Immunophenotyping of hereditary breast cancer

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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

"It was an Emotional Baby": Previvors' Family Planning Decision-Making Styles about Hereditary Breast and Ovarian Cancer Risk.

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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.

Hereditary breast cancer: from molecular pathology to tailored therapies.

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Tan, D S P; Marchiò, C; Reis-Filho, J S

2008-10-01

Hereditary breast cancer accounts for up to 5-10% of all breast carcinomas. Recent studies have demonstrated that mutations in two high-penetrance genes, namely BRCA1 and BRCA2, are responsible for about 16% of the familial risk of breast cancer. Even though subsequent studies have failed to find another high-penetrance breast cancer susceptibility gene, several genes that confer a moderate to low risk of breast cancer development have been identified; moreover, hereditary breast cancer can be part of multiple cancer syndromes. In this review we will focus on the hereditary breast carcinomas caused by mutations in BRCA1, BRCA2, Fanconi anaemia (FANC) genes, CHK2 and ATM tumour suppressor genes. We describe the hallmark histological features of these carcinomas compared with non-hereditary breast cancers and show how an accurate histopathological diagnosis may help improve the identification of patients to be screened for mutations. Finally, novel therapeutic approaches to treat patients with BRCA1 and BRCA2 germ line mutations, including cross-linking agents and PARP inhibitors, are discussed.

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

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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.

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.

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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.

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

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.

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.

The Activities and Impact of State Programs to Address Hereditary Breast and Ovarian Cancer, 2011–2014

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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.

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.

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.

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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.

Management of women at high risk of hereditary breast cancer in the Veneto Regional Program for Prevention.

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Del Sole, Annamaria; Cinquetti, Sandro; Fedato, Chiara; Montagna, Marco; Russo, Francesca; Sbrogiò, Luca Gino; Zorzi, Manuel

2015-01-01

Today it is well-known that high risk of genetic breast cancer concerns a very limited part of the population: no more than 2-3 women are affected every thousand and this condition as a whole accounts for no more than 3%-5% of all breast cancers. Following the directions contained in the 2014-2018 National Prevention Plan, Veneto's 2014-2018 Regional Program of Prevention (PRP), approved by Regional Council Resolution (DGR) No. 749 of 14.5.2015, consolidation of a pathway of diagnosis, observation, and prophylaxis for women at high risk of hereditary breast carcinoma is thus proposed. The principal activities of this policy will be the following: creation of a regional working group, survey of currently existing pathways for the identification of women at risk of hereditary breast cancer and adoption of the same, approval and consolidation of a structured regional pathway for women at high risk of hereditary breast and/or ovarian cancer, from paths of oncogenetic consultation and genetic testing to management of disease risk. Subsequent to the recognition of the pathway of diagnosis, observation, and prophylaxis for women at high risk of hereditary breast carcinoma, the Veneto region undertakes to develop a co-ordinated program of information and training on this pathway directed at the population and healthcare workers. It is firmly hoped that with the inclusion of a program for the management of women at high risk of hereditary breast cancer within the Veneto PRP this topic may become more defined and structured in terms of sustainability, integration with the existing regional networks (mammography network, Breast Unit), contrasting inequality, monitoring and evaluation, in this way pursuing the objectives of a reduction of cause-specific mortality and improvement of quality of life.

Hereditary breast and ovarian cancer: successful systematic implementation of a group approach to genetic counselling.

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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.

Implementing a screening tool for identifying patients at risk for hereditary breast and ovarian cancer: a statewide initiative.

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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.

Organization and Running of the First Comprehensive Hereditary Cancer Clinic in India

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Rajkumar T

2005-11-01

Full Text Available Abstract Hereditary cancers are thought to account for around 5% of cancers, particularly breast/ovarian and colorectal cancers. In India there is a paucity of data on hereditary cancers and the mutations in some of the common genes linked to hereditary cancers, such as BRCA1, BRCA2, hMSH2 and hMLH1. The country's first comprehensive hereditary cancer clinic was established in February 2002. The article describes the organization and running of the Clinic. It also discusses some of the social issues relevant to the given population in running the Hereditary Cancer Clinic.

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.

Drug therapy for hereditary cancers

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Imyanitov Evgeny N

2011-08-01

Full Text Available Abstract Tumors arising in patients with hereditary cancer syndromes may have distinct drug sensitivity as compared to their sporadic counterparts. Breast and ovarian neoplasms from BRCA1 or BRCA2 mutation carriers are characterized by deficient homologous recombination (HR of DNA, that makes them particularly sensitive to platinum compounds or inhibitors of poly (ADP-ribose polymerase (PARP. Outstandingly durable complete responses to high dose chemotherapy have been observed in several cases of BRCA-related metastatic breast cancer (BC. Multiple lines of evidence indicate that women with BRCA1-related BC may derive less benefit from taxane-based treatment than other categories of BC patients. There is virtually no reports directly assessing drug response in hereditary colorectal cancer (CRC patients; studies involving non-selected (i.e., both sporadic and hereditary CRC with high-level microsatellite instability (MSI-H suggest therapeutic advantage of irinotecan. Celecoxib has been approved for the treatment of familial adenomatous polyposis (FAP. Hereditary medullary thyroid cancers (MTC have been shown to be highly responsive to a multitargeted tyrosine kinase inhibitor vandetanib, which exerts specific activity towards mutated RET receptor. Given the rapidly improving accessibility of DNA analysis, it is foreseen that the potential predictive value of cancer-associated germ-line mutations will be increasingly considered in the future studies.

Subjective versus objective risk in genetic counseling for hereditary breast and/or ovarian cancers

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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.

Familial breast cancer: what the radiologist needs to know

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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.)

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.

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.

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.

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.

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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.

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.

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.

Development and validation of a simple questionnaire for the identification of hereditary breast cancer in primary care

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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

Gastric tumours in hereditary cancer syndromes: clinical features, molecular biology and strategies for prevention.

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Sereno, María; Aguayo, Cristina; Guillén Ponce, Carmen; Gómez-Raposo, César; Zambrana, Francisco; Gómez-López, Miriam; Casado, Enrique

2011-09-01

Gastric cancer is the major cause of cancer-related deaths worldwide. The majority of them are classified as sporadic, whereas the remaining 10% exhibit familial clustering. Hereditary diffuse gastric cancer (HDGC) syndrome is the most important condition that leads to hereditary gastric cancer. However, other hereditary cancer syndromes, such as hereditary non-polyposis colorectal cancer, familial adenomatous polyposis, Peutz-Jeghers syndrome, Li-Fraumeni syndrome and hereditary breast and ovarian cancer, entail a higher risk compared to the general population for developing this kind of neoplasia. In this review, we describe briefly the most important aspects related to clinical features, molecular biology and strategies for prevention in hereditary gastric associated to different cancer syndromes.

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

Predictive genetic testing for hereditary breast and ovarian cancer: psychological distress and illness representations 1 year following disclosure.

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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.

African American Women’s Limited Knowledge and Experiences with Genetic Counseling for Hereditary Breast Cancer

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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

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).

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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.

Psychological distress in women at risk for hereditary breast cancer: the role of family communication and perceived social support.

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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.

Psychosocial outcomes and counselee satisfaction following genetic counseling for hereditary breast and ovarian cancer: A patient-reported outcome study.

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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 progress and prospect of application of genetic testing technology-based gene detection technology in the diagnosis and treatment of hereditary cancer].

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He, J X; Jiang, Y F

2017-08-06

Hereditary cancer is caused by specific pathogenic gene mutations. Early detection and early intervention are the most effective ways to prevent and control hereditary cancer. High-throughput sequencing based genetic testing technology (NGS) breaks through the restrictions of pedigree analysis, provide a convenient and efficient method to detect and diagnose hereditary cancer. Here, we introduce the mechanism of hereditary cancer, summarize, discuss and prospect the application of NGS and other genetic tests in the diagnosis of hereditary retinoblastoma, hereditary breast and ovarian cancer syndrome, hereditary colorectal cancer and other complex and rare hereditary tumors.

Tracking the dissemination of a culturally targeted brochure to promote awareness of hereditary breast and ovarian cancer among Black women.

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Scherr, Courtney Lynam; Bomboka, Linda; Nelson, Alison; Pal, Tuya; Vadaparampil, Susan Thomas

2017-05-01

Black women have a higher rate of BRCA1 and BRCA2 (BRCA) mutations, compared with other populations, that increases their risk for hereditary breast and ovarian cancer (HBOC). However, Black women are less likely to know about HBOC and genetic testing. Based on a request from a community advisory panel of breast cancer survivors, community leaders and healthcare providers in the Black community, our team developed a culturally targeted educational brochure to promote awareness of HBOC among Black women. To reach the target population we utilized a passive dissemination strategy. Using Diffusion of Innovations (DOI) as a framework, we traced dissemination of the brochure over a five year period using self-addressed postcards contained inside the brochure that included several open-ended questions about the utility of the brochure, and a field for written comments. Closed-ended responses were analyzed using descriptive statistics and thematic analysis was conducted on the open-ended responses. DOI captured the proliferation of the brochure among Black women across the US. The use of passive dissemination strategies among pre-existing social networks proved to be a useful and sustainable method for increasing knowledge of HBOC among Black women. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

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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

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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

Does Breast or Ovarian Cancer Run in Your Family?

Science.gov (United States)

... 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

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

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.

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.

Evolution of Hereditary Breast Cancer Genetic Services: Are Changes Reflected in the Knowledge and Clinical Practices of Florida Providers?

Science.gov (United States)

Cragun, Deborah; Scherr, Courtney; Camperlengo, Lucia; Vadaparampil, Susan T; Pal, Tuya

2016-10-01

We describe practitioner knowledge and practices related to hereditary breast and ovarian cancer (HBOC) in an evolving landscape of genetic testing. A survey was mailed in late 2013 to Florida providers who order HBOC testing. Descriptive statistics were conducted to characterize participants' responses. Of 101 respondents, 66% indicated either no genetics education or education through a commercial laboratory. Although 79% of respondents were aware of the Supreme Court ruling resulting in the loss of Myriad Genetics' BRCA gene patent, only 19% had ordered testing from a different laboratory. With regard to pretest counseling, 78% of respondents indicated they usually discuss 11 of 14 nationally recommended elements for informed consent. Pretest discussion times varied from 3 to 120 min, with approximately half spending 40% of respondents included (1) possibility of a variant of uncertain significance (VUS) and (2) issues related to life/disability insurance. With regard to genetic testing for HBOC, 88% would test an unaffected sister of a breast cancer patient identified with a BRCA VUS. Results highlight the need to identify whether variability in hereditary cancer service delivery impacts patient outcomes. Findings also reveal opportunities to facilitate ongoing outreach and education.

