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Sample records for breast cancer association

  1. Association between breast and thyroid cancers

    Directory of Open Access Journals (Sweden)

    Lehrer S

    2014-02-01

    Full Text Available Steven Lehrer, Sheryl Green, John A Martignetti, Kenneth E Rosenzweig Departments of Radiation Oncology and Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA Background: The risk of thyroid cancer is known to be slightly increased in women after treatment for breast cancer. In the current study, we analyzed the incidence of thyroid cancer and breast cancer in 50 US states and in the District of Columbia to ascertain how often these two diseases are associated. Methods: Data on the incidence of thyroid cancer were obtained from the Centers for Disease Control and Prevention and the National Cancer Institute and data on the incidence of breast cancer were from the American Cancer Society. Data on the average number of children per family with children and mean household income were sourced from the US Bureau of the Census and prevalence of obesity by state is determined from a paper published in 2010 on state-specific obesity prevalence among US adults by the Centers for Disease Control and Prevention. Results: There was a significant association between breast and thyroid cancer (P=0.002. Since the incidence of breast cancer increases with increasing income and obesity, while decreasing with parity, multiple linear regression was performed. Breast cancer incidence was significantly related to thyroid cancer incidence (β=0.271, P=0.039, inversely related to average number of children per family with children (β=-0.271, P=0.039, unrelated to adult obesity (β=0.134, P=0.369, and significantly related to family income (β=0.642, P<0.001. Conclusion: This study identifies an association between breast and thyroid cancer. The association suggests that unexplored breast-thyroid cancer susceptibility loci exist and warrant further study. Keywords: breast cancer, thyroid cancer, genetics, association

  2. Pregnancy associated breast cancer and pregnancy after breast cancer treatment

    OpenAIRE

    Doğer, Emek; Çalışkan, Eray; Mallmann, Peter

    2011-01-01

    Breast cancer is one of the most common cancers diagnosed during pregnancy and its frequency is increasing as more women postpone their pregnancies to their thirties and forties. Breast cancer diagnosis during pregnancy and lactation is difficult and complex both for the patient and doctors. Delay in diagnosis is frequent and treatment modalities are difficult to accept for the pregnant women. The common treatment approach is surgery after diagnosis, chemotherapy after the first trimester and...

  3. Is human cytomegalovirus associated with breast cancer progression?

    OpenAIRE

    Utrera-Barillas, Dolores; Valdez-Salazar, Hilda-Alicia; Gómez-Rangel, David; Alvarado-Cabrero, Isabel; Aguilera, Penélope; Gómez-Delgado, Alejandro; Ruiz-Tachiquin, Martha-Eugenia

    2013-01-01

    Background It has been hypothesized that human cytomegalovirus (HCMV) may be associated with breast cancer progression. However, the role of HCMV infection in breast cancer remains controversial. We aimed to assess whether HCMV genes (UL122 and UL83) could be detected in breast carcinomas and reinvestigated their possible association with breast cancer progression. DNA from paraffin-embedded tissues was analyzed by real-time PCR. We investigated 20 fibroadenomas and 27 primary breast carcinom...

  4. Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes

    DEFF Research Database (Denmark)

    Broeks, Annegien; Schmidt, Marjanka K; Sherman, Mark E;

    2011-01-01

    Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtype...

  5. Association of breast cancer risk loci with breast cancer survival

    NARCIS (Netherlands)

    Barrdahl, Myrto; Canzian, Federico; Lindström, Sara; Shui, Irene; Black, Amanda; Hoover, Robert N.; Ziegler, Regina G.; Buring, Julie E.; Chanock, Stephen J.; Diver, W. Ryan; Gapstur, Susan M.; Gaudet, Mia M.; Giles, Graham G.; Haiman, Christopher; Henderson, Brian E.; Hankinson, Susan; Hunter, David J.; Joshi, Amit D.; Kraft, Peter; Lee, I. Min; Le Marchand, Loic; Milne, Roger L.; Southey, Melissa C.; Willett, Walter; Gunter, Marc; Panico, Salvatore; Sund, Malin; Weiderpass, Elisabete; Sánchez, María José; Overvad, Kim; Dossus, Laure; Peeters, Petra H.; Khaw, Kay Tee; Trichopoulos, Dimitrios; Kaaks, Rudolf; Campa, Daniele

    2015-01-01

    The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of eviden

  6. BRCA1/2 associated hereditary breast cancer

    Institute of Scientific and Technical Information of China (English)

    Li-song TENG; Yi ZHENG; Hao-hao WANG

    2008-01-01

    Breast cancer is one of the leading causes of death in women today. Some of the patients are hereditary, with a large proportion characterized by mutation in BRCA1 and/or BRCA2 genes. In this review, we provide an overview of these two genes,focusing on their relationship with hereditary breast cancers. BRCA1/2 associated hereditary breast cancers have unique features that differ from the general breast cancers, including alterations in cellular molecules, pathological bases, biological behavior, and a different prevention strategy. But the outcome of BRCA1/2 associated hereditary breast cancers still remains controversial;further studies are needed to elucidate the nature of BRCA1/2 associated hereditary breast cancers.

  7. Common germline polymorphisms associated with breast cancer-specific survival

    DEFF Research Database (Denmark)

    Pirie, Ailith; Guo, Qi; Kraft, Peter;

    2015-01-01

    INTRODUCTION: Previous studies have identified common germline variants nominally associated with breast cancer survival. These associations have not been widely replicated in further studies. The purpose of this study was to evaluate the association of previously reported SNPs with breast cancer......-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium. METHODS: A literature review was conducted of all previously published associations between common germline variants and three survival outcomes......: breast cancer-specific survival, overall survival and disease-free survival. All associations that reached the nominal significance level of P value <0.05 were included. Single nucleotide polymorphisms that had been previously reported as nominally associated with at least one survival outcome were...

  8. Didymin reverses phthalate ester-associated breast cancer aggravation in the breast cancer tumor microenvironment

    OpenAIRE

    Hsu, Ya-Ling; Hsieh, Chia-Jung; Tsai, Eing-Mei; HUNG, JEN-YU; CHANG, WEI-AN; Hou, Ming-Feng; Kuo, Po-Lin

    2015-01-01

    The present study demonstrated two novel findings. To the best of our knowledge, it is the first study to demonstrate that regulated upon activation, normal T-cell expressed and secreted (RANTES), produced by breast tumor-associated monocyte-derived dendritic cells (TADCs) following breast cancer cell exposure to phthalate esters, may contribute to the progression of cancer via enhancement of cancer cell proliferation, migration and invasion. Furthermore, the present study revealed that didym...

  9. Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies

    DEFF Research Database (Denmark)

    Yang, Xiaohong R; Chang-Claude, Jenny; Goode, Ellen L;

    2011-01-01

    Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors.......Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors....

  10. Associations of Breast Cancer Risk Factors With Tumor Subtypes : A Pooled Analysis From the Breast Cancer Association Consortium Studies

    NARCIS (Netherlands)

    Yang, Xiaohong R.; Chang-Claude, Jenny; Goode, Ellen L.; Couch, Fergus J.; Nevanlinna, Heli; Milne, Roger L.; Gaudet, Mia; Schmidt, Marjanka K.; Broeks, Annegien; Cox, Angela; Fasching, Peter A.; Hein, Rebecca; Spurdle, Amanda B.; Blows, Fiona; Driver, Kristy; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Peter; Vrieling, Alina; Heikkinen, Tuomas; Aittomaeki, Kristiina; Heikkilae, Paeivi; Blomqvist, Carl; Lissowska, Jolanta; Peplonska, Beata; Chanock, Stephen; Figueroa, Jonine; Brinton, Louise; Hall, Per; Czene, Kamila; Humphreys, Keith; Darabi, Hatef; Liu, Jianjun; Van 't Veer, Laura J.; Van Leeuwen, Flora E.; Andrulis, Irene L.; Glendon, Gord; Knight, Julia A.; Mulligan, Anna Marie; O'Malley, Frances P.; Weerasooriya, Nayana; John, Esther M.; Beckmann, Matthias W.; Hartmann, Arndt; Weihbrecht, Sebastian B.; Wachter, David L.; Jud, Sebastian M. S.; Loehberg, Christian R.; Baglietto, Laura; English, Dallas R.; Giles, Graham G.; McLean, Catriona A.; Severi, Gianluca; Lambrechts, Diether; Vandorpe, Thijs; Weltens, Caroline; Paridaens, Robert; Smeets, Ann; Neven, Patrick; Wildiers, Hans; Wang, Xianshu; Olson, Janet E.; Cafourek, Victoria; Fredericksen, Zachary; Kosel, Matthew; Vachon, Celine; Cramp, Helen E.; Connley, Daniel; Cross, Simon S.; Balasubramanian, Sabapathy P.; Reed, Malcolm W. R.; Doerk, Thilo; Bremer, Michael; Meyer, Andreas; Karstens, Johann H.; Ay, Aysun; Park-Simon, Tjoung-Won; Hillemanns, Peter; Arias Perez, Jose Ignacio; Menendez Rodriguez, Primitiva; Zamora, Pilar; Bentez, Javier; Ko, Yon-Dschun; Fischer, Hans-Peter; Hamann, Ute; Pesch, Beate; Bruening, Thomas; Justenhoven, Christina; Brauch, Hiltrud; Eccles, Diana M.; Tapper, William J.; Gerty, Sue M.; Sawyer, Elinor J.; Tomlinson, Ian P.; Jones, Angela; Kerin, Michael; Miller, Nicola; McInerney, Niall; Anton-Culver, Hoda; Ziogas, Argyrios; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Yang, Show-Lin; Yu, Jyh-Cherng; Chen, Shou-Tung; Hsu, Giu-Cheng; Haiman, Christopher A.; Henderson, Brian E.; Le Marchand, Loic; Kolonel, Laurence N.; Lindblom, Annika; Margolin, Sara; Jakubowska, Anna; Lubinski, Jan; Huzarski, Tomasz; Byrski, Tomasz; Gorski, Bohdan; Gronwald, Jacek; Hooning, Maartje J.; Hollestelle, Antoinette; van den Ouweland, Ans M. W.; Jager, Agnes; Kriege, Mieke; Tilanus-Linthorst, Madeleine M. A.; Collee, Margriet; Wang-Gohrke, Shan; Pylkaes, Katri; Jukkola-Vuorinen, Arja; Mononen, Kari; Grip, Mervi; Hirvikoski, Pasi; Winqvist, Robert; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana; Kataja, Vesa; Auvinen, Paeivi; Soini, Ylermi; Sironen, Reijo; Bojesen, Stig E.; Orsted, David Dynnes; Kaur-Knudsen, Diljit; Flyger, Henrik; Nordestgaard, Borge G.; Holland, Helene; Chenevix-Trench, Georgia; Manoukian, Siranoush; Barile, Monica; Radice, Paolo; Hankinson, Susan E.; Hunter, David J.; Tamimi, Rulla; Sangrajrang, Suleeporn; Brennan, Paul; Mckay, James; Odefrey, Fabrice; Gaborieau, Valerie; Devilee, Peter; Huijts, P. E. A.; Tollenaar, R. A. E. M.; Seynaeve, C.; Dite, Gillian S.; Apicella, Carmel; Hopper, John L.; Hammet, Fleur; Tsimiklis, Helen; Smith, Letitia D.; Southey, Melissa C.; Humphreys, Manjeet K.; Easton, Douglas; Pharoah, Paul; Sherman, Mark E.; Garcia-Closas, Montserrat

    2011-01-01

    Background Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors. Methods We pooled tumor marker and epidemiological risk factor data from 35 568 invasive breast cancer case patients f

  11. Genetic variants associated with breast size also influence breast cancer risk

    Directory of Open Access Journals (Sweden)

    Eriksson Nicholas

    2012-06-01

    Full Text Available Abstract Background While some factors of breast morphology, such as density, are directly implicated in breast cancer, the relationship between breast size and cancer is less clear. Breast size is moderately heritable, yet the genetic variants leading to differences in breast size have not been identified. Methods To investigate the genetic factors underlying breast size, we conducted a genome-wide association study (GWAS of self-reported bra cup size, controlling for age, genetic ancestry, breast surgeries, pregnancy history and bra band size, in a cohort of 16,175 women of European ancestry. Results We identified seven single-nucleotide polymorphisms (SNPs significantly associated with breast size (p−8: rs7816345 near ZNF703, rs4849887 and (independently rs17625845 flanking INHBB, rs12173570 near ESR1, rs7089814 in ZNF365, rs12371778 near PTHLH, and rs62314947 near AREG. Two of these seven SNPs are in linkage disequilibrium (LD with SNPs associated with breast cancer (those near ESR1 and PTHLH, and a third (ZNF365 is near, but not in LD with, a breast cancer SNP. The other three loci (ZNF703, INHBB, and AREG have strong links to breast cancer, estrogen regulation, and breast development. Conclusions These results provide insight into the genetic factors underlying normal breast development and show that some of these factors are shared with breast cancer. While these results do not directly support any possible epidemiological relationships between breast size and cancer, this study may contribute to a better understanding of the subtle interactions between breast morphology and breast cancer risk.

  12. Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes

    DEFF Research Database (Denmark)

    Broeks, Annegien; Schmidt, Marjanka K; Sherman, Mark E;

    2011-01-01

    were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations......Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes.......016): rs3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P ≤ 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor...

  13. MRI Background Parenchymal Enhancement Is Not Associated with Breast Cancer.

    Directory of Open Access Journals (Sweden)

    Barbara Bennani-Baiti

    Full Text Available Previously, a strong positive association between background parenchymal enhancement (BPE at magnetic resonance imaging (MRI and breast cancer was reported in high-risk populations. We sought to determine, whether this was also true for non-high-risk patients.540 consecutive patients underwent breast MRI for assessment of breast findings (BI-RADS 0-5, non-high-risk screening (no familial history of breast cancer, no known genetic mutation, no prior chest irradiation, or previous breast cancer diagnosis and subsequent histological work-up. For this IRB-approved study, BPE and fibroglandular tissue FGT were retrospectively assessed by two experienced radiologists according to the BI-RADS lexicon. Pearson correlation coefficients were calculated to explore associations between BPE, FGT, age and final diagnosis of breast cancer. Subsequently, multivariate logistic regression analysis, considering covariate colinearities, was performed, using final diagnosis as the target variable and BPE, FGT and age as covariates.Age showed a moderate negative correlation with FGT (r = -0.43, p<0.001 and a weak negative correlation with BPE (r = -0.28, p<0.001. FGT and BPE correlated moderately (r = 0.35, p<0.001. Final diagnosis of breast cancer displayed very weak negative correlations with FGT (r = -0.09, p = 0.046 and BPE (r = -0.156, p<0.001 and weak positive correlation with age (r = 0.353, p<0.001. On multivariate logistic regression analysis, the only independent covariate for prediction of breast cancer was age (OR 1.032, p<0.001.Based on our data, neither BPE nor FGT independently correlate with breast cancer risk in non-high-risk patients at MRI. Our model retained only age as an independent risk factor for breast cancer in this setting.

  14. Association between mammographic density and basal-like and luminal A breast cancer subtypes

    OpenAIRE

    Razzaghi, Hilda; Troester, Melissa A.; Gierach, Gretchen L.; Olshan, Andrew F.; Yankaskas, Bonnie C.; Millikan, Robert C.

    2013-01-01

    Introduction Mammographic density is a strong risk factor for breast cancer overall, but few studies have examined the association between mammographic density and specific subtypes of breast cancer, especially aggressive basal-like breast cancers. Because basal-like breast cancers are less frequently screen-detected, it is important to understand how mammographic density relates to risk of basal-like breast cancer. Methods We estimated associations between mammographic density and breast can...

  15. The Benefit of Sonography in Pregnancy-associated Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Son, Eun Ju; Oh, Ki Keun; Kim, Eun Kyung [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2005-09-15

    To evaluate the sonographic, mammographic and MRI features of pregnancy-associated breast cancer with the major focus on the sonographic benefit in a diagnosis of pregnancy associated breast cancer. From 1998 to 2002, sonography was performed on a total 7 patients (age 23 to 38 years), who were pathologically diagnosed with breast cancer during pregnancy. Six of those patients underwent mammography. Five patients underwent a breast MRI, preoperatively. The radiological findings were evaluated retrospectively. Six patients underwent surgery and 1 patient underwent a core biopsy and chemotherapy. The histological, nuclear grading and pathological staging were evaluated. The sonographic findings showed a mass with irregular shapes (n=6), irregular margins (n=6), a non-parallel orientation (n=5), complex echo patterns (n=5). Associated findings could be observed in 3 patients, including Cooper's ligament thickening (n=2), edema (n=2), skin thickening (n=1) and axillary lymphadenopathy (n=3). The sonographic findings were positive and showed masses in 6 patients. All the patients had a dense breast in mammography. The mammographic findings included masses (n=4), masses with microcalcifications (n=2), masses with axillary lymphadenopathy (n=3), calcifications alone (n=1), an asymmetric density alone (n=1), extremely dense breasts with negative findings (n=2). A breast MRI showed an irregular shaped mass (n=4) with a rim-like enhancement (n=3), linear ductal enhancement without a mass (n= 1), and the time intensity cure revealed the typical pattern and level of enhancement in the carcinoma. Sonography is a valuable tool for diagnosing pregnancy-associated breast cancer. However, mammography should be performed if there is a suspicious lesion on sonography in order to confirm the pregnancy-associated breast cancer. Mammography has a lower sensitivity during pregnancy due to the physiologic changes in the breasts. However, calcifications and associated findings are

  16. The Benefit of Sonography in Pregnancy-associated Breast Cancer

    International Nuclear Information System (INIS)

    To evaluate the sonographic, mammographic and MRI features of pregnancy-associated breast cancer with the major focus on the sonographic benefit in a diagnosis of pregnancy associated breast cancer. From 1998 to 2002, sonography was performed on a total 7 patients (age 23 to 38 years), who were pathologically diagnosed with breast cancer during pregnancy. Six of those patients underwent mammography. Five patients underwent a breast MRI, preoperatively. The radiological findings were evaluated retrospectively. Six patients underwent surgery and 1 patient underwent a core biopsy and chemotherapy. The histological, nuclear grading and pathological staging were evaluated. The sonographic findings showed a mass with irregular shapes (n=6), irregular margins (n=6), a non-parallel orientation (n=5), complex echo patterns (n=5). Associated findings could be observed in 3 patients, including Cooper's ligament thickening (n=2), edema (n=2), skin thickening (n=1) and axillary lymphadenopathy (n=3). The sonographic findings were positive and showed masses in 6 patients. All the patients had a dense breast in mammography. The mammographic findings included masses (n=4), masses with microcalcifications (n=2), masses with axillary lymphadenopathy (n=3), calcifications alone (n=1), an asymmetric density alone (n=1), extremely dense breasts with negative findings (n=2). A breast MRI showed an irregular shaped mass (n=4) with a rim-like enhancement (n=3), linear ductal enhancement without a mass (n= 1), and the time intensity cure revealed the typical pattern and level of enhancement in the carcinoma. Sonography is a valuable tool for diagnosing pregnancy-associated breast cancer. However, mammography should be performed if there is a suspicious lesion on sonography in order to confirm the pregnancy-associated breast cancer. Mammography has a lower sensitivity during pregnancy due to the physiologic changes in the breasts. However, calcifications and associated findings are helpful

  17. Breast Cancer

    Science.gov (United States)

    Breast cancer affects one in eight women during their lives. Breast cancer kills more women in the United States than ... cancer. No one knows why some women get breast cancer, but there are a number of risk factors. ...

  18. Five polymorphisms and breast cancer risk: results from the Breast Cancer Association Consortium

    DEFF Research Database (Denmark)

    Gaudet, Mia M; Milne, Roger L; Cox, Angela;

    2009-01-01

    Previous studies have suggested that minor alleles for ERCC4 rs744154, TNF rs361525, CASP10 rs13010627, PGR rs1042838, and BID rs8190315 may influence breast cancer risk, but the evidence is inconclusive due to their small sample size. These polymorphisms were genotyped in more than 30,000 breast...... cancer cases and 30,000 controls, primarily of European descent, from 30 studies in the Breast Cancer Association Consortium. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) as a measure of association. We found that the minor alleles for these polymorphisms were not related to...... invasive breast cancer risk overall in women of European descent: ECCR4 per-allele OR (95% CI) = 0.99 (0.97-1.02), minor allele frequency = 27.5%; TNF 1.00 (0.95-1.06), 5.0%; CASP10 1.02 (0.98-1.07), 6.5%; PGR 1.02 (0.99-1.06), 15.3%; and BID 0.98 (0.86-1.12), 1.7%. However, we observed significant between...

  19. What Is Breast Cancer?

    Science.gov (United States)

    ... Next Topic Types of breast cancers What is breast cancer? Breast cancer starts when cells in the breast ... breast cancer? ” and Non-cancerous Breast Conditions . How Breast Cancer Spreads Breast cancer can spread through the lymph ...

  20. Prospective association between dietary fiber intake and breast cancer risk

    OpenAIRE

    Zelek, Laurent; Pouchieu, Camille; His, Mathilde; Hercberg, Serge; Galan, Maria del Pilar; Latino-Martel, Paule; Touvier, Mathilde

    2013-01-01

    Background: Mechanistic hypotheses suggest a potential effect of dietary fiber on breast carcinogenesis through the modulation of insulin-like growth factor bioactivity, estrogen metabolism and inflammation. An association between dietary fiber intake and breast cancer risk has been suggested in epidemiological studies but remains inconclusive. In particular, data is lacking regarding the different types of dietary fibers. [br/] Objective: The objective was to investigate the prospective rela...

  1. Didymin reverses phthalate ester-associated breast cancer aggravation in the breast cancer tumor microenvironment

    Science.gov (United States)

    HSU, YA-LING; HSIEH, CHIA-JUNG; TSAI, EING-MEI; HUNG, JEN-YU; CHANG, WEI-AN; HOU, MING-FENG; KUO, PO-LIN

    2016-01-01

    The present study demonstrated two novel findings. To the best of our knowledge, it is the first study to demonstrate that regulated upon activation, normal T-cell expressed and secreted (RANTES), produced by breast tumor-associated monocyte-derived dendritic cells (TADCs) following breast cancer cell exposure to phthalate esters, may contribute to the progression of cancer via enhancement of cancer cell proliferation, migration and invasion. Furthermore, the present study revealed that didymin, a dietary flavonoid glycoside present in citrus fruits, was able to reverse phthalate ester-mediated breast cancer aggravation. MDA-MB-231 cells were treated with butyl benzyl phthalate (BBP), di-n-butyl phthalate (DBP) or di-2-ethylhexyl phthalate (DEHP). Subsequently, the conditioned medium (CM) was harvested and cultured with monocyte-derived dendritic cells (mdDCs). Cultures of MDA-MB-231 cells with the conditioned medium of BBP-, DBP- or DEHP-MDA-MB-231 tumor-associated mdDCs (BBP-, DBP- or DEHP-MDA-TADC-CM) demonstrated enhanced proliferation, migration and invasion. Exposure of the MDA-MB-231 cells to DBP induced the MDA-TADCs to produce the inflammatory cytokine RANTES, which subsequently induced MDA-MB-231 cell proliferation, migration and invasion. Depleting RANTES reversed the effects of DBP-MDA-TADC-mediated MDA-MB-231 cell proliferation, migration and invasion. In addition, didymin was observed to suppress phthalate-mediated breast cancer cell proliferation, migration and invasion. The present study suggested that didymin was capable of preventing phthalate ester-associated cancer aggravation. PMID:26893687

  2. Association of regular aspirin use and breast cancer risk.

    Science.gov (United States)

    Swede, Helen; Mirand, Amy L; Menezes, Ravi J; Moysich, Kirsten B

    2005-01-01

    Of the limited number of epidemiological investigations on aspirin (and other nonsteroidal anti-inflammatory drugs) and breast cancer, the majority observe a protective role, yet only a few report dose-response effects for frequency or duration of use. We studied aspirin use among 1,478 breast cancer patients diagnosed from 1982 to 1998, and 3,383 cancer-free hospital controls at the Roswell Park Cancer Institute. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. Compared to never use,both regular (> or =1 tablet per week for > or =1 year) and occasional use were inversely associated with breast cancer (adjusted OR = 0.84, 95% CI 0.64-0.97; adjusted OR = 0.80, 95% CI 0.67-0.96, respectively). Among regular users, an inverse trend was found for number of tablets consumed per week (1, 2-6, or > or =7) with corresponding ORs of 0.95, 0.80, and 0.74 (P(trend) = 0.01). Daily use spanning 10 or more years was associated with a more pronounced reduction in risk (P(trend) = 0.005). Our findings corroborate the growing body of observational evidence that regular aspirin use may be associated with reduced risk of breast cancer. PMID:15802928

  3. Genetic polymorphism of the OPG gene associated with breast cancer

    International Nuclear Information System (INIS)

    The receptor activator of NF-κB (RANK), its ligand (RANKL) and osteoprotegerin (OPG) have been reported to play a role in the pathophysiological bone turnover and in the pathogenesis of breast cancer. Based on this we investigated the role of single nucleotide polymorphisms (SNPs) within RANK, RANKL and OPG and their possible association to breast cancer risk. Genomic DNA was obtained from Caucasian participants consisting of 307 female breast cancer patients and 396 gender-matched healthy controls. We studied seven SNPs in the genes of OPG (rs3102735, rs2073618), RANK (rs1805034, rs35211496) and RANKL (rs9533156, rs2277438, rs1054016) using TaqMan genotyping assays. Statistical analyses were performed using the χ2-tests for 2 x 2 and 2 x 3 tables. The allelic frequencies (OR: 1.508 CI: 1.127-2.018, p=0.006) and the genotype distribution (p=0.019) of the OPG SNP rs3102735 differed significantly between breast cancer patients and healthy controls. The minor allele C and the corresponding homo- and heterozygous genotypes are more common in breast cancer patients (minor allele C: 18.4% vs. 13.0%; genotype CC: 3.3% vs. 1.3%; genotype CT: 30.3% vs. 23.5%). No significantly changed risk was detected in the other investigated SNPs. Additional analysis showed significant differences when comparing patients with invasive vs. non-invasive tumors (OPG rs2073618) as well as in terms of tumor localization (RANK rs35211496) and body mass index (RANKL rs9533156 and rs1054016). This is the first study reporting a significant association of the SNP rs3102735 (OPG) with the susceptibility to develop breast cancer in the Caucasian population

  4. Common germline polymorphisms associated with breast cancer-specific survival

    OpenAIRE

    Pirie, Ailith; Guo, Qi; Kraft, Peter; Canisius, Sander; Eccles, Diana M; Rahman, Nazneen; Nevanlinna, Heli; Chen, Constance; Khan, Sofia; Tyrer, Jonathan; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Lush, Michael

    2015-01-01

    Funding This work was supported by the following grants. Higher level funding The COGS project was funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175). The Breast Cancer Association Consortium (BCAC) is funded by Cancer Research-UK (C1287/A10118 and C1287/A12014). Meetings of the BCAC have been funded by the European Union COST programme (BM0606). ELAN Program of the University Hospital Erlangen (BBCC). Pers...

  5. Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study

    DEFF Research Database (Denmark)

    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 invasive.......01-1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95% CI 1.07-1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast...... ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case-control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially...

  6. Regulation of Metformin Response by Breast Cancer Associated Gene 2

    Directory of Open Access Journals (Sweden)

    Daniela Buac

    2013-12-01

    Full Text Available Adenosine monophosphate-activated protein kinase (AMPK, a master regulator of cellular energy homeostasis, has emerged as a promising molecular target in the prevention of breast cancer. Clinical trials using the United States Food and Drug Administration (FDA-approved, AMPK-activating, antidiabetic drug metformin are promising in this regard, but the question of why metformin is protective for some women but not others still remains. Breast cancer associated gene 2 (BCA2/Rabring7/RNF115, a novel Really Interesting New Gene (RING finger ubiquitin E3 ligase, is overexpressed in >50% of breast tumors. Herein, we report that BCA2 is an endogenous inhibitor of AMPK activation in breast cancer cells and that BCA2 inhibition increases the efficacy of metformin. BCA2 overexpression inhibited both basal and inducible Thr172 phosphorylation/activation of AMPKα1, while BCA2-specific small interfering RNA (siRNA enhanced phosphorylated AMPKα1 (pAMPKα1. The AMPK-suppressive function of BCA2 requires its E3 ligase-specific RING domain, suggesting that BCA2 targets some protein controlling (dephosphorylation of AMPKα1 for degradation. Activation of AMPK by metformin triggered a growth inhibitory signal but also increased BCA2 protein levels, which correlated with AKT activation and could be curbed by an AMPK inhibitor, suggesting a potential feedback mechanism from pAMPKα1 to pAkt to BCA2. Finally, BCA2 siRNA, or inhibition of its upstream stabilizing kinase AKT, increased the growth inhibitory effect of metformin in multiple breast cancer cell lines, supporting the conclusion that BCA2 weakens metformin's efficacy. Our data suggest that metformin in combination with a BCA2 inhibitor may be a more effective breast cancer treatment strategy than metformin alone.

