample of family caregivers to newly diagnosed breast cancer women.

Science.gov (United States)

Khanjari, Sedigheh; Oskouie, Fatemeh; Langius-Eklöf, Ann

2012-02-01

To translate and test the reliability and validity of the Persian version of the Caregiver Quality of Life Index-Cancer scale. Research across many countries has determined quality of life of cancer patients, but few attempts have been made to measure the quality of life of family caregivers of patients with breast cancer. The Caregiver Quality of Life Index-Cancer scale was developed for this purpose, but until now, it has not been translated into or tested in the Persian language. Methodological research design. After standard translation, the 35-item Caregiver Quality of Life Index-Cancer scale was administered to 166 Iranian family caregivers of patients with breast cancer. A confirmatory factor analysis was carried out using LISREL to test the scale's construct validity. Further, the internal consistency and convergent validity of the instrument were tested. For convergent validity, four instruments were used in the study: sense of coherence scale, spirituality perspective scale, health index and brief religious coping scale. The confirmatory factor analysis resulted in the same four-factor structure as the original, though, with somewhat different item loadings. The Persian version of the Caregiver Quality of Life Index-Cancer scales had satisfactory internal consistency (0·72-0·90). Tests of convergent validity showed that all hypotheses were confirmed. A hierarchical multiple regression analysis additionally confirmed the convergent validity between the total Caregiver Quality of Life Index-Cancer score and sense of coherence (β = 0·34), negative religious coping (β = -0·21), education (β = 0·24) and the more severe stage of breast cancer (β = 0·23), in total explaining 41% of the variance. The Persian version of the Caregiver Quality of Life Index-Cancer scale could be a reliable and valid measure in Iranian family caregivers of patients with breast cancer. The Persian version of the Caregiver Quality of Life Index-Cancer scale is simple to
Genetic factors and breast cancer laterality

International Nuclear Information System (INIS)

Amer, Magid H

2014-01-01

Women are more likely to develop cancer in the left breast than the right. Such laterality may influence subsequent management, especially in elderly patients with heart disease who may require radiation therapy. The purpose of this study was to explore possible factors for such cancer laterality. In this work, clinical data for consecutive patients with histologically confirmed breast cancer were reviewed, with emphasis on clinical presentation and family history. Between 2005 and 2012, 687 patients with breast cancer were seen. Two women with incomplete data and eleven men were excluded. In total, 343 (50.9%) patients presented with left breast cancer, 311 (46.1%) with right breast cancer, and 20 (3.0%) with simultaneous bilateral malignancy. There were no significant differences between the three groups, especially in regards to clinical presentation and tumor characteristics. A total of 622 (92.3%) patients had unilateral primary, 20 (3.0%) had simultaneous bilateral, and 32 (4.7%) had metachronous primary breast cancer with subsequent contralateral breast cancer after 7.5–236 months. The worst 10-year survival was for bilateral simultaneous (18%) compared with unilateral (28%) and metachronous primaries (90%). There were no differences in survival in relation to breast cancer laterality, handedness, and presence or absence of a family history of cancer. There were significant similarities between patients and first-degree relatives in regards to breast cancer laterality, namely same breast (30/66, 45.5%), opposite breast (9/66, 13.6%), and bilateral cancer (27/66, 40.9, P=0.01163). This was more evident among patients and their sisters (17/32, 53.1%) or mothers (11/27, 40.7%, P=0.0689). There were also close similarities in relation to age at initial diagnosis of cancer for patients and their first-degree relatives for age differences of ≤5 years (48/166, 28.9%), 6–10 years (34/166, 20.5%), and >11 years (84/166, 50.6%, P=0.12065). High similarities
From Diagnosis to Gnosis: writing, knowledge, and repair in breast cancer and BRCA memoirs.

Science.gov (United States)

Boesky, Amy

2015-01-01

This essay explores the reparative work of diagnostic retellings in breast cancer and BRCA memoirs (memoirs written by women who learn they carry a mutation predisposing them to develop breast or ovarian cancers). It considers four memoirists (Felicia Knaul, Melanie Norton, Masha Gessen, and Sarah Gabriel) as they illuminate initial moments of "finding out"--learning they have cancer or have tested positive for a BRCA mutation. These memoirists invite readers to appreciate the complexity of cancer as a lived experience. Writing about breast cancer and the risk of its development helps writers and readers alike to understand illness in greater depth, challenging some aspects of care and championing others.
Regulation of semaphorin 4D expression and cell proliferation of ovarian cancer by ERalpha and ERbeta

Directory of Open Access Journals (Sweden)

Y. Liu

Full Text Available Ovarian cancer is one of the most common malignancies in women. Semaphorin 4D (sema 4D is involved in the progress of multiple cancers. In the presence of estrogen-like ligands, estrogen receptors (ERα and ERβ participate in the progress of breast and ovarian cancers by transcriptional regulation. The aim of the study was to investigate the role of sema 4D and elucidate the regulatory pattern of ERα and ERβ on sema 4D expression in ovarian cancers. Sema 4D levels were up-regulated in ovarian cancer SKOV-3 cells. Patients with malignant ovarian cancers had significantly higher sema 4D levels than controls, suggesting an oncogene role of sema 4D in ovarian cancer. ERα expressions were up-regulated in SKOV-3 cells compared with normal ovarian IOSE80 epithelial cells. Conversely, down-regulation of ERβ was observed in SKOV-3 cells. Forced over-expression of ERα and ERβ in SKOV-3 cells was manipulated to establish ERα+ and ERβ+ SKOV-3 cell lines. Incubation of ERα+ SKOV-3 cells with ERs agonist 17β-estradiol (E2 significantly enhanced sema 4D expression and rate of cell proliferation. Incubated with E2, ERβ+ SKOV-3 cells showed lower sema 4D expression and cell proliferation. Blocking ERα and ERβ activities with ICI182-780 inhibitor, sema 4D expressions and cell proliferation of ERα+ and ERβ+ SKOV-3 cells were recovered to control levels. Taken together, the data showed that sema 4D expression was positively correlated with the progress of ovarian cancer. ERα positively regulated sema 4D expression and accelerated cell proliferation. ERβ negatively regulated sema 4D expression and inhibited cell multiplication.
High progesterone levels during the luteal phase related to the use of an aromatase inhibitor in breast cancer patients

DEFF Research Database (Denmark)

Alviggi, C; Marci, R; Vallone, R

2017-01-01

OBJECTIVE: To evaluate the hormonal profile in three breast cancer patients who underwent controlled ovarian stimulation in the presence of the aromatase inhibitor letrozole. PATIENTS AND METHODS: In IVF University referral center, a case series of three breast cancer patients who underwent contr...
Evaluation of therapy response in breast and ovarian cancer patients by positron emission tomography (PET)

Energy Technology Data Exchange (ETDEWEB)

Baum, R. P.; Przetak, C. [Zentralklinik Bad Berka, Clinic of Nuclear Medicine, Center for PET, Bad Berka (Germany)

2001-09-01

Positron emission tomography (PET) has the potential to contribute significantly to treatment planning and to the evaluation of response to therapy in patients with cancer. For disease recurrence PET imaging provides information non-invasively. The final goal is to biologically characterize an individual patients' tumor and to predict the response to treatment at the earliest possible time. Quantitative and/or semi-quantitative PET studies yield valuable information in breast cancer regarding prognosis and response to chemohormontherapy in a timely fashion. In ovarian cancer, up to now only few studies have been performed applying PET techniques for the evaluation of treatment response. These preliminary studies indicate that serial assessment of tumor metabolism by FDG-PET early during effective chemotherapy may predict subsequent response to such therapy. PET studies can be repeated without any side-effects and with low radiation exposure and results can be directly correlated with clinical laboratory data and histology. Therapy monitoring by PET could help to optimize neoadjuvant therapy protocols and to avoid ineffective preoperative therapy in non-responders, but this has to be proven in a larger number of patients and in different neoadjuvant settings such as chemotherapy, radiation therapy, hormone therapy or a combination of these.
Evaluation of therapy response in breast and ovarian cancer patients by positron emission tomography (PET)

International Nuclear Information System (INIS)

Baum, R. P.; Przetak, C.