Hereditary association between testicular cancer and familial ovarian cancer: A Familial Ovarian Cancer Registry study.

Science.gov (United States)

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.

[The clinical study of familial breast cancer - now and the problems].

Science.gov (United States)

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.

Population prevalence of hereditary breast cancer phenotypes and implementation of a genetic cancer risk assessment program in southern Brazil

Science.gov (United States)

2009-01-01

In 2004, a population-based cohort (the Núcleo Mama Porto Alegre - NMPOA Cohort) was started in Porto Alegre, southern Brazil and within that cohort, a hereditary breast cancer study was initiated, aiming to determine the prevalence of hereditary breast cancer phenotypes and evaluate acceptance of a genetic cancer risk assessment (GCRA) program. Women from that cohort who reported a positive family history of cancer were referred to GCRA. Of the 9218 women enrolled, 1286 (13.9%) reported a family history of cancer. Of the 902 women who attended GCRA, 55 (8%) had an estimated lifetime risk of breast cancer ≥ 20% and 214 (23.7%) had pedigrees suggestive of a breast cancer predisposition syndrome; an unexpectedly high number of these fulfilled criteria for Li-Fraumeni-like syndrome (122 families, 66.7%). The overall prevalence of a hereditary breast cancer phenotype was 6.2% (95%CI: 5.67-6.65). These findings identified a problem of significant magnitude in the region and indicate that genetic cancer risk evaluation should be undertaken in a considerable proportion of the women from this community. The large proportion of women who attended GCRA (72.3%) indicates that the program was well-accepted by the community, regardless of the potential cultural, economic and social barriers. PMID:21637504

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.

Endogenous estrogens and the risk of breast, endometrial, and ovarian cancers.

Science.gov (United States)

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

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...

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.

The contribution of self-esteem and self-concept in psychological distress in women at risk of hereditary breast cancer.

Science.gov (United States)

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

2011-11-01

Clarification of the role of several aspects of self-concept regarding psychological distress in women at risk of hereditary breast cancer will help to target counselling and psychosocial interventions more appropriately. In this study, we aimed (1) to examine the role of general self-esteem and specific aspects of self-concept (i.e. stigma, vulnerability, and mastery) in psychological distress in women at risk of hereditary breast cancer and (2) to compare the relative importance of these self-concept aspects in psychological distress in women with low versus high self-esteem. General and breast-cancer-specific distress, self-esteem, self-concept, and demographics were assessed in 246 women being at risk of hereditary breast cancer, who opted either for regular breast surveillance or prophylactic surgery. In the total study group, self-esteem was negatively associated with general distress. Furthermore, feeling stigmatized was strongly associated with more breast-cancer-specific distress, and to a lesser degree with general distress. In women with low-self esteem, feelings of stigmatization were strongly associated with higher levels of both breast-cancer-specific and general distress, while a sense of mastery was associated with less general distress. For women with high self-esteem, feelings of both stigmatization and vulnerability were associated with more breast-cancer-specific distress, whereas there were no significant associations with general distress. Psychosocial interventions or support groups for women at risk of hereditary breast cancer should focus on self-esteem and feelings of stigmatization and isolation, and consequently tailor the interventions on specific items for respective women. Copyright © 2010 John Wiley & Sons, Ltd.

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.

BRCA1 and BRCA2 mutational profile and prevalence in hereditary breast and ovarian cancer (HBOC probands from Southern Brazil: Are international testing criteria appropriate for this specific population?

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Bárbara Alemar

Full Text Available Germline pathogenic variants in BRCA1 and BRCA2 (BRCA are the main cause of Hereditary Breast and Ovarian Cancer syndrome (HBOC.In this study we evaluated the mutational profile and prevalence of BRCA pathogenic/likely pathogenic variants among probands fulfilling the NCCN HBOC testing criteria. We characterized the clinical profile of these individuals and explored the performance of international testing criteria.A pathogenic/likely pathogenic variant was detected in 19.1% of 418 probands, including seven novel frameshift variants. Variants of uncertain significance were found in 5.7% of individuals. We evaluated 50 testing criteria and mutation probability algorithms. There was a significant odds-ratio (OR for mutation prediction (p ≤ 0.05 for 25 criteria; 14 of these had p ≤ 0.001. Using a cutoff point of four criteria, the sensitivity is 83.8%, and the specificity is 53.5% for being a carrier. The prevalence of pathogenic/likely pathogenic variants for each criterion ranged from 22.1% to 55.6%, and criteria with the highest ORs were those related to triple-negative breast cancer or ovarian cancer.This is the largest study of comprehensive BRCA testing among Brazilians to date, and the first to analyze clinical criteria for genetic testing. Several criteria that are not included in the NCCN achieved a higher predictive value. Identification of the most informative criteria for each population will assist in the development of a rational approach to genetic testing, and will enable the prioritization of high-risk individuals as a first step towards offering testing in low-income countries.

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 ...

Women with hereditary breast cancer predispositions should avoid using their smartphones, tablets, and laptops at night.

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Mortazavi, Seyed Ali Reza; Mortazavi, Seyed Mohammad Javad

2018-02-01

Breast cancer is the most common malignancy among women, both in the developed and developing countries. Women with mutations in the BRCA1 and BRCA2 genes have an increased risk of breast and ovarian cancers. Recent studies show that short-wavelength visible light disturb the secretion of melatonin and causes circadian rhythm disruption. We have previously studied the health effects of exposure to different levels of radiofrequency electromagnetic fields (RF-EMFs) such as mobile phones, mobile base stations, mobile phone jammers, laptop computers, and radars. Moreover, over the past several years, we investigated the health effects of exposure to the short wavelength visible light in the blue region emitted from digital screens. The reduction of melatonin secretion after exposure to blue light emitted from smartphone's screen has been reported to be associated with the negative impact of smartphone use at night on sleep. We have shown that both the blue light and RF-EMFs generated by mobile phones are linked to the disruption of the circadian rhythm in people who use their phones at night. Therefore, if women with hereditary breast cancer predispositions use their smartphones, tablets and laptops at night, disrupted circadian rhythms (suppression of melatonin caused by exposure to blue light emitted from the digital screens), amplifies the risk of breast cancer. It can be concluded that women who carry mutated BRCA1 or BRCA2, or women with family history of breast cancer should avoid using their smartphones, tablets and laptops at night. Using sunglasses with amber lenses, or smartphone applications which decrease the users' exposure to blue light before sleep, at least to some extent, can decrease the risk of circadian rhythm disruption and breast cancer.

Women with hereditary breast cancer predispositions should avoid using their smartphones, tablets and laptops at night

Directory of Open Access Journals (Sweden)

Seyed Ali Reza Mortazavi

2018-02-01

Full Text Available Breast cancer is the most common malignancy among women, both in the developed and developing countries. Women with mutations in the BRCA1 and BRCA2 genes have an increased risk of breast and ovarian cancers. Recent studies show that short-wavelength visible light disturb the secretion of melatonin and causes circadian rhythm disruption. We have previously studied the health effects of exposure to different levels of radiofrequency electromagnetic fields (RF-EMFs such as mobile phones, mobile base stations, mobile phone jammers, laptop computers, and radars. Moreover, over the past several years, we investigated the health effects of exposure to the short wavelength visible light in the blue region emitted from digital screens. The reduction of melatonin secretion after exposure to blue light emitted from smartphone’s screen has been reported to be associated with the negative impact of smartphone use at night on sleep. We have shown that both the blue light and RF-EMFs generated by mobile phones are linked to the disruption of the circadian rhythm in people who use their phones at night. Therefore, if women with hereditary breast cancer predispositions use their smartphones, tablets and laptops at night, disrupted circadian rhythms (suppression of melatonin caused by exposure to blue light emitted from the digital screens, amplifies the risk of breast cancer. It can be concluded that women who carry mutated BRCA1 or BRCA2, or women with family history of breast cancer should avoid using their smartphones, tablets and laptops at night. Using sunglasses with amber lenses, or smartphone applications which decrease the users’ exposure to blue light before sleep, at least to some extent, can decrease the risk of circadian rhythm disruption and breast cancer.

A non-synonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers

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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

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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

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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.

[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.

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.

Hypoxia-Activated Alkylating Agents in BRCA1-Mutant Ovarian Serous Carcinoma.

Science.gov (United States)

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.

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

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.

Prevalence of BRCA1 mutations in familial and sporadic greek ovarian cancer cases.

Directory of Open Access Journals (Sweden)

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.

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

Knowledge about hereditary cancer of women with family histories of breast, colorectal, or both types of cancer.

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Campacci, N; de Lima, J O; Ramadan, L; Palmero, E I

2015-03-01

Usually, the mass media do not address hereditary cancer and their risk factors, nor are these topics discussed at the community level. We used an informative guide on cancer and hereditary cancer, followed by a questionnaire on these topics to investigate the relevant knowledge among women at high risk for hereditary breast and/or colorectal cancer from a population-based cohort. The cohort was composed of 81 Brazilian women with positive family histories of breast and/or colorectal cancer. Strauss and Corbin's Grounded Theory was used for qualitative analysis. The average age of the cohort was 49.9 years old. Three participants (3.9%) were illiterate, 45 (59.2%) had attended elementary school, 14 (18.4%) had secondary school, and 14 (18.4%) held higher education degrees. A total of 47 (54.3%) volunteers were unable to fully understand the information provided in the guide because they did not know the meaning of words such as metastasis, malignant, hereditary, sporadic, or oncogenetics. Notwithstanding, the acceptance of the educational tool utilized was satisfactory, and it enhanced the volunteers' interest in a better understanding of cancer and heredity. Thereby, we concluded that the low knowledge of this important subject and the unawareness about fundamental terms required for the comprehension of this specific type of neoplasm made us believe that the use of the informative guide can provide a great value when used previously to the genetic counseling consultations. Besides, educational tools of easy understanding should be part of everyday clinical practice, from primary to specialized patient care.

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.

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.

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.

Comparison of Attitudes Regarding Preimplantation Genetic Diagnosis Among Patients with Hereditary Cancer Syndromes

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Rich, Thereasa A.; Liu, Mei; Etzel, Carol J.; Bannon, Sarah A.; Mork, Maureen E.; Ready, Kaylene; Saraiya, Devki S.; Grubbs, Elizabeth G.; Perrier, Nancy D.; Lu, Karen H.; Arun, Banu K.; Woodard, Terri L.; Schover, Leslie R.; Litton, Jennifer K.