  7. Association of MTHFR gene polymorphisms with breast cancer survival

    International Nuclear Information System (INIS)

    Two functional single nucleotide polymorphisms (SNPs) in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, lead to decreased enzyme activity and affect chemosensitivity of tumor cells. We investigated whether these MTHFR SNPs were associated with breast cancer survival in African-American and Caucasian women. African-American (n = 143) and Caucasian (n = 105) women, who had incident breast cancer with surgery, were recruited between 1993 and 2003 from the greater Baltimore area, Maryland, USA. Kaplan-Meier survival and multivariate Cox proportional hazards regression analyses were used to examine the relationship between MTHFR SNPs and disease-specific survival. We observed opposite effects of the MTHFR polymorphisms A1298C and C677T on breast cancer survival. Carriers of the variant allele at codon 1298 (A/C or C/C) had reduced survival when compared to homozygous carriers of the common A allele [Hazard ratio (HR) = 2.05; 95% confidence interval (CI), 1.05–4.00]. In contrast, breast cancer patients with the variant allele at codon 677 (C/T or T/T) had improved survival, albeit not statistically significant, when compared to individuals with the common C/C genotype (HR = 0.65; 95% CI, 0.31–1.35). The effects were stronger in patients with estrogen receptor-negative tumors (HR = 2.70; 95% CI, 1.17–6.23 for A/C or C/C versus A/A at codon 1298; HR = 0.36; 95% CI, 0.12–1.04 for C/T or T/T versus C/C at codon 677). Interactions between the two MTHFR genotypes and race/ethnicity on breast cancer survival were also observed (A1298C, pinteraction = 0.088; C677T, pinteraction = 0.026). We found that the MTHFR SNPs, C677T and A1298C, were associated with breast cancer survival. The variant alleles had opposite effects on disease outcome in the study population. Race/ethnicity modified the association between the two SNPs and breast cancer survival

  8. Genetic Polymorphisms Associated With Breast Cancer in Malaysian Cohort

    OpenAIRE

    Chahil, Jagdish Kaur; Munretnam, Khamsigan; Samsudin, Nurulhafizah; Lye, Say Hean; Hashim, Nikman Adli Nor; Ramzi, Nurul Hanis; Velapasamy, Sharmila; Wee, Ler Lian; Alex, Livy

    2014-01-01

    Genome-wide association studies have discovered multiple single nucleotide polymorphisms (SNPs) associated with the risk of common diseases. The objective of this study was to demonstrate the replication of previously published SNPs that showed statistical significance for breast cancer in the Malaysian population. In this case–control study, 80 subjects for each group were recruited from various hospitals in Malaysia. A total of 768 SNPs were genotyped and analyzed to distinguish risk and pr...

  9. Breast Cancer Rates by State

    Science.gov (United States)

    ... Associated Lung Ovarian Prostate Skin Uterine Cancer Home Breast Cancer Rates by State Language: English Español (Spanish) Recommend ... from breast cancer each year. Rates of Getting Breast Cancer by State The number of people who get ...

  10. An Integrative Genomics Approach for Associating GWAS Information with Triple-Negative Breast Cancer

    OpenAIRE

    Chindo Hicks; Ranjit Kumar; Antonio Pannuti; Kandis Backus; Alexandra Brown; Jesus Monico; Lucio Miele

    2013-01-01

    Genome-wide association studies (GWAS) have identified genetic variants associated with an increased risk of developing breast cancer. However, the association of genetic variants and their associated genes with the most aggressive subset of breast cancer, the triple-negative breast cancer (TNBC), remains a central puzzle in molecular epidemiology. The objective of this study was to determine whether genes containing single nucleotide polymorphisms (SNPs) associated with an increased risk of ...

  11. Breast Cancer

    Science.gov (United States)

    ... I found something when I did my breast self-exam. What should I do now? How often should I have mammograms? I have breast cancer. What are my treatment options? How often should I do breast self-exams? I have breast cancer. Is my daughter ...

  12. Estrogen receptor positive breast cancers and their association with environmental factors

    Directory of Open Access Journals (Sweden)

    Mannel Sylvio

    2011-05-01

    Full Text Available Abstract Background Epidemiological studies to assess risk factors for breast cancer often do not differentiate between different types of breast cancers. We applied a general linear model to determine whether data from the Surveillance, Epidemiology, and End Results Program on annual county level age-adjusted incidence rates of breast cancer with and without estrogen receptors (ER+ and ER- were associated with environmental pollutants. Results Our final model explained approximately 38% of the variation in the rate of ER+ breast cancer. In contrast, we were only able to explain 14% of the variation in the rate of ER- breast cancer with the same set of environmental variables. Only ER+ breast cancers were positively associated with the EPA's estimated risk of cancer based on toxic air emissions and the proportion of agricultural land in a county. Meteorological variables, including short wave radiation, temperature, precipitation, and water vapor pressure, were also significantly associated with the rate of ER+ breast cancer, after controlling for age, race, premature mortality from heart disease, and unemployment rate. Conclusions Our findings were consistent with what we expected, given the fact that many of the commonly used pesticides and air pollutants included in the EPA cancer risk score are classified as endocrine disruptors and ER+ breast cancers respond more strongly to estrogen than ER- breast cancers. The findings of this study suggest that ER+ and ER- breast cancers have different risk factors, which should be taken into consideration in future studies that seek to understand environmental risk factors for breast cancer.

  13. Synchronous bilateral breast cancer in a male

    OpenAIRE

    Rubio Hernández, María Caridad; Díaz Prado, Yenia Ivet; Pérez, Suanly Rodríguez; Díaz, Ronald Rodríguez; Aleaga, Zaili Gutiérrez

    2013-01-01

    Male breast cancer, which represents only 1% of all breast cancers, is occasionally associated with a family history of breast cancer. Sporadic male breast cancers presenting with another primary breast cancer are extremely rare. In this article, we report on a 70-year-old male patient with bilateral multifocal and synchronous breast cancer and without a family history of breast cancer.

  14. 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. ...

  15. Breast Cancer Screening

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Screening (PDQ®)–Patient Version What is screening? Screening ... cancer screening: Cancer Screening Overview General Information About Breast Cancer Key Points Breast cancer is a disease in ...

  16. Large-scale genotyping identifies 41 new loci associated with breast cancer risk

    DEFF Research Database (Denmark)

    Michailidou, Kyriaki; Hall, Per; Gonzalez-Neira, Anna;

    2013-01-01

    Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10...

  17. Genome-wide association analysis identifies three new breast cancer susceptibility loci

    DEFF Research Database (Denmark)

    Ghoussaini, Maya; Fletcher, Olivia; Michailidou, Kyriaki;

    2012-01-01

    Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for ∼8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in ...

  18. ANALYSES ON DIFFERENTIALLY EXPRESSED GENES ASSOCIATED WITH HUMAN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    MENG Xu-li; DING Xiao-wen; XU Xiao-hong

    2006-01-01

    Objective: To investigate the molecular etiology of breast cancer by way of studying the differential expression and initial function of the related genes in the occurrence and development of breast cancer. Methods: Two hundred and eighty-eight human tumor related genes were chosen for preparation of the oligochips probe. mRNA was extracted from 16 breast cancer tissues and the corresponding normal breast tissues, and cDNA probe was prepared through reverse-transcription and hybridized with the gene chip. A laser focused fluorescent scanner was used to scan the chip. The different gene expressions were thereafter automatically compared and analyzed between the two sample groups. Cy3/Cy5>3.5 meant significant up-regulation. Cy3/Cy5<0.25 meant significant down-regulation. Results: The comparison between the breast cancer tissues and their corresponding normal tissues showed that 84 genes had differential expression in the Chip. Among the differently expressed genes, there were 4 genes with significant down-regulation and 6 with significant up-regulation. Compared with normal breast tissues, differentially expressed genes did partially exist in the breast cancer tissues. Conclusion: Changes in multi-gene expression regulations take place during the occurrence and development of breast cancer; and the research on related genes can help understanding the mechanism of tumor occurrence.

  19. Association of FTO Mutations with Risk and Survival of Breast Cancer in a Chinese Population

    OpenAIRE

    Xianxu Zeng; Zhenying Ban; Jing Cao; Wei Zhang; Tianjiao Chu; Dongmei Lei; Yanmin Du

    2015-01-01

    Recently, several studies have reported associations between fat mass and obesity-associated (FTO) gene mutations and cancer susceptibility. But little is known about their association with risk and survival of breast cancer in Chinese population. The aim of this study is to examine whether cancer-related FTO polymorphisms are associated with risk and survival of breast cancer and BMI levels in controls in a Chinese population. We genotyped six FTO polymorphisms in a case-control study, inclu...

  20. Common genetic variation in adiponectin, leptin, and leptin receptor and association with breast cancer subtypes

    OpenAIRE

    Nyante, Sarah J.; Gammon, Marilie D.; Jay S. Kaufman; Bensen, Jeannette T.; Lin, Dan Yu; Barnholtz-Sloan, Jill S.; Hu, Yijuan; He, Qianchuan; Luo, Jingchun; Millikan, Robert C.

    2011-01-01

    Adipocytokines are produced by visceral fat, and levels may be associated with breast cancer risk. We investigated whether single nucleotide polymorphisms (SNPs) in adipocytokine genes adiponectin (ADIPOQ), leptin (LEP), and the leptin receptor (LEPR) were associated with basal-like or luminal A breast cancer subtypes. 104 candidate and tag SNPs were genotyped in 1776 of 2022 controls and 1972 (200 basal-like, 679 luminal A) of 2311 cases from the Carolina Breast Cancer Study (CBCS), a popula...

  1. Morbidity associated with breast cancer therapy and the place of physiotherapy in its management

    OpenAIRE

    Rodica Păcurar; Codruţa Miclăuş; Marius Miclăuş

    2011-01-01

    Incidence of breast cancer continues to grow while modern diagnosis and treatment techniques improve long-term survival rates of the patients. Hence, more women will experience morbidity associated to breast cancer treatment. The aim of this article is to provide a review of the morbidity associated with breast cancer treatment and to emphasize the role of physiotherapist within the rehabilitation team. Pain, pectoralis tightness and axillary web syndrome are the most frequently encountered s...

  2. Breast cancer

    Science.gov (United States)

    ... perform breast self-exams each month. However, the importance of self-exams for detecting breast cancer is ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  3. FACTORS ASSOCIATED IN BREAST CANCER MORTALITY IN NORTHWEST PARANAENSE

    Directory of Open Access Journals (Sweden)

    Willian Augusto Melo

    2012-12-01

    Full Text Available Cancer is a disease process that begins when an abnormal cell is transformed by genetic mutation of cellular DNA, and breast cancer usually painless. The objective was to analyze the behavior of mortality from breast cancer in women living in Maringá-PR in the period 2000 to 2009. We used the Information System of the Unified Health System (DATASUS for variables related to race/ethnicity, marital status, education, age, place of occurrence of death. Data were analyzed descriptively and by chi-square Yates Fixed considering a confidence interval of 95% with a significance level of 5%. There were 216 deaths from breast cancer with a higher prevalence in women 60-80 years (58.4%, race white (90.2% and married (53.8%. Women over 60 with low education were more likely to breast cancer mortality was statistically significant (OR95% = 4.45, p = <0.0001

  4. Screening a Novel Human Breast Cancer-Associated Antigen from a cDNA Expression Library of Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Shuhua Yang; Lin Zhang; Ruifang Niu; Defa Wang; Yurong Shi; Xiyin Wei; Yi Yang

    2005-01-01

    OBJECTIVE The aim of this research was to clone and express the antigen of the previously prepared monoclonal antibody named M4G3.METHODS Western blots were used to screen a breast cancer cell line that overexpresses the M4G3-associated antigen. A λ zap cDNA expression library of breast cancer cells was constructed and screened using M4G3 as a probe to clone the antigen. The positive clones were subcloned and identified by homologous comparison using BLAST.RESULTS The λ zap cDNA expression library had 1.0x106 independent clones. Fifteen positive clones were isolated following 3 rounds of immunoscreening and identified as being from Mycoplasma pulmonis.CONCLUSION The specific antigen that matched the monoclonal M4G3 antibody is an unknown protein of M. pulmonis. This work is helpful for the further study of the association of M. pulmonis infection with breast cancer.

  5. Breast cancer risk associated with different HRT formulations: a register-based case-control study

    OpenAIRE

    Thai Do; Möhner Sabine; Heinemann Lothar AJ; Dinger Juergen C; Assmann Anita

    2006-01-01

    Abstract Background Previous epidemiological studies have inconsistently shown a modestly increased breast cancer risk associated with hormone replacement therapy (HRT). Limited information is available about different formulations – particularly concerning different progestins. Methods A case-control study was performed within Germany in collaboration with regional cancer registries and tumor centers. Up to 5 controls were matched breast cancer cases. Conditional logistic regression analysis...

  6. Mesothelin expression is associated with poor outcomes in breast cancer

    Science.gov (United States)

    Li, Yun R.; Xian, Rena R.; Ziober, Amy; Conejo-Garcia, Jose; Perales-Puchalt, Alfredo; June, Carl H.; Zhang, Paul J.; Tchou, Julia

    2014-01-01

    Background Mesothelin, previously shown to be expressed in triple negative breast cancer (TNBC), is a potential therapeutic target and prognostic marker in breast cancer. Methods We analyzed clinical data from two cohorts comprising of 141 patients treated between 2009 and 2011 at our institution (discovery cohort) and 844 patients from The Cancer Genome Atlas (TCGA) (validation cohort). Mesothelin expression was quantified by immunohistochemistry (IHC) or by RNA transcript levels as measured by whole-transcriptome sequencing in the discovery and validation cohorts respectively. Results In the discovery cohort, the median follow up was 3.55 years. Univariate analyses demonstrated that tumor size (hazard ratio (HR) =1.30, 95% confidence interval (CI) 1.11–1.51), positive (+) axillary lymph nodes (HR=3.34; 95% CI 1.51–7.39), and mesothelin expression (HR = 2.03; 95% CI 1.10–3.74) were associated with overall and disease-specific survival. We used a Cox-proportional hazard (Cox-PH) model to adjust for the two independent predictors of survival, namely (+) axilla lymph nodes and tumor size, and we found a significant association between mesothelin expression and overall and disease-specific survival in the discovery cohort (HR = 3.06, 95% CI 1.40–6.68). Using the TCGA dataset, we confirmed that, over a median follow-up of 16.0 months, patients with mesothelin-expressing tumors had poorer overall survival (HR=1.46; 95% CI 1.05–2.03). On Cox-PH multivariate analysis, mesothelin-positivity was an independent predictor of worse survival, after adjusting for (+) axillary lymph nodes and tumor size (HR = 1.69; 95%CI 1.17–2.42). Conclusions Our results suggest that mesothelin is a prognostic breast tumor marker whose expression is highly enriched in TNBC tumors, especially in African American women. As there is no existing targeted therapy for TNBC, mesothelin may be a promising drug target for TNBC. Future work is needed to evaluate the efficacy of mesothelin

  7. FGFR2 intronic SNPs and breast cancer risk; associations with tumor characteristics and interactions with exogenous exposures and other known breast cancer risk factors

    OpenAIRE

    Marian, Catalin; Ochs-Balcom, Heather M; Nie, Jing; Kallakury, Bhaskar V.; Ambrosone, Christine B; Trevisan, Maurizio; Edge, Stephen; Shields, Peter G.; Freudenheim, Jo L.

    2010-01-01

    Recent genome-wide association studies have revealed several new candidate genes for breast cancer, including FGFR2. The associations were also replicated in several other independent studies. The next important step is to study whether these common variants interact with known breast cancer risk factors, exogenous exposures, and tumor characteristics. In a population-based case-control study of 1170 breast cancer cases and 2115 controls, we examined genetic associations of four intronic FGFR...

  8. Gene expression analysis in human breast cancer associated blood vessels.

    Directory of Open Access Journals (Sweden)

    Dylan T Jones

    Full Text Available Angiogenesis is essential for solid tumour growth, whilst the molecular profiles of tumour blood vessels have been reported to be different between cancer types. Although presently available anti-angiogenic strategies are providing some promise for the treatment of some cancers it is perhaps not surprisingly that, none of the anti-angiogenic agents available work on all tumours. Thus, the discovery of novel anti-angiogenic targets, relevant to individual cancer types, is required. Using Affymetrix microarray analysis of laser-captured, CD31-positive blood vessels we have identified 63 genes that are upregulated significantly (5-72 fold in angiogenic blood vessels associated with human invasive ductal carcinoma (IDC of the breast as compared with blood vessels in normal human breast. We tested the angiogenic capacity of a subset of these genes. Genes were selected based on either their known cellular functions, their enriched expression in endothelial cells and/or their sensitivity to anti-VEGF treatment; all features implicating their involvement in angiogenesis. For example, RRM2, a ribonucleotide reductase involved in DNA synthesis, was upregulated 32-fold in IDC-associated blood vessels; ATF1, a nuclear activating transcription factor involved in cellular growth and survival was upregulated 23-fold in IDC-associated blood vessels and HEX-B, a hexosaminidase involved in the breakdown of GM2 gangliosides, was upregulated 8-fold in IDC-associated blood vessels. Furthermore, in silico analysis confirmed that AFT1 and HEX-B also were enriched in endothelial cells when compared with non-endothelial cells. None of these genes have been reported previously to be involved in neovascularisation. However, our data establish that siRNA depletion of Rrm2, Atf1 or Hex-B had significant anti-angiogenic effects in VEGF-stimulated ex vivo mouse aortic ring assays. Overall, our results provide proof-of-principle that our approach can identify a cohort of

  9. Identifying association model for single-nucleotide polymorphisms of ORAI1 gene for breast cancer

    OpenAIRE

    Chang, Wei-Chiao; Fang, Yong-Yuan; Chang, Hsueh-Wei; Chuang, Li-Yeh; Lin, Yu-Da; Hou, Ming-Feng; Yang, Cheng-Hong

    2014-01-01

    Background ORAI1 channels play an important role for breast cancer progression and metastasis. Previous studies indicated the strong correlation between breast cancer and individual single nucleotide polymorphisms (SNPs) of ORAI1 gene. However, the possible SNP-SNP interaction of ORAI1 gene was not investigated. Results To develop the complex analyses of SNP-SNP interaction, we propose a genetic algorithm (GA) to detect the model of breast cancer association between five SNPs (rs12320939, rs1...

  10. Genetic Variation in Cell Cycle Regulatory Gene AURKA and Association With Intrinsic Breast Cancer Subtype

    OpenAIRE

    Taylor, Nicholas J.; Bensen, Jeannette T.; Poole, Charles; Troester, Melissa A.; Gammon, Marilie D.; Luo, Jingchun; Millikan, Robert C.; Olshan, Andrew F.

    2014-01-01

    AURKA is a putative low-penetrance tumor susceptibility gene due to its prominent role in cell cycle regulation and centrosomal function. Germline variation in AURKA was evaluated for association with breast cancer and intrinsic breast cancer subtypes in the Carolina Breast Cancer Study (CBCS), a population-based case-control study of African Americans (AA) and Caucasians (Cau). Tag and candidate single nucleotide polymorphisms (SNPs) on AURKA were genotyped in 1946 cases and 1747 controls. I...

  11. The association between LEPR Q223R polymorphisms and breast cancer risk.

    Science.gov (United States)

    Wang, Yadong; Yang, Haiyan; Gao, Huiyan; Wang, Haiyu

    2015-05-01

    Recently, we have read with great interest the article entitled "The association between polymorphisms in the leptin receptor (LEPR) gene and risk of breast cancer: a systematic review and pooled analysis" published online by Wang et al. (Breast Cancer Res Treat 136:231-239, 2012). This article suggests that the A allele of LEPR gene rs1137101 variant was low-penetrant risk factor for developing breast cancer. The result is encouraging. Nevertheless, several key issues are worth noticing. PMID:25863476

  12. Inflammatory breast cancer: high incidence of detection of mixed human cytomegalovirus genotypes associated with disease pathogenesis

    OpenAIRE

    MonaMostafaMohamed; MohamedEl-Shinawi; M.AkramNouh; RobertJ.Schneider; ElsayedTarekElsayed

    2014-01-01

    Inflammatory breast cancer (IBC) is highly metastatic, aggressive and fatal form of breast cancer. Patients presenting with IBC are characterized by a high number of axillary lymph node metastases. Recently, we found that IBC carcinoma tissues contain significantly higher levels of human cytomegalovirus (HCMV) DNA compared to other breast cancer tissues, that may regulate cell signaling pathways. In fact, HCMV pathogenesis and clinical outcome can be statistically associated with multiple HCM...

  13. Inflammatory Breast Cancer: High Incidence of Detection of Mixed Human Cytomegalovirus Genotypes Associated with Disease Pathogenesis

    OpenAIRE

    Mohamed, Hossam Taha; El-Shinawi, Mohamed; Nouh, M. Akram; Bashtar, Abdel-Rahman; Elsayed, Elsayed Tarek; Schneider, Robert J.; Mohamed, Mona Mostafa

    2014-01-01

    Inflammatory breast cancer (IBC) is a highly metastatic, aggressive, and fatal form of breast cancer. Patients presenting with IBC are characterized by a high number of axillary lymph node metastases. Recently, we found that IBC carcinoma tissues contain significantly higher levels of human cytomegalovirus (HCMV) DNA compared to other breast cancer tissues that may regulate cell signaling pathways. In fact, HCMV pathogenesis and clinical outcome can be statistically associated with multiple H...

  14. Factors associated with the prescription of antidepressive medication to breast cancer patients

    DEFF Research Database (Denmark)

    Suppli, Nis P; Deltour, Isabelle; Damkjaer, Lars H;

    2011-01-01

    We evaluated factors associated with use of antidepressant medication subsequent to a diagnosis of breast cancer. We also evaluated the effect of participation in a cancer rehabilitation program on use of antidepressants.......We evaluated factors associated with use of antidepressant medication subsequent to a diagnosis of breast cancer. We also evaluated the effect of participation in a cancer rehabilitation program on use of antidepressants....

  15. Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers

    DEFF Research Database (Denmark)

    Antoniou, Antonis C; Spurdle, Amanda B; Sinilnikova, Olga M;

    2008-01-01

    Germline mutations in BRCA1 and BRCA2 confer high risks of breast cancer. However, evidence suggests that these risks are modified by other genetic or environmental factors that cluster in families. A recent genome-wide association study has shown that common alleles at single nucleotide...... polymorphisms (SNPs) in FGFR2 (rs2981582), TNRC9 (rs3803662), and MAP3K1 (rs889312) are associated with increased breast cancer risks in the general population. To investigate whether these loci are also associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers, we genotyped these SNPs in a sample...... of 10,358 mutation carriers from 23 studies. The minor alleles of SNP rs2981582 and rs889312 were each associated with increased breast cancer risk in BRCA2 mutation carriers (per-allele hazard ratio [HR] = 1.32, 95% CI: 1.20-1.45, p(trend) = 1.7 x 10(-8) and HR = 1.12, 95% CI: 1.02-1.24, p(trend) = 0...

  16. Breast Cancer Treatment

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Treatment (PDQ®)–Patient Version General Information About Breast Cancer Go to Health Professional Version Key Points Breast ...

  17. Stages of Breast Cancer

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Treatment (PDQ®)–Patient Version General Information About Breast Cancer Go to Health Professional Version Key Points Breast ...

  18. 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...

  19. Association of Breast Cancer Susceptibility Variants with Risk of Pancreatic Cancer

    Science.gov (United States)

    Couch, Fergus J.; Wang, Xianshu; McWilliams, Robert R.; Bamlet, William R.; de Andrade, Mariza; Petersen, Gloria M.

    2011-01-01

    Background A number of susceptibility genes are common to breast and pancreatic cancer. Recently, several breast cancer susceptibility loci have been identified through genome-wide association studies. Here we evaluated possible associations between these single nucleotide polymorphisms (SNPs) and pancreatic cancer risk. Methods Ten SNPs from FGFR2, TOX3, MAP3K1, H19, LSP1, chromosome 8q24, CASP8 and LUM were investigated for associations with pancreatic cancer risk following genotyping in 1143 caucasian individuals with pancreatic adenocarcinoma and 1097 unaffected controls from a clinic-based pancreatic cancer case-control study. Results CASP8 rs1045485 (Odds ratio (OR)= 0.78; 95% confidence interval (95%CI), 0.65-0.9; p=0.005) and MAP3K1 rs889312 (OR= 0.85; 95%CI, 0.74-0.97; p=0.017)) showed evidence of association with risk of pancreatic cancer. The CASP8 rs1045485 association was evident in ever-smokers (p=0.002), but not in non-smokers (p=0.55), and the effect was strongest in heavy smokers (OR, 0.52; 95% CI, 0.29- 0.93; p=0.03). In contrast the MAP3K1 rs889312 association was only evident in non-smokers (OR, 0.78; 95%CI, 0.64-0.95; p=0.01). In addition, evaluation of the influence of the ten SNPs on survival detected significant associations between outcome for locally advanced pancreatic cancer cases and both 8q rs6983561 (p=0.045) and LUM rs2268578 (p=0.02). Conclusion Association studies in a large pancreatic case-control study indicates that SNPs associated with breast cancer may also be associated with pancreatic cancer susceptibility and survival. PMID:19843670

  20. 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.; Ramus, S.J.; Kjaer, S.K.; DiCioccio, R.A.; Wozniak, E.; Whittemore, A.S.; McGuire, V.; Ponder, B.A.; Turnbull, C.; Hines, S.; Rahman, N.; Eeles, R.A.; Easton, D.F.; Gayther, S.A.; Dunning, A.M.; Pharoah, P.D.; Høgdall, Estrid Vilma Solyom

    2008-01-01

    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...... cancer [per minor allele OR, 1.19; 95% confidence interval (95% CI), 1.04-1.37; P(trend) = 0.012]. This association was stronger for the serous histologic subtype (OR, 1.29; 95% CI, 1.09-1.53; P = 0.003). SNP rs7931342 (chromosome 11q13) showed some evidence of association with breast cancer (per minor...

  1. Breast cancer

    International Nuclear Information System (INIS)

    More than 20-year follow-up of A-bomb survivors in Hiroshima and Nagasaki has a crucial role in determining the relationship of radiation to the occurrence of breast cancer. In 1967, Wanebo et al have first reported 27 cases of breast cancer during the period 1950-1966 among the Adult Health Study population of A-bomb survivors. Since then, follow-up surveys for breast cancer have been made using the Life Span Study (LSS) cohort, and the incidence of breast cancer has increased year by year; that is breast cancer was identified in 231 cases by the first LSS series (1950-1969), 360 cases by the second LSS series (1950-1974), 564 cases by the third LSS series (1950-1980), and 816 cases in the fourth LSS series (1950-1085). The third LSS series have revealed a high risk for radiation-induced breast cancer in women aged 10 or less at the time of exposure (ATE). Both relative and absolute risks are found to be decreased with increasing ages ATE. Based on the above-mentioned findings and other studies on persons exposed medical radiation, radiation-induced breast cancer is characterized by the following: (1) the incidence of breast cancer is linearly increased with increasing radiation doses; (2) both relative and absolute risks for breast cancer are high in younger persons ATE; (3) age distribution of breast cancer in proximally exposed A-bomb survivors is the same as that in both distally A-bomb survivors and non-exposed persons, and there is no difference in histology between the former and latter groups. Thus, immature mammary gland cells before the age of puberty are found to be most radiosensitive. (N.K.)

  2. Association of single nucleotide polymorphisms in Wnt signaling pathway genes with breast cancer in Saudi patients.

    Directory of Open Access Journals (Sweden)

    Mohammad Saud Alanazi

    Full Text Available Breast cancer is a complex heterogeneous disease involving genetic and epigenetic alterations in genes encoding proteins that are components of various signaling pathways. Candidate gene approach have identified association of genetic variants in the Wnt signaling pathway genes and increased susceptibility to several diseases including breast cancer. Due to the rarity of somatic mutations in key genes of Wnt pathway, we investigated the association of genetic variants in these genes with predisposition to breast cancers. We performed a case-control study to identify risk variants by examining 15 SNPs located in 8 genes associated with Wnt signaling. Genotypic analysis of individual locus showed statistically significant association of five SNPs located in β-catenin, AXIN2, DKK3, SFRP3 and TCF7L2 with breast cancers. Increased risk was observed only with the SNP in β-catenin while the other four SNPs conferred protection against breast cancers. Majority of these associations persisted after stratification of the cases based on estrogen receptor status and age of on-set of breast cancer. The rs7775 SNP in exon 6 of SFRP3 gene that codes for either arginine or glycine exhibited very strong association with breast cancer, even after Bonferroni's correction. Apart from these five variants, rs3923086 in AXIN2 and rs3763511 in DKK4 that did not show any association in the overall population were significantly associated with early on-set and estrogen receptor negative breast cancers, respectively. This is the first study to utilize pathway based approach to identify association of risk variants in the Wnt signaling pathway genes with breast cancers. Confirmation of our findings in larger populations of different ethnicities would provide evidence for the role of Wnt pathway as well as screening markers for early detection of breast carcinomas.

  3. Genome-wide association study identifies a common variant in RAD51B associated with male breast cancer risk

    DEFF Research Database (Denmark)

    Orr, Nick; Lemnrau, Alina; Cooke, Rosie;

    2012-01-01

    We conducted a genome-wide association study of male breast cancer comprising 823 cases and 2,795 controls of European ancestry, with validation in independent sample sets totaling 438 cases and 474 controls. A SNP in RAD51B at 14q24.1 was significantly associated with male breast cancer risk (P ...