2001-01-01

Positron emission tomography (PET) has the potential to contribute significantly to treatment planning and to the evaluation of response to therapy in patients with cancer. For disease recurrence PET imaging provides information non-invasively. The final goal is to biologically characterize an individual patients' tumor and to predict the response to treatment at the earliest possible time. Quantitative and/or semi-quantitative PET studies yield valuable information in breast cancer regarding prognosis and response to chemohormontherapy in a timely fashion. In ovarian cancer, up to now only few studies have been performed applying PET techniques for the evaluation of treatment response. These preliminary studies indicate that serial assessment of tumor metabolism by FDG-PET early during effective chemotherapy may predict subsequent response to such therapy. PET studies can be repeated without any side-effects and with low radiation exposure and results can be directly correlated with clinical laboratory data and histology. Therapy monitoring by PET could help to optimize neoadjuvant therapy protocols and to avoid ineffective preoperative therapy in non-responders, but this has to be proven in a larger number of patients and in different neoadjuvant settings such as chemotherapy, radiation therapy, hormone therapy or a combination of these

Emotional, Biological, and Cognitive Impact of a Brief Expressive Writing Intervention for Women at Familial Breast Cancer Risk

National Research Council Canada - National Science Library

Valdimarsdottir, Heiddis

2006-01-01

Women at familial breast cancer risk have highly inflated perceptions of their risk of developing the disease high levels of cancer-specific distress and lower levels of natural killer cell activity (NKCA...
Modulators of Response to Tumor Necrosis-related Apoptosis Inducing Ligand (TRAIL) Therapy in Ovarian Cancer

Science.gov (United States)

2011-05-01

several human cancers including breast, ovarian, uterine cervical , rhabdomyosarcoma, and hepatocellular carcinoma(9, 18-21). When Six1 is expressed...during HPV-mediated carcinogenesis: a comparison between an in vitro cell model and cervical cancer. Int J Cancer 2008; 123:32-40. 22. Reichenberger KJ...to have recurrent carcinoma in the hernia sac during hernia repair. Of the 9 patients who were first diagnosed with recurrence based on positive
Tuning to optimize SVM approach for assisting ovarian cancer diagnosis with photoacoustic imaging.

Science.gov (United States)

Wang, Rui; Li, Rui; Lei, Yanyan; Zhu, Quing

2015-01-01

Support vector machine (SVM) is one of the most effective classification methods for cancer detection. The efficiency and quality of a SVM classifier depends strongly on several important features and a set of proper parameters. Here, a series of classification analyses, with one set of photoacoustic data from ovarian tissues ex vivo and a widely used breast cancer dataset- the Wisconsin Diagnostic Breast Cancer (WDBC), revealed the different accuracy of a SVM classification in terms of the number of features used and the parameters selected. A pattern recognition system is proposed by means of SVM-Recursive Feature Elimination (RFE) with the Radial Basis Function (RBF) kernel. To improve the effectiveness and robustness of the system, an optimized tuning ensemble algorithm called as SVM-RFE(C) with correlation filter was implemented to quantify feature and parameter information based on cross validation. The proposed algorithm is first demonstrated outperforming SVM-RFE on WDBC. Then the best accuracy of 94.643% and sensitivity of 94.595% were achieved when using SVM-RFE(C) to test 57 new PAT data from 19 patients. The experiment results show that the classifier constructed with SVM-RFE(C) algorithm is able to learn additional information from new data and has significant potential in ovarian cancer diagnosis.
The Potential Contribution of BRCA Mutations to Early Onset and Familial Breast Cancer in Uzbekistan.

Science.gov (United States)

Abdikhakimov, Abdulla; Tukhtaboeva, Mukaddas; Adilov, Bakhtiyar; Turdikulova, Shahlo

2016-01-01

Breast cancer is the most common malignancy in women and affects approximately 1 out of 8 females in the US. Risk of developing breast cancer is strongly influenced by genetic factors. Germ-line mutations in BRCA1 and BRCA2 genes are associated with 5-10% of breast cancer incidence. To reduce the risk of developing cancer and to increase the likelihood of early detection, carriers of BRCA1 or BRCA2 mutations are offered surveillance programs and effective preventive medical interventions. Identification of founder mutations of BRCA1/2 in high risk communities can have a significant impact on the management of hereditary cancer at the level of the national healthcare systems, making genetic testing more affordable and cost-effective. BRCA1 and BRCA2 mutations in breast cancer patients have not been characterized in the Uzbek population. This pilot study aimed to investigate the contribution of BRCA1 and BRCA2 mutation to early onset and familial cases of breast cancer in Uzbekistan. A total of 67 patients with breast cancer and 103 age-matched disease free controls were included in this study. Utilizing SYBR Green based real-time allele-specific PCR, we have analyzed DNA samples of patients with breast cancer and disease free controls to identify the following BRCA1 and BRCA2 mutations: BRCA1 5382insC, BRCA1 4153delA, BRCA1 185delAG, BRCA1 300T>G, BRCA2 6174delT. Three unrelated samples (4.5%) were found to be positive for the heterozygous 5382insCBRCA1 mutation, representing a possible founder mutation in the Uzbek population, supporting the need for larger studies examining the contribution of this mutation to breast cancer incidence in Uzbekistan. We did not find BRCA1 4153delA, BRCA1 185delAG, BRCA1 300T>G, and BRCA2 6174delT mutations. This preliminary evidence suggests a potential contribution of BRCA1 5382insC mutation to breast cancer development in Uzbek population. Taking into account a high disease penetrance in carriers of BRCA1 mutation, it seems
MR-guided intervention in women with a family history of breast cancer

International Nuclear Information System (INIS)

Viehweg, P.; Bernerth, T.; Kiechle, M.; Buchmann, J.; Heinig, A.; Koelbl, H.; Laniado, M.; Heywang-Koebrunner, S.H.

2006-01-01

Objective: A study was undertaken to assess the clinical value of magnetic resonance (MR) imaging-guided interventions in women with a family history, but no personal history of breast cancer. Methods and patients: Retrospective review was performed on 63 consecutive women who had a family history, but no personal history of breast cancer. A total of 97 lesions were referred for an MR-guided intervention. Standardized MR examinations (1.0 T, T1-weighted 3D FLASH, 0.15 mmol Gd-DTPA/kg body weight, prone position) were performed using a dedicated system which allows vacuum assisted breast biopsy or wire localization. Results: Histologic findings in 87 procedures revealed 9 (10%) invasive carcinomas, 12 (14%) ductal carcinomas in situ, 2 atypical ductal hyperplasias (2.5%) and 2 atypical lobular hyperplasias (2.5%). Sixty-two (71%) benign histologic results are verified by an MR-guided intervention, retrospective correlation of imaging and histology and by subsequent follow-up. In ten lesions the indication dropped since the enhancing lesion was no longer visible. Absent enhancement was confirmed by short-term re-imaging of the noncompressed breast and by follow-up. Conclusion: Malignancy was found in 24%, high-risk lesions in 5% of successfully performed MR-guided biopsy procedures. A 57% of MR-detected malignancies were ductal carcinoma in situ. In 10% of the lesions the intervention was not performed, since no enhancing lesion could be reproduced at the date of anticipated intervention. Such problems may be avoided if the initial MRI is performed in the appropriate phase of the menstrual cycle and without hormonal replacement therapy
MR-guided intervention in women with a family history of breast cancer

Energy Technology Data Exchange (ETDEWEB)

Viehweg, P. [Institute of Diagnostic Radiology, Technical University Dresden, Fetscherstrasse 74, 01307 Dresden (Germany)]. E-mail: Petra.Viehweg@uniklinikum-dresden.de; Bernerth, T. [Department of Diagnostic Radiology, Martin-Luther-University Halle-Wittenberg, Magdeburger Strasse 16, 06097 Halle (Germany); Kiechle, M. [Department of Obstetrics and Gynaecology, Technical University Munich, Ismaninger Strasse 22, 81675 Munich (Germany); Buchmann, J. [Department of Pathology, Martin-Luther-University Halle-Wittenberg, Magdeburger Strasse 14, 06097 Halle (Germany); Heinig, A. [Department of Diagnostic Radiology, Martin-Luther-University Halle-Wittenberg, Magdeburger Strasse 16, 06097 Halle (Germany); Koelbl, H. [Department of Obstetrics and Gynaecology, Martin-Luther-University Halle-Wittenberg, Magdeburger Strasse 24, 06097 Halle (Germany); Laniado, M. [Institute of Diagnostic Radiology, Technical University Dresden, Fetscherstrasse 74, 01307 Dresden (Germany); Heywang-Koebrunner, S.H. [Department of Diagnostic Radiology, Martin-Luther-University Halle-Wittenberg, Magdeburger Strasse 16, 06097 Halle (Germany); Department of Diagnostic Radiology, Technical University Munich, Ismaninger Strasse 19, 81675 Munich (Germany)