2014-01-01

Introduction Preimplantation Genetic Diagnosis (PGD) allows couples to avoid having a child with an inherited condition, potentially reducing cancer burden in families with a hereditary cancer predisposition. This study investigated awareness and acceptance of PGD among patients with hereditary cancer syndromes. Methods Questionnaires were mailed to 984 adults with hereditary breast and ovarian cancer, Lynch syndrome, familial adenomatous polyposis, or multiple endocrine neoplasia type 1 or 2. Associations between clinical, demographic, and psychosocial factors and awareness and acceptance of PGD were examined. Results Of 370 respondents (38% return rate), 28% felt their syndrome impacted family planning, 24% were aware of PGD, 72% felt that PGD should be offered, 43% would consider using PGD, and 29% were uncertain. Family experience and syndrome-specific characteristics, such as disease severity, quality of life and availability of medical interventions as well as gender, family planning stage, and religiosity impact perceptions of the acceptability of PGD, though a high level of uncertainty exists. Conclusion Hereditary cancer patients' opinions about the acceptability of PGD are similar to those of genetics and ethical experts. Patients should be told about PGD given that most had not heard of PGD, but feel that PGD should be offered. PMID:24072553

Decision-making on preimplantation genetic diagnosis and prenatal diagnosis: a challenge for couples with hereditary breast and ovarian cancer.

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Derks-Smeets, I A P; Gietel-Habets, J J G; Tibben, A; Tjan-Heijnen, V C G; Meijer-Hoogeveen, M; Geraedts, J P M; van Golde, R; Gomez-Garcia, E; van den Bogaart, E; van Hooijdonk, M; de Die-Smulders, C E M; van Osch, L A D M

2014-05-01

How do couples with a BRCA1/2 mutation decide on preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND) for hereditary breast and ovarian cancer syndrome (HBOC)? BRCA couples primarily classify PGD and/or PND as reproductive options based on the perceived severity of HBOC and moral considerations, and consequently weigh the few important advantages of PGD against numerous smaller disadvantages. Awareness of PGD is generally low among persons at high risk for hereditary cancers. Most persons with HBOC are in favour of offering PGD for BRCA1/2 mutations, although only a minority would consider this option for themselves. Studies exploring the motivations for using or refraining from PGD among well-informed BRCA carriers of reproductive age are lacking. We studied the reproductive decision-making process by interviewing a group of well-informed, reproductive aged couples carrying a BRCA1/2 mutation, regarding their decisional motives and considerations. This exploratory, qualitative study investigated the motives and considerations taken into account by couples with a BRCA1/2 mutation and who have received extensive counselling on PGD and PND and have made a well-informed decision regarding this option. Eighteen couples took part in focus group and dyadic interviews between January and September 2012. Semi-structured focus groups were conducted containing two to four couples, assembled based on the reproductive method the couple had chosen: PGD (n = 6 couples) or conception without testing (n = 8 couples). Couples who had chosen PND for BRCA (n = 4) were interviewed dyadically. Two of the women, of whom one had chosen PND and the other had chosen no testing, had a history of breast cancer. None of the couples who opted for PGD or conception without testing found the use of PND, with possible pregnancy termination, acceptable. PND users chose this method because of decisive, mainly practical reasons (natural conception, high chance of favourable outcome

Paternal lineage early onset hereditary ovarian cancers: A Familial Ovarian Cancer Registry study.

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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.

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...

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.

The Clinical Utility of Next Generation Sequencing Results in a Community-Based Hereditary Cancer Risk Program.

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Bunnell, A E; Garby, C A; Pearson, E J; Walker, S A; Panos, L E; Blum, Joanne L

2017-02-01

Since the 2013 Supreme Court ruling on BRCA1/BRCA2 patenting, hereditary cancer gene panels now include BRCA1 and BRCA2, making these panels an option for first-tier testing. However, questions remain about the clinical utility and implications of these panels for medical management with inclusion of genes of unknown to moderate penetrance. To better understand how use of these panels affected our practice, we reviewed patients who underwent testing in our clinic from July 1, 2013 through May 23, 2014. Indications for testing included personal and/or family history of breast and/or ovarian cancer. A total of 136 patients underwent panel testing via a single commercial laboratory; 12 (8.8 %) patients were positive for a pathogenic or likely pathogenic mutation (four BRCA2 mutations, two TP53 mutations, one CDH1 mutation, two ATM mutations, and one patient each with a CHEK2, NBN, or PALB2 mutation). Of these positive patients, 100 % met the National Comprehensive Cancer Network (NCCN) guidelines for Hereditary Breast and Ovarian Cancer genetic testing (2.2014). Mutations in seven of twelve (58 %) patients led to changes in medical management; three of seven (43 %) had a non-BRCA1 or BRCA2 gene mutation. Our findings suggest that there is clinical utility of panels that include genes of unknown to moderate penetrance.

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.

Mutations in BRCA1 and BRCA2 Uruguayan families with breast / ovarian

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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

A comprehensive custom panel design for routine hereditary cancer testing: preserving control, improving diagnostics and revealing a complex variation landscape.

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Castellanos, Elisabeth; Gel, Bernat; Rosas, Inma; Tornero, Eva; Santín, Sheila; Pluvinet, Raquel; Velasco, Juan; Sumoy, Lauro; Del Valle, Jesús; Perucho, Manuel; Blanco, Ignacio; Navarro, Matilde; Brunet, Joan; Pineda, Marta; Feliubadaló, Lidia; Capellá, Gabi; Lázaro, Conxi; Serra, Eduard

2017-01-04

We wanted to implement an NGS strategy to globally analyze hereditary cancer with diagnostic quality while retaining the same degree of understanding and control we had in pre-NGS strategies. To do this, we developed the I2HCP panel, a custom bait library covering 122 hereditary cancer genes. We improved bait design, tested different NGS platforms and created a clinically driven custom data analysis pipeline. The I2HCP panel was developed using a training set of hereditary colorectal cancer, hereditary breast and ovarian cancer and neurofibromatosis patients and reached an accuracy, analytical sensitivity and specificity greater than 99%, which was maintained in a validation set. I2HCP changed our diagnostic approach, involving clinicians and a genetic diagnostics team from panel design to reporting. The new strategy improved diagnostic sensitivity, solved uncertain clinical diagnoses and identified mutations in new genes. We assessed the genetic variation in the complete set of hereditary cancer genes, revealing a complex variation landscape that coexists with the disease-causing mutation. We developed, validated and implemented a custom NGS-based strategy for hereditary cancer diagnostics that improved our previous workflows. Additionally, the existence of a rich genetic variation in hereditary cancer genes favors the use of this panel to investigate their role in cancer risk.

Identification of a comprehensive spectrum of genetic factors for hereditary breast cancer in a Chinese population by next-generation sequencing.

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Xiaochen Yang

Full Text Available The genetic etiology of hereditary breast cancer has not been fully elucidated. Although germline mutations of high-penetrance genes such as BRCA1/2 are implicated in development of hereditary breast cancers, at least half of all breast cancer families are not linked to these genes. To identify a comprehensive spectrum of genetic factors for hereditary breast cancer in a Chinese population, we performed an analysis of germline mutations in 2,165 coding exons of 152 genes associated with hereditary cancer using next-generation sequencing (NGS in 99 breast cancer patients from families of cancer patients regardless of cancer types. Forty-two deleterious germline mutations were identified in 21 genes of 34 patients, including 18 (18.2% BRCA1 or BRCA2 mutations, 3 (3% TP53 mutations, 5 (5.1% DNA mismatch repair gene mutations, 1 (1% CDH1 mutation, 6 (6.1% Fanconi anemia pathway gene mutations, and 9 (9.1% mutations in other genes. Of seven patients who carried mutations in more than one gene, 4 were BRCA1/2 mutation carriers, and their average onset age was much younger than patients with only BRCA1/2 mutations. Almost all identified high-penetrance gene mutations in those families fulfill the typical phenotypes of hereditary cancer syndromes listed in the National Comprehensive Cancer Network (NCCN guidelines, except two TP53 and three mismatch repair gene mutations. Furthermore, functional studies of MSH3 germline mutations confirmed the association between MSH3 mutation and tumorigenesis, and segregation analysis suggested antagonism between BRCA1 and MSH3. We also identified a lot of low-penetrance gene mutations. Although the clinical significance of those newly identified low-penetrance gene mutations has not been fully appreciated yet, these new findings do provide valuable epidemiological information for the future studies. Together, these findings highlight the importance of genetic testing based on NCCN guidelines and a multi-gene analysis

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,

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

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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.

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....

Familial breast cancer - targeted therapy in secondary and tertiary prevention.

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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.

Prevalence of Germline Mutations in Genes Engaged in DNA Damage Repair by Homologous Recombination in Patients with Triple-Negative and Hereditary Non-Triple-Negative Breast Cancers.

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Pawel Domagala

Full Text Available This study sought to assess the prevalence of common germline mutations in several genes engaged in the repair of DNA double-strand break by homologous recombination in patients with triple-negative breast cancers and hereditary non-triple-negative breast cancers. Tumors deficient in this type of DNA damage repair are known to be especially sensitive to DNA cross-linking agents (e.g., platinum drugs and to poly(ADP-ribose polymerase (PARP inhibitors.Genetic testing was performed for 36 common germline mutations in genes engaged in the repair of DNA by homologous recombination, i.e., BRCA1, BRCA2, CHEK2, NBN, ATM, PALB2, BARD1, and RAD51D, in 202 consecutive patients with triple-negative breast cancers and hereditary non-triple-negative breast cancers.Thirty five (22.2% of 158 patients in the triple-negative group carried mutations in genes involved in DNA repair by homologous recombination, while 10 (22.7% of the 44 patients in the hereditary non-triple-negative group carried such mutations. Mutations in BRCA1 were most frequent in patients with triple-negative breast cancer (18.4%, and mutations in CHEK2 were most frequent in patients with hereditary non-triple-negative breast cancers (15.9%. In addition, in the triple-negative group, mutations in CHEK2, NBN, and ATM (3.8% combined were found, while mutations in BRCA1, NBN, and PALB2 (6.8% combined were identified in the hereditary non-triple-negative group.Identifying mutations in genes engaged in DNA damage repair by homologous recombination other than BRCA1/2 can substantially increase the proportion of patients with triple-negative breast cancer and hereditary non-triple-negative breast cancer who may be eligible for therapy using PARP inhibitors and platinum drugs.

Assessment of SLX4 Mutations in Hereditary Breast Cancers.

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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.