  4. A case control study of risk factors associated with female breast cancer

    International Nuclear Information System (INIS)

    To find the association of various risk factors with breast cancer. Study Design: It was a case-control study. Place and Duration of Study: The study was carried out in NORI Hospital Islamabad and Combined Military Hospital Rawalpindi between August, 2013 and February, 2014. Material and Methods: Two hundred breast cancer patients and 200 control subjects were inducted. A short approved and planned questionnaire was used to collect data regarding basic demographic, menstrual and reproductive characteristics of participating females. Cases and controls were then interviewed after taking written consent. Results: Breast cancer patients and control subjects did not differ regarding age (p = 0.15), early menarche (OR for menarche at <13 years vs. ?13=1.3, 95% CI = 0.84 - 2.02), and history of breast cancer in 1st degree relatives did not increase breast cancer risk (OR = 1.0, 95% CI = 0.57 - 1.74). Nulliparous women had significantly higher risk than parous women (OR = 2.43, 95% CI = 1.22 - 4.84) and women with late menopause compared to women with early onset of menopause were also at higher risk for breast cancer (OR for menopause at ? 50 vs. < 50 = 5.16, 95% CI = 2.59 - 10.29). Conclusion: Nulliparity and menopausal age of more than 50 years was associated with increased breast cancer risk. Breast feeding and age less than 25 years at first live birth was not protective against breast cancer. (author)

  5. Breast Cancer: Treatment Options

    Science.gov (United States)

    ... Breast Cancer > Breast Cancer - Treatment Options Request Permissions Breast Cancer - Treatment Options Approved by the Cancer.Net Editorial ... recommendations for ovarian ablation . Hormonal therapy for metastatic breast cancer Hormonal therapies are also commonly used to treat ...

  6. Consumption of coffee, but not black tea, is associated with decreased risk of premenopausal breast cancer.

    Science.gov (United States)

    Baker, Julie A; Beehler, Gregory P; Sawant, Abhishek C; Jayaprakash, Vijayvel; McCann, Susan E; Moysich, Kirsten B

    2006-01-01

    Caffeine has been suggested as a possible risk factor for breast cancer, potentially through its effect of facilitating the development of benign breast disease. However, coffee and tea also contain polyphenols, which exhibit anticarcinogenic properties. A hospital-based, case-control study was conducted to evaluate the role of coffee, decaffeinated coffee, and black tea in breast cancer etiology. Study participants included 1932 cases with primary, incident breast cancer and 1895 hospital controls with nonneoplastic conditions. All participants completed a comprehensive epidemiological questionnaire. Among premenopausal women, consumption of regular coffee was associated with linear declines in breast cancer risk (P for trend = 0.03); consumers of >or=4 cups/d experienced a 40% risk reduction (odds ratio = 0.62, 95% CI 0.39-0.98). No clear associations between intake of black tea or decaffeinated coffee and breast cancer risk were noted among premenopausal women, although black tea was associated with a protective effect unique to a subsample of cases with lobular histology. Among postmenopausal women, breast cancer risk was not associated with consumption of coffee, tea, or decaffeinated coffee. Results among postmenopausal women did not differ by histologic subtype. Our findings support a protective effect of coffee intake on premenopausal, but not postmenopausal breast cancer risk. Further studies are warranted to confirm these findings. PMID:16365077

  7. Low ERK phosphorylation in cancer-associated fibroblasts is associated with tamoxifen resistance in pre-menopausal breast cancer.

    Directory of Open Access Journals (Sweden)

    Susann Busch

    Full Text Available PURPOSE: The aim of this study was to evaluate ERK phosphorylation as a stromal biomarker for breast cancer prognosis and tamoxifen treatment prediction within a randomized tamoxifen trial. PATIENTS AND METHODS: Tissue microarrays of two breast cancer cohorts including in total 743 invasive breast cancer samples were analyzed for ERK phosphorylation (pERK and smooth muscle actin-alpha expression (SMAα in cancer-associated fibroblasts (CAFs and links to clinico-pathological data and treatment-predictive values were delineated. RESULTS: By analyzing a unique randomized tamoxifen trial including breast cancer patients receiving no adjuvant treatment we show for the first time that patients low in ERK phosphorylation in CAFs did not respond to tamoxifen treatment despite having estrogen-receptor alpha (ERα-positive tumors compared to patients with high pERK levels in CAFs (P = 0.015, multivariate Cox regression interaction analysis. In both clinical materials we further show a significant association between pERK and SMAα, a characteristic marker for activated fibroblasts. SMAα expression however was not linked to treatment-predictive information but instead had prognostic qualities. CONCLUSION: The data suggests that the presence of a subpopulation of CAFs, defined by minimal activated ERK signaling, is linked to an impaired tamoxifen response. Thus, this report illustrates the importance of the stroma for monitoring treatment effects in pre-menopausal breast cancer.

  8. Identification of a DMBT1 polymorphism associated with increased breast cancer risk and decreased promoter activity

    DEFF Research Database (Denmark)

    Tchatchou, Sandrine; Riedel, Angela; Lyer, Stefan;

    2010-01-01

    According to present estimations, the unfavorable combination of alleles with low penetrance but high prevalence in the population might account for the major part of hereditary breast cancer risk. Deleted in Malignant Brain Tumors 1 (DMBT1) has been proposed as a tumor suppressor for breast cancer......,466 unrelated German controls. Promoter studies in breast cancer cells demonstrate that the risk-increasing DMBT1 -93T allele displays significantly decreased promoter activity compared to the DMBT1 -93C allele, resulting in a loss of promoter activity. The data suggest that DMBT1 polymorphisms in the 5'-region...... and other cancer types. Genomewide mapping in mice further identified Dmbt1 as a potential modulator of breast cancer risk. Here, we report the association of two frequent and linked single-nucleotide polymorphisms (SNPs) with increased breast cancer risk in women above the age of 60 years: DMBT1 c...

  9. Genome-wide association study of susceptibility loci for breast cancer in Sardinian population

    International Nuclear Information System (INIS)

    Despite progress in identifying genes associated with breast cancer, many more risk loci exist. Genome-wide association analyses in genetically-homogeneous populations, such as that of Sardinia (Italy), could represent an additional approach to detect low penetrance alleles. We performed a genome-wide association study comparing 1431 Sardinian patients with non-familial, BRCA1/2-mutation-negative breast cancer to 2171 healthy Sardinian blood donors. DNA was genotyped using GeneChip Human Mapping 500 K Arrays or Genome-Wide Human SNP Arrays 6.0. To increase genomic coverage, genotypes of additional SNPs were imputed using data from HapMap Phase II. After quality control filtering of genotype data, 1367 cases (9 men) and 1658 controls (1156 men) were analyzed on a total of 2,067,645 SNPs. Overall, 33 genomic regions (67 candidate SNPs) were associated with breast cancer risk at the p < 10−6 level. Twenty of these regions contained defined genes, including one already associated with breast cancer risk: TOX3. With a lower threshold for preliminary significance to p < 10−5, we identified 11 additional SNPs in FGFR2, a well-established breast cancer-associated gene. Ten candidate SNPs were selected, excluding those already associated with breast cancer, for technical validation as well as replication in 1668 samples from the same population. Only SNP rs345299, located in intron 1 of VAV3, remained suggestively associated (p-value, 1.16x10−5), but it did not associate with breast cancer risk in pooled data from two large, mixed-population cohorts. This study indicated the role of TOX3 and FGFR2 as breast cancer susceptibility genes in BRCA1/2-wild-type breast cancer patients from Sardinian population. The online version of this article (doi:10.1186/s12885-015-1392-9) contains supplementary material, which is available to authorized users

  10. Common genetic variation in adiponectin, leptin, and leptin receptor and association with breast cancer subtypes.

    Science.gov (United States)

    Nyante, Sarah J; Gammon, Marilie D; Kaufman, Jay S; Bensen, Jeannette T; Lin, Dan Yu; Barnholtz-Sloan, Jill S; Hu, Yijuan; He, Qianchuan; Luo, Jingchun; Millikan, Robert C

    2011-09-01

    Adipocytokines are produced by visceral fat, and levels may be associated with breast cancer risk. We investigated whether single nucleotide polymorphisms (SNPs) in adipocytokine genes adiponectin (ADIPOQ), leptin (LEP), and the leptin receptor (LEPR) were associated with basal-like or luminal A breast cancer subtypes. 104 candidate and tag SNPs were genotyped in 1776 of 2022 controls and 1972 (200 basal-like, 679 luminal A) of 2311 cases from the Carolina Breast Cancer Study (CBCS), a population-based case-control study of whites and African Americans. Breast cancer molecular subtypes were determined by immunohistochemistry. Genotype odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. Haplotype ORs and 95% CIs were estimated using Hapstat. Interactions with waist-hip ratio were evaluated using a multiplicative interaction term. Ancestry was estimated from 144 ancestry informative markers (AIMs), and included in models to control for population stratification. Candidate SNPs LEPR K109R (rs1137100) and LEPR Q223R (rs1137101) were positively associated with luminal A breast cancer, whereas ADIPOQ +45 T/G (rs2241766), ADIPOQ +276 G/T (rs1501299), and LEPR K656N (rs8129183) were not associated with either subtype. Few patterns were observed among tag SNPs, with the exception of 3 LEPR SNPs (rs17412175, rs9436746, and rs9436748) that were in moderate LD and inversely associated with basal-like breast cancer. However, no SNP associations were statistically significant after adjustment for multiple comparisons. Haplotypes in LEP and LEPR were associated with both basal-like and luminal A subtypes. There was no evidence of interaction with waist-hip ratio. Data suggest associations between LEPR candidate SNPs and luminal A breast cancer in the CBCS and LEPR intron 2 tag SNPs and basal-like breast cancer. Replication in additional studies where breast cancer subtypes have been defined is necessary to confirm these

  11. Factors Associated With the Development of Breast Cancer-Related Lymphedema After Whole-Breast Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Shah, Chirag; Wilkinson, John Ben; Baschnagel, Andrew [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Ghilezan, Mihai [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); William Beaumont School of Medicine, Oakland University, Royal Oak, MI (United States); Riutta, Justin; Dekhne, Nayana; Balaraman, Savitha [Beaumont Cancer Institute, William Beaumont Hospital, Royal Oak, MI (United States); William Beaumont School of Medicine, Oakland University, Royal Oak, MI (United States); Mitchell, Christina; Wallace, Michelle [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Vicini, Frank, E-mail: fvicini@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI (United States); Beaumont Cancer Institute, William Beaumont Hospital, Royal Oak, MI (United States); William Beaumont School of Medicine, Oakland University, Royal Oak, MI (United States)

    2012-07-15

    Purpose: To determine the rates of breast cancer-related lymphedema (BCRL) in patients undergoing whole-breast irradiation as part of breast-conserving therapy (BCT) and to identify clinical, pathologic, and treatment factors associated with its development. Methods and Materials: A total of 1,861 patients with breast cancer were treated at William Beaumont Hospital with whole-breast irradiation as part of their BCT from January 1980 to February 2006, with 1,497 patients available for analysis. Determination of BCRL was based on clinical assessment. Differences in clinical, pathologic, and treatment characteristics between patients with BCRL and those without BCRL were evaluated, and the actuarial rates of BCRL by regional irradiation technique were determined. Results: The actuarial rate of any BCRL was 7.4% for the entire cohort and 9.9%, 14.7%, and 8.3% for patients receiving a supraclavicular field, posterior axillary boost, and internal mammary irradiation, respectively. BCRL was more likely to develop in patients with advanced nodal status (11.4% vs. 6.3%, p = 0.001), those who had a greater number of lymph nodes removed (14 nodes) (9.5% vs. 6.0%, p = 0.01), those who had extracapsular extension (13.4% vs. 6.9%, p = 0.009), those with Grade II/III disease (10.8% vs. 2.9%, p < 0.001), and those who received adjuvant chemotherapy (10.5% vs. 6.7%, p = 0.02). Regional irradiation showed small increases in the rates of BCRL (p = not significant). Conclusions: These results suggest that clinically detectable BCRL will develop after traditional BCT in up to 10% of patients. High-risk subgroups include patients with advanced nodal status, those with more nodes removed, and those who receive chemotherapy, with patients receiving regional irradiation showing a trend toward increased rates.

  12. Breast cancer-specific intrusions are associated with increased cortisol responses to daily life stressors in healthy women without personal or family histories of breast cancer.

    Science.gov (United States)

    Dettenborn, Lucia; James, Gary D; Valdimarsdottir, Heiddis B; Montgomery, Guy H; Bovbjerg, Dana H

    2006-10-01

    Studies indicate that women fear breast cancer more than any other disease and that women's levels of breast cancer-specific intrusions are related to their perceived risk of breast cancer. Here, we explore possible biological consequences of higher breast cancer risk perceptions and intrusions in healthy women without personal or family histories of the disease. We hypothesized that women with higher perceived risk would have more intrusions about breast cancer, which would constitute a background stressor sufficient to increase hypothalamus-pituitary-adrenal axis (HPA) responsivity to daily stress. HPA responses to an ordinary life stressor (work) were assessed in 141 employed women (age = 37.2+/-9.2) without personal or family histories of breast cancer. Urinary cortisol excretion rates were assessed with timed sample collections at work, home, and during sleep. Repeated measures ANOVA revealed a significant Group by Time interaction with higher work cortisol levels in women with breast cancer-specific intrusions compared to women without intrusions (p < 0.02). Regression analyses revealed a significant association between risk perceptions and intrusions (p < 0.001). Regression analysis with intrusions and risk perceptions predicting work cortisol indicated a significant contribution of intrusions (p < 0.04), but not risk perceptions (p = 0.53). Overestimation of breast cancer risk is associated with higher levels of breast cancer-specific intrusions that can result in increased cortisol responsivity to daily stressors. This heightened responsivity could have long-term negative health implications. PMID:16944305

  13. Breast cancer

    CERN Multimedia

    2002-01-01

    "Cancer specialists will soon be able to compare mammograms with computerized images of breast cancer from across Europe, in a bid to improve diagnosis and treatment....The new project, known as MammoGrid, brings together computer and medical imaging experts, cancer specialists, radiologists and epidemiologists from Bristol, Oxford, Cambridge, France and Italy" (1 page).

  14. Familial breast cancer.

    OpenAIRE

    Phipps, R. F.; Perry, P M

    1988-01-01

    Familial breast cancer is important because of all the known risk factors associated with developing the disease. The one with the most predictability is a positive family history. It is also important because a family history causes anxiety in the families concerned, and young women will often ask their chance of developing the disease. This form of breast cancer accounts for 10% of causes and has factors that distinguish it from the sporadic variety. Relatives of familial breast cancer pati...

  15. [The fertility-associated treatment of young breast cancer patients].

    Science.gov (United States)

    Lu, Y S; Wu, K J

    2016-01-01

    There is no treatment norm on the fertility issue of breast cancer patients. The clinical studies show that the effects of chemotherapy and endocrine treatment on menstrual cycle and ovarian function have connection with patients' age, therapeutic regimen and drug dose. The time to be pregnant should be decided according to the stage of tumor and the therapeutic regimen. The trimester of pregnancy and tumor stage should be considered when making the therapeutic regimen for the breast cancer patients during pregnancy. And it is not recommended to choose the induced abortion for the therapeutic aim. Theoretically, ovarian function inhibition drugs have great application prospects, while, of which the long-term affect on human body and the relation with tumor development need more researches to study. The available evidence-based practices consider that the pregnancy after breast cancer treatment has no adverse affects on the prognosis of early and middle stage breast cancer patients. More study results are needed to normalize and detail the therapeutic regimen and fertility guidance. PMID:26792357

  16. Breast Cancer

    Science.gov (United States)

    ... click the brackets in the lower right-hand corner of the video screen. To reduce the videos, ... with breast cancer are under way. With early detection, and prompt and appropriate treatment, the outlook for ...

  17. Breast cancer

    International Nuclear Information System (INIS)

    This article is about the diagnosis, treatment and monitoring of breast cancer. Positive diagnosis is based on clinical mammary exam, mammography, mammary ultrasonography, and histological study. Before the chemotherapy and radiotherapy treatment are evaluated the risks

  18. Surgery for Breast Cancer

    Science.gov (United States)

    ... Next Topic Breast-conserving surgery (lumpectomy) Surgery for breast cancer Most women with breast cancer have some type ... Relieve symptoms of advanced cancer Surgery to remove breast cancer There are two main types of surgery to ...

  19. Learning about Breast Cancer

    Science.gov (United States)

    ... genetic terms used on this page Learning About Breast Cancer What do we know about heredity and breast ... Cancer What do we know about heredity and breast cancer? Breast cancer is a common disease. Each year, ...

  20. Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the breast cancer association consortium: a combined case-control study

    DEFF Research Database (Denmark)

    Milne, Roger L; Gaudet, Mia M; Spurdle, Amanda B;

    2010-01-01

    Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating in the...... Breast Cancer Association Consortium....

  1. Rare BRCA1 haplotypes including 3′UTR SNPs associated with breast cancer risk

    OpenAIRE

    Pelletier, Cory; Speed, William C; Paranjape, Trupti; Keane, Katie; Blitzblau, Rachel; Hollestelle, Antoinette; Safavi, Kyan; Van Den Ouweland, Ans; Zelterman, Daniel; Slack, Frank J; Kidd, Kenneth K.; Weidhaas, Joanne B

    2011-01-01

    Genetic markers identifying women at an increased risk of developing breast cancer exist, yet the majority of inherited risk remains elusive. While numerous BRCA1 coding sequence mutations are associated with breast cancer risk, BRCA1 mutations account for less then 5% of breast cancer risk. Since 3′ untranslated region (3′UTR) polymorphisms disrupting microRNA (miRNA) binding can be functional and can act as genetic markers of cancer risk, we tested the hypothesis that such polymorphisms in ...

  2. 6 Common Cancers - Breast Cancer

    Science.gov (United States)

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Breast Cancer Past Issues / Spring 2007 Table of Contents For ... her down. Photo: AP Photo/Brett Flashnick Breast Cancer Breast cancer is a malignant (cancerous) growth that ...

  3. 6 Common Cancers - Breast Cancer

    Science.gov (United States)

    ... Home Current Issue Past Issues 6 Common Cancers - Breast Cancer Past Issues / Spring 2007 Table of Contents For ... slow her down. Photo: AP Photo/Brett Flashnick Breast Cancer Breast cancer is a malignant (cancerous) growth that ...

  4. Excessive milk production during breast-feeding prior to breast cancer diagnosis is associated with increased risk for early events.

    OpenAIRE

    Gustbée, Emma; Anesten, Charlotte; Markkula, Andrea; Simonsson, Maria; Rose, Carsten; Ingvar, Christian; Jernström, Helena

    2013-01-01

    Breast-feeding is a known protective factor against breast cancer. Breast-feeding duration is influenced by hormone levels, milk production, and lifestyle factors. The aims were to investigate how breast-feeding duration and milk production affected tumor characteristics and risk for early breast cancer events in primary breast cancer patients. Between 2002 and 2008, 634 breast cancer patients in Lund, Sweden, took part in an ongoing prospective cohort study. Data were extracted from question...

  5. Factors associated to persistence with hormonal therapy in women with breast cancer

    OpenAIRE

    Brito, Cláudia; Portela, Margareth Crisóstomo; Vasconcellos, Mauricio Teixeira Leite de

    2014-01-01

    OBJECTIVE To analyze factors associated with persistence to breast cancer hormone therapy in order to contribute to the quality of care improvement. METHODS Retrospective longitudinal study, based on secondary data. A cohort of 5,861 women with breast cancer registered in different datasets of the Brazilian National Cancer Institute and the Brazilian Unified Health System were analyzed. All women were treated at this hospital, which provides free medication, and the follow-up period was from ...

  6. The ‘Pokemon’ (ZBTB7) Gene: No Evidence of Association with Sporadic Breast Cancer

    OpenAIRE

    Antonio Salas; Ana Vega; Milne, Roger L.; Manuel García-Magariños; Álvaro Ruibal; Javier Benítez; Ángel Carracedo

    2008-01-01

    It has been proposed that the excess of familiar risk associated with breast cancer could be explained by the cumulative effect of multiple weakly predisposing alleles. The transcriptional repressor FBI1, also known as Pokemon, has recently been identified as a critical factor in oncogenesis. This protein is encoded by the ZBTB7 gene. Here we aimed to determine whether polymorphisms in ZBTB7 are associated with breast cancer risk in a sample of cases and controls collected in hospitals from N...

  7. Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis

    OpenAIRE

    Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

    2009-01-01

    Introduction Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite...

  8. Expression of eag1 channel associated with the aggressive clinicopathological features and subtype of breast cancer

    OpenAIRE

    Liu, Guang-Xu; Yu, Yun-Cui; He, Xiang-ping; Ren, Sheng-Nan; Fang, Xue-Dong; Liu, Fen; He, Yan

    2015-01-01

    Backgrounds: Expression of eag1 channel (Eag1) is associated with cell malignant transformation, tumor cell metastasis and poor prognosis of the patient. This study aimed at examining whether expression of the Eag1 associated with aggressive clinicopathological feature and the molecular subtype of breast cancer. Materials and Methods: 109 patients who received breast cancer operation during January 2009 to December 2010 in Chinese-Japanese Friendship Hospital of Jilin University were recruite...

  9. The associations between a polygenic score, reproductive and menstrual risk factors and breast cancer risk

    OpenAIRE

    Andersen, Shaneda Warren; Trentham-Dietz, Amy; Gangnon, Ronald E.; Hampton, John M.; Figueroa, Jonine D; Skinner, Halcyon G.; Engelman, Corinne D; Klein, Barbara E.; Titus, Linda J.; Newcomb, Polly A.

    2013-01-01

    We evaluated whether 13 single nucleotide polymorphisms (SNPs) identified in genome-wide association studies interact with one another and with reproductive and menstrual risk factors in association with breast cancer risk. DNA samples and information on parity, breastfeeding, age at menarche, age at first birth, and age at menopause were collected through structured interviews from 1484 breast cancer cases and 1307 controls who participated in a population-based case-control study conducted ...

  10. Low expression of leptin and its association with breast cancer: A transcriptomic study.

    Science.gov (United States)

    Karim, Sajjad; Merdad, Adnan; Schulten, Hans-Juergen; Jayapal, Manikandan; Dallol, Ashraf; Buhmeida, Abdelbaset; Al-Thubaity, Fatima; Mirza, Zeenat; Gari, Mamdooh A; Chaudhary, Adeel G; Abuzenadah, Adel M; Al-Qahtani, Mohammed H

    2016-07-01

    The incidence of breast cancer is alarmingly increasing worldwide and also among Saudi women. Obesity is linked with an increased cancer risk and studies have also revealed that leptin may be involved in breast tumorigenesis particularly among obese women. Numerous transcriptomic studies have been carried out worldwide; however, molecular studies among breast cancer patients of diverse ethnic groups from the Arabian Peninsula are scarce. In the present study, whole transcriptome analysis of 45 surgically resected breast tumors from Saudi Arabian female patients was carried out. Expression data were analyzed, and molecular networks and canonical pathways were identified. We identified 1,159 differentially expressed genes using p-value with a false discovery rate 2 as a cut-off. Using ingenuity pathway analysis tool, we identified many canonical pathways that were implicated in breast cancer for the first time. Notably, along with other lipid metabolism molecules, leptin (LEP)was one of the most downregulated genes (fold cut-off, -7.03) with significant differences between the breast cancer and the control groups (pcancer from a Saudi female population revealed downregulation of LEP. Molecular pathway analysis demonstrated the role of LEP and other associated molecules of the lipid metabolism pathway. Involvement of leptin and lipid metabolism in breast cancer was highlighted. The majority of cases presented were of late stage, stressing the need to educate individuals concerning early diagnostic testing and the life-style risk factors for breast cancer such as unhealthy diet and obesity. PMID:27177292

  11. CHEK2*1100delC Heterozygosity in Women With Breast Cancer Associated With Early Death, Breast Cancer-Specific Death, and Increased Risk of a Second Breast Cancer

    DEFF Research Database (Denmark)

    Weischer, Maren; Nordestgaard, Børge G; Pharoah, Paul; Bolla, Manjeet K; Nevanlinna, Heli; Van't Veer, Laura J; Garcia-Closas, Montserrat; Hopper, John L; Hall, Per; Andrulis, Irene L; Devilee, Peter; Fasching, Peter A; Anton-Culver, Hoda; Lambrechts, Diether; Hooning, Maartje; Cox, Angela; Giles, Graham G; Burwinkel, Barbara; Lindblom, Annika; Couch, Fergus J; Mannermaa, Arto; Grenaker Alnæs, Grethe; John, Esther M; Dörk, Thilo; Flyger, Henrik; Dunning, Alison M; Wang, Qin; Muranen, Taru A; van Hien, Richard; Figueroa, Jonine; Southey, Melissa C; Czene, Kamila; Knight, Julia A; Tollenaar, Rob A E M; Beckmann, Matthias W; Ziogas, Argyrios; Christiaens, Marie-Rose; Collée, Johanna Margriet; Reed, Malcolm W R; Severi, Gianluca; Marme, Frederik; Margolin, Sara; Olson, Janet E; Kosma, Veli-Matti; Kristensen, Vessela N; Miron, Alexander; Bogdanova, Natalia; Shah, Mitul; Blomqvist, Carl; Broeks, Annegien; Sherman, Mark; Phillips, Kelly-Anne; Li, Jingmei; Liu, Jianjun; Glendon, Gord; Seynaeve, Caroline; Ekici, Arif B; Leunen, Karin; Kriege, Mieke; Cross, Simon S; Baglietto, Laura; Sohn, Christof; Wang, Xianshu; Kataja, Vesa; Børresen-Dale, Anne-Lise; Meyer, Andreas; Easton, Douglas F; Schmidt, Marjanka K; Bojesen, Stig E

    2012-01-01

    PURPOSE We tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer-specific death, and risk of a second breast cancer in women with a first breast cancer. PATIENTS AND METHODS From 22 studies participating in the Breast Cancer...... Association Consortium, 25,571 white women with invasive breast cancer were genotyped for CHEK2*1100delC and observed for up to 20 years (median, 6.6 years). We examined risk of early death and breast cancer-specific death by estrogen receptor status and risk of a second breast cancer after a first breast...... cancer in prospective studies. Results CHEK2*1100delC heterozygosity was found in 459 patients (1.8%). In women with estrogen receptor-positive breast cancer, multifactorially adjusted hazard ratios for heterozygotes versus noncarriers were 1.43 (95% CI, 1.12 to 1.82; log-rank P = .004) for early death...

  12. Lower heart rate variability is associated with cancer-related fatigue in breast cancer survivors

    Directory of Open Access Journals (Sweden)

    Alexandra Dupont

    2012-09-01

    Full Text Available Background : Fatigue is the most common and distressing symptom reported by breast cancer survivors and yet the pathophysiology of cancer-related fatigue remains largely unknown. Fatigue is associated with lower parasympathetic and higher sympathetic nervous system activity in non-cancer samples, but only one study has demonstrated this same relationship in breast cancer survivors. This study evaluates the relationship between fatigue and basal autonomic nervous system activity as measured by heart rate variability (HRV in a sample of breast cancer survivors. Methods : Women who had been diagnosed with early stage breast cancer before the age of 50 were recruited from the UCLA tumor registry and completed psychological questionnaires, including measures of fatigue. A subset of these women (n=30 participated in a follow-up study in which they completed measures of fatigue, energy and mood four times per day for 5 days using electronic diaries, provided 3 days of saliva samples for cortisol assessment and underwent physiological assessment including electrocardiogram (ECG. HRV was assessed via ECG R-R wave spectral and time sequence analysis. Results : Questionnaire measures of fatigue were negatively associated with indices of parasympathetic nervous system activity, B= − 3.85, p = 0.04 for RMSSD (root of the mean squared difference of successive normal to normal waves and B= − 76.97, p = 0.04 for LF power % (low-frequency wave power percentage. Daily fatigue was also associated with lower basal HRV, B= − 15.1, p = 0.04 for RMSSD. However, fatigue indices were not associated with sympathetic nervous system activity as measured by low- to high-frequency wave ratio. Of note, fatigue was not associated with average daily cortisol output (AUC. Conclusions : Lower HRV has been associated with increased chronic inflammation, which is elevated in cancer survivors reporting persistent fatigue, thus providing insight into

  13. Association between Metformin Therapy and Breast Cancer Incidence and Mortality: Evidence from a Meta-Analysis

    OpenAIRE

    Yang, Ting; Yang, Yuan; Liu, Shengchun

    2015-01-01

    Purpose Metformin may be associated with a decreased risk of breast cancer. We performed a meta-analysis to assess the effect of metformin intake on breast cancer risk and mortality. Methods We performed a PubMed and EMbase search for all available studies that described the risk of breast cancer and all-cause mortality in relation to the use of metformin among patients with type 2 diabetes mellitus. Pooled relative risks (RRs) were determined using a random effects model to assess the streng...

  14. Metabolic Syndrome Is Associated with Increased Breast Cancer Risk: A Systematic Review with Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Ruchi Bhandari

    2014-01-01

    Full Text Available Background. Although individual metabolic risk factors are reported to be associated with breast cancer risk, controversy surrounds risk of breast cancer from metabolic syndrome (MS. We report the first systematic review and meta-analysis of the association between MS and breast cancer risk in all adult females. Methods. Studies were retrieved by searching four electronic reference databases [PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL, Web of Science, and ProQuest through June 30, 2012] and cross-referencing retrieved articles. Eligible for inclusion were longitudinal studies reporting associations between MS and breast cancer risk among females aged 18 years and older. Relative risks and 95% confidence intervals were calculated for each study and pooled using random-effects models. Publication bias was assessed quantitatively (Trim and Fill and qualitatively (funnel plots. Heterogeneity was examined using Q and I2 statistics. Results. Representing nine independent cohorts and 97,277 adult females, eight studies met the inclusion criteria. A modest, positive association was observed between MS and breast cancer risk (RR: 1.47, 95% CI, 1.15–1.87; z=3.13; p=0.002; Q=26.28, p=0.001; I2=69.55%. No publication bias was observed. Conclusions. MS is associated with increased breast cancer risk in adult women.