2006-01-15

Objective: A study was undertaken to assess the clinical value of magnetic resonance (MR) imaging-guided interventions in women with a family history, but no personal history of breast cancer. Methods and patients: Retrospective review was performed on 63 consecutive women who had a family history, but no personal history of breast cancer. A total of 97 lesions were referred for an MR-guided intervention. Standardized MR examinations (1.0 T, T1-weighted 3D FLASH, 0.15 mmol Gd-DTPA/kg body weight, prone position) were performed using a dedicated system which allows vacuum assisted breast biopsy or wire localization. Results: Histologic findings in 87 procedures revealed 9 (10%) invasive carcinomas, 12 (14%) ductal carcinomas in situ, 2 atypical ductal hyperplasias (2.5%) and 2 atypical lobular hyperplasias (2.5%). Sixty-two (71%) benign histologic results are verified by an MR-guided intervention, retrospective correlation of imaging and histology and by subsequent follow-up. In ten lesions the indication dropped since the enhancing lesion was no longer visible. Absent enhancement was confirmed by short-term re-imaging of the noncompressed breast and by follow-up. Conclusion: Malignancy was found in 24%, high-risk lesions in 5% of successfully performed MR-guided biopsy procedures. A 57% of MR-detected malignancies were ductal carcinoma in situ. In 10% of the lesions the intervention was not performed, since no enhancing lesion could be reproduced at the date of anticipated intervention. Such problems may be avoided if the initial MRI is performed in the appropriate phase of the menstrual cycle and without hormonal replacement therapy.
African American Women: Surviving Breast Cancer Mortality against the Highest Odds

Directory of Open Access Journals (Sweden)

Shelley White-Means

2015-12-01

Full Text Available Among the country’s 25 largest cities, the breast cancer mortality disparity is highest in Memphis, Tennessee, where African American women are twice as likely to die from breast cancer as White women. This qualitative study of African-American breast cancer survivors explores experiences during and post treatment that contributed to their beating the high odds of mortality. Using a semi-structured interview guide, a focus group session was held in 2012 with 10 breast cancer survivors. Thematic analysis and a deductive a priori template of codes were used to analyze the data. Five main themes were identified: family history, breast/body awareness and preparedness to manage a breast cancer event, diagnosis experience and reaction to the diagnosis, family reactions, and impact on life. Prayer and family support were central to coping, and survivors voiced a cultural acceptance of racial disparities in health outcomes. They reported lack of provider sensitivity regarding pain, financial difficulties, negative responses from family/friends, and resiliency strategies for coping with physical and mental limitations. Our research suggested that a patient-centered approach of demystifying breast cancer (both in patient-provider communication and in community settings would impact how women cope with breast cancer and respond to information about its diagnosis.
African American Women: Surviving Breast Cancer Mortality against the Highest Odds

Science.gov (United States)

White-Means, Shelley; Rice, Muriel; Dapremont, Jill; Davis, Barbara; Martin, Judy

2015-01-01

Among the country’s 25 largest cities, the breast cancer mortality disparity is highest in Memphis, Tennessee, where African American women are twice as likely to die from breast cancer as White women. This qualitative study of African-American breast cancer survivors explores experiences during and post treatment that contributed to their beating the high odds of mortality. Using a semi-structured interview guide, a focus group session was held in 2012 with 10 breast cancer survivors. Thematic analysis and a deductive a priori template of codes were used to analyze the data. Five main themes were identified: family history, breast/body awareness and preparedness to manage a breast cancer event, diagnosis experience and reaction to the diagnosis, family reactions, and impact on life. Prayer and family support were central to coping, and survivors voiced a cultural acceptance of racial disparities in health outcomes. They reported lack of provider sensitivity regarding pain, financial difficulties, negative responses from family/friends, and resiliency strategies for coping with physical and mental limitations. Our research suggested that a patient-centered approach of demystifying breast cancer (both in patient-provider communication and in community settings) would impact how women cope with breast cancer and respond to information about its diagnosis. PMID:26703655
Risk of ovarian cancer in women with first-degree relatives with cancer

DEFF Research Database (Denmark)

Soegaard, Marie; Frederiksen, Kirsten; Jensen, Allan

2009-01-01

OBJECTIVE: To assess the risk of ovarian cancer in women with first-degree relatives with cancer at one of the four most frequent hereditary sites based on validated cancer diagnoses and to examine the association according to age at diagnosis of ovarian cancer and histology. DESIGN: Case......-control study. SETTING AND POPULATION: First-degree relatives of 554 women with invasive epithelial ovarian cancer and 1,564 controls were included. METHODS: Analyses were performed using multiple logistic regression models. RESULTS: Ovarian cancer in a first-degree relative was significantly associated...... with increased risk of ovarian cancer (OR, 2.4; 95% CI, 1.4-4.1 (mother or sister)). Ovarian cancer in a first-degree relative appeared to be a stronger risk factor for early-onset (cancer than late-onset (OR, 5.3; 95% CI, 2.0-14.1 vs. OR, 1.8; 95% CI, 1.0-3.4). The positive association...
Efficacy of breast conservation therapy in early stage bilateral breast cancer

International Nuclear Information System (INIS)

Lee, Misa M.; Chen, Luci M.; Heimann, Ruth; Powers, Claire; Weichselbaum, Ralph R.

1996-01-01

-up was 50 months for synchronous patients, 45 months for metachronous patients, and 52 months for unilateral patients. Local control and survival were analyzed in patients with (1) synchronous bilateral breast cancer (SBBC), (2) metachronous breast cancer (MBBC), (3) unilateral breast cancer (UBC). The interval to development of local recurrence and survival were calculated from the time of development of the second breast lesion in patients with metachronous breast cancer. RESULTS: There were no differences in survival and failure free survival in patients with SBBC, MBBC, or UBC. Five year overall survival by lifetable analysis was 76% for SBBC, 78% for MBBC, and 87% for UBC patients; the p-value was 0.32 by logrank analysis. The five year failure-free survival was 79% for SBBC, 73% for MBBC, and 85% for UBC patients; the p-value was 0.28 by logrank analysis. There were no significant differences in median age, tumor size, pathologic node status, tamoxifen use, chemotherapy use, or median total dose of radiation therapy for SBBC, MBBC, or UBC patients. A significant difference was found in the incidence of family history of breast cancer in patients with unilateral (28%) versus bilateral breast cancer (40%) (p=0.0028 by chi-square analysis). However, there was no difference seen in outcome of patients by family history of breast cancer. The local control was identical in both bilateral and UBC patients with a crude failure rate of 3%. CONCLUSION: In our patients, no differences were observed in both local control and overall survival. Therefore, breast conservation therapy in local-regional, early stage breast cancer is a rational treatment modality for patients with SBBC and MBBC as well as UBC
Pelvic Inflammatory Disease and the Risk of Ovarian Cancer and Borderline Ovarian Tumors

DEFF Research Database (Denmark)

Rasmussen, Christina B; Kjaer, Susanne K; Albieri, Vanna

2017-01-01

Inflammation has been implicated in ovarian carcinogenesis. However, studies investigating the association between pelvic inflammatory disease (PID) and ovarian cancer risk are few and inconsistent. We investigated the association between PID and the risk of epithelial ovarian cancer according to...
Cross-cancer genome-wide analysis of lung, ovary, breast, prostate and colorectal cancer reveals novel pleiotropic associations

Science.gov (United States)

Fehringer, Gordon; Kraft, Peter; Pharoah, Paul D.; Eeles, Rosalind A.; Chatterjee, Nilanjan; Schumacher, Fred; Schildkraut, Joellen; Lindström, Sara; Brennan, Paul; Bickeböller, Heike; Houlston, Richard S.; Landi, Maria Teresa; Caporaso, Neil; Risch, Angela; Olama, Ali Amin Al; Berndt, Sonja I; Giovannucci, Edward; Grönberg, Henrik; Kote-Jarai, Zsofia; Ma, Jing; Muir, Kenneth; Stampfer, Meir; Stevens, Victoria L.; Wiklund, Fredrik; Willett, Walter; Goode, Ellen L.; Permuth, Jennifer; Risch, Harvey A.; Reid, Brett M.; Bezieau, Stephane; Brenner, Hermann; Chan, Andrew T.; Chang-Claude, Jenny; Hudson, Thomas J.; Kocarnik, Jonathan K.; Newcomb, Polly A.; Schoen, Robert E.; Slattery, Martha L.; White, Emily; Adank, Muriel A.; Ahsan, Habibul; Aittomäki, Kristiina; Baglietto, Laura; Blomquist, Carl; Canzian, Federico; Czene, Kamila; dos-Santos-Silva, Isabel; Eliassen, A. Heather; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Garcia-Closas, Montserrat; Gaudet, Mia M.; Johnson, Nichola; Hall, Per; Hazra, Aditi; Hein, Rebecca; Hofman, Albert; Hopper, John L.; Irwanto, Astrid; Johansson, Mattias; Kaaks, Rudolf; Kibriya, Muhammad G.; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Meindl, Alfons; Müller-Myhsok, Bertram; Muranen, Taru A.; Nevanlinna, Heli; Peeters, Petra H.; Peto, Julian; Prentice, Ross L.; Rahman, Nazneen; Sanchez, Maria Jose; Schmidt, Daniel F.; Schmutzler, Rita K.; Southey, Melissa C.; Tamimi, Rulla; Travis, Ruth C.; Turnbull, Clare; Uitterlinden, Andre G.; Wang, Zhaoming; Whittemore, Alice S.; Yang, Xiaohong R.; Zheng, Wei; Rafnar, Thorunn; Gudmundsson, Julius; Stacey, Simon N.; Stefansson, Kari; Sulem, Patrick; Chen, Y. Ann; Tyrer, Jonathan P.; Christiani, David C.; Wei, Yongyue; Shen, Hongbing; Hu, Zhibin; Shu, Xiao-Ou; Shiraishi, Kouya; Takahashi, Atsushi; Bossé, Yohan; Obeidat, Ma’en; Nickle, David; Timens, Wim; Freedman, Matthew L.; Li, Qiyuan; Seminara, Daniela; Chanock, Stephen J.; Gong, Jian; Peters, Ulrike; Gruber, Stephen B.; Amos, Christopher I.; Sellers, Thomas A.; Easton, Douglas F.; Hunter, David J.; Haiman, Christopher A.; Henderson, Brian E.; Hung, Rayjean J.