Exploring the course of psychological distress around two successive control visits in women at hereditary risk of breast cancer

NARCIS (Netherlands)

van Dooren, Silvia; Seynaeve, Caroline; Rijnsburger, Adriana J.; Duivenvoorden, Hugo J.; Essink-Bot, Marie-Louise; Tilanus-Linthorst, Madeleine M. A.; Klijn, Jan G. M.; de Koning, Harry J.; Tibben, Aad

2005-01-01

In this article we determined the course of psychological distress during a breast cancer surveillance program in women at increased risk of developing hereditary breast cancer (BC). The sample comprised of 357 unaffected women (mean age 40.5 years) adhering to a surveillance programme

Development and validation of a 36-gene sequencing assay for hereditary cancer risk assessment

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Valentina S. Vysotskaia

2017-02-01

Full Text Available The past two decades have brought many important advances in our understanding of the hereditary susceptibility to cancer. Numerous studies have provided convincing evidence that identification of germline mutations associated with hereditary cancer syndromes can lead to reductions in morbidity and mortality through targeted risk management options. Additionally, advances in gene sequencing technology now permit the development of multigene hereditary cancer testing panels. Here, we describe the 2016 revision of the Counsyl Inherited Cancer Screen for detecting single-nucleotide variants (SNVs, short insertions and deletions (indels, and copy number variants (CNVs in 36 genes associated with an elevated risk for breast, ovarian, colorectal, gastric, endometrial, pancreatic, thyroid, prostate, melanoma, and neuroendocrine cancers. To determine test accuracy and reproducibility, we performed a rigorous analytical validation across 341 samples, including 118 cell lines and 223 patient samples. The screen achieved 100% test sensitivity across different mutation types, with high specificity and 100% concordance with conventional Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA. We also demonstrated the screen’s high intra-run and inter-run reproducibility and robust performance on blood and saliva specimens. Furthermore, we showed that pathogenic Alu element insertions can be accurately detected by our test. Overall, the validation in our clinical laboratory demonstrated the analytical performance required for collecting and reporting genetic information related to risk of developing hereditary cancers.

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.

FROM FAMILIES SYNDROMES TO GENES… THE FIRST CLINICAL AND GENETIC CHARACTERIZATIONS OF HEREDITARY SYNDROMES PREDISPOSING TO CANCER: WHAT WAS THE BEGINNING?

Directory of Open Access Journals (Sweden)

Charité Ricker, MS, LCGC

2017-07-01

Full Text Available Assessment for hereditary susceptibility to cancer is considered standard of care, as it impacts not only a clinician's understanding of cancer causation but also options for prevention and treatment. The roots of our current knowledge about hereditary cancer syndromes can be traced to early reports of families with striking cancer histories. The purpose of this article is to review the historical timeline of the two most commonly assessed hereditary cancer syndromes, hereditary breast and ovarian cancer (HBOC and Lynch syndrome (LS. While many individuals identified with these syndromes today come from families similar to those seen in the early historical reports, our understanding of these syndromes, their expression and penetrance, has evolved over the years. In addition, the increased utilization of broad multi-gene panels continues to add to the complexity of defining associated phenotypes. These findings can lead to challenges with translating results to clinical management for patients and families, but also provide an opportunity to continue to gain understanding of the genetic underpinnings of cancer etiology.

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

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

Frequency of breast cancer with hereditary risk features in Spain: Analysis from GEICAM "El Álamo III" retrospective study.

Science.gov (United States)

Márquez-Rodas, Iván; Pollán, Marina; Escudero, María José; Ruiz, Amparo; Martín, Miguel; Santaballa, Ana; Martínez Del Prado, Purificación; Batista, Norberto; Andrés, Raquel; Antón, Antonio; Llombart, Antonio; Fernandez Aramburu, Antonio; Adrover, Encarnación; González, Sonia; Seguí, Miguel Angel; Calvo, Lourdes; Lizón, José; Rodríguez Lescure, Álvaro; Ramón Y Cajal, Teresa; Llort, Gemma; Jara, Carlos; Carrasco, Eva; López-Tarruella, Sara

2017-01-01

To determine the frequency of breast cancer (BC) patients with hereditary risk features in a wide retrospective cohort of patients in Spain. a retrospective analysis was conducted from 10,638 BC patients diagnosed between 1998 and 2001 in the GEICAM registry "El Álamo III", dividing them into four groups according to modified ESMO and SEOM hereditary cancer risk criteria: Sporadic breast cancer group (R0); Individual risk group (IR); Familial risk group (FR); Individual and familial risk group (IFR) with both individual and familial risk criteria. 7,641 patients were evaluable. Of them, 2,252 patients (29.5%) had at least one hereditary risk criteria, being subclassified in: FR 1.105 (14.5%), IR 970 (12.7%), IFR 177 (2.3%). There was a higher frequency of newly diagnosed metastatic patients in the IR group (5.1% vs 3.2%, p = 0.02). In contrast, in RO were lower proportion of big tumors (> T2) (43.8% vs 47.4%, p = 0.023), nodal involvement (43.4% vs 48.1%, p = 0.004) and lower histological grades (20.9% G3 for the R0 vs 29.8%) when compared to patients with any risk criteria. Almost three out of ten BC patients have at least one hereditary risk cancer feature that would warrant further genetic counseling. Patients with hereditary cancer risk seems to be diagnosed with worse prognosis factors.

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

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.

Ovarian, Fallopian Tube, and Primary Peritoneal Cancer Prevention

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 ...

Is there a genetic anticipation in breast and/or ovarian cancer families with the germline c.3481_3491del11 mutation?

Science.gov (United States)

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

Family history of cancer other than breast or ovarian cancer in first-degree relatives is associated with poor breast cancer prognosis.

Science.gov (United States)

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.

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...

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

Breast Cancer

Science.gov (United States)

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. ...

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....

Mutation analysis of the ERCC4/FANCQ gene in hereditary breast cancer.

Directory of Open Access Journals (Sweden)

Sandra Kohlhase

Full Text Available The ERCC4 protein forms a structure-specific endonuclease involved in the DNA damage response. Different cancer syndromes such as a subtype of Xeroderma pigmentosum, XPF, and recently a subtype of Fanconi Anemia, FA-Q, have been attributed to biallelic ERCC4 gene mutations. To investigate whether monoallelic ERCC4 gene defects play some role in the inherited component of breast cancer susceptibility, we sequenced the whole ERCC4 coding region and flanking untranslated portions in a series of 101 Byelorussian and German breast cancer patients selected for familial disease (set 1, n = 63 or for the presence of the rs1800067 risk haplotype (set 2, n = 38. This study confirmed six known and one novel exonic variants, including four missense substitutions but no truncating mutation. Missense substitution p.R415Q (rs1800067, a previously postulated breast cancer susceptibility allele, was subsequently screened for in a total of 3,698 breast cancer cases and 2,868 controls from Germany, Belarus or Russia. The Gln415 allele appeared protective against breast cancer in the German series, with the strongest effect for ductal histology (OR 0.67; 95%CI 0.49; 0.92; p = 0.003, but this association was not confirmed in the other two series, with the combined analysis yielding an overall Mantel-Haenszel OR of 0.94 (95% CI 0.81; 1.08. There was no significant effect of p.R415Q on breast cancer survival in the German patient series. The other three detected ERCC4 missense mutations included two known rare variants as well as a novel substitution, p.E17V, that we identified on a p.R415Q haplotype background. The p.E17V mutation is predicted to be probably damaging but was present in just one heterozygous patient. We conclude that the contribution of ERCC4/FANCQ coding mutations to hereditary breast cancer in Central and Eastern Europe is likely to be small.

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

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

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 ...

Synchronous Onset of Breast and Pancreatic Cancers: Results of Germline and Somatic Genetic Analysis

Directory of Open Access Journals (Sweden)

Michael Castro

2016-07-01

Full Text Available Background: Synchronous cancers have occasionally been detected at initial diagnosis among patients with breast and ovarian cancer. However, simultaneous coexistence and diagnosis of breast and pancreas cancer has not previously been reported. Case Report: Paternal transmission of a germline BRCA2 mutation to a patient who was diagnosed at age 40 with locally advanced breast and pancreas cancer is presented. Somatic genomic analysis of both cancers with next-generation DNA sequencing confirmed the germline result and reported a variety of variants of unknown significance alterations, of which two were present in both the breast and pancreas cancers. Discussion: The possibility that genomic alterations could have been responsible for modulating the phenotypic or clinical expression of this rare presentation is considered. The authors call attention to the practice of privatizing the clinicogenetic information gained from genetic testing and call for health policy that will facilitate sharing in order to advance the outcomes of patients diagnosed with hereditary cancers.

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.

["Screening" in special situations. Assessing predictive genetic screening for hereditary breast and colorectal cancer].

Science.gov (United States)

Jonas, Susanna; Wild, Claudia; Schamberger, Chantal

2003-02-01

The aim of this health technology assessment was to analyse the current scientific and genetic counselling on predictive genetic testing for hereditary breast and colorectal cancer. Predictive genetic testing will be available for several common diseases in the future and questions related to financial issues and quality standards will be raised. This report is based on a systematic/nonsystematic literature search in several databases (e.g. EmBase, Medline, Cochrane Library) and on a specific health technology assessment report (CCOHTA) and review (American Gastroenterological Ass.), respectively. Laboratory test methods, early detection methods and the benefit from prophylactic interventions were analysed and social consequences interpreted. Breast and colorectal cancer are counted among the most frequently cancer diseases. Most of them are based on random accumulation of risk factors, 5-10% show a familial determination. A hereditary modified gene is responsible for the increased cancer risk. In these families, high tumour frequency, young age at diagnosis and multiple primary tumours are remarkable. GENETIC DIAGNOSIS: Sequence analysis is the gold standard. Denaturing high performance liquid chromatography is a quick alternative method. The identification of the responsible gene defect in an affected family member is important. If the test result is positive there is an uncertainty whether the disease will develop or not, when and in which degree, which is founded in the geno-/phenotype correlation. The individual risk estimation is based upon empirical evidence. The test results affect the whole family. Currently, primary prevention is possible for familial adenomatous polyposis (celecoxib, prophylactic colectomy) and for hereditary mamma carcinoma (prophylactic mastectomy). The so-called preventive medical check-ups are early detection examinations. The evidence about early detection methods for colorectal cancer is better than for breast cancer. Prophylactic

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

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

Disparities in breast cancer and african ancestry: a global perspective.