  15. Serum soluble ST2 is associated with ER-positive breast cancer

    International Nuclear Information System (INIS)

    ST2, a member of the interleukin (IL)-1receptor family, regulates Th1/Th2 immune responses in autoimmune and inflammatory conditions. However, the role of ST2 signaling in tumor growth and metastasis of breast cancers has not been investigated. This study investigated the possible role of soluble ST2 (sST2) in breast cancer. The serum levels of IL-33, sST2, and vascular endothelial growth factor (VEGF) in 150 breast cancer patients and 90 healthy women were measured by enzyme-linked immunosorbent assay. Estrogen receptor(ER), progesterone receptor, human epithelial receptor (HER)-2, and cell cycle regulated protein Ki-67 were measured. Clinical stage, tumor size, lymph node metastasis, and histological type were also recorded. The serum levels of sST2, IL-33, and VEGF were significantly higher in breast cancer patients than in the control group (P < 0.05, each). Serum sST2 levels in ER-positive breast cancer patients were significantly associated with age, histological type, clinical stage, tumor size, and Ki-67 status (P < 0.05, each). Moreover, the serum levels of IL-33 and sST2 in breast cancers significantly correlated with VEGF levels (IL-33: r = 0.375, P < 0.0001; sST2: r = 0.164, P = 0.045). Serum levels of sST2, IL-33, and VEGF decreased after modified radical mastectomy in ER-positive breast cancers. Serum levels of IL-33, sST2, and VEGF and clinicopathological factors were not significantly correlated with disease-free survival and overall survival of ER-positive breast cancer women during follow-up. Serum sST2 levels in ER-positive breast cancer patients are significantly associated with factors that indicate poor prognosis

  16. The associations between the environmental exposure to polychlorinated biphenyls (PCBs) and breast cancer risk and progression

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Polychlorinated biphenyls(PCBs) are chlorinated biphenyl compounds with wide applications in the industry.In spite of a ban on their production in the late 1970s,PCBs,as a group of POPs,are still persistent and widely spread in the environment,posing potential threats to human health.The role of PCBs as etiologic agents for breast cancer has been intensively explored in a variety of in vivo,animal and epidemiologic studies.Initial investigations indicated higher levels of PCBs in mammary tissues or sera corresponded to the occurrence of breast cancer,but later studies showed no positive association between PCB exposure and breast cancer development.More recent data suggested that the CYP1A1 m2 polymorphisms might add increased risk to the etiology of breast cancer in women with environmental exposure to PCBs.PCBs are implicated in advancing breast cancer progression,and our unpublished data reveals that PCBs activate the ROCK signaling to enhance breast cancer metastasis.Therefore,the correlation between PCB exposure and breast cancer risk warrants further careful investigations.

  17. Association between body mass index and risk of breast cancer among females of north India

    Directory of Open Access Journals (Sweden)

    Mahavir Singh

    2013-01-01

    Full Text Available Background: Worldwide, breast cancer is most common cancer among women. In India and other developing countries, breast carcinoma ranks second only to cervical carcinoma among women. Although studies have been done globally, to find association between BMI and breast cancer, very few studies in India document any such association. Purpose: To find out the association between BMI and breast cancer. Materials and Methods: A Case-control study was done from August 2009 - July 2010 in the wards of General Surgery and Oncosurgery at Pt.B.D.Sharma, PGIMS Rohtak, Haryana. A total of 128 histopathologically confirmed new cases of breast cancer during the study period were taken as cases. Equal number of controls was selected by simple random sampling. Controls were matched for age with range of ±2 years. Subjects were interviewed using a pretested questionnaire after obtaining written informed consent. Data were analyzed by applying appropriate statistical tests using SPSS version 17. Results: Age group of the cases was 25 - 78 years, while that of the controls was 24 - 79 years. Proportion of cases and controls living in rural areas were more than those living in urban areas. A significant association of breast cancer cases was found with high BMI and high fat intake Conclusion: Obesity and high fat intake are the significant risk factors, which are modifiable. So women should be encouraged to take care of all these factors. Maximum cases presented in late stages so public awareness of this fatal disease must be developed.

  18. An association of vertebral breast cancer metastasis and multiple myeloma, revealed by a spinal cord compression

    OpenAIRE

    Kherfani, Abdelhakim; Amri, Khalil; Hachem, Mahjoub; Abid, Leila; Bouaziz, Mouna; Mestiri, Mondher

    2014-01-01

    Authors describe the case of a patient with breast cancer and multiple myeloma as the second metachronous disease responsible for spinal cord compression. Synchronous occurrence of bone marrow breast cancer disease and multiple myeloma has not been described in the literature, as in this case. By presenting this case, we point to possible association between both diseases and the possible factors involved in the development of second malignant disease.

  19. Association of diabetes and diabetes treatment with incidence of breast cancer

    OpenAIRE

    García-Esquinas, Esther; Guinó, Elisabeth; Castaño-Vinyals, Gemma; Pérez-Gómez, Beatriz; Llorca, Javier; Altzibar, Jone M.; Peiró-Pérez, Rosana; Martín, Vicente; Moreno-Iribas, Concepción; Tardón, Adonina; Caballero, Francisco Javier; Puig-Vives, Montse; Guevara, Marcela; Villa, Tania Fernández; Salas, Dolores

    2015-01-01

    Aims The aim of this study was to evaluate the association of diabetes and diabetes treatment with risk of postmenopausal breast cancer. Methods Histologically confirmed incident cases of postmenopausal breast (N = 916) cancer were recruited from 23 Spanish public hospitals. Population-based controls (N = 1094) were randomly selected from primary care center lists within the catchment areas of the participant hospitals. ORs (95 % CI) were estimated using mixed-effects logistic regression mode...

  20. Association of diabetes and diabetes treatment with incidence of breast cancer

    OpenAIRE

    Garc??a-Esquinas, Esther; Casta??o Vinyals, Gemma; Sala Serra Maria, Maria; Kogevinas, Manolis; Pollan, Marina

    2015-01-01

    AIMS: The aim of this study was to evaluate the association of diabetes and diabetes treatment with risk of postmenopausal breast cancer. METHODS: Histologically confirmed incident cases of postmenopausal breast (N = 916) cancer were recruited from 23 Spanish public hospitals. Population-based controls (N = 1094) were randomly selected from primary care center lists within the catchment areas of the participant hospitals. ORs (95 % CI) were estimated using mixed-effects logistic regression mo...

  1. Activated FXR Inhibits Leptin Signaling and Counteracts Tumor-promoting Activities of Cancer-Associated Fibroblasts in Breast Malignancy

    OpenAIRE

    Cinzia Giordano; Ines Barone; Valentina Vircillo; Salvatore Panza; Rocco Malivindi; Luca Gelsomino; Michele Pellegrino; Vittoria Rago; Loredana Mauro; Marilena Lanzino; Maria Luisa Panno; Daniela Bonofiglio; Stefania Catalano; Sebastiano Andò

    2016-01-01

    Cancer-associated fibroblasts (CAFs), the principal components of the tumor stroma, play a central role in cancer development and progression. As an important regulator of the crosstalk between breast cancer cells and CAFs, the cytokine leptin has been associated to breast carcinogenesis. The nuclear Farnesoid X Receptor-(FXR) seems to exert an oncosuppressive role in different tumors, including breast cancer. Herein, we demonstrated, for the first time, that the synthetic FXR agonist GW4064,...

  2. Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium

    OpenAIRE

    Milne, Roger L; Burwinkel, Barbara; Michailidou, Kyriaki; Arias-Perez, Jose-Ignacio; Zamora, M. Pilar; Men?ndez-Rodr?guez, Primitiva; Hardisson, David; Mendiola, Marta; Gonz?lez-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Dennis, Joe; WANG, QIN; Bolla, Manjeet K; Swerdlow, Anthony

    2014-01-01

    BCAC is funded by Cancer Research UK (C1287/A10118, C1287/A12014) and by the European Community?s Seventh Framework Programme under grant agreement n8 223175 (HEALTH-F2?2009-223175) (COGS). Meetings of the BCAC have been funded by the European Union COST programme (BM0606). Genotyping of the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710), the Canadian Institutes of Health Research for the ?CIHR Team in Familial Risks of Breast Can...

  3. Characterization of genomic alterations in radiation-associated breast cancer among childhood cancer survivors, using comparative genomic hybridization (CGH arrays.

    Directory of Open Access Journals (Sweden)

    Xiaohong R Yang

    Full Text Available Ionizing radiation is an established risk factor for breast cancer. Epidemiologic studies of radiation-exposed cohorts have been primarily descriptive; molecular events responsible for the development of radiation-associated breast cancer have not been elucidated. In this study, we used array comparative genomic hybridization (array-CGH to characterize genome-wide copy number changes in breast tumors collected in the Childhood Cancer Survivor Study (CCSS. Array-CGH data were obtained from 32 cases who developed a second primary breast cancer following chest irradiation at early ages for the treatment of their first cancers, mostly Hodgkin lymphoma. The majority of these cases developed breast cancer before age 45 (91%, n = 29, had invasive ductal tumors (81%, n = 26, estrogen receptor (ER-positive staining (68%, n = 19 out of 28, and high proliferation as indicated by high Ki-67 staining (77%, n = 17 out of 22. Genomic regions with low-copy number gains and losses and high-level amplifications were similar to what has been reported in sporadic breast tumors, however, the frequency of amplifications of the 17q12 region containing human epidermal growth factor receptor 2 (HER2 was much higher among CCSS cases (38%, n = 12. Our findings suggest that second primary breast cancers in CCSS were enriched for an "amplifier" genomic subgroup with highly proliferative breast tumors. Future investigation in a larger irradiated cohort will be needed to confirm our findings.

  4. The influence of genetic ancestry and ethnicity on breast cancer survival associated with genetic variation in the TGF-β-signaling pathway: The Breast Cancer Health Disparities Study

    OpenAIRE

    Slattery, Martha L.; Lundgreen, Abbie; Stern, Marianna C.; Hines, Lisa; Wolff, Roger K.; Giuliano, Anna R.; Baumgartner, Kathy B.; John, Esther M.

    2013-01-01

    The TGF-β signaling pathway regulates cellular proliferation and differentiation. We evaluated genetic variation in this pathway, its association with breast cancer survival, and survival differences by genetic ancestry and self-reported ethnicity.

  5. Most random gene expression signatures are significantly associated with breast cancer outcome.

    Directory of Open Access Journals (Sweden)

    David Venet

    2011-10-01

    Full Text Available Bridging the gap between animal or in vitro models and human disease is essential in medical research. Researchers often suggest that a biological mechanism is relevant to human cancer from the statistical association of a gene expression marker (a signature of this mechanism, that was discovered in an experimental system, with disease outcome in humans. We examined this argument for breast cancer. Surprisingly, we found that gene expression signatures-unrelated to cancer-of the effect of postprandial laughter, of mice social defeat and of skin fibroblast localization were all significantly associated with breast cancer outcome. We next compared 47 published breast cancer outcome signatures to signatures made of random genes. Twenty-eight of them (60% were not significantly better outcome predictors than random signatures of identical size and 11 (23% were worst predictors than the median random signature. More than 90% of random signatures >100 genes were significant outcome predictors. We next derived a metagene, called meta-PCNA, by selecting the 1% genes most positively correlated with proliferation marker PCNA in a compendium of normal tissues expression. Adjusting breast cancer expression data for meta-PCNA abrogated almost entirely the outcome association of published and random signatures. We also found that, in the absence of adjustment, the hazard ratio of outcome association of a signature strongly correlated with meta-PCNA (R(2 = 0.9. This relation also applied to single-gene expression markers. Moreover, >50% of the breast cancer transcriptome was correlated with meta-PCNA. A corollary was that purging cell cycle genes out of a signature failed to rule out the confounding effect of proliferation. Hence, it is questionable to suggest that a mechanism is relevant to human breast cancer from the finding that a gene expression marker for this mechanism predicts human breast cancer outcome, because most markers do. The methods we

  6. Aromatase inhibitor-associated bone loss and its management with bisphosphonates in patients with breast cancer

    OpenAIRE

    Bauer M; Bryce J; Hadji P

    2012-01-01

    M Bauer,1 J Bryce,2 P Hadji11University of Marburg, Marburg, Germany; 2National Cancer Institute, Naples, ItalyAbstract: Postmenopausal women have an increased risk of osteopenia and osteoporosis due to loss of the bone-protective effects of estrogen. Disease-related processes may also contribute to the risk of bone loss in postmenopausal women with breast cancer. One of the most common and severe safety issues associated with cancer therapy for patients with breast cancer is bone loss and th...

  7. Methylation of the claudin 1 promoter is associated with loss of expression in estrogen receptor positive breast cancer.

    Directory of Open Access Journals (Sweden)

    Francescopaolo Di Cello

    Full Text Available Downregulation of the tight junction protein claudin 1 is a frequent event in breast cancer and is associated with recurrence, metastasis, and reduced survival, suggesting a tumor suppressor role for this protein. Tumor suppressor genes are often epigenetically silenced in cancer. Downregulation of claudin 1 via DNA promoter methylation may thus be an important determinant in breast cancer development and progression. To investigate if silencing of claudin 1 has an epigenetic etiology in breast cancer we compared gene expression and methylation data from 217 breast cancer samples and 40 matched normal samples available through the Cancer Genome Atlas (TCGA. Moreover, we analyzed claudin 1 expression and methylation in 26 breast cancer cell lines. We found that methylation of the claudin 1 promoter CpG island is relatively frequent in estrogen receptor positive (ER+ breast cancer and is associated with low claudin 1 expression. In contrast, the claudin 1 promoter was not methylated in most of the ER-breast cancers samples and some of these tumors overexpress claudin 1. In addition, we observed that the demethylating agents, azacitidine and decitabine can upregulate claudin 1 expression in breast cancer cell lines that have a methylated claudin 1 promoter. Taken together, our results indicate that DNA promoter methylation is causally associated with downregulation of claudin 1 in a subgroup of breast cancer that includes mostly ER+ tumors, and suggest that epigenetic therapy to restore claudin 1 expression might represent a viable therapeutic strategy in this subtype of breast cancer.

  8. Association of common variants in mismatch repair genes and breast cancer susceptibility: a multigene study

    International Nuclear Information System (INIS)

    MMR is responsible for the repair of base-base mismatches and insertion/deletion loops. Besides this, MMR is also associated with an anti-recombination function, suppressing homologous recombination. Losses of heterozygosity and/or microsatellite instability have been detected in a large number of skin samples from breast cancer patients, suggesting a potential role of MMR in breast cancer susceptibility. We carried out a hospital-based case-control study in a Caucasian Portuguese population (287 cases and 547 controls) to estimate the susceptibility to non-familial breast cancer associated with some polymorphisms in mismatch repair genes (MSH3, MSH4, MSH6, MLH1, MLH3, PMS1 and MUTYH). Using unconditional logistic regression we found that MLH3 (L844P, G>A) polymorphism GA (Leu/Pro) and AA (Pro/Pro) genotypes were associated with a decreased risk: OR = 0.65 (0.45-0.95) (p = 0.03) and OR = 0.62 (0.41-0.94) (p = 0.03), respectively. Analysis of two-way SNP interaction effects on breast cancer revealed two potential associations to breast cancer susceptibility: MSH3 Ala1045Thr/MSH6 Gly39Glu - AA/TC [OR = 0.43 (0.21-0.83), p = 0.01] associated with a decreased risk; and MSH4 Ala97Thr/MLH3 Leu844Pro - AG/AA [OR = 2.35 (1.23-4.49), p = 0.01], GG/AA [OR = 2.11 (1.12-3,98), p = 0.02], and GG/AG [adjusted OR = 1.88 (1.12-3.15), p = 0.02] all associated with an increased risk for breast cancer. It is possible that some of these common variants in MMR genes contribute significantly to breast cancer susceptibility. However, further studies with a large sample size will be needed to support our results

  9. Methylxanthines and breast cancer.

    Science.gov (United States)

    Schairer, C; Brinton, L A; Hoover, R N

    1987-10-15

    We investigated the relationship between methylxanthine consumption and breast cancer using data from a case-control study which included 1,510 cases and 1,882 controls identified through a nation-wide breast cancer screening program. There was no evidence of a positive association between methylxanthine consumption and risk of breast cancer. In fact, there was some suggestion of a negative association, particularly in women diagnosed after age 50. In addition, there was no evidence of increased risk with past or recent methylxanthine consumption, or with the consumption of caffeine or specific beverages, most notably brewed or instant caffeinated coffee and tea. PMID:3117709

  10. The association between different kinds of fat intake and breast cancer risk in women

    Directory of Open Access Journals (Sweden)

    Mahdieh Khodarahmi

    2014-01-01

    Full Text Available So far several animal and case-control studies have confirmed this hypothesis that dietary fat increases the risk of breast cancer. However, cohort studies have not shown this relationship. The aim of this study was to review the studies on the relationship between dietary fat intake and breast cancer risk among women. Electronic database PubMed and Google Scholar were searched using the key words: Breast cancer, dietary fat, serum estrogen, saturated fatty acids (SFAs, monounsaturated fatty acids (MUFAs and polyunsaturated fatty acids (PUFAs. The evidence of the studies regarding to the association of total and subtypes of fat intake with breast cancer risk are inconsistent. Several studies have shown that, among several types of fat, SFAs and w-3 PUFA intake are associated with an increased and reduced risk of breast cancer, respectively. The relationship between MUFAs intake and breast cancer risk is conflicting. Narrow ranges of fat intake among populations, measurement errors, high correlation between specific types of dietary fat, the confounding variables like body fatness and high-energy intake and other dietary components such as fiber and antioxidants might be probable explanations for these inconsistent results. Although we are not at a stage where we can justifiably advise women to reduce their fat intake to decrease the risk of developing breast cancer, it seems the current guidelines to lower total fat consumption and recommendation to consumption of unsaturated fats such as MUFAs and w-3 fatty acids and also reduction of SFAs (meat and dairy products intake to avoid heart disease is also useful for breast cancer risk.

  11. Health seeking behavioral analysis associated with breast cancer screening among Asian American women

    Directory of Open Access Journals (Sweden)

    Ma GX

    2012-05-01

    Full Text Available Grace X Ma,1 Wanzhen Gao,1 Sunmin Lee,2 MinQi Wang,3 Yin Tan,1 Steven E Shive,1,41Department of Public Health, Center for Asian Health, College of Health Professions, Temple University, Philadelphia, PA, USA; 2Department of Epidemiology and Biostatistics, School of Public Health, University of Maryland, College Park, MD, USA; 3Department of Public and Community Health, University of Maryland, College Park, Maryland, MD, USA; 4East Stroudsburg University, East Stroudsburg, PA, USAObjective: The purpose of this community-based study was to apply a Sociocultural Health Behavior Model to determine the association of factors proposed in the model with breast cancer screening behaviors among Asian American women.Methods: A cross-sectional design included a sample of 682 Chinese, Korean, and Vietnamese women aged 40 years and older. The frequency distribution analysis and Chi-square analysis were used for the initial screening of the following variables: sociodemographic, cultural, enabling, environmental, and social support. Univariate and multivariate analyses were conducted on factors for breast cancer screening using multinomial logistic regression analysis.Results: Correlates to positive breast cancer screening included demographics (ethnicity, cultural factors (living in the United States for 15 years or more, speaking English well, enabling factors (having a regular physician to visit, health insurance covering the screening, and family/social support factors (those who had a family/friend receiving a mammogram.Conclusions: The results of this study suggest that breast cancer screening programs will be more effective if they include the cultural and health beliefs, enabling, and social support factors associated with breast cancer screening. The use of community organizations may play a role in helping to increase breast cancer screening rates among Asian American women.Keywords: breast cancer screening, Vietnamese, Korean, Chinese, breast

  12. Modification of BRCA1-Associated Breast and Ovarian Cancer Risk by BRCA1 Interacting Genes

    OpenAIRE

    Rebbeck, Timothy R.; Mitra, Nandita; Domchek, Susan M.; Wan, Fei; Friebel, Tara M.; Tran, Teo V.; Singer, Christian F.; Tea, Muy-Kheng Maria; Blum, Joanne L.; Tung, Nadine; Olopade, Olufunmilayo I.; Weitzel, Jeffrey N.; Lynch, Henry T.; Snyder, Carrie L.; Garber, Judy E.

    2011-01-01

    Inherited BRCA1 mutations confer elevated breast cancer risk. Recent studies have identified genes that encode proteins that interact with BRCA1 as modifiers of BRCA1-associated breast cancer. We evaluated a comprehensive set of genes that encode most known BRCA1 interactors to evaluate the role of these genes as modifiers of cancer risk. A cohort of 2,825 BRCA1 mutation carriers was used to evaluate the association of haplotypes at ATM, BRCC36, BRCC45 (BRE), BRIP1 (BACH1/FANCJ), CTIP, ABRA1 ...

  13. Higher cardiorespiratory fitness levels are associated with greater hippocampal volume in breast cancer survivors

    OpenAIRE

    Laura Chaddock-Heyman

    2015-01-01

    As breast cancer treatment is associated with declines in brain and cognitive health, it is important to identify strategies to enhance the cognitive vitality of cancer survivors. In particular, the hippocampus is known to play an important role in brain and memory declines following cancer treatment. The hippocampus is also known for its plasticity and positive association with cardiorespiratory fitness. The present study explores whether cardiorespiratory fitness may hold promise for lesse...

  14. Breast Cancer -- Male

    Science.gov (United States)

    ... Home > Types of Cancer > Breast Cancer in Men Breast Cancer in Men This is Cancer.Net’s Guide to Breast Cancer in Men. Use the menu below to choose ... social workers, and patient advocates. Cancer.Net Guide Breast Cancer in Men Overview Statistics Risk Factors and Prevention ...

  15. Potential utility of natural products as regulators of breast cancer-associated aromatase promoters

    Directory of Open Access Journals (Sweden)

    Walker Larry A

    2011-06-01

    Full Text Available Abstract Aromatase, the key enzyme in estrogen biosynthesis, converts androstenedione to estrone and testosterone to estradiol. The enzyme is expressed in various tissues such as ovary, placenta, bone, brain, skin, and adipose tissue. Aromatase enzyme is encoded by a single gene CYP 19A1 and its expression is controlled by tissue-specific promoters. Aromatase mRNA is primarily transcribed from promoter I.4 in normal breast tissue and physiological levels of aromatase are found in breast adipose stromal fibroblasts. Under the conditions of breast cancer, as a result of the activation of a distinct set of aromatase promoters (I.3, II, and I.7 aromatase expression is enhanced leading to local overproduction of estrogen that promotes breast cancer. Aromatase is considered as a potential target for endocrine treatment of breast cancer but due to nonspecific reduction of aromatase activity in other tissues, aromatase inhibitors (AIs are associated with undesirable side effects such as bone loss, and abnormal lipid metabolism. Inhibition of aromatase expression by inactivating breast tumor-specific aromatase promoters can selectively block estrogen production at the tumor site. Although several synthetic chemical compounds and nuclear receptor ligands are known to inhibit the activity of the tumor-specific aromatase promoters, further development of more specific and efficacious drugs without adverse effects is still warranted. Plants are rich in chemopreventive agents that have a great potential to be used in chemotherapy for hormone dependent breast cancer which could serve as a source for natural AIs. In this brief review, we summarize the studies on phytochemicals such as biochanin A, genistein, quercetin, isoliquiritigenin, resveratrol, and grape seed extracts related to their effect on the activation of breast cancer-associated aromatase promoters and discuss their aromatase inhibitory potential to be used as safer chemotherapeutic agents for

  16. Association of EP2 receptor and SLC19A3 in regulating breast cancer metastasis.

    Science.gov (United States)

    Cheuk, Isabella W; Shin, Vivian Y; Siu, Man T; Tsang, Julia Y; Ho, John C; Chen, Jiawei; Tse, Gary M; Wang, Xian; Kwong, Ava

    2015-01-01

    Breast cancer is the most common cancer in women worldwide. Triple-negative breast cancer patients have higher metastatic rate than patients with other breast cancer subtypes. Distant metastasis is one of the causes leading to the high mortality rates. Cyclooxygenase-2 (COX2) is associated with breast cancer metastasis and the downstream prostaglandin E2 (PGE2) exerted its effect through EP receptors (EP1-EP4). However, the exact molecular events of EP receptors in breast cancer metastasis remain undefined. Expressions of EP receptors were determined during cancer development in NOD-SCID mice inoculated with MB-231 and MB-231-EP2 clone. EP2 overexpressing stable clone was constructed to investigate the proliferation and invasion potentials in vivo and in vitro. Drug transporter array was used to identify EP2 receptor-associated drug transported genes in breast cancer metastasis. Localization of EP2 receptor in primary tissues and xenografts were examined by immunostaining. Stable EP2-expression cells formed larger tumors than parental cells in mice model and was highly expressed in both primary and metastatic tissues. Silencing of EP2 receptor by siRNA and antagonist (AH 6809) significantly decreased cell proliferation and invasion, concomitant with reduced MMP-2 and MMP-9 expressions. Results from array data showed that expression of SLC19A3 was markedly increased in EP2 siRNA transfected cells. Ectopic expression of SLC19A3 retarded cell proliferation, invasion and MMPs expressions. Notably, SLC19A3 had a lower expression in primary tissues and was negatively correlated with EP2 receptor expression. Our novel finding revealed that EP2 receptor regulated metastasis through downregulation of SLC19A3. Thus, targeting EP2-SLC19A3 signaling is a potential therapeutic therapy for treating metastatic breast cancer. PMID:26807319

  17. Association of COMT Val158Met polymorphism and breast cancer risk: an updated meta-analysis

    Directory of Open Access Journals (Sweden)

    Qin Xue

    2012-10-01

    Full Text Available Abstract Background Catechol-O-methyltransferase (COMT is one of the most important enzymes involved in estrogen metabolism and its functional genetic polymorphisms may be associated with breast cancer (BC risk. Many epidemiological studies have been conducted to explore the association between the COMT Val158Met polymorphism and breast cancer risk. However, the results remain inconclusive. In order to derive a more precise estimation of this relationship, a large meta-analysis was performed in this study. Methods Systematic searches of the PubMed, Embase and Cochrane Library were performed. Crude odds ratios (ORs with 95% confidence intervals (CIs were calculated to estimate the strength of the association. Results A total of 56 studies including 34,358 breast cancer cases and 45,429 controls were included. Overall, no significant associations between the COMT Val158Met polymorphism and breast cancer risk were found for LL versus HH, HL versus HH, LL versus HL, recessive model LL versus HL+HH, and dominant model LL+HL versus HH. In subgroup analysis by ethnicity, source of controls, and menopausal status, there was still no significant association detected in any of the genetic models. Conclusion Our meta-analysis results suggest that the COMT Val158Met polymorphism may not contribute to breast cancer susceptibility. Virtual slides The virtual slides(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs4806123577708417

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

    Directory of Open Access Journals (Sweden)

    Anne-Laure Renault

    Full Text Available 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.