2016-01-01

Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-staged approach to conduct genome-wide association studies for lung, ovary, breast, prostate and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. PMID:27197191
Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)

Science.gov (United States)

Mavaddat, Nasim; Barrowdale, Daniel; Andrulis, Irene L.; Domchek, Susan M.; Eccles, Diana; Nevanlinna, Heli; Ramus, Susan J.; Spurdle, Amanda; Robson, Mark; Sherman, Mark; Mulligan, Anna Marie; Couch, Fergus J.; Engel, Christoph; McGuffog, Lesley; Healey, Sue; Sinilnikova, Olga M.; Southey, Melissa C.; Terry, Mary Beth; Goldgar, David; O’Malley, Frances; John, Esther M.; Janavicius, Ramunas; Tihomirova, Laima; Hansen, Thomas v O; Nielsen, Finn C.; Osorio, Ana; Stavropoulou, Alexandra; Benítez, Javier; Manoukian, Siranoush; Peissel, Bernard; Barile, Monica; Volorio, Sara; Pasini, Barbara; Dolcetti, Riccardo; Putignano, Anna Laura; Ottini, Laura; Radice, Paolo; Hamann, Ute; Rashid, Muhammad U.; Hogervorst, Frans B.; Kriege, Mieke; van der Luijt, Rob B.; Peock, Susan; Frost, Debra; Evans, D. Gareth; Brewer, Carole; Walker, Lisa; Rogers, Mark T.; Side, Lucy E.; Houghton, Catherine; Weaver, JoEllen; Godwin, Andrew K.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Meindl, Alfons; Kast, Karin; Arnold, Norbert; Niederacher, Dieter; Sutter, Christian; Deissler, Helmut; Gadzicki, Doroteha; Preisler-Adams, Sabine; Varon-Mateeva, Raymonda; Schönbuchner, Ines; Gevensleben, Heidrun; Stoppa-Lyonnet, Dominique; Belotti, Muriel; Barjhoux, Laure; Isaacs, Claudine; Peshkin, Beth N.; Caldes, Trinidad; de al Hoya, Miguel; Cañadas, Carmen; Heikkinen, Tuomas; Heikkilä, Päivi; Aittomäki, Kristiina; Blanco, Ignacio; Lazaro, Conxi; Brunet, Joan; Agnarsson, Bjarni A.; Arason, Adalgeir; Barkardottir, Rosa B.; Dumont, Martine; Simard, Jacques; Montagna, Marco; Agata, Simona; D’Andrea, Emma; Yan, Max; Fox, Stephen; Rebbeck, Timothy R.; Rubinstein, Wendy; Tung, Nadine; Garber, Judy E.; Wang, Xianshu; Fredericksen, Zachary; Pankratz, Vernon S.; Lindor, Noralane M.; Szabo, Csilla; Offit, Kenneth; Sakr, Rita; Gaudet, Mia M.; Singer, Christian F.; Tea, Muy-Kheng; Rappaport, Christine; Mai, Phuong L.; Greene, Mark H.; Sokolenko, Anna; Imyanitov, Evgeny; Toland, Amanda Ewart; Senter, Leigha; Sweet, Kevin; Thomassen, Mads; Gerdes, Anne-Marie; Kruse, Torben; Caligo, Maria; Aretini, Paolo; Rantala, Johanna; von Wachenfeld, Anna; Henriksson, Karin; Steele, Linda; Neuhausen, Susan L.; Nussbaum, Bob; Beattie, Mary; Odunsi, Kunle; Sucheston, Lara; Gayther, Simon A; Nathanson, Kate; Gross, Jenny; Walsh, Christine; Karlan, Beth; Chenevix-Trench, Georgia; Easton, Douglas F.; Antoniou, Antonis C.

2011-01-01

Background Previous small studies found that BRCA1 and BRCA2 breast tumors differ in their pathology. Analysis of larger datasets of mutation carriers should allow further tumor characterization. Methods We used data from 4,325 BRCA1 and 2,568 BRCA2 mutation carriers to analyze the pathology of invasive breast, ovarian and contralateral breast cancers. Results There was strong evidence that the proportion of estrogen receptor (ER)-negative breast tumors decreased with age at diagnosis among BRCA1 (p-trend=1.2×10−5) but increased with age at diagnosis among BRCA2 carriers (p-trend=6.8×10−6). The proportion of triple negative tumors decreased with age at diagnosis in BRCA1 carriers but increased with age at diagnosis of BRCA2 carriers. In both BRCA1 and BRCA2 carriers, ER-negative tumors were of higher histological grade than ER-positive tumors (Grade 3 vs. Grade 1, p=1.2×10−13 for BRCA1 and p=0.001 for BRCA2). ER and progesterone receptor (PR) expression were independently associated with mutation carrier status (ER-positive odds ratio (OR) for BRCA2=9.4, 95%CI:7.0-12.6 and PR-positive OR=1.7, 95%CI:1.3-2.3, under joint analysis). Lobular tumors were more likely to be BRCA2-related (OR for BRCA2=3.3, 95%CI:2.4-4.4, p=4.4×10−14), and medullary tumors BRCA1-related (OR for BRCA2=0.25, 95%CI:0.18-0.35, p=2.3×10−15). ER-status of the first breast cancer was predictive of ER-status of asynchronous contralateral breast cancer (p=0.0004 for BRCA1; p=0.002 for BRCA2). There were no significant differences in ovarian cancer morphology between BRCA1 and BRCA2 carriers (serous:67%; mucinous:1%; endometriod:12%; clear-cell:2%). Conclusions/Impact Pathology characteristics of BRCA1 and BRCA2 tumors may be useful for improving risk prediction algorithms and informing clinical strategies for screening and prophylaxis. PMID:22144499
Breast Cancer Genetic Counseling: A Surgeon’s Perspective

Directory of Open Access Journals (Sweden)

Doreen Marie Agnese

2016-01-01

Full Text Available As surgeons who care for patients with breast cancer, the possibility of a cancer diagnosis being related to a hereditary predisposition is always a consideration. Not only are we as surgeons always trying to identify these patients and families, but also we are often asked about a potential hereditary component by the patients and their family members. It is therefore critical that we accurately assess patients to determine who may benefit from genetic testing. Importantly, the potential benefit for identifying a hereditary breast cancer extends beyond the patient to other family members and the risk may not be only for the development of breast cancers, but for other cancers as well. As a surgeon with additional training in clinical cancer genetics, I have perhaps a unique perspective on the issue and feel that a review of some of the more practical considerations is important.
Satisfaction with fertility- and sexuality-related information in young women with breast cancer--ELIPPSE40 cohort.