Science.gov (United States)

Newman, Lisa A

2015-01-01

Recognition of breast cancer disparities between African-American and White American women has generated exciting research opportunities investigating the biologic and hereditary factors that contribute to the observed outcome differences, leading to international studies of breast cancer in Africa. The study of breast cancer in women with African ancestry has opened the door to unique investigations regarding breast cancer subtypes and the genetics of this disease. International research efforts can advance our understanding of race/ethnicity-associated breast cancer disparities within the USA; the pathogenesis of triple negative breast cancer; and hereditary susceptibility for breast cancer. © 2015 Wiley Periodicals, Inc.

Hereditary Diffuse Gastric Cancer

Science.gov (United States)

... Hereditary Diffuse Gastric Cancer Request Permissions Hereditary Diffuse Gastric Cancer Approved by the Cancer.Net Editorial Board , 10/2017 What is hereditary diffuse gastric cancer? Hereditary diffuse gastric cancer (HDGC) is a rare ...

Finnish Fanconi anemia mutations and hereditary predisposition to breast and prostate cancer.

Science.gov (United States)

Mantere, T; Haanpää, M; Hanenberg, H; Schleutker, J; Kallioniemi, A; Kähkönen, M; Parto, K; Avela, K; Aittomäki, K; von Koskull, H; Hartikainen, J M; Kosma, V-M; Laasanen, S-L; Mannermaa, A; Pylkäs, K; Winqvist, R

2015-07-01

Mutations in downstream Fanconi anemia (FA) pathway genes, BRCA2, PALB2, BRIP1 and RAD51C, explain part of the hereditary breast cancer susceptibility, but the contribution of other FA genes has remained questionable. Due to FA's rarity, the finding of recurrent deleterious FA mutations among breast cancer families is challenging. The use of founder populations, such as the Finns, could provide some advantage in this. Here, we have resolved complementation groups and causative mutations of five FA patients, representing the first mutation confirmed FA cases in Finland. These patients belonged to complementation groups FA-A (n = 3), FA-G (n = 1) and FA-I (n = 1). The prevalence of the six FA causing mutations was then studied in breast (n = 1840) and prostate (n = 565) cancer cohorts, and in matched controls (n = 1176 females, n = 469 males). All mutations were recurrent, but no significant association with cancer susceptibility was observed for any: the prevalence of FANCI c.2957_2969del and c.3041G>A mutations was even highest in healthy males (1.7%). This strengthens the exclusive role of downstream genes in cancer predisposition. From a clinical point of view, current results provide fundamental information of the mutations to be tested first in all suspected FA cases in Finland. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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...

Distinct gene expression profiles in ovarian cancer linked to Lynch syndrome

DEFF Research Database (Denmark)

Jönsson, Jenny-Maria; Bartuma, Katarina; Dominguez-Valentin, Mev

2014-01-01

Ovarian cancer linked to Lynch syndrome represents a rare subset that typically presents at young age as early-stage tumors with an overrepresentation of endometrioid and clear cell histologies. We investigated the molecular profiles of Lynch syndrome-associated and sporadic ovarian cancer...... with the aim to identify key discriminators and central tumorigenic mechanisms in hereditary ovarian cancer. Global gene expression profiling using whole-genome c-DNA-mediated Annealing, Selection, extension, and Ligation was applied to 48 histopathologically matched Lynch syndrome-associated and sporadic...... ovarian cancers. Lynch syndrome-associated and sporadic ovarian cancers differed by 349 significantly deregulated genes, including PTPRH, BIRC3, SHH and TNFRSF6B. The genes involved were predominantly linked to cell growth, proliferation, and cell-to-cell signaling and interaction. When stratified...

Ionizing radiation-induced DNA injury and damage detection in patients with breast cancer

Energy Technology Data Exchange (ETDEWEB)

Borrego-Soto, Gissela; Ortiz-Lopez, Rocio; Rojas-Martinez, Augusto, E-mail: arojasmtz@gmail.com, E-mail: augusto.rojasm@uanl.mx [Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León (Mexico)

2015-10-15

Breast cancer is the most common malignancy in women. Radiotherapy is frequently used in patients with breast cancer, but some patients may be more susceptible to ionizing radiation, and increased exposure to radiation sources may be associated to radiation adverse events. This susceptibility may be related to deficiencies in DNA repair mechanisms that are activated after cell-radiation, which causes DNA damage, particularly DNA double strand breaks. Some of these genetic susceptibilities in DNA-repair mechanisms are implicated in the etiology of hereditary breast/ovarian cancer (pathologic mutations in the BRCA 1 and 2 genes), but other less penetrant variants in genes involved in sporadic breast cancer have been described. These same genetic susceptibilities may be involved in negative radiotherapeutic outcomes. For these reasons, it is necessary to implement methods for detecting patients who are susceptible to radiotherapy-related adverse events. This review discusses mechanisms of DNA damage and repair, genes related to these functions, and the diagnosis methods designed and under research for detection of breast cancer patients with increased radiosensitivity. (author)

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

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...

Different Array CGH profiles within hereditary breast cancer tumors associated to BRCA1 expression and overall survival

International Nuclear Information System (INIS)

Alvarez, Carolina; Aravena, Andrés; Tapia, Teresa; Rozenblum, Ester; Solís, Luisa; Corvalán, Alejandro; Camus, Mauricio; Alvarez, Manuel; Munroe, David; Maass, Alejandro; Carvallo, Pilar

2016-01-01

Array CGH analysis of breast tumors has contributed to the identification of different genomic profiles in these tumors. Loss of DNA repair by BRCA1 functional deficiency in breast cancer has been proposed as a relevant contribution to breast cancer progression for tumors with no germline mutation. Identifying the genomic alterations taking place in BRCA1 not expressing tumors will lead us to a better understanding of the cellular functions affected in this heterogeneous disease. Moreover, specific genomic alterations may contribute to the identification of potential therapeutic targets and offer a more personalized treatment to breast cancer patients. Forty seven tumors from hereditary breast cancer cases, previously analyzed for BRCA1 expression, and screened for germline BRCA1 and 2 mutations, were analyzed by Array based Comparative Genomic Hybridization (aCGH) using Agilent 4x44K arrays. Overall survival was established for tumors in different clusters using Log-rank (Mantel-Cox) Test. Gene lists obtained from aCGH analysis were analyzed for Gene Ontology enrichment using GOrilla and DAVID tools. Genomic profiling of the tumors showed specific alterations associated to BRCA1 or 2 mutation status, and BRCA1 expression in the tumors, affecting relevant cellular processes. Similar cellular functions were found affected in BRCA1 not expressing and BRCA1 or 2 mutated tumors. Hierarchical clustering classified hereditary breast tumors in four major, groups according to the type and amount of genomic alterations, showing one group with a significantly poor overall survival (p = 0.0221). Within this cluster, deletion of PLEKHO1, GDF11, DARC, DAG1 and CD63 may be associated to the worse outcome of the patients. These results support the fact that BRCA1 lack of expression in tumors should be used as a marker for BRCAness and to select these patients for synthetic lethality approaches such as treatment with PARP inhibitors. In addition, the identification of specific

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.

Anxiety and depression symptoms among women attending group-based patient education courses for hereditary breast and ovarian cancer

OpenAIRE

List?l, Wenche; H?berg-Vetti, Hildegunn; Eide, Geir Egil; Bjorvatn, Cathrine

2017-01-01

Background 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 ovaria...

Lactose intolerance and risk of lung, breast and ovarian cancers: aetiological clues from a population-based study in Sweden.

Science.gov (United States)

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.

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...

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.

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.

Knowledge, attitudes, and beliefs of Arab-American women regarding inherited cancer risk.

Science.gov (United States)

Mellon, Suzanne; Gauthier, Jacqueline; Cichon, Michelle; Hammad, Adnan; Simon, Michael S

2013-04-01

The increasing incidence of breast cancer in the Arab world, coupled with a relatively early age of onset, raises concern for the presence of hereditary risk factors in this population. However, due to potential structural and cultural barriers, Arab Americans make up the smallest percentage of individuals tested for Hereditary Breast and Ovarian Cancer Syndrome in the United States. The objectives of this qualitative pilot focus group of 13 Arab-American women were to explore attitudes, knowledge and beliefs regarding hereditary breast cancer in the Arab-American community in metropolitan Detroit, identify barriers that would prevent women from seeking hereditary cancer screening/testing and determine who women would talk to about inherited cancer. Results indicated that cultural beliefs and personal experiences with cancer influenced the women's perspectives on hereditary cancer risk. A high level of secrecy about cancer within Arab-American families was present, which may prevent accurate risk assessment and referral for genetic services. Other identified barriers that may influence hereditary risk assessment included stigma, fears and misconceptions of cancer. While these barriers were present, participants also expressed a strong need for education and tailored cancer risk information for their community.

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.

Knowledge, Attitudes, and Beliefs of Arab-American Women Regarding Inherited Cancer Risk

OpenAIRE

Mellon, Suzanne; Gauthier, Jacqueline; Cichon, Michelle; Hammad, Adnan; Simon, Michael S.

2012-01-01

The increasing incidence of breast cancer in the Arab world, coupled with a relatively early age of onset, raises concern for the presence of hereditary risk factors in this population. However, due to potential structural and cultural barriers, Arab Americans make up the smallest percentage of individuals tested for Hereditary Breast and Ovarian Cancer Syndrome in the United States. The objectives of this qualitative pilot focus group of 13 Arab-American women were to explore attitudes, know...

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.

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.

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

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

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.

Patient-Centered Care in Breast Cancer Genetic Clinics

Directory of Open Access Journals (Sweden)

Anne Brédart

2018-02-01

Full Text Available With advances in breast cancer (BC gene panel testing, risk counseling has become increasingly complex, potentially leading to unmet psychosocial needs. We assessed psychosocial needs and correlates in women initiating testing for high genetic BC risk in clinics in France and Germany, and compared these results with data from a literature review. Among the 442 counselees consecutively approached, 212 (83% in France and 180 (97% in Germany, mostly BC patients (81% and 92%, respectively, returned the ‘Psychosocial Assessment in Hereditary Cancer’ questionnaire. Based on the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA BC risk estimation model, the mean BC lifetime risk estimates were 19% and 18% in France and Germany, respectively. In both countries, the most prevalent needs clustered around the “living with cancer” and “children-related issues” domains. In multivariate analyses, a higher number of psychosocial needs were significantly associated with younger age (b = −0.05, higher anxiety (b = 0.78, and having children (b = 1.51, but not with country, educational level, marital status, depression, or loss of a family member due to hereditary cancer. These results are in line with the literature review data. However, this review identified only seven studies that quantitatively addressed psychosocial needs in the BC genetic counseling setting. Current data lack understandings of how cancer risk counseling affects psychosocial needs, and improves patient-centered care in that setting.