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

    Science.gov (United States)

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

    2016-01-01

    Approximately half of the familial aggregation of breast cancer remains unexplained. This proportion is less for early-onset disease where familial aggregation is greater, suggesting that other susceptibility genes remain to be discovered. The majority of known breast cancer susceptibility genes are involved in the DNA double-strand break repair pathway. ABRAXAS is involved in this pathway and mutations in this gene impair BRCA1 recruitment to DNA damage foci and increase cell sensitivity to ionizing radiation. Moreover, a recurrent germline mutation was reported in Finnish high-risk breast cancer families. To determine if ABRAXAS could be a breast cancer susceptibility gene in other populations, we conducted a population-based case-control mutation screening study of the coding exons and exon/intron boundaries of ABRAXAS in the Breast Cancer Family Registry. In addition to the common variant p.Asp373Asn, sixteen distinct rare variants were identified. Although no significant difference in allele frequencies between cases and controls was observed for the identified variants, two variants, p.Gly39Val and p.Thr141Ile, were shown to diminish phosphorylation of gamma-H2AX in MCF7 human breast adenocarcinoma cells, an important biomarker of DNA double-strand breaks. Overall, likely damaging or neutral variants were evenly represented among cases and controls suggesting that rare variants in ABRAXAS may explain only a small proportion of hereditary breast cancer. PMID:27270457

  20. Ultrasonographic screening for breast cancer using the recall criteria established by the Japan Association of Breast and Thyroid Sonology (JABTS)

    International Nuclear Information System (INIS)

    As is the case in many other countries, mammography is currently used in Japan for breast cancer screening. However, as it cannot detect lesions in dense breasts such as those of young women, ultrasound (US) imaging is used for this purpose. Although there have been numerous reports of US screening, the results obtained using the recall criteria stipulated by the Japan Association of Breast and Thyroid Sonology (JABTS) has not yet been reported. We have performed US screening based on the JABTS guidelines for three years. Technologists perform the examinations, and physicians select recall cases on the basis of these criteria. So far there have been 17,089 attendees, of whom 90% were less than 50 years old. The recall rate was 3.6% (616/17,089). The results of further examinations were confirmed in 452 of these 616 recalled women, and breast cancer was detected in 48 (0.28%) of them. Cancer was detected early in 37 (80.5%) of these 48 cases. Mammography was unable to detect cancer in 16 (43%) of the cases. Although the high recall rate of US screening has been mentioned previously, we wish to emphasize that US breast cancer screening is effective, particularly in younger women. Furthermore, the reasonable recall rate ensures that a high quality of detection is maintained. (author)

  1. A novel duplication polymorphism in the FANCA promoter and its association with breast and ovarian cancer

    International Nuclear Information System (INIS)

    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

  2. Association of two mutations in the CHEK2 gene with breast cancer

    International Nuclear Information System (INIS)

    Cell-cycle checkpoint kinase 2 (CHEK2) is a central mediator of cellular responses to DNA damage. Ionizing radiation activates the CHEK2 protein via ATM-mediated phosphorylation and activated CHEK2 kinase can phosphorylate several substrates, including Cdc25A, p53 and E2F1, which mediate cell cycle arrest and apoptosis. CHEK2 phosphorylation of the breast cancer susceptibility protein BRCA1 regulates DNA double-strand break repair, and deletion of CHEK2 potentiate the incidence of mammary carcinomas in BRCA1 conditional mutant mice. A truncating variant of CHEK2, the 1100 delC mutation, has been identified as a low-penetrance breast-cancer susceptibility allele. Heterozygous 1100 delC carriers have an approximately 2-fold increased risk for breast cancer. The role of variants in CHEK2 other than 1100 delC is less clear. To assess the role of these CHEK2 variants in breast cancer, we conducted an association study of the I157T and IVS211G>A mutations in breast cancer case-control settings from the Belarus populations. Our series consisted of 424 breast cancer patients and 307 population controls. The missense substitution I157T was identified in 24/424 cases (5.7%) vs. 4/307 controls (1.3%; OR 54.5, 95% CI 1.6-13.2, p 5 0.005) in investigated cohorts. The splicing mutation IVS211G > A was infrequent, being observed 4/424 patients (0.9%). Heterozygous CHEK2 mutation carriers tended to be diagnosed at an earlier age, but these differences did not reach statistical significance. Family history of breast cancer did not differ between carriers and non carriers. Our data indicate that the I157T allele, and possibly the IVS211G > A allele, of the CHEK2 gene contribute to inherited breast cancer susceptibility. (authors)

  3. Investigation of VOCs associated with different characteristics of breast cancer cells.

    Science.gov (United States)

    Lavra, Luca; Catini, Alexandro; Ulivieri, Alessandra; Capuano, Rosamaria; Baghernajad Salehi, Leila; Sciacchitano, Salvatore; Bartolazzi, Armando; Nardis, Sara; Paolesse, Roberto; Martinelli, Eugenio; Di Natale, Corrado

    2015-01-01

    The efficacy of breath volatile organic compounds (VOCs) analysis for the screening of patients bearing breast cancer lesions has been demonstrated by using gas chromatography and artificial olfactory systems. On the other hand, in-vitro studies suggest that VOCs detection could also give important indications regarding molecular and tumorigenic characteristics of tumor cells. Aim of this study was to analyze VOCs in the headspace of breast cancer cell lines in order to ascertain the potentiality of VOCs signatures in giving information about these cells and set-up a new sensor system able to detect breast tumor-associated VOCs. We identified by Gas Chromatography-Mass Spectrometry analysis a VOCs signature that discriminates breast cancer cells for: i) transformed condition; ii) cell doubling time (CDT); iii) Estrogen and Progesterone Receptors (ER, PgR) expression, and HER2 overexpression. Moreover, the signals obtained from a temperature modulated metal oxide semiconductor gas sensor can be classified in order to recognize VOCs signatures associated with breast cancer cells, CDT and ER expression. Our results demonstrate that VOCs analysis could give clinically relevant information about proliferative and molecular features of breast cancer cells and pose the basis for the optimization of a low-cost diagnostic device to be used for tumors characterization. PMID:26304457

  4. The phosphorylation-specific association of STMN1 with GRP78 promotes breast cancer metastasis.

    Science.gov (United States)

    Kuang, Xia-Ying; Jiang, He-Sheng; Li, Kai; Zheng, Yi-Zi; Liu, Yi-Rong; Qiao, Feng; Li, Shan; Hu, Xin; Shao, Zhi-Ming

    2016-07-10

    Metastasis is a major cause of death in patients with breast cancer. Stathmin1 (STMN1) is a phosphoprotein associated with cancer metastasis. It exhibits a complicated phosphorylation pattern in response to various extracellular signals, but its signaling mechanism is poorly understood. In this study, we report that phosphorylation of STMN1 at Ser25 and Ser38 is necessary to maintain cell migration capabilities and is associated with shorter disease-free survival (DFS) in breast cancer. In addition, we report that glucose-regulated protein of molecular mass 78 (GRP78) is a novel phospho-STMN1 binding protein upon STMN1 Ser25/Ser38 phosphorylation. This phosphorylation-dependent interaction is regulated by MEK kinase and is required for STMN1-GRP78 complex stability and STMN1-mediated migration. We also propose a prognostic model based on phospho-STMN1 and GRP78 to assess metastatic risk in breast cancer patients. PMID:27130664

  5. Fibroblast Activation Protein Expression by Stromal Cells and Tumor-Associated Macrophages in Human Breast Cancer

    Science.gov (United States)

    Julia, Tchou; Zhang Paul, J; Yingtao, Bi; Celine, Satija; Rajrupa, Marjumdar; Stephen, TL; Lo, A; Haiying, Chen; Carolyn, Mies; June, Carl H; Jose, Conejo-Garcia; Ellen, Puré

    2013-01-01

    Summary Fibroblast activation protein (FAP) has long been known to be expressed in the stroma of breast cancer. However, very little is known if the magnitude of FAP expression within the stroma may have prognostic value and reflect the heterogeneous biology of the tumor cell. An earlier study had suggested that stromal FAP expression in breast cancer was inversely proportional to prognosis. We, therefore, hypothesized that stromal FAP expression may correlate with clinicopathologic variables and may serve as an adjunct prognostic factor in breast cancer. We evaluated the expression of FAP in a panel of breast cancer tissues (n=52) using a combination of immunostain analyses at the tissue and single cell level using freshly frozen or freshly digested human breast tumor samples respectively. Our results showed that FAP expression was abundantly expressed in the stroma across all breast cancer subtypes without significant correlation with clinicopathologic factors. We further identified a subset of FAP positive or FAP+ stromal cells that also expressed CD45, a pan-leukocyte marker. Using freshly dissociated human breast tumor specimens (n=5), we demonstrated that some of these FAP+ CD45+ cells were CD11b+CD14+MHC-II+ indicating that they were likely tumor associated macrophages (TAMs). Although FAP+CD45+ cells have been demonstrated in the mouse tumor stroma, our results demonstrating that human breast TAMs expressed FAP was novel and suggested that existing and future FAP directed therapy may have dual therapeutic benefits targeting both stromal mesenchymal cells and immune cells such as TAMs. More work is needed to explore the role of FAP as a potential targetable molecule in breast cancer treatment. PMID:24074532

  6. Moderate Physical Activity Mediates the Association between White Matter Lesion Volume and Memory Recall in Breast Cancer Survivors.

    Science.gov (United States)

    Cooke, Gillian E; Wetter, Nathan C; Banducci, Sarah E; Mackenzie, Michael J; Zuniga, Krystle E; Awick, Elizabeth A; Roberts, Sarah A; Sutton, Brad P; McAuley, Edward; Kramer, Arthur F

    2016-01-01

    Increased survival rates among breast cancer patients have drawn significant attention to consequences of both the presence of cancer, and the subsequent treatment-related impact on the brain. The incidence of breast cancer and the effects of treatment often result in alterations in the microstructure of white matter and impaired cognitive functioning. However, physical activity is proving to be a successful modifiable lifestyle factor in many studies that could prove beneficial to breast cancer survivors. This study investigates the link between white matter lesion volume, moderate physical activity, and cognition in breast cancer survivors following treatment compared to non-cancer age-matched controls. Results revealed that brain structure significantly predicted cognitive function via mediation of physical activity in breast cancer survivors. Overall, the study provided preliminary evidence suggesting moderate physical activity may help reduce the treatment related risks associated with breast cancer, including changes to WM integrity and cognitive impairment. PMID:26915025

  7. Breast Cancer Overview

    Science.gov (United States)

    ... Other less common types of breast cancer include: Medullary Mucinous Tubular Metaplastic Papillary breast cancer Inflammatory breast cancer is a faster-growing type of cancer that accounts for about 1% to 5% of all breast cancers. Paget’s disease is a type of cancer that begins in ...

  8. Factors Associated with Preoperative Magnetic Resonance Imaging Use among Medicare Beneficiaries with Nonmetastatic Breast Cancer.

    Science.gov (United States)

    Henderson, Louise M; Weiss, Julie; Hubbard, Rebecca A; O'Donoghue, Cristina; DeMartini, Wendy B; Buist, Diana S M; Kerlikowske, Karla; Goodrich, Martha; Virnig, Beth; Tosteson, Anna N A; Lehman, Constance D; Onega, Tracy

    2016-01-01

    Preoperative breast magnetic resonance imaging (MRI) use among Medicare beneficiaries with breast cancer has substantially increased from 2005 to 2009. We sought to identify factors associated with preoperative breast MRI use among women diagnosed with ductal carcinoma in situ (DCIS) or stage I-III invasive breast cancer (IBC). Using Surveillance, Epidemiology, and End Results and Medicare data from 2005 to 2009 we identified women ages 66 and older with DCIS or stage I-III IBC who underwent breast-conserving surgery or mastectomy. We compared preoperative breast MRI use by patient, tumor and hospital characteristics stratified by DCIS and IBC using multivariable logistic regression. From 2005 to 2009, preoperative breast MRI use increased from 5.9% to 22.4% of women diagnosed with DCIS and 7.0% to 24.3% of women diagnosed with IBC. Preoperative breast MRI use was more common among women who were younger, married, lived in higher median income zip codes and had no comorbidities. Among women with IBC, those with lobular disease, smaller tumors (2 cm). The likelihood of receiving preoperative breast MRI is similar for women diagnosed with DCIS and IBC. Use of MRI is more common in women with IBC for tumors that are lobular and smaller while for DCIS MRI is used for evaluation of larger lesions. PMID:26511204

  9. Breast cancer screenings

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000837.htm Breast cancer screenings To use the sharing features on this page, please enable JavaScript. Breast cancer screenings can help find breast cancer early, before ...

  10. Male Breast Cancer

    Science.gov (United States)

    Although breast cancer is much more common in women, men can get it too. It happens most often to men between ... 60 and 70. Breast lumps usually aren't cancer. However, most men with breast cancer have lumps. ...

  11. Male Breast Cancer

    Science.gov (United States)

    Although breast cancer is much more common in women, men can get it too. It happens most often to men ... usually aren't cancer. However, most men with breast cancer have lumps. Other breast symptoms can include Dimpled ...

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

    OpenAIRE

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

    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 ...

  13. Low expression of TFPI-2 associated with poor survival outcome in patients with breast cancer

    International Nuclear Information System (INIS)

    The purpose of this study is to evaluate the prognostic value of TFPI-2 expression in breast cancer patients through examining the correlation between TFPI-2 expression and breast cancer clinicopathologic features. Immunohistochemical staining combined with digital image analysis was used to quantify the expression of TFPI-2 protein in breast tumor tissues. For evaluation of the prognostic value of TFPI-2 expression to each clinicopathologic factor, Kaplan-Meier method and COX’s Proportional Hazard Model were employed. TFPI-2 expression was significantly correlated with tumor size, lymph node metastasis, histologic grade, clinical stage, and vessel invasion. More importantly, TFPI-2 expression was also associated with disease-free survival (DFS) of breast cancer patients. We found that patients with high TFPI-2 expression had longer DFS compared with those with low or negative expression of TFPI-2 (P <0.05, log-rank test). Cox’s regression analysis indicated that TFPI-2 expression, histologic grade, and vessel invasion might be significant prognostic factors for DFS, while TFPI-2 expression and histologic grade were the most significant independent predictors for tumor recurrence. Compared with the group with low/high TFPI-2 expression, the TFPI-2 negative group was more likely to have tumor relapse. The hazard ratio of DFS is 0.316 (P <0.01). Low or negative expression of TFPI-2 is associated with breast cancer progression, recurrence and poor survival outcome after breast cancer surgery. TFPI-2 expression in breast tumors is a potential prognostic tool for breast cancer patients

  14. Associations of ATR and CHEK1 single nucleotide polymorphisms with breast cancer.

    Directory of Open Access Journals (Sweden)

    Wei-Yu Lin

    Full Text Available DNA damage and replication checkpoints mediated by the ATR-CHEK1 pathway are key to the maintenance of genome stability, and both ATR and CHEK1 have been proposed as potential breast cancer susceptibility genes. Many novel variants recently identified by the large resequencing projects have not yet been thoroughly tested in genome-wide association studies for breast cancer susceptibility. We therefore used a tagging SNP (tagSNP approach based on recent SNP data available from the 1000 genomes projects, to investigate the roles of ATR and CHEK1 in breast cancer risk and survival. ATR and CHEK1 tagSNPs were genotyped in the Sheffield Breast Cancer Study (SBCS; 1011 cases and 1024 controls using Illumina GoldenGate assays. Untyped SNPs were imputed using IMPUTE2, and associations between genotype and breast cancer risk and survival were evaluated using logistic and Cox proportional hazard regression models respectively on a per allele basis. Significant associations were further examined in a meta-analysis of published data or confirmed in the Utah Breast Cancer Study (UBCS. The most significant associations for breast cancer risk in SBCS came from rs6805118 in ATR (p=7.6 x 10(-5 and rs2155388 in CHEK1 (p=3.1 x 10(-6, but neither remained significant after meta-analysis with other studies. However, meta-analysis of published data revealed a weak association between the ATR SNP rs1802904 (minor allele frequency is 12% and breast cancer risk, with a summary odds ratio (confidence interval of 0.90 (0.83-0.98 [p=0.0185] for the minor allele. Further replication of this SNP in larger studies is warranted since it is located in the target region of 2 microRNAs. No evidence of any survival effects of ATR or CHEK1 SNPs were identified. We conclude that common alleles of ATR and CHEK1 are not implicated in breast cancer risk or survival, but we cannot exclude effects of rare alleles and of common alleles with very small effect sizes.

  15. Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the Breast Cancer Association Consortium: a combined case-control study.

    OpenAIRE

    Milne, Roger L.; Gaudet, Mia M.; Spurdle, Amanda B.; Fasching, Peter A.; Couch, Fergus J.; Benitez, Javier; Arias Perez, Jose Ignacio; Zamora, Maria Pilar; Malats, Nuria; dos Santos Silva, Isabel; Gibson, Lorna J.; Fletcher, Olivia; Johnson, Nichola; Anton-Culver, Hoda; Ziogas, Argyrios

    2010-01-01

    Abstract Introduction Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating in the Breast Cancer Association Consortium. Methods We evaluated two-way interactions between each of age at menarche, ever having had a live birth, number of liv...

  16. Preeclampsia and breast cancer

    DEFF Research Database (Denmark)

    Pacheco, Nadja Livia Pekkola; Andersen, Anne-Marie Nybo; Kamper-Jørgensen, Mads

    2015-01-01

    BACKGROUND: In parous women preeclampsia has been associated with reduced risk of developing breast cancer. Characteristics of births following preeclamptic pregnancies may help understand mechanisms involved in the breast cancer risk reduction inferred by preeclampsia. METHODS: We conducted...... a register-based cohort study of all Danish women giving birth during 1978-2010 (n = 778,701). The association between preeclampsia and breast cancer was evaluated overall and according to birth characteristics by means of incidence rate ratios (IRR) estimated in Poisson regression models. RESULTS: Compared...... with women with non-preeclamptic pregnancies only, women with one or more preeclamptic pregnancies were 19% significantly less likely to develop breast cancer (IRR = 0.81 [95% CI 0.72-0.93]). We found some indication of greater risk reduction in women with term births, one or more previous births...

  17. Up-regulation of microRNA-10b is associated with the development of breast cancer brain metastasis

    OpenAIRE

    Ahmad, Aamir; Sethi, Seema; Chen, Wei; Ali-Fehmi, Rouba; Mittal, Sandeep; Fazlul H. Sarkar

    2014-01-01

    Brain metastases from primary breast cancer are difficult to treat and associated with poor prognosis. Our understanding of the molecular basis for the development of such cancers is sparse. We hypothesized that the pro-metastatic microRNA-10b (miR-10b) plays a role in breast cancer brain metastasis. The study cohort comprised of twenty patients with breast cancer and brain metastasis as well as ten control patients (age, stage, and follow-up matched) with breast cancer without brain metastas...

  18. A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population

    DEFF Research Database (Denmark)

    Antoniou, Antonis C; Wang, Xianshu; Fredericksen, Zachary S;

    2010-01-01

    Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagn...

  19. A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population

    NARCIS (Netherlands)

    Antoniou, Antonis C.; Wang, Xianshu; Fredericksen, Zachary S.; McGuffog, Lesley; Tarrell, Robert; Sinilnikova, Olga M.; Healey, Sue; Morrison, Jonathan; Kartsonaki, Christiana; Lesnick, Timothy; Ghoussaini, Maya; Barrowdale, Daniel; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Eccles, Diana; Evans, D. Gareth; Eeles, Ros; Izatt, Louise; Chu, Carol; Douglas, Fiona; Paterson, Joan; Stoppa-Lyonnet, Dominique; Houdayer, Claude; Mazoyer, Sylvie; Giraud, Sophie; Lasset, Christine; Remenieras, Audrey; Caron, Olivier; Hardouin, Agnes; Berthet, Pascaline; Hogervorst, Frans B. L.; Rookus, Matti A.; Jager, Agnes; van den Ouweland, Ans; Hoogerbrugge, Nicoline; van der Luijt, Rob B.; Meijers-Heijboer, Hanne; Garcia, Encarna B. Gomez; Devilee, Peter; Vreeswijk, Maaike P. G.; Lubinski, Jan; Jakubowska, Anna; Gronwald, Jacek; Huzarski, Tomasz; Byrski, Tomasz; Gorski, Bohdan; Cybulski, Cezary; Spurdle, Amanda B.; Holland, Helene; Goldgar, David E.; John, Esther M.; Hopper, John L.; Southey, Melissa; Buys, Saundra S.; Daly, Mary B.; Terry, Mary-Beth; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Preisler-Adams, Sabine; Arnold, Norbert; Niederacher, Dieter; Sutter, Christian; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy; Blum, Joanne L.; Piedmonte, Marion; Rodriguez, Gustavo C.; Wakeley, Katie; Boggess, John F.; Basil, Jack; Blank, Stephanie V.; Friedman, Eitan; Kaufman, Bella; Laitman, Yael; Milgrom, Roni; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Kirchhoff, Tomas; Vijai, Joseph; Gaudet, Mia M.; Altshuler, David; Guiducci, Candace; Loman, Niklas; Harbst, Katja; Rantala, Johanna; Ehrencrona, Hans; Gerdes, Anne-Marie; Thomassen, Mads; Sunde, Lone; Peterlongo, Paolo; Manoukian, Siranoush; Bonanni, Bernardo; Viel, Alessandra; Radice, Paolo; Caldes, Trinidad; de la Hoya, Miguel; Singer, Christian F.; Fink-Retter, Anneliese; Greene, Mark H.; Mai, Phuong L.; Loud, Jennifer T.; Guidugli, Lucia; Lindor, Noralane M.; Hansen, Thomas V. O.; Nielsen, Finn C.; Blanco, Ignacio; Lazaro, Conxi; Garber, Judy; Ramus, Susan J.; Gayther, Simon A.; Phelan, Catherine; Narod, Stephen; Szabo, Csilla I.; Benitez, Javier; Osorio, Ana; Nevanlinna, Heli; Heikkinen, Tuomas; Caligo, Maria A.; Beattie, Mary S.; Hamann, Ute; Godwin, Andrew K.; Montagna, Marco; Casella, Cinzia; Neuhausen, Susan L.; Karlan, Beth Y.; Tung, Nadine; Toland, Amanda E.; Weitzel, Jeffrey; Olopade, Olofunmilayo; Simard, Jacques; Soucy, Penny; Rubinstein, Wendy S.; Arason, Adalgeir; Rennert, Gad; Martin, Nicholas G.; Montgomery, Grant W.; Chang-Claude, Jenny; Flesch-Janys, Dieter; Brauch, Hiltrud; Severi, Gianluca; Baglietto, Laura; Cox, Angela; Cross, Simon S.; Miron, Penelope; Gerty, Sue M.; Tapper, William; Yannoukakos, Drakoulis; Fountzilas, George; Fasching, Peter A.; Beckmann, Matthias W.; Silva, Isabel dos Santos; Peto, Julian; Lambrechts, Diether; Paridaens, Robert; Ruediger, Thomas; Foersti, Asta; Winqvist, Robert; Pylkaes, Katri; Diasio, Robert B.; Lee, Adam M.; Eckel-Passow, Jeanette; Vachon, Celine; Blows, Fiona; Driver, Kristy; Dunning, Alison; Pharoah, Paul P. D.; Offit, Kenneth; Pankratz, V. Shane; Hakonarson, Hakon; Chenevix-Trench, Georgia; Easton, Douglas F.; Couch, Fergus J.

    2010-01-01

    Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosi

  20. A genome-wide association study of breast cancer in women of African ancestry

    OpenAIRE

    Chen, Fang; Chen, Gary K.; Stram, Daniel O.; Millikan, Robert C.; Ambrosone, Christine B.; John, Esther M; Bernstein, Leslie; Zheng, Wei; Palmer, Julie R.; Jennifer J Hu; Rebbeck, Tim R.; Ziegler, Regina G.; Nyante, Sarah; Bandera, Elisa V.; Sue A Ingles

    2012-01-01

    Genome-wide association studies (GWAS) in diverse populations are needed to reveal variants that are more common and/or limited to defined populations. We conducted a GWAS of breast cancer in women of African ancestry, with genotyping of > 1,000,000 SNPs in 3,153 African American cases and 2,831 controls, and replication testing of the top 66 associations in an additional 3,607 breast cancer cases and 11,330 controls of African ancestry. Two of the 66 SNPs replicated (p < 0.05) in stage 2, wh...

  1. The association between glucose-lowering drug use and mortality among breast cancer patients with type 2 diabetes.

    Science.gov (United States)

    Vissers, Pauline A J; Cardwell, Chris R; van de Poll-Franse, Lonneke V; Young, Ian S; Pouwer, Frans; Murray, Liam J

    2015-04-01

    This study assessed the association between glucose-lowering drug (GLD) use, including metformin, sulphonylurea derivatives and insulin, after breast cancer diagnosis and breast cancer-specific and all-cause mortality. 1763 breast cancer patients, diagnosed between 1998 and 2010, with type 2 diabetes were included. Cancer information was retrieved from English cancer registries, prescription data from the UK Clinical Practice Research Datalink and mortality data from the Office of National Statistics (up to January 2012). Time-varying Cox regression models were used to calculate HRs and 95 % CIs for the association between GLD use and breast cancer-specific and all-cause mortality. In 1057 patients with diabetes before breast cancer, there was some evidence that breast cancer-specific mortality decreased with each year of metformin use (adjusted HR 0.88; 95 % CI 0.75-1.04), with a strong association seen with over 2 years of use (adjusted HR 0.47; 95 % CI 0.26-0.82). Sulphonylurea derivative use for less than 2 years was associated with increased breast cancer-specific mortality (adjusted HR 1.70; 95 % CI 1.18-2.46), but longer use was not (adjusted HR 0.94; 95 % CI 0.54-1.66). In 706 patients who developed diabetes after breast cancer, similar patterns were seen for metformin, but sulphonylurea derivative use was strongly associated with cancer-specific mortality (adjusted HR 3.64; 95 % CI 2.16-6.16), with similar estimates for short- and long-term users. This study provides some support for an inverse association between, mainly long-term, metformin use and (breast cancer-specific) mortality. In addition, sulphonylurea derivative use was associated with increased breast cancer-specific mortality, but this should be interpreted cautiously, as it could reflect selective prescribing in advanced cancer patients. PMID:25762476

  2. Breast cancer risk factors

    OpenAIRE

    Marzena Kamińska; Tomasz Ciszewski; Karolina Łopacka-Szatan; Paweł Miotła; Elżbieta Starosławska

    2015-01-01

    Breast cancer is the most frequently diagnosed neoplastic disease in women around menopause often leading to a significant reduction of these women's ability to function normally in everyday life. The increased breast cancer incidence observed in epidemiological studies in a group of women actively participating in social and professional life implicates the necessity of conducting multidirectional studies in order to identify risk factors associated with the occurrence of this type of neopla...

  3. Diet and breast cancer

    OpenAIRE

    Isabelle Romieu

    2011-01-01

    Both diet and nutrition have been studied in relationship with breast cancer risk, as the great variation among different countries in breast cancer incidence could possibly be explained through the inflammatory and immune response, as well as antioxidant intake, among others.To date, no clear association with diet beyond overweight and weight gain has been found, except for alcohol consumption. Nonetheless, the small number of studies done in middle to low income countries where variability ...

  4. Targeting Breast Cancer Metastasis

    OpenAIRE

    Xin Jin; Ping Mu

    2015-01-01

    Metastasis is the leading cause of breast cancer-associated deaths. Despite the significant improvement in current therapies in extending patient life, 30–40% of patients may eventually suffer from distant relapse and succumb to the disease. Consequently, a deeper understanding of the metastasis biology is key to developing better treatment strategies and achieving long-lasting therapeutic efficacies against breast cancer. This review covers recent breakthroughs in the discovery of various me...

  5. The association between different night shiftwork factors and breast cancer: a case–control study

    Science.gov (United States)

    Fritschi, L; Erren, T C; Glass, D C; Girschik, J; Thomson, A K; Saunders, C; Boyle, T; El-Zaemey, S; Rogers, P; Peters, S; Slevin, T; D'Orsogna, A; de Vocht, F; Vermeulen, R; Heyworth, J S

    2013-01-01

    Background: Research on the possible association between shiftwork and breast cancer is complicated because there are many different shiftwork factors, which might be involved including: light at night, phase shift, sleep disruption and changes in lifestyle factors while on shiftwork (diet, physical activity, alcohol intake and low sun exposure). Methods: We conducted a population-based case–control study in Western Australia from 2009 to 2011 with 1205 incident breast cancer cases and 1789 frequency age-matched controls. A self-administered questionnaire was used to collect demographic, reproductive, and lifestyle factors and lifetime occupational history and a telephone interview was used to obtain further details about the shiftwork factors listed above. Results: A small increase in risk was suggested for those ever doing the graveyard shift (work between midnight and 0500 hours) and breast cancer (odds ratio (OR)=1.16, 95% confidence interval (CI)=0.97–1.39). For phase shift, we found a 22% increase in breast cancer risk (OR=1.22, 95% CI=1.01–1.47) with a statistically significant dose–response relationship (P=0.04). For the other shiftwork factors, risks were marginally elevated and not statistically significant. Conclusion: We found some evidence that some of the factors involved in shiftwork may be associated with breast cancer but the ORs were low and there were inconsistencies in duration and dose–response relationships. PMID:24022188

  6. Association of interleukin-10 gene polymorphisms with breast cancer in a Chinese population

    Directory of Open Access Journals (Sweden)

    Song Bao

    2010-06-01

    Full Text Available Abstract Backgroud Interleukin-10(IL-10 is a multifunctional cytokine with both immunosuppressive and antiangiogenic functions. Polymorphisms in the IL-10 gene promoter genetically determine interindividual differences in IL-10 production. This study was performed to determined whether polymorphisms in the IL-10 gene promoter were associated with breast cancer in a Chinese Han population. Methods We genotyped 315 patients with breast cancer and 322 healthy control subjects for -1082A/G, -819T/C and -592A/C single nucleotide polymorphisms in the promoter region of the IL-10 gene by polymerase chain reactionerestriction fragment length polymorphism (PCR-RFLP. Results There were no significant differences in genotype, allele, or haplotype frequencies in all three loci between patients and healthy controls. Analysis of breast cancer prognostic and predictive factors revealed that the -1082AA genotype was associated with a significantly increased risk of lymph node (LN involvement (P = 0.041 and larger tumor size (P = 0.039 at the time of diagnosis. Furthermore, in the haplotype analysis of IL-10 gene, we found that patients carrying ATA haplotype were in higher LN involvement (p = 0.022 and higher tumor stage(p = 0.028 of breast cancer at the time of diagnosis compared with others. Conclusions Our findings suggest that IL-10 promoter polymorphisms participate in the progression of breast cancer rather than in its initial development in Chinese Han women.

  7. Breast cancer risk and 6q22.33: combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2.

    Directory of Open Access Journals (Sweden)

    Tomas Kirchhoff

    Full Text Available Recently, a locus on chromosome 6q22.33 (rs2180341 was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC. In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA. Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR = 1.03, 95% CI 1.00-1.06, p = 0.023. There was evidence for heterogeneity in the ORs among studies (I(2 = 49.3%; p = <0.004. In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95%CI 0.80-1.00, p = 0.048, indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk.