Science.gov (United States)

Ben Charif, Ali; Bouhnik, Anne-Déborah; Rey, Dominique; Provansal, Magali; Courbiere, Blandine; Spire, Bruno; Mancini, Julien

2015-08-05

Young breast cancer survivors are often dissatisfied with the information provided on fertility and sexuality. Our aim was to discuss possible contributing factors and to propose strategies to increase patient satisfaction with such information. Using the French National Health Insurance System database, we constituted the ELIPPSE40 regional cohort of 623 women, aged 18-40, diagnosed with breast cancer between 2005 and 2011. As of January 2014, 319 women had taken part in the 10-, 16-, 28 and 48-month telephone interviews. Satisfaction with the information provided about the potential impact of cancer and its treatment on fertility and sexuality was assessed at 48 months after diagnosis on 5-point Likert scales. Four years after diagnosis, only 53.0 and 42.6% of women were satisfied with fertility- and sexuality-related information, respectively, without any significant change over the 2009-2014 period (P = 0.585 and P = 0.676 respectively). The two issues were moderately correlated (ρ = 0.60; P fertility-related information was greater among women with a family history of breast/ovarian cancer who had the opportunity to ask questions at the time of cancer disclosure. Satisfaction with sexuality-related information increased with the spontaneous provision of information by physicians at cancer disclosure. Promoting both patients' question asking behavior and more systematic information could improve communication between caregivers and young breast cancer survivors and address distinct unmet needs regarding fertility- and sexuality- related information.
Breast cancer screening (breast self-examination, clinical breast exam, and mammography) in women referred to health centers in Tabriz, Iran.

Science.gov (United States)

Khalili, Azizeh Farshbaf; Shahnazi, Mahnaz

2010-04-01

Breast cancer is the most common cancer and the most common cause of death in Iranian women aged 35-55 years. Breast cancer screening comprises breast self-examination (BSE), clinical breast examination (CBE) and mammography. The study aimed to examine the performance of screening methods among women referring to health centers of Tabriz, Iran. This was a descriptive-analytical research carried out on 400 women aged 20-50 years. The samples were chosen through random multistage sampling among health centers of Tabriz then active records of women. A questionnaire and observational checklist was used to elicit socio-demographic information and performance of women towards breast cancer screening methods. Descriptive and inferential statistics (chi-square and Fisher's exact test) were used to analyze the data. Only 18.8% of women did breast self-examination, 19.1% had clinical breast examination and 3.3% had mammogram. Statistical test showed a significant relationship between performing BSE and educational level, employment, income, number of children, breastfeeding history, breastfeeding quality and family history of breast cancer. There was a significant correlation between performing CBE and history of breast tumor and also, between performing the mammography and family history of breast cancer and history of breast tumor (P pre marriage counseling periods seems necessary.
A case-control study to assess the impact of mammographic density on breast cancer risk in women aged 40-49 at intermediate familial risk.

Science.gov (United States)

Assi, Valentina; Massat, Nathalie J; Thomas, Susan; MacKay, James; Warwick, Jane; Kataoka, Masako; Warsi, Iqbal; Brentnall, Adam; Warren, Ruth; Duffy, Stephen W

2015-05-15

Mammographic density is a strong risk factor for breast cancer, but its potential application in risk management is not clear, partly due to uncertainties about its interaction with other breast cancer risk factors. We aimed to quantify the impact of mammographic density on breast cancer risk in women aged 40-49 at intermediate familial risk of breast cancer (average lifetime risk of 23%), in particular in premenopausal women, and to investigate its relationship with other breast cancer risk factors in this population. We present the results from a case-control study nested with the FH01 cohort study of 6,710 women mostly aged 40-49 at intermediate familial risk of breast cancer. One hundred and three cases of breast cancer were age-matched to one or two controls. Density was measured by semiautomated interactive thresholding. Absolute density, but not percent density, was a significant risk factor for breast cancer in this population after adjusting for area of nondense tissue (OR per 10 cm(2) = 1.07, 95% CI 1.00-1.15, p = 0.04). The effect was stronger in premenopausal women, who made up the majority of the study population. Absolute density remained a significant predictor of breast cancer risk after adjusting for age at menarche, age at first live birth, parity, past or present hormone replacement therapy, and the Tyrer-Cuzick 10-year relative risk estimate of breast cancer. Absolute density can improve breast cancer risk stratification and delineation of high-risk groups alongside the Tyrer-Cuzick 10-year relative risk estimate. © 2014 UICC.
Plasma and ovarian tissue sphingolipids profiling in patients with advanced ovarian cancer.

Science.gov (United States)

Knapp, Paweł; Bodnar, Lubomir; Błachnio-Zabielska, Agnieszka; Świderska, Magdalena; Chabowski, Adrian

2017-10-01

The role of lipids in carcinogenesis through induction of abnormal cell lines in the human body is currently undisputable. Based on the literature, bioactive sphingolipids play an essential role in the development and progression of cancer and are involved in the metastatic process. The aim of this study was to determine the concentration of selected sphingolipids in patients with advanced ovarian cancer (AOC, FIGO III/IV, high grade ovarian cancer). Seventy-four patients with ovarian cancer were enrolled. Plasma concentrations of C16-Cer, C18:1-Cer and C18-Cer were assessed by LC/MS/MS. The content of tissue sphingolipids was measured using a UHPLC/MS/MS. Plasma concentration of 3 ceramides: C16-Cer, C18:1-Cer and C18-Cer was significantly elevated in women with advanced ovarian cancer compared to control group (P=0.031; 0.022; 0.020; respectively). There were increases in concentration of 5 ceramides: C16-Cer, C18:1-Cer, C18-Cer, C24:1-Cer, C24-Cer (P=0.025; 0.049; 0.032; 0.005; 0.013, respectively) and S1P (P=0.004) in ovarian tissue of women with advanced ovarian cancer compared to healthy individuals. Importantly, significantly higher risk of ovarian cancer when the plasma concentration of C16-Cer>311.88ng/100μl (AUC: 0.76, P=0.0261); C18:1-Cer>4.75ng/100μl (AUC: 0.77, P=0.0160) and C18-Cer>100.76ng/100μl (AUC:0.77, P=0.0136) was noticed. Bioactive sphingolipids play an essential role in the development and progression of cancer and they also take part in the process of metastasizing. This study suggests that some sphingolipids can be used as potential biomarkers of advanced ovarian cancer and that they can play an important role in the pathogenesis of this disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Identification of six new susceptibility loci for invasive epithelial ovarian cancer

DEFF Research Database (Denmark)

Kuchenbaecker, Karoline B; Ramus, Susan J; Tyrer, Jonathan

2015-01-01

associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded......Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed...
Inherited variants affecting RNA editing may contribute to ovarian cancer susceptibility

DEFF Research Database (Denmark)

Permuth, Jennifer B; Reid, Brett; Earp, Madalene

2016-01-01

RNA editing in mammals is a form of post-transcriptional modification in which adenosine is converted to inosine by the adenosine deaminases acting on RNA (ADAR) family of enzymes. Based on evidence of altered ADAR expression in epithelial ovarian cancers (EOC), we hypothesized that single nucleo......, including rs1127313 (G/A), a SNP in the 3' untranslated region. In summary, germline variation involving RNA editing genes may influence EOC susceptibility, warranting further investigation of inherited and acquired alterations affecting RNA editing.......RNA editing in mammals is a form of post-transcriptional modification in which adenosine is converted to inosine by the adenosine deaminases acting on RNA (ADAR) family of enzymes. Based on evidence of altered ADAR expression in epithelial ovarian cancers (EOC), we hypothesized that single...... nucleotide polymorphisms (SNPs) in ADAR genes modify EOC susceptibility, potentially by altering ovarian tissue gene expression. Using directly genotyped and imputed data from 10,891 invasive EOC cases and 21,693 controls, we evaluated the associations of 5,303 SNPs in ADAD1, ADAR, ADAR2, ADAR3, and SND1...

Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial

Science.gov (United States)

Jacobs, Ian J; Menon, Usha; Ryan, Andy; Gentry-Maharaj, Aleksandra; Burnell, Matthew; Kalsi, Jatinderpal K; Amso, Nazar N; Apostolidou, Sophia; Benjamin, Elizabeth; Cruickshank, Derek; Crump, Danielle N; Davies, Susan K; Dawnay, Anne; Dobbs, Stephen; Fletcher, Gwendolen; Ford, Jeremy; Godfrey, Keith; Gunu, Richard; Habib, Mariam; Hallett, Rachel; Herod, Jonathan; Jenkins, Howard; Karpinskyj, Chloe; Leeson, Simon; Lewis, Sara J; Liston, William R; Lopes, Alberto; Mould, Tim; Murdoch, John; Oram, David; Rabideau, Dustin J; Reynolds, Karina; Scott, Ian; Seif, Mourad W; Sharma, Aarti; Singh, Naveena; Taylor, Julie; Warburton, Fiona; Widschwendter, Martin; Williamson, Karin; Woolas, Robert; Fallowfield, Lesley; McGuire, Alistair J; Campbell, Stuart; Parmar, Mahesh; Skates, Steven J

2016-01-01

Summary Background Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect of early detection by screening on ovarian cancer mortality. Methods In this randomised controlled trial, we recruited postmenopausal women aged 50–74 years from 13 centres in National Health Service Trusts in England, Wales, and Northern Ireland. Exclusion criteria were previous bilateral oophorectomy or ovarian malignancy, increased risk of familial ovarian cancer, and active non-ovarian malignancy. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer-generated random numbers to annual multimodal screening (MMS) with serum CA125 interpreted with use of the risk of ovarian cancer algorithm, annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. The primary outcome was death due to ovarian cancer by Dec 31, 2014, comparing MMS and USS separately with no screening, ascertained by an outcomes committee masked to randomisation group. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have ovarian cancer, or had exited the registry before recruitment. Investigators and participants were aware of screening type. This trial is registered with ClinicalTrials.gov, number NCT00058032. Findings Between June 1, 2001, and Oct 21, 2005, we randomly allocated 202 638 women: 50 640 (25·0%) to MMS, 50 639 (25·0%) to USS, and 101 359 (50·0%) to no screening. 202 546 (>99·9%) women were eligible for analysis: 50 624 (>99·9%) women in the MMS group, 50 623 (>99·9%) in the USS group, and 101 299 (>99·9%) in the no screening group. Screening ended on Dec 31, 2011, and included 345 570 MMS and 327 775 USS annual screening episodes. At a median follow-up of 11·1 years (IQR 10·0–12·0), we diagnosed ovarian cancer in
The comparison between presenting symptoms of ovarian cancer ...