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

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

Germline truncating-mutations in BRCA1 and MSH6 in a patient with early onset endometrial cancer

International Nuclear Information System (INIS)

Kast, Karin; Schackert, Hans K; Neuhann, Teresa M; Görgens, Heike; Becker, Kerstin; Keller, Katja; Klink, Barbara; Aust, Daniela; Distler, Wolfgang; Schröck, Evelin

2012-01-01

Hereditary Breast and Ovarian Cancer Syndrome (HBOCS) and Hereditary Non-Polyposis Colorectal Cancer Syndrome (HNPCC, Lynch Syndrome) are two tumor predisposition syndromes responsible for the majority of hereditary breast and colorectal cancers. Carriers of both germline mutations in breast cancer genes BRCA1 or BRCA2 and in mismatch repair (MMR) genes MLH1, MSH2, MSH6 or PMS2 are very rare. We identified germline mutations in BRCA1 and in MSH6 in a patient with increased risk for HBOC diagnosed with endometrial cancer at the age of 46 years. Although carriers of mutations in both MMR and BRCA genes are rare in Caucasian populations and anamnestical and histopathological findings may guide clinicians to identify these families, both syndromes can only be diagnosed through a complete gene analysis of the respective genes

Germline truncating-mutations in BRCA1 and MSH6 in a patient with early onset endometrial cancer

Energy Technology Data Exchange (ETDEWEB)

Kast, Karin [Department of Gynecology and Obstetrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Schackert, Hans K [Department of Surgical Research, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Neuhann, Teresa M [Institute for Clinical Genetics, Technische Universität Dresden, Dresden (Germany); Medical Genetic Center, Munich (Germany); Görgens, Heike [Department of Surgical Research, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Becker, Kerstin [Institute for Clinical Genetics, Technische Universität Dresden, Dresden (Germany); Keller, Katja [Department of Gynecology and Obstetrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Klink, Barbara [Institute for Clinical Genetics, Technische Universität Dresden, Dresden (Germany); Aust, Daniela [Institute of Pathology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Distler, Wolfgang [Department of Gynecology and Obstetrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Schröck, Evelin [Institute for Clinical Genetics, Technische Universität Dresden, Dresden (Germany)

2012-11-20

Hereditary Breast and Ovarian Cancer Syndrome (HBOCS) and Hereditary Non-Polyposis Colorectal Cancer Syndrome (HNPCC, Lynch Syndrome) are two tumor predisposition syndromes responsible for the majority of hereditary breast and colorectal cancers. Carriers of both germline mutations in breast cancer genes BRCA1 or BRCA2 and in mismatch repair (MMR) genes MLH1, MSH2, MSH6 or PMS2 are very rare. We identified germline mutations in BRCA1 and in MSH6 in a patient with increased risk for HBOC diagnosed with endometrial cancer at the age of 46 years. Although carriers of mutations in both MMR and BRCA genes are rare in Caucasian populations and anamnestical and histopathological findings may guide clinicians to identify these families, both syndromes can only be diagnosed through a complete gene analysis of the respective genes.

Germline truncating-mutations in BRCA1 and MSH6 in a patient with early onset endometrial cancer.

Science.gov (United States)

Kast, Karin; Neuhann, Teresa M; Görgens, Heike; Becker, Kerstin; Keller, Katja; Klink, Barbara; Aust, Daniela; Distler, Wolfgang; Schröck, Evelin; Schackert, Hans K

2012-11-20

Hereditary Breast and Ovarian Cancer Syndrome (HBOCS) and Hereditary Non-Polyposis Colorectal Cancer Syndrome (HNPCC, Lynch Syndrome) are two tumor predisposition syndromes responsible for the majority of hereditary breast and colorectal cancers. Carriers of both germline mutations in breast cancer genes BRCA1 or BRCA2 and in mismatch repair (MMR) genes MLH1, MSH2, MSH6 or PMS2 are very rare. We identified germline mutations in BRCA1 and in MSH6 in a patient with increased risk for HBOC diagnosed with endometrial cancer at the age of 46 years. Although carriers of mutations in both MMR and BRCA genes are rare in Caucasian populations and anamnestical and histopathological findings may guide clinicians to identify these families, both syndromes can only be diagnosed through a complete gene analysis of the respective genes.

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)

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.

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

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 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

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...

Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer.

Science.gov (United States)

Li, Junyan; Jing, Ruilin; Wei, Hongyi; Wang, Minghao; Qi, Xiaowei; Liu, Haoxi; Liu, Jian; Ou, Jianghua; Jiang, Weihua; Tian, Fuguo; Sheng, Yuan; Li, Hengyu; Xu, Hong; Zhang, Ruishan; Guan, Aihua; Liu, Ke; Jiang, Hongchuan; Ren, Yu; He, Jianjun; Huang, Weiwei; Liao, Ning; Cai, Xiangjun; Ming, Jia; Ling, Rui; Xu, Yan; Hu, Chunyan; Zhang, Jianguo; Guo, Baoliang; Ouyang, Lizhi; Shuai, Ping; Liu, Zhenzhen; Zhong, Ling; Zeng, Zhen; Zhang, Ting; Xuan, Zhaoling; Tan, Xuanni; Liang, Junbin; Pan, Qinwen; Chen, Li; Zhang, Fan; Fan, Linjun; Zhang, Yi; Yang, Xinhua; Li, Jingbo; Chen, Chongjian; Jiang, Jun

2018-05-12

Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n=937). Clinical information was collected and next-generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non-BRCA1/2 gene. Major mutant non-BRCA1/2 genes were TP53 (n=18), PALB2 (n=11), CHEK2 (n=6), ATM (n=6), and BARD1 (n=5). No factors predicted pathologic mutations in non-BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER-2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non-BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rates (1.9% and 1.2%). Although no factors predicted for detrimental mutations in non-BRCA1/2 genes, some clinical features were associated with mutations of several particular genes. This article is protected by copyright. All rights reserved. © 2018 UICC.

Germline truncating-mutations in BRCA1 and MSH6 in a patient with early onset endometrial cancer

Directory of Open Access Journals (Sweden)

Kast Karin

2012-11-01

Full Text Available Abstract Background Hereditary Breast and Ovarian Cancer Syndrome (HBOCS and Hereditary Non-Polyposis Colorectal Cancer Syndrome (HNPCC, Lynch Syndrome are two tumor predisposition syndromes responsible for the majority of hereditary breast and colorectal cancers. Carriers of both germline mutations in breast cancer genes BRCA1 or BRCA2 and in mismatch repair (MMR genes MLH1, MSH2, MSH6 or PMS2 are very rare. Case presentation We identified germline mutations in BRCA1 and in MSH6 in a patient with increased risk for HBOC diagnosed with endometrial cancer at the age of 46 years. Conclusions Although carriers of mutations in both MMR and BRCA genes are rare in Caucasian populations and anamnestical and histopathological findings may guide clinicians to identify these families, both syndromes can only be diagnosed through a complete gene analysis of the respective genes.

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. Kapuscinski (Miroslav K.); Karlan, B.Y. (Beth Y.); S. Khan (Sofia); L.A.L.M. Kiemeney (Bart); M. Kjaer (Michael); J.A. Knight (Julia); I. Konstantopoulou (I.); V-M. Kosma (Veli-Matti); V. Kristensen (Vessela); J. Kupryjanczyk (Jolanta); A. Kwong (Ava); M. de La Hoya (Miguel); Y. Laitman (Yael); Lambrechts, D. (Diether); N.D. Le (Nhu D.); K. De Leeneer (Kim); K.J. Lester (Kathryn); D.A. Levine (Douglas); J. Li (Jingmei); A. Lindblom (Annika); J. Long (Jirong); A. Lophatananon (Artitaya); J.T. Loud (Jennifer); K.H. Lu (Karen); J. Lubinski (Jan); A. Mannermaa (Arto); S. Manoukian (Siranoush); L. Le Marchand (Loic); S. Margolin (Sara); F. Marme (Frederick); L.F. Massuger (Leon); K. Matsuo (Keitaro); S. Mazoyer (Sylvie); L. McGuffog (Lesley); C.A. McLean (Catriona Ann); I. McNeish (Iain); A. Meindl (Alfons); U. Menon (Usha); Mensenkamp, A.R. (Arjen R.); R.L. Milne (Roger); M. Montagna (Marco); K.B. Moysich (Kirsten); K.R. Muir (K.); A.-M. Mulligan (Anna-Marie); K.L. 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. (Magalie); J.-P. Peyrat; J. Fournier (Joëlle); F. Révillion (Françoise); C. Adenis (Claude); L. Vénat-Bouvet (Laurence); M. Léone (Mélanie); N. Boutry-Kryza (N.); A. Calender (Alain); S. Giraud (Sophie); C. Verny-Pierre (Carole); C. Lasset (Christine); V. Bonadona (Valérie); Barjhoux, L. (Laure); H. Sobol (Hagay); V. Bourdon (Violaine); Noguchi, T. (Tetsuro); A. Remenieras (Audrey); I. Coupier (Isabelle); P. Pujol (Pascal); J. Sokolowska (Johanna); M. Bronner (Myriam); C.D. Delnatte (Capucine); Bézieau, S. (Stéphane); Mari, V. (Véronique); M. Gauthier-Villars (Marion); B. Buecher (Bruno); E. Rouleau (Etienne); L. Golmard (Lisa); V. Moncoutier (Virginie); M. Belotti (Muriel); A. de Pauw (Antoine); Elan, C. (Camille); Fourme, E. (Emmanuelle); Birot, A.-M. (Anne-Marie); Saule, C. (Claire); Laurent, M. (Maïté); C. Houdayer (Claude); F. Lesueur (Fabienne); N. Mebirouk (Noura); F. Coulet (Florence); C. Colas (Chrystelle); F. Soubrier; Warcoin, M. (Mathilde); F. Prieur (Fabienne); M. 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

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.

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...

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

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.

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)

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...

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.

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

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.

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

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

Breast MR imaging in women at high-risk of breast cancer. Is something changing in early breast cancer detection?