  8. Enhanced NFκB and AP-1 transcriptional activity associated with antiestrogen resistant breast cancer

    International Nuclear Information System (INIS)

    Signaling pathways that converge on two different transcription factor complexes, NFκB and AP-1, have been identified in estrogen receptor (ER)-positive breast cancers resistant to the antiestrogen, tamoxifen. Two cell line models of tamoxifen-resistant ER-positive breast cancer, MCF7/HER2 and BT474, showing increased AP-1 and NFκB DNA-binding and transcriptional activities, were studied to compare tamoxifen effects on NFκB and AP-1 regulated reporter genes relative to tamoxifen-sensitive MCF7 cells. The model cell lines were treated with the IKK inhibitor parthenolide (PA) or the proteasome inhibitor bortezomib (PS341), alone and in combination with tamoxifen. Expression microarray data available from 54 UCSF node-negative ER-positive breast cancer cases with known clinical outcome were used to search for potential genes signifying upregulated NFκB and AP-1 transcriptional activity in association with tamoxifen resistance. The association of these genes with patient outcome was further evaluated using node-negative ER-positive breast cancer cases identified from three other published data sets (Rotterdam, n = 209; Amsterdam, n = 68; Basel, n = 108), each having different patient age and adjuvant tamoxifen treatment characteristics. Doses of parthenolide and bortezomib capable of sensitizing the two endocrine resistant breast cancer models to tamoxifen were capable of suppressing NFκB and AP-1 regulated gene expression in combination with tamoxifen and also increased ER recruitment of the transcriptional co-repressor, NCoR. Transcript profiles from the UCSF breast cancer cases revealed three NFκB and AP-1 upregulated genes – cyclin D1, uPA and VEGF – capable of dichotomizing node-negative ER-positive cases into early and late relapsing subsets despite adjuvant tamoxfien therapy and most prognostic for younger age cases. Across the four independent sets of node-negative ER-positive breast cancer cases (UCSF, Rotterdam, Amsterdam, Basel), high expression of

  9. Enhanced NFκB and AP-1 transcriptional activity associated with antiestrogen resistant breast cancer

    Directory of Open Access Journals (Sweden)

    Moore Dan H

    2007-04-01

    Full Text Available Abstract Background Signaling pathways that converge on two different transcription factor complexes, NFκB and AP-1, have been identified in estrogen receptor (ER-positive breast cancers resistant to the antiestrogen, tamoxifen. Methods Two cell line models of tamoxifen-resistant ER-positive breast cancer, MCF7/HER2 and BT474, showing increased AP-1 and NFκB DNA-binding and transcriptional activities, were studied to compare tamoxifen effects on NFκB and AP-1 regulated reporter genes relative to tamoxifen-sensitive MCF7 cells. The model cell lines were treated with the IKK inhibitor parthenolide (PA or the proteasome inhibitor bortezomib (PS341, alone and in combination with tamoxifen. Expression microarray data available from 54 UCSF node-negative ER-positive breast cancer cases with known clinical outcome were used to search for potential genes signifying upregulated NFκB and AP-1 transcriptional activity in association with tamoxifen resistance. The association of these genes with patient outcome was further evaluated using node-negative ER-positive breast cancer cases identified from three other published data sets (Rotterdam, n = 209; Amsterdam, n = 68; Basel, n = 108, each having different patient age and adjuvant tamoxifen treatment characteristics. Results Doses of parthenolide and bortezomib capable of sensitizing the two endocrine resistant breast cancer models to tamoxifen were capable of suppressing NFκB and AP-1 regulated gene expression in combination with tamoxifen and also increased ER recruitment of the transcriptional co-repressor, NCoR. Transcript profiles from the UCSF breast cancer cases revealed three NFκB and AP-1 upregulated genes – cyclin D1, uPA and VEGF – capable of dichotomizing node-negative ER-positive cases into early and late relapsing subsets despite adjuvant tamoxfien therapy and most prognostic for younger age cases. Across the four independent sets of node-negative ER-positive breast cancer cases

  10. Fine-scale mapping of the 4q24 locus identifies two independent loci associated with breast cancer risk

    DEFF Research Database (Denmark)

    Guo, Xingyi; Long, Jirong; Zeng, Chenjie;

    2015-01-01

    BACKGROUND: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. METHODS: We conducted a fine-mapping analysis in 55,540 breast...... cancer cases and 51,168 controls from the Breast Cancer Association Consortium. RESULTS: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10(-4); OR, 1.04; 95% confidence interval (CI), 1.02-1.07] and rs......62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. CONCLUSION: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2...

  11. Dietary fiber is associated with circulating concentrations of C-reactive protein in breast cancer survivors: the HEAL study

    OpenAIRE

    Villaseñor, Adriana; Ambs, Anita; Ballard-Barbash, Rachel; Baumgartner, Kathy B.; McTiernan, Anne; Ulrich, Cornelia M; Neuhouser, Marian L.

    2011-01-01

    Inflammation is a suspected risk factor for breast cancer and its subsequent prognosis. The extent to which dietary and lifestyle factors might influence inflammation is important to examine. Specifically, dietary fiber may reduce systemic inflammation, but this relationship has not been examined among breast cancer survivors. We examined associations between dietary fiber and serum concentrations of C-reactive protein (CRP) and serum amyloid-A (SAA), among 698 female breast cancer survivors ...

  12. Differential promoter methylation of kinesin family member 1a in plasma is associated with breast cancer and DNA repair capacity.

    Science.gov (United States)

    Guerrero-Preston, Rafael; Hadar, Tal; Ostrow, Kimberly Laskie; Soudry, Ethan; Echenique, Miguel; Ili-Gangas, Carmen; Pérez, Gabriela; Perez, Jimena; Brebi-Mieville, Priscilla; Deschamps, José; Morales, Luisa; Bayona, Manuel; Sidransky, David; Matta, Jaime

    2014-08-01

    Methylation alterations of CpG islands, CpG island shores and first exons are key events in the formation and progression of human cancer, and an increasing number of differentially methylated regions and genes have been identified in breast cancer. Recent studies of the breast cancer methylome using deep sequencing and microarray platforms are providing a novel insight on the different roles aberrant methylation plays in molecular subtypes of breast cancer. Accumulating evidence from a subset of studies suggests that promoter methylation of tumor-suppressor genes associated with breast cancer can be quantified in circulating DNA. However, there is a paucity of studies that examine the combined presence of genetic and epigenetic alterations associated with breast cancer using blood-based assays. Dysregulation of DNA repair capacity (DRC) is a genetic risk factor for breast cancer that has been measured in lymphocytes. We isolated plasma DNA from 340 participants in a breast cancer case control project to study promoter methylation levels of five genes previously shown to be associated with breast cancer in frozen tissue and in cell line DNA: MAL, KIF1A, FKBP4, VGF and OGDHL. Methylation of at least one gene was found in 49% of the cases compared to 20% of the controls. Three of the four genes had receiver characteristic operator curve values of ≥ 0.50: MAL (0.64), KIF1A (0.51) and OGDHL (0.53). KIF1A promoter methylation was associated with breast cancer and inversely associated with DRC. This is the first evidence of a significant association between genetic and epigenetic alterations in breast cancer using blood-based tests. The potential diagnostic utility of these biomarkers and their relevance for breast cancer risk prediction should be examined in larger cohorts. PMID:24927296

  13. Nectin-4 is a new histological and serological tumor associated marker for breast cancer

    International Nuclear Information System (INIS)

    Breast cancer is a complex and heterogeneous disease at the molecular level. Evolution is difficult to predict according to classical histoclinical prognostic factors. Different studies highlight the importance of large-scale molecular expression analyses to improve taxonomy of breast cancer and prognostic classification. Identification of new molecular markers that refine this taxonomy and improve patient management is a priority in the field of breast cancer research. Nectins are cell adhesion molecules involved in the regulation of epithelial physiology. We present here Nectin-4/PVRL4 as a new histological and serological tumor associated marker for breast carcinoma. Expression of Nectin-4 protein was measured on a panel of 78 primary cells and cell lines from different origins and 57 breast tumors by FACS analysis and immunohistochemistry (IHC), respectively. mRNA expression was measured by quantitative PCR. Serum Nectin-4 was detected by ELISA and compared with CEA and CA15.3 markers, on panels of 45 sera from healthy donors, 53 sera from patients with non-metastatic breast carcinoma (MBC) at diagnosis, and 182 sera from patients with MBC. Distribution of histological/serological molecular markers and histoclinical parameters were compared using the standard Chi-2 test. Nectin-4 was not detected in normal breast epithelium. By contrast, Nectin-4 was expressed in 61% of ductal breast carcinoma vs 6% in lobular type. Expression of Nectin-4 strongly correlated with the basal-like markers EGFR, P53, and P-cadherin, and negatively correlated with the luminal-like markers ER, PR and GATA3. All but one ER/PR-negative tumors expressed Nectin-4. The detection of Nectin-4 in serum improves the follow-up of patients with MBC: the association CEA/CA15.3/Nectin-4 allowed to monitor 74% of these patients compared to 67% with the association CEA/CA15.3. Serum Nectin-4 is a marker of disease progression, and levels correlate with the number of metastases (P = 0.038). Serum

  14. Nectin-4 is a new histological and serological tumor associated marker for breast cancer

    Directory of Open Access Journals (Sweden)

    Sauvan Richard

    2007-05-01

    Full Text Available Abstract Introduction Breast cancer is a complex and heterogeneous disease at the molecular level. Evolution is difficult to predict according to classical histoclinical prognostic factors. Different studies highlight the importance of large-scale molecular expression analyses to improve taxonomy of breast cancer and prognostic classification. Identification of new molecular markers that refine this taxonomy and improve patient management is a priority in the field of breast cancer research. Nectins are cell adhesion molecules involved in the regulation of epithelial physiology. We present here Nectin-4/PVRL4 as a new histological and serological tumor associated marker for breast carcinoma. Methods Expression of Nectin-4 protein was measured on a panel of 78 primary cells and cell lines from different origins and 57 breast tumors by FACS analysis and immunohistochemistry (IHC, respectively. mRNA expression was measured by quantitative PCR. Serum Nectin-4 was detected by ELISA and compared with CEA and CA15.3 markers, on panels of 45 sera from healthy donors, 53 sera from patients with non-metastatic breast carcinoma (MBC at diagnosis, and 182 sera from patients with MBC. Distribution of histological/serological molecular markers and histoclinical parameters were compared using the standard Chi-2 test. Results Nectin-4 was not detected in normal breast epithelium. By contrast, Nectin-4 was expressed in 61% of ductal breast carcinoma vs 6% in lobular type. Expression of Nectin-4 strongly correlated with the basal-like markers EGFR, P53, and P-cadherin, and negatively correlated with the luminal-like markers ER, PR and GATA3. All but one ER/PR-negative tumors expressed Nectin-4. The detection of Nectin-4 in serum improves the follow-up of patients with MBC: the association CEA/CA15.3/Nectin-4 allowed to monitor 74% of these patients compared to 67% with the association CEA/CA15.3. Serum Nectin-4 is a marker of disease progression, and levels

  15. Gadolinium-enhanced MR angiography of the breast: Is breast cancer associated with ipsilateral higher vascularity?

    International Nuclear Information System (INIS)

    The aim of this study was to assess a possible association between breast malignancy and ipsilateral higher vascularity on gadolinium-enhanced MR angiography. One hundred six patients were examined by dynamic gadolinium-enhanced 3D MR imaging. Magnetic resonance angiographic views were generated by image subtraction and maximum intensity projection. The study included 85 patients with unilateral malignant breast neoplasms and 21 with unilateral benign lesions. Three blinded readers independently reviewed the MR angiograms after masking the lesions and the corresponding contralateral sites. The readers were asked to determine whether vascularity was higher on the right side, higher on the left side, or equal on both sides. The results were analyzed by the Kappa statistic and Pearson's chi-square test. The blood vessels of the breasts were clearly seen in all cases. There was good agreement among the observers (kappa > 0.54) in assessing vascularity on both sides. Breasts harboring malignant neoplasms were found to have a higher vascularity than the contralateral breasts (p < 0.005). This sign of malignancy had a sensitivity of 76.5 %, a specificity of 57 %, and an accuracy of 72.6 %. Blood vessels of the breast can be depicted by MR angiography. Unilateral malignant neoplasms are associated with a higher ipsilateral vascularity. In conjunction with other indications of malignancy on gadolinium-enhanced MR images, a higher ipsilateral vascularity may serve as an additional sign of malignancy. (orig.)

  16. Factors Associated with Waiting Time for Breast Cancer Treatment in a Teaching Hospital in Ghana

    Science.gov (United States)

    Dedey, Florence; Wu, Lily; Ayettey, Hannah; Sanuade, Olutobi A.; Akingbola, Titilola S.; Hewlett, Sandra A.; Tayo, Bamidele O.; Cole, Helen V.; de-Graft Aikins, Ama; Ogedegbe, Gbenga; Adanu, Richard

    2016-01-01

    Background: Breast cancer is the leading cause of cancer-related mortality among women in Ghana. Data are limited on the predictors of poor outcomes in breast cancer patients in low-income countries; however, prolonged waiting time has been implicated. Among breast cancer patients who received treatment at Korle Bu Teaching Hospital, this study…

  17. Expression level of novel tumor suppressor gene FATS is associated with the outcome of node positive breast cancer

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jun; GU Lin; ZHAO Lu-jun; ZHANG Xi-feng; QIU Li; LI Zheng

    2011-01-01

    Background Recently, we reported the identification of a previously uncharacterized and evolutionarily conserved gene, fragile-site associated tumor suppressor (FATS), at a frequently deleted region in irradiation (IR)-induced tumors.However, the role of FATS in breast cancer development and its clinical significance has not been defined. The aim of this study was to determine the role of FA7S in breast cancer development and to evaluate its clinical significance in breast cancer.Methods The expression level of FATS mRNA was determined in 106 breast carcinomas and 23 paired normal breast tissues using quantitative real time reverse transcription-polymerase chain reaction (RT-PCR). The relationship between FATS expression and clinicopathological parameters were also analyzed.Results The mRNA level of FATS was down-regulated in breast cancer compared with paired normal tissues. Low expression of FATS was correlated with high nuclear grade. There was a tendency to a favorable outcome for patients with high expression of FATS (P=0.346). However, low expression of FATS was associated with poor outcome of breast cancer patients with node positive (P=0.011). Furthermore, the mRNA level of FATS showed an independent value in predicting the outcome of breast cancer patients with positive lymph nodes.Conclusion FATS is involved in the carcinogenesis and development of breast cancer and could be a potential biomarker and prognostic factor for breast cancer therapy.

  18. IL-17 expression by breast-cancer-associated macrophages: IL-17 promotes invasiveness of breast cancer cell lines

    OpenAIRE

    ZHU, XINGWU; Mulcahy, Lori A; Mohammed, Rabab AA; Lee, Andrew HS; Franks, Hester A; Kilpatrick, Laura; Yilmazer, Acelya; Paish, E. Claire; Ellis, Ian O; Patel, Poulam M; Jackson, Andrew M

    2008-01-01

    Introduction IL-17 plays an important role in autoimmunity, promoting autoimmunity, inflammation and invasion in multiple sclerosis, rheumatoid arthritis and type I diabetes. The role of IL-17 in cancer is unclear, however, as there are few studies examining IL-17 protein expression in cancer. We therefore examined IL-17 protein expression in human breast cancer and modelled its potential biological significance in vitro. Methods Immunohistochemistry was used to determine IL-17 expression in ...

  19. A human monoclonal autoantibody to breast cancer identifies the PDZ domain containing protein GIPC1 as a novel breast cancer-associated antigen

    International Nuclear Information System (INIS)

    We have been studying the native autoimmune response to cancer through the isolation of human monoclonal antibodies that are cancer specific from cancer patients. To facilitate this work we previously developed a fusion partner cell line for human lymphocytes, MFP-2, that fuses efficiently with both human lymph node lymphocytes and peripheral blood lymphocytes. Using this unique trioma fusion partner cell line we isolated a panel of autologous human monoclonal antibodies, from both peripheral blood and lymph node lymphocytes, which are representative of the native repertoire of anti-cancer specific antibodies from breast cancer patients. The current study employs immunocytochemistry, immunohistochemistry, Western blot analysis as well as Northern blots, Scatchard binding studies and finally SEREX analysis for target antigen identification. By application of an expression cloning technique known as SEREX, we determined that the target antigen for two monoclonal antibodies, 27.B1 and 27.F7, derived from lymph node B-cells of a breast cancer patient, is the PDZ domain-containing protein known as GIPC1. This protein is highly expressed not only in cultured human breast cancer cells, but also in primary and metastatic tumor tissues and its overexpression appears to be cancer cell specific. Confocal microscopy revealed cell membrane and cytoplasmic localization of the target protein, which is consistent with previous studies of this protein. We have determined that GIPC1 is a novel breast cancer-associated immunogenic antigen that is overexpressed in breast cancer. Its role, however, in the initiation and/or progression of breast cancer remains unclear and needs further clarification

  20. Breast Cancer Disparities

    Science.gov (United States)

    ... 2.65 MB] Read the MMWR Science Clips Breast Cancer Black Women Have Higher Death Rates from Breast ... of Page U.S. State Info Number of Additional Breast Cancer Deaths Among Black Women, By State SOURCE: National ...

  1. Breast cancer

    International Nuclear Information System (INIS)

    This book contains outstanding papers presented at the 3rd International Copenhagen Symposium on Detection of Breast Cancer, 1985. The Symposium was an opportunity to learn from extensive screening procedures carried out at outstanding centers in the United States, Sweden, the Netherlands, and England. Furthermore, the symposium dealt with new modalities such as ultrasonography, magnification techniques, and magnetic resonance; and very important contributions concerning self-examination, fine needle aspiration biopsy, and radiation risks were presented. A whole section was also dedicated to the highly important cooperation between radiologist, surgeon, and pathologist. (orig./MG)

  2. The 'Pokemon' (ZBTB7) Gene: No Evidence of Association with Sporadic Breast Cancer.

    Science.gov (United States)

    Salas, Antonio; Vega, Ana; Milne, Roger L; García-Magariños, Manuel; Ruibal, Alvaro; Benítez, Javier; Carracedo, Angel

    2008-01-01

    It has been proposed that the excess of familiar risk associated with breast cancer could be explained by the cumulative effect of multiple weakly predisposing alleles. The transcriptional repressor FBI1, also known as Pokemon, has recently been identified as a critical factor in oncogenesis. This protein is encoded by the ZBTB7 gene. Here we aimed to determine whether polymorphisms in ZBTB7 are associated with breast cancer risk in a sample of cases and controls collected in hospitals from North and Central Spanish patients. We genotyped 15 SNPs in ZBTB7, including the flanking regions, with an average coverage of 1 SNP/2.4 Kb, in 360 sporadic breast cancer cases and 402 controls. Comparison of allele, genotype and haplotype frequencies between cases and controls did not reveal associations using Pearson's chi-square test and a permutation procedure to correct for multiple test. In this, the first study of the ZBTB7 gene in relation to, sporadic breast cancer, we found no evidence of an association. PMID:21892298

  3. The ‘Pokemon’ (ZBTB7 Gene: No Evidence of Association with Sporadic Breast Cancer

    Directory of Open Access Journals (Sweden)

    Antonio Salas

    2008-01-01

    Full Text Available It has been proposed that the excess of familiar risk associated with breast cancer could be explained by the cumulative effect of multiple weakly predisposing alleles. The transcriptional repressor FBI1, also known as Pokemon, has recently been identified as a critical factor in oncogenesis. This protein is encoded by the ZBTB7 gene. Here we aimed to determine whether polymorphisms in ZBTB7 are associated with breast cancer risk in a sample of cases and controls collected in hospitals from North and Central Spanish patients. We genotyped 15 SNPs in ZBTB7, including the flanking regions, with an average coverage of 1 SNP/2.4 Kb, in 360 sporadic breast cancer cases and 402 controls. Comparison of allele, genotype and haplotype frequencies between cases and controls did not reveal associations using Pearson’s chi-square test and a permutation procedure to correct for multiple test. In this, the first study of the ZBTB7 gene in relation to, sporadic breast cancer, we found no evidence of an association.

  4. Genetic variation at CYP3A is associated with age at menarche and breast cancer risk

    DEFF Research Database (Denmark)

    Johnson, Nichola; Dudbridge, Frank; Orr, Nick;

    2014-01-01

    INTRODUCTION: We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age <=50 years. METHO...

  5. Weight Change and Associated Factors in Long-Term Breast Cancer Survivors

    Science.gov (United States)

    Koo, Hye-Yeon; Seo, Young-Gyun; Cho, Mi-Hee; Kim, Min-Jung; Choi, Ho-Chun

    2016-01-01

    Purpose Weight gain often occurs after breast cancer diagnosis and significantly impacts the general health of cancer survivors. While the number of breast cancer survivors is increasing, few studies have reported data on weight change beyond 5 years post-diagnosis. We investigated weight change and associated factors in long-term survivors of breast cancer. Patients and Methods Medical records were reviewed on 1363 breast cancer patients and a total of 822 women who had survived beyond 5 years since diagnosis were included in the final analysis. The association between demographic, anthropometric, lifestyle, cancer related factors (including time since diagnosis, treatment modality, pathologic stage, and hormone receptor status), and weight-change over 5 years were examined. Results During an average 8.2 years of follow-up time, mean weight gain was 0.32kg (p = 0.017). 175 (21.3%) patients had gained more than 5% of their weight at diagnosis and their average gain was 5.55kg. Body mass index (BMI) at diagnosis, age at diagnosis, aromatase inhibitor (AI) use, heavy drinking, and type of surgery were associated with relative weight gain (≥5%) in univariate analysis (all p-valuesAI showed odds ratio of 2.2 (p = 0.006) relative to women who did. Conclusion Long-term breast cancer survivors who were non-obese at diagnosis are more likely to gain weight than obese survivors. Younger survivors and survivors who have never used AI are also likely to gain weight. PMID:27391162

  6. Diagnosis and Treatment Experience of 14 Cases of Breast Cancer Associated with Pregnancy or Lactation

    Institute of Scientific and Technical Information of China (English)

    ZHENG Zhixiang; WU Zhiyong

    2006-01-01

    Objective: To explore the diagnosis and treatment experience of breast cancer associated with pregnancy or lactation. Methods: From January 1990 to December 2005, 14 cases with breast cancer associated with pregnancy or lactation were analyzed retrospectively (TNM stage Ⅱ, 2 cases; stage Ⅲ, 11 cases; stage Ⅳ, 1 case). Diagnosis was established by fine needle aspiration biopsy primarily or routine pathological method if necessary. Abortion was used for discontinuation of pregnancy in 1 case with early pregnancy and 1 case with meddle pregnancy. 2 patients with late pregnancy received cesarean section,10patients of breast cancer associated with lactation received multidisciplinary and-tumor treatment after discontinuation of lactation. Results: Diagnosis was confirmed by fine noodle aspiration biopsy in 9 cases and by secondary routine pathological method in the other 5 cases, 12 cases were followed up, 1 case of stage Ⅳ died of metastasis 5 months after diagnosis. 3-, 5-year survival rates in 10 cases of stage Ⅲ were 66% and 30% respectively. One case remained alive without recurrence for 8 years up to now. Conclusion: A thorough breast examination is necessary at the first antenatal visit physicians should aggressively pursue work-up in women with a palpable breast tass. In the patients during the second and third trimness,the various modalities available for treatment inholding abortion and their risks and beneath modalities available for treatment including abortion and their risks and benefits must be discussed openly with patients and their families.

  7. Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC.

    Directory of Open Access Journals (Sweden)

    Rebecca Hein

    Full Text Available The 6q25.1 locus was first identified via a genome-wide association study (GWAS in Chinese women and marked by single nucleotide polymorphism (SNP rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR and 95% confidence intervals (CI. Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+ versus negative (ER- tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G = 1.36 (95% CI 1.26-1.48, p = 7.6 × 10(-14 in Asians and 1.09 (95% CI 1.07-1.11, p = 6.8 × 10(-18 in Europeans. rs12662670: OR (G/T = 1.29 (95% CI 1.19-1.41, p = 1.2 × 10(-9 in Asians and 1.12 (95% CI 1.08-1.17, p = 3.8 × 10(-9 in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER- = 1.20 (95% CI 1.15-1.25, p = 1.8 × 10(-17 versus OR (ER+ = 1.07 (95% CI 1.04-1.1, p = 1.3 × 10(-7, p(heterogeneity = 5.1 × 10(-6]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater

  8. The association between general practitioners’ attitudes towards breast cancer screening and women’s screening participation

    Directory of Open Access Journals (Sweden)

    Jensen Line

    2012-06-01

    Full Text Available Abstract Background Breast cancer screening in Denmark is organised by the health services in the five regions. Although general practitioners (GPs are not directly involved in the screening process, they are often the first point of contact to the health care system and thus play an important advisory role. No previous studies, in a health care setting like the Danish system, have investigated the association between GPs’ attitudes towards breast cancer screening and women’s participation in the screening programme. Methods Data on women’s screening participation was obtained from the regional screening authorities. Data on GPs’ attitudes towards breast cancer screening was taken from a previous survey among GPs in the Central Denmark Region. This study included women aged 50-69 years who were registered with a singlehanded GP who had participated in the survey. Results The survey involved 67 singlehanded GPs with a total of 13,288 women on their lists. Five GPs (7% had a negative attitude towards breast cancer screening. Among registered women, 81% participated in the first screening round. Multivariate analyses revealed that women registered with a GP with a negative attitude towards breast cancer screening were 17% (95% CI: 2-34% more likely to be non-participants compared with women registered with a GP with a positive attitude towards breast cancer screening. Conclusion The GPs' attitudes may influence the participation rate even in a system where GPs are not directly involved in the screening process. However, further studies are needed to investigate this association.

  9. Breast cancer in men

    Science.gov (United States)

    ... in situ-male; Intraductal carcinoma-male; Inflammatory breast cancer-male; Paget disease of the nipple-male; Breast cancer-male ... The cause of breast cancer is not clear. But there are risk ... breast cancer more likely in men: Exposure to radiation Higher ...

  10. Opioids and breast cancer recurrence

    DEFF Research Database (Denmark)

    Cronin-Fenton, Deirdre P; Heide-Jørgensen, Uffe; Ahern, Thomas P;

    2015-01-01

    BACKGROUND: Opioids may alter immune function, thereby potentially affecting cancer recurrence. The authors investigated the association between postdiagnosis opioid use and breast cancer recurrence. METHODS: Patients with incident, early stage breast cancer who were diagnosed during 1996 through...... 2008 in Denmark were identified from the Danish Breast Cancer Cooperative Group Registry. Opioid prescriptions were ascertained from the Danish National Prescription Registry. Follow-up began on the date of primary surgery for breast cancer and continued until breast cancer recurrence, death......, emigration, 10 years, or July 31, 2013, whichever occurred first. Cox regression models were used to compute hazard ratios and 95% confidence intervals associating breast cancer recurrence with opioid prescription use overall and by opioid type and strength, immunosuppressive effect, chronic use (≥6 months...

  11. Dietary isoflavone intake is not statistically significantly associated with breast cancer risk in the Multiethnic Cohort

    OpenAIRE

    Morimoto, Yukiko; Maskarinec, Gertraud; Park, Song-Yi; Ettienne, Reynolette; Matsuno, Rayna K.; Long, Camonia; Steffen, Alana D.; Brian E Henderson; Kolonel, Laurence N; Le Marchand, Loïc; Wilkens, Lynne R.

    2014-01-01

    Given high soy intake and low incidence rates in Asian countries, isoflavones, substances with an estrogen-like structure occurring principally in soybeans, are postulated to be cancer-protective. We examined the association of dietary isoflavone intake with breast cancer risk in 84,450 women (896 in situ and 3,873 invasive cases) who were part of the Multiethnic Cohort (Japanese Americans, whites, Latinos, African Americans, and Native Hawaiians) with wide ranges of soy intake. The absolute ...

  12. DIET QUALITY IS ASSOCIATED WITH THE RISK OF ESTROGEN RECEPTOR-NEGATIVE BREAST CANCER IN POSTMENOPAUSAL WOMEN

    Science.gov (United States)

    Emerging evidence suggests that diet quality indices may serve as prognostic indicators of disease. However, the ability of these indices to predict breast cancer risk has not been evaluated previously. We assessed the association between several diet quality scores and the risk of breast cancer in ...

  13. Association of common variants in mismatch repair genes and breast cancer susceptibility: a multigene study

    Directory of Open Access Journals (Sweden)

    Pina Julieta

    2009-09-01

    Full Text Available Abstract Background MMR is responsible for the repair of base-base mismatches and insertion/deletion loops. Besides this, MMR is also associated with an anti-recombination function, suppressing homologous recombination. Losses of heterozygosity and/or microsatellite instability have been detected in a large number of skin samples from breast cancer patients, suggesting a potential role of MMR in breast cancer susceptibility. Methods We carried out a hospital-based case-control study in a Caucasian Portuguese population (287 cases and 547 controls to estimate the susceptibility to non-familial breast cancer associated with some polymorphisms in mismatch repair genes (MSH3, MSH4, MSH6, MLH1, MLH3, PMS1 and MUTYH. Results Using unconditional logistic regression we found that MLH3 (L844P, G>A polymorphism GA (Leu/Pro and AA (Pro/Pro genotypes were associated with a decreased risk: OR = 0.65 (0.45-0.95 (p = 0.03 and OR = 0.62 (0.41-0.94 (p = 0.03, respectively. Analysis of two-way SNP interaction effects on breast cancer revealed two potential associations to breast cancer susceptibility: MSH3 Ala1045Thr/MSH6 Gly39Glu - AA/TC [OR = 0.43 (0.21-0.83, p = 0.01] associated with a decreased risk; and MSH4 Ala97Thr/MLH3 Leu844Pro - AG/AA [OR = 2.35 (1.23-4.49, p = 0.01], GG/AA [OR = 2.11 (1.12-3,98, p = 0.02], and GG/AG [adjusted OR = 1.88 (1.12-3.15, p = 0.02] all associated with an increased risk for breast cancer. Conclusion It is possible that some of these common variants in MMR genes contribute significantly to breast cancer susceptibility. However, further studies with a large sample size will be needed to support our results.