African Journals Online (AJOL)

The sensation of abdominal mass was more common in women with ovarian cancer than other abdominalpelvic cancers (P=0.00l). Constipation was documented in the patients with colon cancer more than women with ovarian cancer (P=0.012), whereas urinary symptoms were more common in patients with ovarian ...
Molecular genetics of breast cancer

International Nuclear Information System (INIS)

Radice, P.; Pierotti, M. A.

1997-01-01

In the last two decades, molecular studies have enlightened the complexity of the genetic alterations that occur in breast cancer cells. To date, more than 40 different genes or loci have been found to be altered in breast carcinomas. Although some of these genes, as for example ERBB2, appear to be mutated in a high proportion of cases, their mechanism of action and their role in the different stages of cancer development are still poorly understood. More recently, two major determinants of the inherited predisposition to breast cancer, BRCA1 and BRCA2, have been isolated. As a consequence, it is now possible to screen families with a positive history of breast carcinomas for the identification of mutations carriers, in order to address these individuals into adequate programs of cancer surveillance and prevention
Evaluating the ovarian cancer gonadotropin hypothesis

DEFF Research Database (Denmark)

Lee, Alice W; Tyrer, Jonathan P; Doherty, Jennifer A

2015-01-01

OBJECTIVE: Ovarian cancer is a hormone-related disease with a strong genetic basis. However, none of its high-penetrance susceptibility genes and GWAS-identified variants to date are known to be involved in hormonal pathways. Given the hypothesized etiologic role of gonadotropins, an assessment...... of how variability in genes involved in the gonadotropin signaling pathway impacts disease risk is warranted. METHODS: Genetic data from 41 ovarian cancer study sites were pooled and unconditional logistic regression was used to evaluate whether any of the 2185 SNPs from 11 gonadotropin signaling pathway...... genes was associated with ovarian cancer risk. A burden test using the admixture likelihood (AML) method was also used to evaluate gene-level associations. RESULTS: We did not find any genome-wide significant associations between individual SNPs and ovarian cancer risk. However, there was some...
Family history of cancer predicts endometrial cancer risk independently of Lynch Syndrome: Implications for genetic counselling.

Science.gov (United States)

Johnatty, Sharon E; Tan, Yen Y; Buchanan, Daniel D; Bowman, Michael; Walters, Rhiannon J; Obermair, Andreas; Quinn, Michael A; Blomfield, Penelope B; Brand, Alison; Leung, Yee; Oehler, Martin K; Kirk, Judy A; O'Mara, Tracy A; Webb, Penelope M; Spurdle, Amanda B

2017-11-01

To determine endometrial cancer (EC) risk according to family cancer history, including assessment by degree of relatedness, type of and age at cancer diagnosis of relatives. Self-reported family cancer history was available for 1353 EC patients and 628 controls. Logistic regression was used to quantify the association between EC and cancer diagnosis in ≥1 first or second degree relative, and to assess whether level of risk differed by degree of relationship and/or relative's age at diagnosis. Risk was also evaluated for family history of up to three cancers from known familial syndromes (Lynch, Cowden, hereditary breast and ovarian cancer) overall, by histological subtype and, for a subset of 678 patients, by EC tumor mismatch repair (MMR) gene expression. Report of EC in ≥1 first- or second-degree relative was associated with significantly increased risk of EC (P=3.8×10 -7 ), independent of lifestyle risk factors. There was a trend in increasing EC risk with closer relatedness and younger age at EC diagnosis in relatives (P Trend =4.43×10 -6 ), and with increasing numbers of Lynch cancers in relatives (P Trend ≤0.0001). EC risk associated with family history did not differ by proband tumor MMR status, or histological subtype. Reported EC in first- or second-degree relatives remained associated with EC risk after conservative correction for potential misreported family history (OR 2.0; 95% CI, 1.24-3.37, P=0.004). The strongest predictor of EC risk was closer relatedness and younger EC diagnosis age in ≥1 relative. Associations remained significant irrespective of proband MMR status, and after excluding MMR pathogenic variant carriers, indicating that Lynch syndrome genes do not fully explain familial EC risk. Copyright © 2017 Elsevier Inc. All rights reserved.
The detection of ovarian cancer using 123I monoclonal antibody

International Nuclear Information System (INIS)

Granowska, M.; Britton, K.E.; Shepherd, J.

1984-01-01

The technique of the production of monoclonal antibodies is described. Antibodies show reactivity with epithelial surfaces of cancer of breast, colon and ovary. The iodogen reaction is used for labelling monoclonal antibodies with 123 I. Description of labelling technique and quality control. After intravenous injection of 74 MBq 123 I-labelled monoclonal antibody (0.5 mg) static camera images of the abdomen were recorded at 10 min, 4 and 22 hours in anterior and posterior position. 20 out of 22 patients with ovarian cancer with and without metastases were correctly diagnosed and confirmed at surgery. (author)
[Breast cancer update in primary care: (V/V)].

Science.gov (United States)

Díaz García, Noiva; Cuadrado Rouco, Carmen; Vich, Pilar; Alvarez-Hernandez, Cristina; Brusint, Begoña; Redondo Margüello, Esther

2015-03-01

Breast cancer is a prevalent disease affecting all areas of patients' lives. Therefore, family physicians ought to know thoroughly this pathology to optimize the health care services for these patients making the best use of available resources. A series of five articles on breast cancer is presented below. It is based on a review of the scientific literature over the last ten years. In this final section, the social, psychological, occupational and family issues related to the disease will be reviewed, as well as presenting some special situations of breast cancer, including breast cancer in men, during pregnancy and last stages of life. This summary report aims to provide a current and practical review about this disease, providing answers to family doctors and helping them to be by the patients for their benefit throughout their illness. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.
Jung-Min Lee, M.D. | Center for Cancer Research

Science.gov (United States)

Conducts early clinical trials targeting BRCA mutation-associated breast or ovarian cancer, epithelial ovarian cancer, and triple negative breast cancer at the National Cancer Institute, NIH Clinical Center.
Random Start Ovarian Stimulation for Oocyte or Embryo Cryopreservation in Women Desiring Fertility Preservation Prior to Gonadotoxic Cancer Therapy.

Science.gov (United States)

Danis, Rachel B; Pereira, Nigel; Elias, Rony T

2017-11-10

Women of reproductive age diagnosed with cancer are often interested in preserving gametes or reproductive tissue that would allow for future genetic parenthood. Preservation of fertility is often accomplished in young cancer patients via ovarian stimulation followed by oocyte or embryo cryopreservation. Conventional stimulation protocols, however, require 2-4 weeks to complete ovarian stimulation, oocyte retrieval and possible fertilization. Such a strategy may not be feasible in patients requiring urgent cancer treatment. Recent studies have highlighted that random start ovarian stimulation can be initiated irrespective of the phase of the menstrual cycle and is an attractive alternative to conventional ovarian stimulation. The primary aim of the current review is to discuss the feasibility and success of random start ovarian stimulation for oocyte or embryo cryopreservation in women desiring fertility preservation prior to gonadotoxic cancer therapy. We performed a systematic review of medical literature published between January 2000 to June 2017 reporting the utility of random start ovarian stimulation for fertility preservation. Search terms included "fertility preservation," "cancer," "ovarian stimulation," "random-start ovarian stimulation," "embryo cryopreservation, and" "oocyte cryopreservation." Publications were included in this review only if patients underwent random start ovarian stimulation prior to cancer therapy. Nineteen publications were identified and perused by the authors. Most publications described the utility of random start ovarian stimulation in the setting of breast cancer. Radom-start stimulation was associated with a reduced time interval between ovarian stimulation initiation and oocyte or embryo cryopreservation. The yield of mature oocytes and their developmental potential into embryos was comparable between conventional and random-start protocols, albeit with higher gonadotropin doses in the latter. The current review suggests
Ethnic, racial and cultural identity and perceived benefits and barriers related to genetic testing for breast cancer among at-risk women of African descent in New York City.