International Nuclear Information System (INIS)

Sardanelli, Francesco; Podo, Franca

2007-01-01

In the last few years, several papers have addressed the introduction of contrast-enhanced MR imaging for screening women at high risk for breast cancer. Taking in consideration five prospective studies, on 3,571 screened women with hereditary predisposition to the disease and 9,652 rounds, we found that 168 patients were diagnosed with breast cancer (155 screen-detected, eight interval, and five cancers excluded from analysis) with a detection rate per year of 1.7%. These cancers were small (49% equal to or less than 10 mm in diameter) but aggressive, 82% being invasive and 49% with histologic grade 3; however, only 19% of these invasive cancers were associated with nodal involvement. The pooled sensitivity was 16% for clinical breast examination, 40% for mammography, 43% for ultrasound, and 81% for MR. The positive predictive value (calculated on the basis of the number of invasive diagnostic procedures due to false positives) was 33%, 47%, 18%, and 53%, respectively. Aim of the present article is to present the historical development of MR imaging of breast tumors that made this application theoretically and technically possible, to explain what strategic problems we face in the presence of a hereditary predisposition to the disease, to review the main results of the published studies, and to outline open problems and future perspectives. (orig.)

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

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

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

BRCA2 Mutations in 154 Finnish Male Breast Cancer Patients

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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.

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

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

Breast cancer correlates in a cohort of breast screening program participants in Riyadh, KSA

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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.

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...

The current social, political, and medical role of genetic testing in familial breast and ovarian carcinomas.

Science.gov (United States)

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.

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.

A novel loss-of-function heterozygous BRCA2 c.8946_8947delAG mutation found in a Chinese woman with family history of breast cancer.

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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.

New treatment option for women with hormone-sensitive breast cancer

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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

Psychological impact of receiving a BRCA1/BRCA2 test result

NARCIS (Netherlands)

Lodder, L.; Frets, P. G.; Trijsburg, R. W.; Meijers-Heijboer, E. J.; Klijn, J. G.; Duivenvoorden, H. J.; Tibben, A.; Wagner, A.; van der Meer, C. A.; van den Ouweland, A. M.; Niermeijer, M. F.

2001-01-01

Mutation analysis for autosomal dominant hereditary breast/ovarian cancer genes (BRCA1/BRCA2) became an important technique for women at risk of carrying these mutations. Healthy female mutation carriers have a high lifetime risk for breast and/or ovarian cancer and may opt for frequent breast and

Latent class joint model of ovarian function suppression and DFS for premenopausal breast cancer patients.

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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.

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....

Efficacy of Neoadjuvant Cisplatin in Triple-Negative Breast Cancer

DEFF Research Database (Denmark)

Szallasi, Zoltan Imre; Eklund, Aron Charles; Li, Qiyuan

2010-01-01

PURPOSE Cisplatin is a chemotherapeutic agent not used routinely for breast cancer treatment. As a DNA cross-linking agent, cisplatin may be effective treatment for hereditary BRCA1-mutated breast cancers. Because sporadic triple-negative breast cancer (TNBC) and BRCA1-associated breast cancer...... samples were evaluated for selected biomarkers. Results Six (22%) of 28 patients achieved pathologic complete responses, including both patients with BRCA1 germline mutations;18 (64%) patients had a clinical complete or partial response. Fourteen (50%) patients showed good pathologic responses (Miller...

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...

Identification and Functional Testing of ERCC2 Mutations in a Multi-national Cohort of Patients with Familial Breast- and Ovarian Cancer.

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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.

Dietary influence on estrogens and cytokines in breast cancer

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Xin Nian

2017-07-01

Full Text Available Breast cancer affects one out of eight women in their lifetime. Many factors contribute to the development of breast cancer, such as hereditary mutations and lifetime exposure to environmental factors, including estrogen. In addition, overweight and obesity, especially with increased waist circumference, are known to be associated with breast cancer risk. This review will summarize our understanding of the effect of diet on breast cancer incidence and progression. Since some inflammatory cytokines that are changed by a high-fat diet are known to promote the growth of breast cancer cells, these cytokines may serve as biomarkers to monitor the dietary influence for women at high risk of breast cancer and as future therapeutic targets for breast cancer treatment.

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.

Informing family members about a hereditary predisposition to cancer: attitudes and practices among clinical geneticists

NARCIS (Netherlands)

Stol, Y.; Menko, F.H.; Westerman, M.J.; Janssens, M.J.P.A.

2010-01-01

If a hereditary predisposition to colorectal cancer or breast cancer is diagnosed, most guidelines state that clinical geneticists should request index patients to inform their at-risk relatives about the existence of this condition in their family, thus enabling them to consider presymptomatic

Ovarian Cancer Risk Factors by Histologic Subtype: An Analysis From the Ovarian Cancer Cohort Consortium.

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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.

BRCA1-Associated Protein BRCC36: A Novel Target for Breast Cancer Therapy

Science.gov (United States)

2009-10-01

Godwin, A.K. (2002) In Pasqualini , J.R. (eds), Breast Cancer: Prognosis, Treatment and Prevention. Marcel Dekker Inc., pp. 555–624. 5. King, M.C...Dunbrack R, Godwin AK (2002). BRAC 1, BRAC2, and hereditary breast cancer. In: Pasqualini J (ed). Breast Cancer: Prognosis, Treatment and Prevention

A case-control study of risk factors for epithelial ovarian cancer

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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.

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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.

Hereditary gynaecologic cancers in Nepal: a proposed model of care to serve high risk populations in developing countries.

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Pokharel, Hanoon P; Hacker, Neville F; Andrews, Lesley

2017-01-01

Endometrial, ovarian and breast cancers are paradigms for global health disparity. Women living in the developing world continue to present in later stages of disease and have fewer options for treatment than those in developed countries. Risk reducing surgery is of proven benefit for women at high risk of gynaecological cancer. There is no specific model for identification and management of such women in the developing world. We have integrated data from our published audit of a major gynaecological oncology centre at Royal Hospital for Women in Australia, with data from our survey and a focus group discussion of Nepalese gynaecological health care professionals regarding genetic testing, and findings from the literature. These data have been used to identify current barriers to multidisciplinary gynaecological oncology care in developing nations, and to develop a model to integrate hereditary cancer services into cancer care in Nepal, as a paradigm for other developing nations. The ability to identify women with hereditary gynaecological cancer in developing nations is influenced by their late presentation (if active management is declined or not appropriate), limited access to specialised services and cultural and financial barriers. In order to include genetic assessment in multidisciplinary gynaecological cancer care, education needs to be provided to all levels of health care providers to enable reporting of family history, and appropriate ordering of investigations. Training of genetic counsellors is needed to assist in the interpretation of results and extending care to unaffected at-risk relatives. Novel approaches will be required to overcome geographic and financial barriers, including mainstreaming of genetic testing, telephone counselling, use of mouth swabs and utilisation of international laboratories. Women in Nepal have yet to receive benefits from the advances in early cancer diagnosis and management. There is a potential of extending the benefits

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

Rapid genetic counseling and testing in newly diagnosed breast cancer : Surgical and psychosocial implications

NARCIS (Netherlands)

Wevers, M.R.

2018-01-01

Genetic counseling and testing for breast cancer have traditionally been offered to eligible patients after completion of their primary treatment. Women with hereditary breast cancer, caused by a germline mutation in the BRCA1 or BRCA2 gene, have an increased risk of contralateral breast cancer and

BRCA1 and BRCA2 mutations in ethnic Lebanese Arab women with high hereditary risk breast cancer.

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El Saghir, Nagi S; Zgheib, Nathalie K; Assi, Hussein A; Khoury, Katia E; Bidet, Yannick; Jaber, Sara M; Charara, Raghid N; Farhat, Rania A; Kreidieh, Firas Y; Decousus, Stephanie; Romero, Pierre; Nemer, Georges M; Salem, Ziad; Shamseddine, Ali; Tfayli, Arafat; Abbas, Jaber; Jamali, Faek; Seoud, Muhieddine; Armstrong, Deborah K; Bignon, Yves-Jean; Uhrhammer, Nancy

2015-04-01

Breast cancer is the most common malignancy among women in Lebanon and in Arab countries, with 50% of cases presenting before the age of 50 years. Between 2009 and 2012, 250 Lebanese women with breast cancer who were considered to be at high risk of carrying BRCA1 or BRCA2 mutations because of presentation at young age and/or positive family history (FH) of breast or ovarian cancer were recruited. Clinical data were analyzed statistically. Coding exons and intron-exon boundaries of BRCA1 and BRCA2 were sequenced from peripheral blood DNA. All patients were tested for BRCA1 rearrangements using multiplex ligation-dependent probe amplification (MLPA). BRCA2 MLPA was done in selected cases. Overall, 14 of 250 patients (5.6%) carried a deleterious BRCA mutation (7 BRCA1, 7 BRCA2) and 31 (12.4%) carried a variant of uncertain significance. Eight of 74 patients (10.8%) aged ≤40 years with positive FH and only 1 of 74 patients (1.4%) aged ≤40 years without FH had a mutated BRCA. Four of 75 patients (5.3%) aged 41-50 years with FH had a deleterious mutation. Only 1 of 27 patients aged >50 years at diagnosis had a BRCA mutation. All seven patients with BRCA1 mutations had grade 3 infiltrating ductal carcinoma and triple-negative breast cancer. Nine BRCA1 and 17 BRCA2 common haplotypes were observed. Prevalence of deleterious BRCA mutations is lower than expected and does not support the hypothesis that BRCA mutations alone cause the observed high percentage of breast cancer in young women of Lebanese and Arab descent. Studies to search for other genetic mutations are recommended. ©AlphaMed Press.

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.

Almost 2% of Spanish breast cancer families are associated to germline pathogenic mutations in the ATM gene.

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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.

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

Genetics Home Reference: hereditary diffuse gastric cancer

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... Health Conditions Hereditary diffuse gastric cancer Hereditary diffuse gastric cancer Printable PDF Open All Close All Enable Javascript ... Diffuse Gastric Cancer MedlinePlus Encyclopedia: Gastric Cancer National Cancer ... Option Overview General Information from MedlinePlus ( ...

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

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....

A Molecularly Targeted Theranostic Probe for Ovarian Cancer

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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

Early detection of ovarian cancer in FB&H - role of family medicine team

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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.

A monograph proposing the use of canine mammary tumours as a model for the study of hereditary breast cancer susceptibility genes in humans.

Science.gov (United States)

Goebel, Katie; Merner, Nancy D

2017-05-01

Canines are excellent models for cancer studies due to their similar physiology and genomic sequence to humans, companion status and limited intra-breed heterogeneity. Due to their affliction to mammary cancers, canines can serve as powerful genetic models of hereditary breast cancers. Variants within known human breast cancer susceptibility genes only explain a fraction of familial cases. Thus, further discovery is necessary but such efforts have been thwarted by genetic heterogeneity. Reducing heterogeneity is key, and studying isolated human populations have helped in the endeavour. An alternative is to study dog pedigrees, since artificial selection has resulted in extreme homogeneity. Identifying the genetic predisposition to canine mammary tumours can translate to human discoveries - a strategy currently underutilized. To explore this potential, we reviewed published canine mammary tumour genetic studies and proposed benefits of next generation sequencing canine cohorts to facilitate moving beyond incremental advances.