  14. Association of genetic ancestry with breast cancer in ethnically diverse women from Chicago.

    Directory of Open Access Journals (Sweden)

    Umaima Al-Alem

    Full Text Available INTRODUCTION: Non-Hispanic (nH Black and Hispanic women are disproportionately affected by early onset disease, later stage, and with more aggressive, higher grade and ER/PR negative breast cancers. The purpose of this analysis was to examine whether genetic ancestry could account for these variation in breast cancer characteristics, once data were stratified by self-reported race/ethnicity and adjusted for potential confounding by social and behavioral factors. METHODS: We used a panel of 100 ancestry informative markers (AIMs to estimate individual genetic ancestry in 656 women from the "Breast Cancer Care in Chicago" study, a multi-ethnic cohort of breast cancer patients to examine the association between individual genetic ancestry and breast cancer characteristics. In addition we examined the association of individual AIMs and breast cancer to identify genes/regions that may potentially play a role in breast cancer disease disparities. RESULTS: As expected, nH Black and Hispanic patients were more likely than nH White patients to be diagnosed at later stages, with higher grade, and with ER/PR negative tumors. Higher European genetic ancestry was protective against later stage at diagnosis (OR 0.7 95%CI: 0.54-0.92 among Hispanic patients, and higher grade (OR 0.73, 95%CI: 0.56-0.95 among nH Black patients. After adjustment for multiple social and behavioral risk factors, the association with later stage remained, while the association with grade was not significant. We also found that the AIM SNP rs10954631 on chromosome 7 was associated with later stage (p = 0.02 and higher grade (p = 0.012 in nH Whites and later stage (p = 0.03 in nH Blacks. CONCLUSION: Non-European genetic ancestry was associated with later stage at diagnosis in ethnic minorities. The relation between genetic ancestry and stage at diagnosis may be due to genetic factors and/or unmeasured environmental factors that are overrepresented within certain racial

  15. NAT2 polymorphisms combining with smoking associated with breast cancer susceptibility: a meta-analysis.

    Science.gov (United States)

    Zhang, Jian; Qiu, Li-Xin; Wang, Zhong-Hua; Wang, Jia-Lei; He, Shuang-Shuang; Hu, Xi-Chun

    2010-10-01

    To derive a more precise estimation of the relationship between the slow or rapid acetylation resulting from N-acetyltransferase 2 (NAT2) polymorphisms and breast cancer risk, a meta-analysis was performed. PubMed, Medline, Embase, and Web of Science were searched. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess strength of association. The pooled ORs were performed for slow versus rapid acetylation genotypes. A total of 26 studies including 9,215 cases and 10,443 controls were included in the meta-analysis. Overall, no significantly elevated breast cancer risk was associated with NAT2 slow genotypes when all studies were pooled into the meta-analysis (OR = 1.026, 95% CI = 0.968-1.087). In the subgroup analysis by ethnicity, increased risks were not found for either Caucasians (OR = 1.001, 95% CI = 0.938-1.068) or Asians (OR = 1.155, 95% CI = 0.886-1.506). When stratified by study design, statistically significantly elevated risk associated with NAT2 slow genotypes was only found among hospital-based studies (OR = 1.178, 95% CI = 1.037-1.339). In the subgroup analysis by menopausal status, no statistically significantly increased risk was found in either premenopausal (OR = 1.053, 95% CI = 0.886-1.252) or postmenopausal women (OR = 0.965, 95% CI = 0.844-1.104). When stratified by cumulative smoking exposure, in the subgroup of smokers with high pack-years, NAT2 slow genotypes were significantly associated with increased breast cancer risk (OR = 1.400, 95% CI = 1.099-1.784). In conclusion, this meta-analysis suggested that there is overall lack of association between NAT2 genotypes and breast cancer risk, however, NAT2 polymorphisms when combining with heavy smoking history may contribute to breast cancer susceptibility. PMID:20180012

  16. Morbidity associated with breast cancer therapy and the place of physiotherapy in its management

    Directory of Open Access Journals (Sweden)

    Rodica Păcurar

    2011-06-01

    Full Text Available Incidence of breast cancer continues to grow while modern diagnosis and treatment techniques improve long-term survival rates of the patients. Hence, more women will experience morbidity associated to breast cancer treatment. The aim of this article is to provide a review of the morbidity associated with breast cancer treatment and to emphasize the role of physiotherapist within the rehabilitation team. Pain, pectoralis tightness and axillary web syndrome are the most frequently encountered surgical side effects. They contribute to upper arm dysfunction and reduced range of motion. Radiotherapy may lead to skin and pulmonary morbidity, lymphedema and dysfunction of the muscles caught in the radiation field. Chemotherapy and hormone therapy are associated with osteoporosis and weight gain, the latter representing an important risk factor to lymphedema. Secondary lymphedema is the most frequent complication of breast cancer treatment, mostly related to axillary surgery and radiotherapy. Physiotherapeutic techniques may prevent and control lymphedema, scar adherence and pulmonary complications, reduce pain and improve range of motion, which results in a better quality of life for the patients.

  17. Elevated expression of chemokine C-C ligand 2 in stroma is associated with recurrent basal-like breast cancers.

    Science.gov (United States)

    Yao, Min; Yu, Elaine; Staggs, Vincent; Fan, Fang; Cheng, Nikki

    2016-08-01

    Despite advances in treatment, up to 30% of breast cancer patients experience disease recurrence accompanied by more aggressive disease and poorer prognosis. Treatment of breast cancer is complicated by the presence of multiple breast cancer subtypes, including: luminal, Her2 overexpressing, and aggressive basal-like breast cancers. Identifying new biomarkers specific to breast cancer subtypes could enhance the prediction of patient prognosis and contribute to improved treatment strategies. The microenvironment influences breast cancer progression through expression of growth factors, angiogenic factors and other soluble proteins. In particular, chemokine C-C ligand 2 (CCL2) regulates macrophage recruitment to primary tumors and signals to cancer cells to promote breast tumor progression. Here we employed a software-based approach to evaluate the prognostic significance of CCL2 protein expression in breast cancer subtypes in relation to its expression in the epithelium or stroma or in relation to fibroblast-specific protein 1 (Fsp1), a mesenchymal marker. Immunohistochemistry analysis of tissue microarrays revealed that CCL2 significantly correlated with Fsp1 expression in the stroma and tumor epithelium of invasive ductal carcinoma. In the overall cohort of invasive ductal carcinomas (n=427), CCL2 and Fsp1 expression in whole tissues, stroma and epithelium were inversely associated with cancer stage and tumor size. When factoring in molecular subtype, stromal CCL2 was observed to be most highly expressed in basal-like breast cancers. By Cox regression modeling, stromal CCL2, but not epithelial CCL2, expression was significantly associated with decreased recurrence-free survival. Furthermore, stromal CCL2 (HR=7.51 P=0.007) was associated with a greater hazard than cancer stage (HR=2.45, P=0.048) in multivariate analysis. These studies indicate that stromal CCL2 is associated with decreased recurrence-free survival in patients with basal-like breast cancer, with

  18. Gly71Arg UGT1A1 polymorphism is associated with breast cancer susceptibility in Han Chinese women.

    Science.gov (United States)

    Shi, J; Li, L H; Duan, X Y; Liu, Q; Sun, L L; Tian, Y T

    2016-01-01

    Breast cancer is among the most common causes of cancer-related death in women worldwide. Previous studies have demonstrated an association between prolonged estrogen exposure and increased risk of breast cancer. Uridine 5'-diphospho-glucuronosyltransferase 1-1 (UGT1A1) plays a significant role in the detoxification of estrogens. Two major genetic polymorphisms have been identified in the UGT1A1 locus. UGT1A1*28 has been previously linked to increased risk of breast cancer. The aim of this study was to elucidate the possible correlation between UGT1A1*6, a single nucleotide polymorphism causing a Gly71Arg substitution, and breast cancer susceptibility. Forty-six women diagnosed with breast cancer, 15 patients with gastrointestinal cancer, and 13 healthy women were recruited to this study. The genotype in the polymorphic UGT1A1 locus was determined by DNA sequencing. The frequency of each genotype was compared among the three groups. The frequency of the UGT1A1*6 allele was significantly higher in breast cancer and gastrointestinal cancer patients than that in healthy females (both P 0.05). Therefore, the UGT1A1*6 polymorphism was deduced to be a risk factor for breast cancer in women of Han Chinese ethnicity. UGT1A1 may serve as a therapeutic target for the prevention and treatment of breast cancer and other estrogen-related diseases. PMID:27525948

  19. A genome-wide association study of breast and prostate cancer in the NHLBI's Framingham Heart Study

    OpenAIRE

    Kreger Bernard E; Finger Daniel; Rosenberg Carol L; Murabito Joanne M; Levy Daniel; Splansky Greta; Antman Karen; Hwang Shih-Jen

    2007-01-01

    Abstract Background Breast and prostate cancer are two commonly diagnosed cancers in the United States. Prior work suggests that cancer causing genes and cancer susceptibility genes can be identified. Methods We conducted a genome-wide association study (Affymetrix 100K SNP GeneChip) of cancer in the community-based Framingham Heart Study. We report on 2 cancer traits – prostate cancer and breast cancer – in up to 1335 participants from 330 families (54% women, mean entry age 33 years). Multi...

  20. Preliminary study on association between toxoplasmosis and breast cancer in Iran

    Institute of Scientific and Technical Information of China (English)

    Narges; Kalantari; Salman; Ghaffari; Masomeh; Bayani; Maryam; Mitra; Elmi; Daryush; Moslemi; Novin; Nikbakhsh; Fariedh; Ghavipanjeh

    2015-01-01

    Objective:To investigate the possible association between Toxoplasma gondii(T.gondii)infection and breast cancer by examining the seropositivity and serointensity rate of anti-T gondii antibodies in breast cancer patients and healthy volunteers.Methods:This study was carried out on 66 women with breast cancer which consists of 29 newly diagnosed patients(Group 1) and 37 cases undergoing treatment and regular checkups(Group 2).Also,60 healthy women(Group 3) with no history of cancer confirmed by clinical examination and imaging participated in this study.The participants were tested for T.gondii immunoglobulin G(IgG) and immunoglobulin M(IgM) antibodies by enzyme-linked immunoassays.Results:The mean age of Groups 1.2 and 3 were 43.3±6.8,41.8±5.5 and 42.3±4.9.respectively(P=0.72).Overall.104(82.5%) and 8(6.3%) out of 126 women were positive for anti-T gondii IgG and IgM antibodies,respectively.Higher seropositivity rate of anti-T.gondii antibodies(IgG) was seen in breast cancer patients(86.4%) compared with control group(78.3%)(P=0.24).IgG antibodies were detected in 89.2%of cancer patients under treatment.82.7%of newly diagnosed patients(P=0.18).IgM antibodies were found in 3(10.3%),2(5.4%)and 3(5%) in Groups 1.2 and 3.No significant difference was found between the mean titers of T.gondii IgG antibody among these groups(P=0.87).Conclusions:This study did not find any significant association between toxoplasmosis and breast cancer besides higher rates of seropositivity and serointensity in patients compared with healthy volunteers.

  1. Imaging male breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Doyle, S., E-mail: sdoyle2@nhs.net [Primrose Breast Care Unit, Derriford Hospital, Plymouth (United Kingdom); Steel, J.; Porter, G. [Primrose Breast Care Unit, Derriford Hospital, Plymouth (United Kingdom)

    2011-11-15

    Male breast cancer is rare, with some pathological and radiological differences from female breast cancer. There is less familiarity with the imaging appearances of male breast cancer, due to its rarity and the more variable use of preoperative imaging. This review will illustrate the commonest imaging appearances of male breast cancer, with emphasis on differences from female breast cancer and potential pitfalls in diagnosis, based on a 10 year experience in our institution.

  2. Breast Cancer Detection

    Science.gov (United States)

    2000-01-01

    The BioScan System was developed by OmniCorder Technologies, Inc. at the Jet Propulsion Laboratory. The system is able to locate cancerous lesions by detecting the cancer's ability to recruit a new blood supply. A digital sensor detects infrared energy emitted from the body and identifies the minute differences accompanying the blood flow changes associated with cancerous cells. It also has potential use as a monitoring device during cancer treatment. This technology will reduce the time taken to detect cancerous cells and allow for earlier intervention, therefore increasing the overall survival rates of breast cancer patients.

  3. Population attributable risk of breast cancer in white women associated with immediately modifiable risk factors

    Directory of Open Access Journals (Sweden)

    Glaser Sally L

    2006-06-01

    Full Text Available Abstract Background Estrogen/progestin replacement therapy (EPRT, alcohol consumption, physical activity, and breast-feeding duration differ from other factors associated with breast cancer in being immediately modifiable by the individual, thereby representing attractive targets for future breast cancer prevention efforts. To justify such efforts, it is vital to quantify the potential population-level impacts on breast cancer considering population variations in behavior prevalence, risk estimate, and baseline incidence. Methods For each of these four factors, we calculated population attributable risk percents (PARs using population-based survey (2001 and cancer registry data (1998–2002 for 41 subpopulations of white, non-Hispanic California women aged 40–79 years, and ranges of relative risk (RR estimates from the literature. Results Using a single RR estimate, subpopulation PARs ranged from 2.5% to 5.6% for hormone use, from 0.0% to 6.1% for recent consumption of >= 2 alcoholic drinks daily, and 4.6% to 11.0% for physical inactivity. Using a range of RR estimates, PARs were 2–11% for EPRT use, 1–20% for alcohol consumption and 2–15% for physical inactivity. Subpopulation data were unavailable for breastfeeding, but PARs using published RR estimates ranged from 2% to 11% for lifetime breastfeeding >= 31 months. Thus, of 13,019 breast cancers diagnosed annually in California, as many as 1,432 attributable to EPRT use, 2,604 attributable to alcohol consumption, 1,953 attributable to physical inactivity, and 1,432 attributable to never breastfeeding might be avoidable. Conclusion The relatively feasible lifestyle changes of discontinuing EPRT use, reducing alcohol consumption, increasing physical activity, and lengthening breastfeeding duration could lower population breast cancer incidence substantially.

  4. Cancer-Associated Adipocytes Exhibit an ActivatedPhenotype and Contribute to Breast Cancer Invasion

    OpenAIRE

    2011-01-01

    Early local tumor invasion in breast cancer results in a likely encounter between cancer cells and matureadipocytes, but the role of these fat cells in tumor progression remains unclear. We show that murine and humantumor cells cocultivated with mature adipocytes exhibit increased invasive capacities in vitro and in vivo, usingan original two-dimensional coculture system. Likewise, adipocytes cultivated with cancer cells also exhibit analtered phenotype in terms of delipidation and decreased ...

  5. Viruses and Breast Cancer

    International Nuclear Information System (INIS)

    Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify viruses which may have a role in breast cancer. Despite these efforts, the establishment of conclusive evidence for such a role has been elusive. However, the development of extremely sophisticated new experimental techniques has allowed the recent development of evidence that human papilloma virus, Epstein-Barr virus, mouse mammary tumor virus and bovine leukemia virus may each have a role in the causation of human breast cancers. This is potentially good news as effective vaccines are already available to prevent infections from carcinogenic strains of human papilloma virus, which causes cancer of the uterine cervix

  6. Viruses and Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lawson, James S., E-mail: james.lawson@unsw.edu.au; Heng, Benjamin [School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney (Australia)

    2010-04-30

    Viruses are the accepted cause of many important cancers including cancers of the cervix and anogenital area, the liver, some lymphomas, head and neck cancers and indirectly human immunodeficiency virus associated cancers. For over 50 years, there have been serious attempts to identify viruses which may have a role in breast cancer. Despite these efforts, the establishment of conclusive evidence for such a role has been elusive. However, the development of extremely sophisticated new experimental techniques has allowed the recent development of evidence that human papilloma virus, Epstein-Barr virus, mouse mammary tumor virus and bovine leukemia virus may each have a role in the causation of human breast cancers. This is potentially good news as effective vaccines are already available to prevent infections from carcinogenic strains of human papilloma virus, which causes cancer of the uterine cervix.

  7. Association between reproductive factors and breast cancer in an urban set up at central India: A case-control study

    Directory of Open Access Journals (Sweden)

    R Lodha

    2011-01-01

    Full Text Available Background: Epigenetic changes, geography and environmental factors do surpass the genetic factors in the development of breast cancer. This study investigates the association of reproductive factors with the breast cancer in this context. Objective: To detect the association of reproductive risk factors with breast cancer in an urban set up at central India. Study Design: Matched paired community-based case-control study. Materials and Methods: The study was conducted for a period of a year from October 2008 to August 2009 in Bhopal (MP. Demographic data and reproductive risk factor related information were collected using structured questionnaire. Data analysis was done by Epi-info and SPSS 16. Results: History of using oral contraceptive pills (OR = 3.02, 95% CI: 1.28-7.11, history of not having breastfeeding (OR = 3.62, 95% CI: 1.29-10.16 and family history of breast cancer (OR = 3.98, 95%CI: 1.06-14.826 were associated significantly with the occurrence of breast cancer in multivariate analysis. Conclusions: The findings of the present study suggests that positive family history of breast cancer and history of using OCP may be the epigenetic factors promoting the occurrence of breast cancer while breastfeeding reduces the possibility of acquiring breast cancer.

  8. Molecular Subtypes of Breast Cancer Are Not Associated with the Clinical Under- or Overstaging of Breast Cancer.

    Science.gov (United States)

    Espinola, Juliana Pinho; Peres, Raquel Mary Rodrigues; Serra, Kátia Piton; Derchain, Sophie Françoise Mauricette; Sarian, Luis Otávio

    2016-05-01

    Purpose to evaluate the agreement between the clinical and pathological stagings of breast cancer based on clinical and molecular features. Methods this was a cross-sectional study, in which clinical, epidemiological and pathological data were collected from 226 patients who underwent surgery at the Prof. Dr. José Aristodemo Pinotti Women's Hospital (CAISM/Unicamp) from January 2008 to September 2010. Patients were staged clinically and pathologically, and were classified as: understaged, when the clinical staging was lower than the pathological staging; correctly staged, when the clinical staging was the same as the pathological one; and overstaged, when the clinical staging was greater than the pathological staging. Results understaged patients were younger (52.2 years; p < 0.01) and more symptomatic at diagnosis (p = 0.04) when compared with correctly or overstaged patients. Clinicopathological surrogate subtype, menopausal status, parity, hormone replace therapy and histology were not associated with differences in staging. Women under 57 years of age were clinically understaged mainly due to underestimation of T (tumor staging) (p < 0.001), as were the premenopausal women (p < 0.01). Patients whose diagnosis was made due to clinical complaints, and not by screening, were clinically understaged due to underestimation of N (lymph nodes staging) (p < 0.001). Conclusion the study shows that the clinicopathological surrogate subtype is not associated with differences in staging, while younger women diagnosed because of clinical complaints tend to have their breast tumors understaged during clinical evaluation. PMID:27187929

  9. High expression of KIF26B in breast cancer associates with poor prognosis.

    Science.gov (United States)

    Wang, Qun; Zhao, Zong-Bin; Wang, Geng; Hui, Zhen; Wang, Ming-Hua; Pan, Jun-Feng; Zheng, Hong

    2013-01-01

    To date, a great number of studies have demonstrated that altered expression of kinesins is associated with development and progression of various human cancers. Kinesin family member 26B (KIF26B), a member of the kinesin superfamily proteins (KIFs), is essential for kidney development. However, the role of KIF26B during tumorigenesis and progression is limited. Here, we demonstrate that both KIF26B mRNA and protein are overexpression in breast cancer tissues by RT-qPCR and western blot. Immunohistochemistry revealed that KIF26B expression significantly correlated with clinicopathological factors, including tumor size (P = 0.011), grade (P = 0.017), lymph node status (P = 0.009) and ER status (P = 0.012). Moreover, the Kaplan-Meier analysis indicated that breast cancer patients with high KIF26B expression had a shorter survival than those with low KIF26B expression. In addition, multivariate analysis indicated that KIF26B is an independent prognostic for outcome in breast cancer (HR, 2.356; 95%CI, 1.268-4.378; P = 0.007). Collectively, our study demonstrated that KIF26B was overexpression in breast cancer and could be served as a potential prognostic marker. PMID:23585914

  10. Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis

    Science.gov (United States)

    Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

    2009-01-01

    Introduction Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. Methods To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. Results We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor

  11. DNA Double Strand Break Repair and its Association with Inherited Predispositions to Breast Cancer

    Directory of Open Access Journals (Sweden)

    Scott Rodney J

    2004-02-01

    Full Text Available Abstract Mutations in BRCA1 account for the majority of familial aggregations of early onset breast and ovarian cancer (~70% and about 1/5 of all early onset breast cancer families; in contrast, mutations in BRCA2 account for a smaller proportion of breast/ovarian cancer families and a similar proportion of early onset breast cancer families. BRCA2 has also been shown to be associated with a much more pleiotropic disease spectrum compared to BRCA1. Since the identification of both BRCA1 and BRCA2 investigations into the functions of these genes have revealed that both are associated with the maintenance of genomic integrity via their apparent roles in cellular response to DNA damage, especially their involvement in the process of double strand DNA break repair. This review will focus on the specific roles of both genes and how functional differences may account for the diverse clinical findings observed between families that harbour BRCA1 or BRCA2 mutations.

  12. Fatty metamorphosis of the liver in patients with breast cancer:Possible associated factors

    Institute of Scientific and Technical Information of China (English)

    Cheng-Hsin Chu; Shee-Chan Lin; Shou-Chuan Shih; Chin-Roa Kao; Sun-Yen Chou

    2003-01-01

    AIM: To investigate the relationship between breast cancer and fatty liver in Chinese patients.METHODS: The study group consisted of 217 patients with newly diagnosed breast cancers and the control group of 182 subjects undergoing routine health examination in the same hospital. All subjects were female and the groups were matched for date of study. Ultrasound scanning was performed by the same operator using a 3.5 mHz transducer.Steatosis of the liver was diagnosed based on the criteria of Saverymuttu et al. Clinical variables were statistically analyzed.RESULTS: Fatty liver was diagnosed in 98 patients of the study group and 37 patients of the control group, a significant difference was found in incidence (98/217, 45.2 % and 37/182, 20.3 %; P<0.0001). On univariate analysis, fatty liver in breast cancer patients was associated with overweight,hyperlipidemia, and hepatitis. On multivariate analysis in the same patients, obesity and hyperlipidemia were significantly associated with fatty liver.CONCLUSION: The cause of fatty liver in women with breast cancer may be multifactorial. The present study confirms its link with overweight and hyperlipidemia.

  13. Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk

    DEFF Research Database (Denmark)

    Lin, Wei-Yu; Camp, Nicola J; Ghoussaini, Maya;

    2015-01-01

    Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide po...

  14. Breast cancer-associated venous thromboembolism: A case-control study.

    Science.gov (United States)

    Rebouças, Danilo; Costa, Maria; Thuler, Luiz; Garces, Alvaro; Aquino, Luciana; Bines, José

    2016-08-01

    Breast cancer is frequently associated with venous thromboembolism (VTE). VTE may result in significant morbidity, a substantial economic burden and even leads to patients' death. Risk factor identification and management of VTE in breast cancer patients remains poorly studied. We evaluated breast cancer patients' baseline and treatment characteristics in predicting VTE occurrence as well as its prognosis. We conducted a case-control study of all breast cancer patients with a VTE diagnosed between January 2007 and December 2011 at the Instituto Nacional de Câncer (INCA) in Brazil. Two hundred and twenty five patients developed VTE and were compared with 225 controls, in the 5-year study period. The bulk of the thrombotic events were unilateral (94.2%) VTEs of the lower extremity (78.7%), largely proximally located (78%). VTE occurred more often within the first 3 years after the diagnosis of cancer (66.2%), being more common in the first 6 months (21.8%). Significant predictors of developing VTE were age 50 years and over (OR 1.85, 95% CI: 1.16-2.95), PS equal to or above 3 (OR 2.01, 95% CI: 1.24-3.26), and the presence of a CVC (OR 2.56, 95% CI: 1.42-4.62). This large retrospective analysis of VTE in breast cancer patients confirms that most events occur early in the treatment course. The incidence of VTE was associated with patients' age, PS, and the presence of CVC. Prospective studies are needed to evaluate outpatient thromboprophylaxis for selected groups of patients. PMID:27253153

  15. Longitudinal association of hemostatic factors with risk for cancers of the breast, colorectum, and lung among postmenopausal women.

    Science.gov (United States)

    Kabat, Geoffrey C; Salazar, Christian R; Zaslavsky, Oleg; Lane, Dorothy S; Rohan, Thomas E

    2016-09-01

    The aim of this study was to examine whether hemostatic factors associated with coagulation and inflammation pathways are associated with cancer risk in postmenopausal women. We used data from the Women's Health Initiative study to examine the association of plasma fibrinogen levels, factor VII antigen activity, and factor VII concentration measured at baseline and during follow-up with the risk for cancers of the breast, colorectum, and lung. Among 5287 women who were followed up for a median of 11.4 years, 275 cases of breast cancer, 102 cases of colorectal cancer, and 90 cases of lung cancer were identified. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for the association of hemostatic factors with each cancer. Hemostatic factors were not associated with breast cancer in either baseline or longitudinal analyses. Baseline hemostatic factors showed weak associations with colorectal cancer; however, no association was seen in longitudinal analyses. Fibrinogen was positively associated with lung cancer in both baseline and longitudinal analyses; the association was seen only in never and former smokers, not in current smokers. We found no evidence of an association between hemostatic factors and breast or colorectal cancer in postmenopausal women. The positive association of fibrinogen levels with lung cancer requires confirmation in larger studies. PMID:26317383

  16. Genome-wide association study identifies multiple loci associated with both mammographic density and breast cancer risk

    Science.gov (United States)

    Lindström, Sara; Thompson, Deborah J.; Paterson, Andrew D.; Li, Jingmei; Gierach, Gretchen L.; Scott, Christopher; Stone, Jennifer; Douglas, Julie A.; dos-Santos-Silva, Isabel; Fernandez-Navarro, Pablo; Verghase, Jajini; Smith, Paula; Brown, Judith; Luben, Robert; Wareham, Nicholas J.; Loos, Ruth J.F.; Heit, John A.; Pankratz, V. Shane; Norman, Aaron; Goode, Ellen L.; Cunningham, Julie M.; deAndrade, Mariza; Vierkant, Robert A.; Czene, Kamila; Fasching, Peter A.; Baglietto, Laura; Southey, Melissa C.; Giles, Graham G.; Shah, Kaanan P.; Chan, Heang-Ping; Helvie, Mark A.; Beck, Andrew H.; Knoblauch, Nicholas W.; Hazra, Aditi; Hunter, David J.; Kraft, Peter; Pollan, Marina; Figueroa, Jonine D.; Couch, Fergus J.; Hopper, John L.; Hall, Per; Easton, Douglas F.; Boyd, Norman F.; Vachon, Celine M.; Tamimi, Rulla M.

    2015-01-01

    Mammographic density reflects the amount of stromal and epithelial tissues in relation to adipose tissue in the breast and is a strong risk factor for breast cancer. Here we report the results from meta-analysis of genome-wide association studies (GWAS) of three mammographic density phenotypes: dense area, non-dense area and percent density in up to 7,916 women in stage 1 and an additional 10,379 women in stage 2. We identify genome-wide significant (P<5×10−8) loci for dense area (AREG, ESR1, ZNF365, LSP1/TNNT3, IGF1, TMEM184B, SGSM3/MKL1), non-dense area (8p11.23) and percent density (PRDM6, 8p11.23, TMEM184B). Four of these regions are known breast cancer susceptibility loci, and four additional regions were found to be associated with breast cancer (P<0.05) in a large meta-analysis. These results provide further evidence of a shared genetic basis between mammographic density and breast cancer and illustrate the power of studying intermediate quantitative phenotypes to identify putative disease susceptibility loci. PMID:25342443

  17. Reduced risk of breast cancer associated with recreational physical activity varies by HER2 status

    International Nuclear Information System (INIS)

    Convincing epidemiologic evidence indicates that physical activity is inversely associated with breast cancer risk. Whether this association varies by the tumor protein expression status of the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), or p53 is unclear. We evaluated the effects of recreational physical activity on risk of invasive breast cancer classified by the four biomarkers, fitting multivariable unconditional logistic regression models to data from 1195 case and 2012 control participants in the population-based Women’s Contraceptive and Reproductive Experiences Study. Self-reported recreational physical activity at different life periods was measured as average annual metabolic equivalents of energy expenditure [MET]-hours per week. Our biomarker-specific analyses showed that lifetime recreational physical activity was negatively associated with the risks of ER-positive (ER+) and of HER2-negative (HER2−) subtypes (both Ptrend ≤ 0.04), but not with other subtypes (all Ptrend > 0.10). Analyses using combinations of biomarkers indicated that risk of invasive breast cancer varied only by HER2 status. Risk of HER2–breast cancer decreased with increasing number of MET-hours of recreational physical activity in each specific life period examined, although some trend tests were only marginally statistically significant (all Ptrend ≤ 0.06). The test for homogeneity of trends (HER2– vs. HER2+) reached statistical significance only when evaluating physical activity during the first 10 years after menarche (Phomogeneity = 0.03). Our data suggest that physical activity reduces risk of invasive breast cancers that lack HER2 overexpression, increasing our understanding of the biological mechanisms by which physical activity acts

  18. Associations between Diabetes and Quality of Life among Breast Cancer Survivors.

    Directory of Open Access Journals (Sweden)

    Zheng Tang

    Full Text Available We aimed to investigate the associations between diabetes and quality of life (QOL among breast cancer survivors.A cross-sectional survey was conducted at 34 Cancer Recovery Clubs across China from May 2014 to January 2015. Quality of life was measured by the Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30 and the Quality of Life Questionnaire-Breast Cancer Module 23 (QLQ-BR23, simplified Chinese version. Information on social-demography, diagnosis and treatment of tumors, and diabetes mellitus were collected by self-reported questionnaires. Univariate analyses of covariance (ANCOVA was performed to assess the difference in QOL between patients with or without diabetes mellitus, and multiple linear regression models were used to examine the associations after controlling for confounders.Diabetes, both of type 1 diabetes (T1DM and type 2 diabetes (T2DM significantly reduced QOL. This effect of diabetes on QOL is independent of tumor size, regional lymph node metastasis, distant metastasis and tumor stage index (TNM. After adjusting for different social-demography, diagnosis and treatment of the tumor, the tumor's stage and other chronic comorbidities, breast cancer survivors with diabetes got significantly lower scores in functional dimensions (including physical, role, emotional and social functionings measured by EORTC QLQ-C30; body image (BRBI and future perspective (BRFU measured by QLQ-BR23, as well as economic difficulties than those without diabetes (Padjusted<0.05. Diabetic patients also obtained higher scores in symptom dimensions, including fatigue, nausea and vomiting, pain, dyspnoea, insomnia, constipation and diarrhoea measured by EORTC QLQ-C30; side effects, breast symptoms and upset by hair loss measured by QLQ-BR23 (Padjusted<0.05. Compared to patients with T1DM, those with T2DM are likely to suffer more by loss of functioning.Diabetes was associated with the decreased QOL for breast cancer survivors.