Science.gov (United States)

Sussner, K M; Edwards, T A; Thompson, H S; Jandorf, L; Kwate, N O; Forman, A; Brown, K; Kapil-Pair, N; Bovbjerg, D H; Schwartz, M D; Valdimarsdottir, H B

2011-01-01

Due to disparities in the use of genetic services, there has been growing interest in examining beliefs and attitudes related to genetic testing for breast and/or ovarian cancer risk among women of African descent. However, to date, few studies have addressed critical cultural variations among this minority group and their influence on such beliefs and attitudes. We assessed ethnic, racial and cultural identity and examined their relationships with perceived benefits and barriers related to genetic testing for cancer risk in a sample of 160 women of African descent (49% self-identified African American, 39% Black-West Indian/Caribbean, 12% Black-Other) who met genetic risk criteria and were participating in a larger longitudinal study including the opportunity for free genetic counseling and testing in New York City. All participants completed the following previously validated measures: (a) the multi-group ethnic identity measure (including ethnic search and affirmation subscales) and other-group orientation for ethnic identity, (b) centrality to assess racial identity, and (c) Africentrism to measure cultural identity. Perceived benefits and barriers related to genetic testing included: (1) pros/advantages (including family-related pros), (2) cons/disadvantages (including family-related cons, stigma and confidentiality concerns), and (3) concerns about abuses of genetic testing. In multivariate analyses, several ethnic identity elements showed significant, largely positive relationships to perceived benefits about genetic testing for breast and/or ovarian cancer risk, the exception being ethnic search, which was positively associated with cons/disadvantages, in general, and family-related cons/disadvantages. Racial identity (centrality) showed a significant association with confidentiality concerns. Cultural identity (Africentrism) was not related to perceived benefits and/or barriers. Ethnic and racial identity may influence perceived benefits and barriers
Psychosocial outcomes and counselee satisfaction following genetic counseling for hereditary breast and ovarian cancer: A patient-reported outcome study.

Science.gov (United States)

Oberguggenberger, Anne; Sztankay, Monika; Morscher, Raphael Johannes; Sperner-Unterweger, Barbara; Weber, Ingrid; Hubalek, Michael; Kemmler, Georg; Zschocke, Johannes; Martini, Caroline; Egle, Daniel; Dünser, Martina; Gamper, Eva; Meraner, Verena

2016-10-01

We investigated the psychosocial consequences of genetic counseling and testing (GCT) for hereditary breast and ovarian cancer (HBOC) at follow-up in a "real-life" sample of counselees at an Austrian tertiary care center. The study cohort included counselees who had undergone genetic counseling for HBOC and completed a follow-up self-report questionnaire battery on psychosocial outcomes (quality of life, psychological distress, satisfaction with counseling and decisions). For comparison of distress, we recruited a reference sample of breast cancer survivors (BCS; n=665) who had not requested GCT in the same setting. Overall, counselees did not exhibit increased levels of anxiety and depression when compared to BCS. No specific follow-up deleterious psychosocial consequences were detected among the former group. Of the 137 counselees, 22.6% and 9.8% experienced clinically relevant levels of anxiety and depression, respectively, at an average follow-up time of 1.8years. However, both anxiety and depression significantly decreased with time and were alike between counselees with and without cancer diagnosis. Follow-up cancer worry seems to be significantly higher among counselees who had not undergone genetic testing or were undecided about it than among counselees who had been tested. Our results strongly support GCT as part of routine care for patients with HBOC. The risk factors of increased distress in specific subgroups of counselees, such as recent cancer diagnosis or uncertainty about testing, warrant further exploration and specific attention in clinical routines. Particularly, the psychological needs of undecided counselees warrant ongoing attention and potential follow-ups. Copyright © 2016 Elsevier Inc. All rights reserved.
[The molecular biology of epithelial ovarian cancer].

Science.gov (United States)

Leary, Alexandra; Pautier, Patricia; Tazi, Youssef; Morice, Philippe; Duvillard, Pierre; Gouy, Sébastien; Uzan, Catherine; Gauthier, Hélène; Balleyguier, Corinne; Lhommé, Catherine

2012-12-01

Epithelial ovarian cancer frequently presents at an advanced stage where the cornerstone of management remains surgery and platinum-based chemotherapy. Unfortunately, despite sometimes dramatic initial responses, advanced ovarian cancer almost invariably relapses. Little progress has been made in the identification of effective targeted-therapies for ovarian cancer. The majority of clinical trials investigating novel agents have been negative and the only approved targeted-therapy is bevacizumab, for which reliable predictive biomarkers still elude us. Ovarian cancer is treated as a uniform disease. Yet, biological studies have highlighted the heterogeneity of this malignancy with marked differences in histology, oncogenesis, prognosis, chemo-responsiveness, and molecular profile. Recent high throughput molecular analyses have identified a huge number of genomic/phenotypic alterations. Broadly speaking, high grade serous carcinomas (type II) display significant genomic instability and numerous amplifications and losses; low grade (type I) tumors are genomically stable but display frequent mutations. Importantly, many of these genomic alterations relate to known oncogenes for which targeted-therapies are available or in development. There is today a real potential for personalized medicine in ovarian cancer. We will review the current literature regarding the molecular characterization of epithelial ovarian cancer and discuss the biological rationale for a number of targeted strategies. In order to translate these biological advances into meaningful clinical improvements for our patients, it is imperative to incorporate translational research in ovarian cancer trials, a number of strategies will be proposed such as the acquisition of quality tumor samples, including sequential pre- and post-treatment biopsies, the potential of liquid biopsies, and novel trial designs more adapted to the molecular era of ovarian cancer research.
Validation of Version 3.0 of the Breast Cancer Genetics Referral Screening Tool (B-RST™).

Science.gov (United States)

Bellcross, Cecelia; Hermstad, April; Tallo, Christine; Stanislaw, Christine

2018-05-08

Despite increased awareness of hereditary breast and ovarian cancer among clinicians and the public, many BRCA1/2 mutation carriers remain unaware of their risk status. The Breast Cancer Genetics Referral Screening Tool (B-RST™) was created and validated to easily identify individuals at increased risk for hereditary breast and ovarian cancer for referral to cancer genetics services. The purpose of this study was to revise B-RST™ to maximize sensitivity against BRCA1/2 mutation status. We analyzed pedigrees of 277 individuals who had undergone BRCA1/2 testing to determine modifications to the B-RST™ 2.0 algorithm that would maximize sensitivity for mutations, while maintaining simplicity. We used McNemar's chi-square test to compare validation measures between the revised version (3.0) and the 2.0 version. Algorithmic changes made to B-RST™ 2.0 increased the sensitivity against BRCA1/2 mutation analysis from 71.1 to 94.0% (P 3.0 demonstrates high sensitivity for BRCA1/2 mutations, yet remains a simple and quick screening tool for at-risk individuals.
Sex Steroid Hormone Receptor Expression Affects Ovarian Cancer Survival

DEFF Research Database (Denmark)

Jönsson, Jenny-Maria; Skovbjerg Arildsen, Nicolai; Malander, Susanne

2015-01-01

BACKGROUND AND AIMS: Although most ovarian cancers express estrogen (ER), progesterone (PR), and androgen (AR) receptors, they are currently not applied in clinical decision making. We explored the prognostic impact of sex steroid hormone receptor protein and mRNA expression on survival...... in epithelial ovarian cancer. METHODS: Immunohistochemical stainings for ERα, ERβ, PR, and AR were assessed in relation to survival in 118 serous and endometrioid ovarian cancers. Expression of the genes encoding the four receptors was studied in relation to prognosis in the molecular subtypes of ovarian cancer...... in ovarian cancer and support that tumors should be stratified based on molecular as well as histological subtypes in future studies investigating the role of endocrine treatment in ovarian cancer....
Re-expression of ARHI (DIRAS3) induces autophagy in breast cancer cells and enhances the inhibitory effect of paclitaxel

International Nuclear Information System (INIS)

Zou, Chun-Fang; Yu, Yinhua; Jia, Luoqi; Jin, Hongyan; Yao, Ming; Zhao, Naiqing; Huan, Jin; Lu, Zhen; Bast, Robert C Jr; Feng, Youji