Development of the Informing Relatives Inventory (IRI): Assessing Index Patients' Knowledge, Motivation and Self-Efficacy Regarding the Disclosure of Hereditary Cancer Risk Information to Relatives.

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de Geus, Eveline; Aalfs, Cora M; Menko, Fred H; Sijmons, Rolf H; Verdam, Mathilde G E; de Haes, Hanneke C J M; Smets, Ellen M A

2015-08-01

Despite the use of genetic services, counselees do not always share hereditary cancer information with at-risk relatives. Reasons for not informing relatives may be categorized as a lack of: knowledge, motivation, and/or self-efficacy. This study aims to develop and test the psychometric properties of the Informing Relatives Inventory, a battery of instruments that intend to measure counselees' knowledge, motivation, and self-efficacy regarding the disclosure of hereditary cancer risk information to at-risk relatives. Guided by the proposed conceptual framework, existing instruments were selected and new instruments were developed. We tested the instruments' acceptability, dimensionality, reliability, and criterion-related validity in consecutive index patients visiting the Clinical Genetics department with questions regarding hereditary breast and/or ovarian cancer or colon cancer. Data of 211 index patients were included (response rate = 62%). The Informing Relatives Inventory (IRI) assesses three barriers in disclosure representing seven domains. Instruments assessing index patients' (positive) motivation and self-efficacy were acceptable and reliable and suggested good criterion-related validity. Psychometric properties of instruments assessing index patients knowledge were disputable. These items were moderately accepted by index patients and the criterion-related validity was weaker. This study presents a first conceptual framework and associated inventory (IRI) that improves insight into index patients' barriers regarding the disclosure of genetic cancer information to at-risk relatives. Instruments assessing (positive) motivation and self-efficacy proved to be reliable measurements. Measuring index patients knowledge appeared to be more challenging. Further research is necessary to ensure IRI's dimensionality and sensitivity to change.

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

Breast Cancer Screening in Women with Hereditary or Familial Risk

NARCIS (Netherlands)

S. Saadatmand (Sepideh)

2015-01-01

markdownabstract__Abstract__ We estimated influence of tumor size and number of positive lymph nodes at breast cancer detection on survival in the current era of new system (neo) adjuvant therapies. We showed that early breast cancer detection remains of great influence. Relative 5-year survival

Five-year analysis of magnetic resonance imaging as a screening tool in women at hereditary risk of breast cancer

International Nuclear Information System (INIS)

Kam, Jeffrey K.P.; Naidu, Paayal; Rose, Allison K.; Mann, Bruce G.

2013-01-01

Women at very high risk of breast cancer are recommended to undertake enhanced surveillance with annual MRI in addition to mammography. We aimed to review the performance of breast MRI as a screening modality over its first 5 years at our institution. The study used a retrospective review using prospectively collected data from a consecutive series of women at high risk of developing breast cancer undergoing surveillance MRI. Two hundred twenty-three women had at least one screening MRI. The median age was 42 years old. Sixty-nine (30.9%) were confirmed genetic mutation carriers. The remaining 154 (69.1%) women were classified as high risk based on family history, without a confirmed genetic mutation. Three hundred forty screening MRI studies were performed. Of these, 69 patients (20.3%) were recalled for further assessment. There was a significant reduction in the recall rate throughout the study for prevalent screens, from 50% (17/34) in 2008 to 14% (9/54) in 2011 (P=0.004). The overall biopsy rate was 39 in 340 screens (11.5%). Four cancers were identified. Three were in confirmed BRCA1/BRCA2 mutation carriers, and one was found to be a carrier after the cancer was diagnosed. All four were identified as suspicious on MRI, with two having normal mammography. The cancer detection rate of MRI was 1.2% (4/340 screens). The overall positive predictive value was 7.0%, 6.7% for prevalent screens and 7.1% for subsequent screens. Breast MRI as a screening modality for malignant lesions in women with high hereditary risk is valuable. The recall rate, especially in the prevalent round, improved with radiologist experience.

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

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

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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.

Ovarian Suppression With Triptorelin During Adjuvant Breast Cancer Chemotherapy and Long-term Ovarian Function, Pregnancies, and Disease-Free Survival: A Randomized Clinical Trial.

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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

[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

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.

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.

The Pink Underside: The Commercialization of Medical Risk Assessment and Decision-Making Tools for Hereditary Breast Cancer Risk.

Science.gov (United States)

Hesse-Biber, Sharlene; Flynn, Bailey; Farrelly, Keeva

2018-04-01

The growth of the Internet since the millennium has opened up a myriad of opportunities for education, particularly in medicine. Although those looking for health care information used to have to turn to a face-to-face doctor's visit, an immense library of medical advice is now available at their fingertips. The BRCA genetic predispositions (mutations of the BRCA1 and BRCA2 breast cancer genes) which expose men and women to greater risk of breast, ovarian, and other cancers can be researched extensively online. Several nonprofit organizations now offer online risk assessment and decision-making tools meant to supplement conversation with medical professionals, which in actuality are quickly replacing it. We argue here through a critical qualitative template analysis of several such tools that the discursive frameworks utilized are prone to fearmongering, commercialization, and questionable validity. Left unchecked, these assessment tools could do more harm than good in driving young women especially to take unnecessary extreme surgical action.

Cost-effectiveness analysis of a low-fat diet in the prevention of breast and ovarian cancer.

Science.gov (United States)

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

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.

Somatic mutations in breast and serous ovarian cancer young patients: a systematic review and meta-analysis

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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.

Complex Landscape of Germline Variants in Brazilian Patients With Hereditary and Early Onset Breast Cancer

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Giovana T. Torrezan

2018-05-01

Full Text Available Pathogenic variants in known breast cancer (BC predisposing genes explain only about 30% of Hereditary Breast Cancer (HBC cases, whereas the underlying genetic factors for most families remain unknown. Here, we used whole-exome sequencing (WES to identify genetic variants associated to HBC in 17 patients of Brazil with familial BC and negative for causal variants in major BC risk genes (BRCA1/2, TP53, and CHEK2 c.1100delC. First, we searched for rare variants in 27 known HBC genes and identified two patients harboring truncating pathogenic variants in ATM and BARD1. For the remaining 15 negative patients, we found a substantial vast number of rare genetic variants. Thus, for selecting the most promising variants we used functional-based variant prioritization, followed by NGS validation, analysis in a control group, cosegregation analysis in one family and comparison with previous WES studies, shrinking our list to 23 novel BC candidate genes, which were evaluated in an independent cohort of 42 high-risk BC patients. Rare and possibly damaging variants were identified in 12 candidate genes in this cohort, including variants in DNA repair genes (ERCC1 and SXL4 and other cancer-related genes (NOTCH2, ERBB2, MST1R, and RAF1. Overall, this is the first WES study applied for identifying novel genes associated to HBC in Brazilian patients, in which we provide a set of putative BC predisposing genes. We also underpin the value of using WES for assessing the complex landscape of HBC susceptibility, especially in less characterized populations.

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.

Prophylactic procedures in women with gene mutations BRCA1 and BRCA2

International Nuclear Information System (INIS)

Bella, V.

2012-01-01

Breast cancer is the most common oncologic disease in the female population. Besides the sporadic occurrence, it occurs in the familial or hereditary form. Genetic testing for mutation BRCA1 and BRCA2 helps to identify women, who are at increased risk of developing breast and ovarian cancer. Women with the hereditary form of breast cancer occurs in 5 -10%. Women with mutations BRCA1 and BRCA2 have to be classified to intensive dispensaration, and may consider several options for breast cancer prevention, as prophylactic mastectomy, prophylactic salpingo-oophorectomy or chemo prevention. (author)

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...

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.

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

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...

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.

Therapeutic Strategies for Hereditary Kidney Cancer.

Science.gov (United States)

Sidana, Abhinav; Srinivasan, Ramaprasad

2016-08-01

The study of hereditary forms of kidney cancer has vastly increased our understanding of metabolic and genetic pathways involved in the development of both inherited and sporadic kidney cancers. The recognition that diverse molecular events drive different forms of kidney cancers has led to the preclinical and clinical development of specific pathway-directed strategies tailored to treat distinct subgroups of kidney cancer. Here, we describe the molecular mechanisms underlying the pathogenesis of several different types of hereditary renal cancers, review their clinical characteristics, and summarize the treatment strategies for the management of these cancers.

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

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

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...

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

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.

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...

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.

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 ...

Mutation and Methylation Analysis of the Chromodomain-Helicase-DNA Binding 5 Gene in Ovarian Cancer

Directory of Open Access Journals (Sweden)

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...

Sammenhaenge mellem patientens genotype og sygdommens forløb ved arvelige kraeftsygdomme

DEFF Research Database (Denmark)

Bisgaard, Marie Luise

2006-01-01

largest hereditary cancer groups, namely hereditary colorectal cancer and hereditary breast (and ovarian) cancer. It is concluded that knowledge about genotype-phenotype correlations is essential in the cancer genetic clinic; otherwise, the patient tends to base decisions on personal experience......The majority of hereditary cancers demonstrate extended variation of phenotype, not only between families, but also within a particular family, who supposedly have inherited the same pathogenic mutation. The present paper reviews genotype-phenotype correlations with examples mainly from the two...

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)

Presymptomatic testing for BRCA1 and BRCA2: how distressing are the pre-test weeks? Rotterdam/Leiden Genetics Working Group

NARCIS (Netherlands)

L.N. Lodder; P. Devilee (Peter); M.F. Niermeijer (Martinus); C.J. Cornelisse (Cees); P.G. Frets; R.W. Trijsburg (Wim); E.J. Meijers-Heijboer (Hanne); J.G.M. Klijn (Jan); H.J. Duivenvoorden (Hugo); A. Tibben (Arend); A. Wagner (Anja); C.A. van der Meer

1999-01-01

textabstractPresymptomatic DNA testing for autosomal dominant hereditary breast/ovarian cancer (HBOC) became an option after the identification of the BRCA1 and BRCA2 genes in 1994-1995. Healthy female mutation carriers have a high lifetime risk for breast cancer

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.

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....

G1738R is a BRCA1 founder mutation in Greek breast/ovarian cancer patients: evaluation of its pathogenicity and inferences on its genealogical history.

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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

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

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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

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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.

ABRAXAS (FAM175A) and Breast Cancer Susceptibility: No Evidence of Association in the Breast Cancer Family Registry.

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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.