2011-01-01

ARHI is a Ras-related imprinted gene that inhibits cancer cell growth and motility. ARHI is downregulated in the majority of breast cancers, and loss of its expression is associated with its progression from ductal carcinoma in situ (DCIS) to invasive disease. In ovarian cancer, re-expression of ARHI induces autophagy and leads to autophagic death in cell culture; however, ARHI re-expression enables ovarian cancer cells to remain dormant when they are grown in mice as xenografts. The purpose of this study is to examine whether ARHI induces autophagy in breast cancer cells and to evaluate the effects of ARHI gene re-expression in combination with paclitaxel. Re-expression of ARHI was achieved by transfection, by treatment with trichostatin A (TSA) or by a combination of TSA and 5-aza-2'-deoxycytidine (DAC) in breast cancer cell cultures and by liposomal delivery of ARHI in breast tumor xenografts. ARHI re-expression induces autophagy in breast cancer cells, and ARHI is essential for the induction of autophagy. When ARHI was re-expressed in breast cancer cells treated with paclitaxel, the growth inhibitory effect of paclitaxel was enhanced in both the cell culture and the xenografts. Although paclitaxel alone did not induce autophagy in breast cancer cells, it enhanced ARHI-induced autophagy. Conversely, ARHI re-expression promoted paclitaxel-induced apoptosis and G2/M cell cycle arrest. ARHI re-expression induces autophagic cell death in breast cancer cells and enhances the inhibitory effects of paclitaxel by promoting autophagy, apoptosis, and G2/M cell cycle arrest
Methylation of the RASSF1A, RARβ2, and SEMA3B genes in epithelial breast and ovarian tumors, and in patients with polyneoplasia

Directory of Open Access Journals (Sweden)

T. P. Kazubskaya

2012-01-01

Full Text Available The methylation status of the tumor suppressor genes RASSF1A, RARβ2, and SEMA3B was studied in the samples of cancer and its histologically normal tissue of the breast and ovaries. The high rate of abnormal methylation of the CpG islet in the RASSF1A, RARβ2, and SEMA3B genes was found in the tumors of the breast (78% (32/41, 46% (26/56, and 35% (22/65, respectively and ovaries 73% (33/45, 30% (15/50, and 50% (25/51. Hypermethylation in the CpG islets belonging to the RASSF1A and RARβ2 genes was first ascertained in 90% of the patients with polyneoplasms involving the breast and ovaries. Abnormal methylation of the promotor region of the RASSF1A gene was shown to be detectable in preclinical-stage and anaplasia-degree breast and ovarian cancer. There was a correlation of the rate of methylation in the promoter regions of the RARβ2 and SEMA3B genes with clinical-stage and anaplasia-degree breast and ovarian cancer. Analysis of gene methylation in biological fluids provides considerable opportunity to use methylation of DNA as a marker in clinical practice.
A prospective investigation of predictive and modifiable risk factors for breast cancer in unaffected BRCA1 and BRCA2 gene carriers

International Nuclear Information System (INIS)

Guinan, Emer M; Hussey, Juliette; McGarrigle, Sarah A; Healy, Laura A; O’Sullivan, Jacintha N; Bennett, Kathleen; Connolly, Elizabeth M

2013-01-01

Breast cancer is the most common female cancer worldwide. The lifetime risk of a woman being diagnosed with breast cancer is approximately 12.5%. For women who carry the deleterious mutation in either of the BRCA genes, BRCA1 or BRCA2, the risk of developing breast or ovarian cancer is significantly increased. In recent years there has been increased penetrance of BRCA1 and BRCA2 associated breast cancer, prompting investigation into the role of modifiable risk factors in this group. Previous investigations into this topic have relied on participants recalling lifetime weight changes and subjective methods of recording physical activity. The influence of obesity-related biomarkers, which may explain the link between obesity, physical activity and breast cancer risk, has not been investigated prospectively in this group. This paper describes the design of a prospective cohort study investigating the role of predictive and modifiable risk factors for breast cancer in unaffected BRCA1 and BRCA2 gene mutation carriers. Participants will be recruited from breast cancer family risk clinics and genetics clinics. Lifestyle risk factors that will be investigated will include body composition, metabolic syndrome and its components, physical activity and dietary intake. PBMC telomere length will be measured as a potential predictor of breast cancer occurrence. Measurements will be completed on entry to the study and repeated at two years and five years. Participants will also be followed annually by questionnaire to track changes in risk factor status and to record cancer occurrence. Data will be analysed using multiple regression models. The study has an accrual target of 352 participants. The results from this study will provide valuable information regarding the role of modifiable lifestyle risk factors for breast cancer in women with a deleterious mutation in the BRCA gene. Additionally, the study will attempt to identify potential blood biomarkers which may be predictive
Emotional, Biological, and Cognitive Impact of a Brief Expressive Writing Intervention for African American Women at Familial Breast Cancer

National Research Council Canada - National Science Library

Valdimarsdottir, Heiddis

2007-01-01

Women at familial breast cancer risk have highly inflated perceptions of their risk of developing the disease high levels of cancer-specific distress and lower levels of natural killer cell activity (NKCA...
Curcumin induces chemo/radio-sensitization in ovarian cancer cells and curcumin nanoparticles inhibit ovarian cancer cell growth

Directory of Open Access Journals (Sweden)

Yallapu Murali M

2010-04-01

Full Text Available Abstract Background Chemo/radio-resistance is a major obstacle in treating advanced ovarian cancer. The efficacy of current treatments may be improved by increasing the sensitivity of cancer cells to chemo/radiation therapies. Curcumin is a naturally occurring compound with anti-cancer activity in multiple cancers; however, its chemo/radio-sensitizing potential is not well studied in ovarian cancer. Herein, we demonstrate the effectiveness of a curcumin pre-treatment strategy for chemo/radio-sensitizing cisplatin resistant ovarian cancer cells. To improve the efficacy and specificity of curcumin induced chemo/radio sensitization, we developed a curcumin nanoparticle formulation conjugated with a monoclonal antibody specific for cancer cells. Methods Cisplatin resistant A2780CP ovarian cancer cells were pre-treated with curcumin followed by exposure to cisplatin or radiation and the effect on cell growth was determined by MTS and colony formation assays. The effect of curcumin pre-treatment on the expression of apoptosis related proteins and β-catenin was determined by Western blotting or Flow Cytometry. A luciferase reporter assay was used to determine the effect of curcumin on β-catenin transcription activity. The poly(lactic acid-co-glycolic acid (PLGA nanoparticle formulation of curcumin (Nano-CUR was developed by a modified nano-precipitation method and physico-chemical characterization was performed by transmission electron microscopy and dynamic light scattering methods. Results Curcumin pre-treatment considerably reduced the dose of cisplatin and radiation required to inhibit the growth of cisplatin resistant ovarian cancer cells. During the 6 hr pre-treatment, curcumin down regulated the expression of Bcl-XL and Mcl-1 pro-survival proteins. Curcumin pre-treatment followed by exposure to low doses of cisplatin increased apoptosis as indicated by annexin V staining and cleavage of caspase 9 and PARP. Additionally, curcumin pre
Targeting tissue factor as a novel therapeutic oncotarget for eradication of cancer stem cells isolated from tumor cell lines, tumor xenografts and patients of breast, lung and ovarian cancer.

Science.gov (United States)

Hu, Zhiwei; Xu, Jie; Cheng, Jijun; McMichael, Elizabeth; Yu, Lianbo; Carson, William E

2017-01-03

Targeting cancer stem cell (CSC) represents a promising therapeutic approach as it can potentially fight cancer at its root. The challenge is to identify a surface therapeutic oncotarget on CSC. Tissue factor (TF) is known as a common yet specific surface target for cancer cells and tumor neovasculature in several solid cancers. However, it is unknown if TF is expressed by CSCs. Here we demonstrate that TF is constitutively expressed on CD133 positive (CD133+) or CD24-CD44+ CSCs isolated from human cancer cell lines, tumor xenografts from mice and breast tumor tissues from patients. TF-targeted agents, i.e., a factor VII (fVII)-conjugated photosensitizer (fVII-PS for targeted photodynamic therapy) and fVII-IgG1Fc (Immunoconjugate or ICON for immunotherapy), can eradicate CSC via the induction of apoptosis and necrosis and via antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, respectively. In conclusion, these results demonstrate that TF is a novel surface therapeutic oncotarget for CSC, in addition to cancer cell TF and tumor angiogenic vascular endothelial TF. Moreover, this research highlights that TF-targeting therapeutics can effectively eradicate CSCs, without drug resistance, isolated from breast, lung and ovarian cancer with potential to translate into other most commonly diagnosed solid cancer, in which TF is also highly expressed.

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