  19. XRCC1 Polymorphism Associated With Late Toxicity After Radiation Therapy in Breast Cancer Patients

    International Nuclear Information System (INIS)

    Purpose: To identify single-nucleotide polymorphisms (SNPs) in oxidative stress–related genes associated with risk of late toxicities in breast cancer patients receiving radiation therapy. Methods and Materials: Using a 2-stage design, 305 SNPs in 59 candidate genes were investigated in the discovery phase in 753 breast cancer patients from 2 prospective cohorts from Germany. The 10 most promising SNPs in 4 genes were evaluated in the replication phase in up to 1883 breast cancer patients from 6 cohorts identified through the Radiogenomics Consortium. Outcomes of interest were late skin toxicity and fibrosis of the breast, as well as an overall toxicity score (Standardized Total Average Toxicity). Multivariable logistic and linear regression models were used to assess associations between SNPs and late toxicity. A meta-analysis approach was used to summarize evidence. Results: The association of a genetic variant in the base excision repair gene XRCC1, rs2682585, with normal tissue late radiation toxicity was replicated in all tested studies. In the combined analysis of discovery and replication cohorts, carrying the rare allele was associated with a significantly lower risk of skin toxicities (multivariate odds ratio 0.77, 95% confidence interval 0.61-0.96, P=.02) and a decrease in Standardized Total Average Toxicity scores (−0.08, 95% confidence interval −0.15 to −0.02, P=.016). Conclusions: Using a stage design with replication, we identified a variant allele in the base excision repair gene XRCC1 that could be used in combination with additional variants for developing a test to predict late toxicities after radiation therapy in breast cancer patients

  20. XRCC1 Polymorphism Associated With Late Toxicity After Radiation Therapy in Breast Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Seibold, Petra; Behrens, Sabine [Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg (Germany); Schmezer, Peter [Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center, Heidelberg (Germany); Helmbold, Irmgard [Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg (Germany); Barnett, Gillian; Coles, Charlotte [Department of Oncology, Oncology Centre, Cambridge University Hospital NHS Foundation Trust, United Kingdom (UK) (United Kingdom); Yarnold, John [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London (United Kingdom); Talbot, Christopher J. [Department of Genetics, University of Leicester, Leicester (United Kingdom); Imai, Takashi [Advanced Radiation Biology Research Program, National Institute of Radiological Sciences, Chiba (Japan); Azria, David [Department of Radiation Oncology and Medical Physics, I.C.M. – Institut regional du Cancer Montpellier, Montpellier (France); Koch, C. Anne [Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Dunning, Alison M. [Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Cambridge (United Kingdom); Burnet, Neil [Department of Oncology, Oncology Centre, Cambridge University Hospital NHS Foundation Trust, University of Cambridge, Cambridge (United Kingdom); Bliss, Judith M. [The Institute of Cancer Research, Clinical Trials and Statistics Unit, Sutton (United Kingdom); Symonds, R. Paul; Rattay, Tim [Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester (United Kingdom); Suga, Tomo [Advanced Radiation Biology Research Program, National Institute of Radiological Sciences, Chiba (Japan); Kerns, Sarah L. [Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NH (United States); and others

    2015-08-01

    Purpose: To identify single-nucleotide polymorphisms (SNPs) in oxidative stress–related genes associated with risk of late toxicities in breast cancer patients receiving radiation therapy. Methods and Materials: Using a 2-stage design, 305 SNPs in 59 candidate genes were investigated in the discovery phase in 753 breast cancer patients from 2 prospective cohorts from Germany. The 10 most promising SNPs in 4 genes were evaluated in the replication phase in up to 1883 breast cancer patients from 6 cohorts identified through the Radiogenomics Consortium. Outcomes of interest were late skin toxicity and fibrosis of the breast, as well as an overall toxicity score (Standardized Total Average Toxicity). Multivariable logistic and linear regression models were used to assess associations between SNPs and late toxicity. A meta-analysis approach was used to summarize evidence. Results: The association of a genetic variant in the base excision repair gene XRCC1, rs2682585, with normal tissue late radiation toxicity was replicated in all tested studies. In the combined analysis of discovery and replication cohorts, carrying the rare allele was associated with a significantly lower risk of skin toxicities (multivariate odds ratio 0.77, 95% confidence interval 0.61-0.96, P=.02) and a decrease in Standardized Total Average Toxicity scores (−0.08, 95% confidence interval −0.15 to −0.02, P=.016). Conclusions: Using a stage design with replication, we identified a variant allele in the base excision repair gene XRCC1 that could be used in combination with additional variants for developing a test to predict late toxicities after radiation therapy in breast cancer patients.

  1. Association of HADHA expression with the risk of breast cancer: targeted subset analysis and meta-analysis of microarray data

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    Mamtani Manju

    2012-01-01

    Full Text Available Abstract Background The role of n-3 fatty acids in prevention of breast cancer is well recognized, but the underlying molecular mechanisms are still unclear. In view of the growing need for early detection of breast cancer, Graham et al. (2010 studied the microarray gene expression in histologically normal epithelium of subjects with or without breast cancer. We conducted a secondary analysis of this dataset with a focus on the genes (n = 47 involved in fat and lipid metabolism. We used stepwise multivariate logistic regression analyses, volcano plots and false discovery rates for association analyses. We also conducted meta-analyses of other microarray studies using random effects models for three outcomes--risk of breast cancer (380 breast cancer patients and 240 normal subjects, risk of metastasis (430 metastatic compared to 1104 non-metastatic breast cancers and risk of recurrence (484 recurring versus 890 non-recurring breast cancers. Results The HADHA gene [hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein, alpha subunit] was significantly under-expressed in breast cancer; more so in those with estrogen receptor-negative status. Our meta-analysis showed an 18.4%-26% reduction in HADHA expression in breast cancer. Also, there was an inconclusive but consistent under-expression of HADHA in subjects with metastatic and recurring breast cancers. Conclusions Involvement of mitochondria and the mitochondrial trifunctional protein (encoded by HADHA gene in breast carcinogenesis is known. Our results lend additional support to the possibility of this involvement. Further, our results suggest that targeted subset analysis of large genome-based datasets can provide interesting association signals.

  2. Response to chemotherapy and association with three tumour markers in breast cancer patients in Ghana

    Directory of Open Access Journals (Sweden)

    Emmanuel Amankwaa Frempong

    2014-08-01

    Full Text Available Purpose: Oestrogen receptor (ER, progesterone receptor (PR and human epidermal growth factor 2 (HER2/neu expression in breast cancer patients predict response to chemotherapy though recorded extent vary. This retrospective study aimed to investigate the relationship between ER, PR and HER2/neu expression and response of breast cancer to chemotherapy at a tertiary hospital in Ghana. Methods: Records of all breast cancer cases seen from 2009 through 2011 were reviewed. Their receptor status, first line treatment [4 cycles of Adriamycin (60mg/m2 + Cyclophosphamide (600mg/m2], second line treatment [Capecitabine (1g/m2 + Paclitaxel (170mg/m2] and clinical response were extracted.Results: Complete remission after first and second line treatments were observed in 36 (38.3%, 95% CI: 28.5 to 48.9 and 34 (58.6%, 95% CI: .44.9 to 71.4 respectively. After both first and second line treatment 70 (74.5%, 95% CI: 64.4 - 82.9 had gone into remission. Prevalence of ER, PR, HER2/neu and Triple negative breast cancer (TNBC were 34.0% (95% CI: 24.6 to 44.5, 20.2% (95% CI: 12.6 to 29.7, 8.5% (95% CI: 3.7 to 16.1 and 59.6% (95%CI: 48.9 to 69.6 respectively. ER and PR positivity were independently associated with complete remission after first line treatment while TNBC was associated with non-remission. Conversely ER was independently associated with non-remission after second line treatment while TNBC was associated with complete remission. Conclusion: ER and TNBC status are significant predictors of complete remission and non-remission respectively after chemotherapy for breast cancer patient in Ghana.................................................................Cite this article as:Amankwaa-Frempong E, Yeboah FA, Nguah SB, Afriyie OO. Response to chemotherapy and association with three tumour markers in breast cancer patients in Ghana. Int J Cancer Ther Oncol 2014; 2(3:02034. DOI: 10.14319/ijcto.0203.4

  3. Elevated HMGA2 expression is associated with cancer aggressiveness and predicts poor outcome in breast cancer.

    Science.gov (United States)

    Wu, Jingjing; Zhang, Shizhen; Shan, Jinlan; Hu, Zujian; Liu, Xiyong; Chen, Lirong; Ren, Xingchang; Yao, Lifang; Sheng, Hongqiang; Li, Ling; Ann, David; Yen, Yun; Wang, Jian; Wang, Xiaochen

    2016-07-01

    High mobility group AT-hook 2 (HMGA2) is involved in a wide spectrum of biological processes and is upregulated in several tumors. Here, we collected 273 breast cancer (BC) specimens as a training set and 310 specimens as a validation set to examine the expression of HMGA2 by immunohistochemical staining. It was found that HMGA2 expression was significantly positively correlated with advanced tumor grade and poor survival. Subgroup analysis indicated that high level of HMGA2 was significantly correlated with poor prognosis, especially in the subgroups of stage II-III, low pathological grade and non-triple negative breast cancer cases. Gene set enrichment analysis (GSEA) demonstrated a significant positive correlation between HMGA2 level and the gene expression signature of metaplastic and mesenchymal phenotype. Importantly, we also observed that ectopic expression of HMGA2 promoted the migration and invasion of breast cancer cells, and protected cancer cells against genotoxic stress from agents stimulating P53 (Ser15) phosphorylation. As a conclusion, expression of HMGA2 might indicate more advanced malignancy of breast cancer. Thus we believe HMGA2 could serve as a biomarker of poor prognosis and a novel target in treating BC tumors. PMID:27063096

  4. Expression of the glioma-associated oncogene homolog (GLI) 1 in human breast cancer is associated with unfavourable overall survival

    International Nuclear Information System (INIS)

    the hedgehog pathway that was previously analysed on the same tissue microarray. Our study presents a systematic expression analysis of GLI1 in human breast cancer. Elevated levels of GLI1 protein in human breast cancer are associated with unfavourable prognosis and progressive stages of disease. Thus GLI1 protein expression measured e.g. by an IHC based scoring system might have an implication in future multi-marker panels for human breast cancer prognosis or molecular sub typing. The highly significant correlation between SHH and GLI1 expression characterises GLI1 as a potential functional downstream target of the hedgehog signalling pathway in human breast cancer as well. Furthermore, our study indicates that altered hedgehog signalling may represent a key disease pathway in the progression of human breast cancer

  5. LSD1 overexpression is associated with poor prognosis in basal-like breast cancer, and sensitivity to PARP inhibition.

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    Satoi Nagasawa

    Full Text Available LSD1, a lysine-specific histone demethylase, is overexpressed in several types of cancers and linked to poor outcomes. In breast cancer, the significance of LSD1 overexpression is not clear. We have performed an in silico analysis to assess the relationship of LSD1 expression to clinical outcome. We demonstrate that LSD1 overexpression is a poor prognostic factor in breast cancer, especially in basal-like breast cancer, a subtype of breast cancer with aggressive clinical features. This link is also observed in samples of triple negative breast cancer. Interestingly, we note that overexpression of LSD1 correlates with down-regulation of BRCA1 in triple negative breast cancer. This phenomenon is also observed in in vitro models of basal-like breast cancer, and is associated with an increased sensitivity to PARP inhibitors. We propose therefore that high expression levels of the demethylase LSD1 is a potential prognostic factor of poor outcome in basal-like breast cancer, and that PARP inhibition may be a therapeutic strategy of interest in this poor prognostic subtype with overexpression of LSD1.

  6. 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.

  7. 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

  8. Cancer Associated Fibroblasts express pro-inflammatory factors in human breast and ovarian tumors

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-08-02

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

  9. PTIP associated protein 1, PA1, is an independent prognostic factor for lymphnode negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Takashi Takeshita

    Full Text Available Pax transactivation domain interacting protein (PTIP associated protein 1, PA1, was a newly found protein participating in the modulation of transactivity of nuclear receptor super family members such as estrogen receptor (ER, androgen receptor (AR and glucocorticoid receptor (GR. Breast cancer is one of the most life threatening diseases for women and has tight association with estrogen and ER. This study was performed to understand the function of PA1 in breast cancer. The expression of PA1 had been evaluated in a total of 344 primary invasive breast cancer samples and examined the relationship with clinical output, relapse free survival (RFS, breast cancer-specific survival (BCSS. PA1 expression was observed in both nucleus and cytoplasm, however, appeared mainly in nuclear. PA1 nuclear expression was correlated with postmenopausal (P = 0.0097, smaller tumor size (P = 0.0025, negative Ki67 (P = 0.02, positive AR (P = 0.049 and positive ERβ (P = 0.0020. Kaplan-Meier analysis demonstrated PA1 nuclear positive cases seemed to have a longer survival than negative ones for RFS (P = 0.023 but not for BCSS (P = 0.23. In the Cox hazards model, PA1 nuclear protein expression proved to be a significant prognostic univariate parameter for RFS (P = 0.03, but not for BCSS (P = 0.20. In addition, for those patients without lymphnode metastasis PA1 was found to be an independent prognostic factor for RFS (P = 0.025, which was verified by univariate and multivariate analyses. These investigations suggested PA1 expression could be a potential prognostic indicator for RFS in breast cancer.

  10. Factors Associated With Waiting Time for Breast Cancer Treatment in a Teaching Hospital in Ghana.

    Science.gov (United States)

    Dedey, Florence; Wu, Lily; Ayettey, Hannah; Sanuade, Olutobi A; Akingbola, Titilola S; Hewlett, Sandra A; Tayo, Bamidele O; Cole, Helen V; de-Graft Aikins, Ama; Ogedegbe, Gbenga; Adanu, Richard

    2016-08-01

    Background Breast cancer is the leading cause of cancer-related mortality among women in Ghana. Data are limited on the predictors of poor outcomes in breast cancer patients in low-income countries; however, prolonged waiting time has been implicated. Among breast cancer patients who received treatment at Korle Bu Teaching Hospital, this study evaluated duration and factors that influenced waiting time from first presentation to start of definitive treatment. Method We conducted a hospital-based retrospective study of 205 breast cancer patients starting definitive treatment at Korle Bu Teaching Hospital between May and December 2013. We used descriptive statistics to summarize patient characteristics. Mann-Whitney U and Kruskal-Wallis tests and Spearman rank correlation were performed to examine the patients, health system, and health worker factors associated with median waiting time. Poisson regression was used to examine the determinants of waiting time. Results The mean age of the patients was 51.1 ± 11.8 years. The median waiting time was 5 weeks. The determinants of waiting time were level of education, age, income, marital status, ethnicity, disease stage, health insurance status, study sites, time interval between when biopsy was requested and when results were received and receipt of adequate information from health workers. Conclusion A prolonged waiting time to treatment occurs for breast cancer patients in Ghana, particularly for older patients, those with minimal or no education, with lower income, single patients, those with late disease, those who are insured, and who did not receive adequate information from the health workers. Time to obtain biopsy reports should be shortened. Patients and providers need education on timely treatment to improve prognosis. PMID:27091222

  11. Specific kinesin expression profiles associated with taxane resistance in basal-like breast cancer.

    Science.gov (United States)

    Tan, Min Han; De, Sarmishtha; Bebek, Gurkan; Orloff, Mohammed S; Wesolowski, Robert; Downs-Kelly, Erinn; Budd, G Thomas; Stark, George R; Eng, Charis

    2012-02-01

    Breast cancer is a genetically heterogenous disease with subtypes differing in prognosis and chemosensitivity. The basal-like breast cancer (BLBC) molecular subtype is associated with poorer outcomes, but is more responsive to taxane-based chemotherapy. Kinesins are intracellular transport proteins that interact with microtubules, which are also the mechanistic target for taxanes. We investigated the relationship between taxane resistance in BLBC and kinesins using both expression and functional studies. Kinesin (KIF) expression was evaluated in three settings in relation to taxane resistance: (i) the NCI-60 cancer cell lines, (ii) pre-treatment samples from four BLBC patient cohorts receiving neoadjuvant chemotherapy regimens with and without taxanes, and (iii) post-treatment samples from residual breast cancer following neoadjuvant taxane-containing chemotherapy. We used a novel functional approach to gene modification, validation-based insertional mutagenesis, to select kinesin-overexpressing clones of BLBC cells for evaluation of related mechanisms of taxane resistance. In the NCI-60 cell line dataset, overexpression of the kinesin KIFC3 is significantly correlated with resistance to both docetaxel (P breast cancers (2.8-fold-change). Functional studies established that overexpression of KIFC3, KIF5A, and KIF12 were specific in mediating resistance to docetaxel and not vincristine or doxorubicin. Mutation of the ATP-binding domain of a kinesin abolished its ability to mediate docetaxel resistance. Overall, kinesin overexpression correlates with specific taxane resistance in BLBC cell lines and tissues. Our results suggest a novel approach for drug development to overcome taxane resistance in breast cancer through concurrent or sequential use of kinesin inhibitors. PMID:21479552

  12. Atrial Fibrillation is Associated With Morphine Treatment in Female Breast Cancer Patients

    Science.gov (United States)

    Lee, Cynthia Wei-Sheng; Muo, Chih-Hsin; Liang, Ji-An; Lin, Ming-Chia; Kao, Chia-Hung

    2016-01-01

    Abstract We investigated the relationship between morphine treatment and the risk of atrial fibrillation (AF) in female patients with breast cancer. We identified a malignancy cohort of 73,917 female breast cancer patients without an AF history before the date of breast cancer diagnosis between 2000 and 2010 by using the Longitudinal Health Insurance Database for Catastrophic Illness Patients in Taiwan. This malignancy cohort was divided into morphine and comparison cohorts comprising 18,671 and 55,246 patients, respectively, and the incidences of newly diagnosed AF were calculated. We used the Cox proportional hazard model with time-dependent exposure covariates to estimate the risk of AF. The effect of morphine was assessed through multivariable Cox proportional hazard regression controlling for age, the Charlson comorbidity index (CCI) score, and the use of bisphosphonates and paclitaxel. Compared with nonmorphine users, patients who received morphine exhibited a 4.37-fold (95% CI = 3.56–5.36) increase in the risk of developing AF. The risk of AF increased as the CCI score increased, but decreased in patients with tamoxifen treatment. This risk is especially significant in current morphine users of all ages and with low CCI score. AF risk increased as the duration of morphine use lengthened (P for trend breast cancer patients in Taiwan is associated with morphine, but prevented by tamoxifen treatment. PMID:26986153

  13. Diagnosis delay of breast cancer and its associated factors in Malaysian women

    International Nuclear Information System (INIS)

    Breast cancer is the leading cause of cancer mortality among women in Malaysia. Delayed diagnosis is preventable and has major effects on patients' prognosis and survival. The objectives of our study were to identify the magnitude of delayed diagnosis and its associated factors in women with breast cancer in Malaysia. This study had a cross-sectional design. Respondents had histologically confirmed breast cancer and were registered at five medical centres between 2005 and 2007. All breast cancer patients who attended hospital clinics at the East Coast were included. Patients at Kuala Lumpur hospitals were selected by systematic sampling. A standardised questionnaire was developed to interview respondents. We measured the time from the first recognition of symptoms to the first general practitioners' consultation and to the histological diagnosis of breast cancer. Diagnosis delay was defined when there was more than 6 months from the recognition of symptoms to the histological diagnosis. Multiple logistic regression was used for analysis. In total, 328 respondents were included. The mean (standard deviation) age was 47.9 (9.4) years. Most respondents were of Malay ethnicity, were married housewives with a median family income of RM1500 a month. Most respondents had ductal carcinoma (89.3%) and the stage distribution was as follows: 5.2% stage I, 38.7% stage II, 44.8% stage III and 11.3% stage IV. The median time to consultation was 2 months and the median time to diagnosis was 5.5 months. The frequency of diagnosis delay of more than 3 months was 72.6% and delay of more than 6 months occurred in 45.5% of the cases. The factors associated with diagnosis delay included the use of alternative therapy (odds ratio (OR) 1.77; 95% confidence interval (CI): 1.06, 2.94), breast ulcer (OR 5.71; 95% CI: 1.59, 20.47), palpable axillary lymph nodes (OR 2.19; 95% CI: 1.23, 3.90), false-negative diagnostic test (OR 5.32; 95% CI: 2.32, 12.21), non-cancer interpretation

  14. The p53 codon 72 polymorphism is associated with risk and early onset of breast cancer among Saudi women

    Science.gov (United States)

    Al-Qasem, Abeer; Toulimat, Mohamed; Tulbah, Asma; Elkum, Naser; Al-Tweigeri, Taher; Aboussekhra, Abdelilah

    2012-01-01

    Breast cancer has a major impact on the health of women worldwide. In the Kingdom of Saudi Arabia (KSA), breast cancer incidence is on the increase and is characterized by early onset and aggressiveness. Owing to the importance of the TP53 gene in breast carcinogenesis, we analyzed the possible link between TP53 single nucleotide polymorphisms (SNPs) and the risk of breast cancer in Saudi women by direct sequencing of the TP53 gene exon 4 from 100 breast cancer tissues. The proportion of the polymorphic forms of SNP72 in the Saudi breast cancer patients were: Arg/Arg (RR), 39%; Pro/Pro (PP), 36%; and Arg/Pro (RP), 25%. The frequencies of these forms in disease-free Saudi women were 7.59, 22.22 and 60.19%, respectively. This indicates that the RR form of the codon 72 polymorphism is a potential risk factor, whereas the RP form is a protection factor against breast cancer among Saudi women (p=0.0001). Moreover, the results have shown that the p53 R72P SNP is significantly associated with the early onset of breast cancer in the Saudi population (p=0.0138). However, the codon 47 polymorphism appears to have no role in this disease among Saudi women. These results indicate that the TP53 gene could play a major role in breast carcinogenesis and the early onset of the disease among Saudi women. PMID:22741010

  15. The p53 codon 72 polymorphism is associated with risk and early onset of breast cancer among Saudi women.

    Science.gov (United States)

    Al-Qasem, Abeer; Toulimat, Mohamed; Tulbah, Asma; Elkum, Naser; Al-Tweigeri, Taher; Aboussekhra, Abdelilah

    2012-04-01

    Breast cancer has a major impact on the health of women worldwide. In the Kingdom of Saudi Arabia (KSA), breast cancer incidence is on the increase and is characterized by early onset and aggressiveness. Owing to the importance of the TP53 gene in breast carcinogenesis, we analyzed the possible link between TP53 single nucleotide polymorphisms (SNPs) and the risk of breast cancer in Saudi women by direct sequencing of the TP53 gene exon 4 from 100 breast cancer tissues. The proportion of the polymorphic forms of SNP72 in the Saudi breast cancer patients were: Arg/Arg (RR), 39%; Pro/Pro (PP), 36%; and Arg/Pro (RP), 25%. The frequencies of these forms in disease-free Saudi women were 7.59, 22.22 and 60.19%, respectively. This indicates that the RR form of the codon 72 polymorphism is a potential risk factor, whereas the RP form is a protection factor against breast cancer among Saudi women (p=0.0001). Moreover, the results have shown that the p53 R72P SNP is significantly associated with the early onset of breast cancer in the Saudi population (p=0.0138). However, the codon 47 polymorphism appears to have no role in this disease among Saudi women. These results indicate that the TP53 gene could play a major role in breast carcinogenesis and the early onset of the disease among Saudi women. PMID:22741010

  16. Genome-wide association studies identify four ER negative–specific breast cancer risk loci

    OpenAIRE

    Garcia-Closas, Montserrat; Couch, Fergus J.; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K.; Brook, Mark N.; Orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather s; Le Marchand, Loic; Buring, Julie E.; Eccles, Diana; Miron, Penelope; Fasching, Peter A.

    2013-01-01

    Estrogen receptor (ER)-negative tumors represent 20–30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry1. The etiology2 and clinical behavior3 of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition4. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast can...

  17. Lack of association between level of Plasminogen Activator Inhibitor-1 and estimates of tumor angiogenesis in early breast cancer

    DEFF Research Database (Denmark)

    Offersen, Birgitte Vrou; Riisbro, Rikke; Knoop, Ann;

    2007-01-01

    Plasminogen Activator Inhibitor type-1 (PAI-1) is involved in tumor invasion and progression. High levels of PAI-1 are associated with poor prognosis in breast cancer, and PAI-1 has been shown to play a role in angiogenic processes. Since estimates of tumor angiogenesis may predict poor prognosis...... we studied the relationship between PAI-1 and estimates of angiogenesis in breast cancer. Tumor tissue specimens from 438 breast cancer patients were included. Median follow-up was 10.3 years. Protein levels of PAI-1 were measured using an ELISA. Angiogenesis scores were performed using a Chalkley.......009) were independent markers of death from breast cancer. This study confirms high PAI-1 or high Chalkley counts as markers of poor prognosis in breast cancer patients, and suggests that the prognostic impact of PAI-1 is independent of its supposed involvement in tumor angiogenesis. Udgivelsesdato: 2007...

  18. Decreased expression of miR-204 is associated with poor prognosis in patients with breast cancer

    OpenAIRE

    Li, Weidong; Jin, Xuejun; Zhang, Qianbing; Zhang, Gong; Deng, Xubin; Ma, Lei

    2014-01-01

    The identification of biomarkers in breast cancer diagnosis and therapy is important in achieving early cancer diagnosis and improving patient outcomes. The aim of this study was to examine clinical significance of miR-204 expression in tissues from breast cancer patients. The relationship between miR-204 expression and clinicopathological characteristics was investigated. MiR-204 expression was significantly associated with TNM stage and metastasis. Patients with low miR-204 expression had p...

  19. Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer

    Science.gov (United States)

    Guiducci, Candace; Segrè, Ayellet V.; McGee, Kate; McGuffog, Lesley; Kartsonaki, Christiana; Morrison, Jonathan; Healey, Sue; Sinilnikova, Olga M.; Stoppa-Lyonnet, Dominique; Mazoyer, Sylvie; Gauthier-Villars, Marion; Sobol, Hagay; Longy, Michel; Frenay, Marc; GEMO Study Collaborators; Hogervorst, Frans B. L.; Rookus, Matti A.; Collée, J. Margriet; Hoogerbrugge, Nicoline; van Roozendaal, Kees E. P.; Piedmonte, Marion; Rubinstein, Wendy; Nerenstone, Stacy; Van Le, Linda; Blank, Stephanie V.; Caldés, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomäki, Kristiina; Lazaro, Conxi; Blanco, Ignacio; Arason, Adalgeir; Johannsson, Oskar T.; Barkardottir, Rosa B.; Devilee, Peter; Olopade, Olofunmilayo I.; Neuhausen, Susan L.; Wang, Xianshu; Fredericksen, Zachary S.; Peterlongo, Paolo; Manoukian, Siranoush; Barile, Monica; Viel, Alessandra; Radice, Paolo; Phelan, Catherine M.; Narod, Steven; Rennert, Gad; Lejbkowicz, Flavio; Flugelman, Anath; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Toland, Amanda E.; Montagna, Marco; D'Andrea, Emma; Friedman, Eitan; Laitman, Yael; Borg, Ake; Beattie, Mary; Ramus, Susan J.; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Tim; Spurdle, Amanda B.; Chen, Xiaoqing; Holland, Helene; John, Esther M.; Hopper, John L.; Buys, Saundra S.; Daly, Mary B.; Southey, Melissa C.; Terry, Mary Beth; Tung, Nadine; Overeem Hansen, Thomas V.; Nielsen, Finn C.; Greene, Mark I.; Mai, Phuong L.; Osorio, Ana; Durán, Mercedes; Andres, Raquel; Benítez, Javier; Weitzel, Jeffrey N.; Garber, Judy; Hamann, Ute; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Platte, Radka; Evans, D. Gareth; Lalloo, Fiona; Eeles, Ros; Izatt, Louise; Walker, Lisa; Eason, Jacqueline; Barwell, Julian; Godwin, Andrew K.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engert, Stefanie; Arnold, Norbert; Gadzicki, Dorothea; Dean, Michael; Gold, Bert; Klein, Robert J.; Couch, Fergus J.; Chenevix-Trench, Georgia; Easton, Douglas F.; Daly, Mark J.; Antoniou, Antonis C.; Altshuler, David M.; Offit, Kenneth

    2010-01-01

    The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (<40 years) affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (λ) was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values<10−5 and 39 SNPs had p-values<10−4. These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499) and chromosome 10 (rs16917302). The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR) and 95% confidence intervals (CI) for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66–0.86, ) and for rs311499 was 0.72 (95% CI 0.61–0.85, ). FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18–1.39, ). These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer. PMID:21060860

  20. Common genetic variants and modification of penetrance of BRCA2-associated breast cancer.

    Directory of Open Access Journals (Sweden)

    Mia M Gaudet

    2010-10-01

    Full Text Available The considerable uncertainty regarding cancer risks associated with inherited mutations of BRCA2 is due to unknown factors. To investigate whether common genetic variants modify penetrance for BRCA2 mutation carriers, we undertook a two-staged genome-wide association study in BRCA2 mutation carriers. In stage 1 using the Affymetrix 6.0 platform, 592,163 filtered SNPs genotyped were available on 899 young (<40 years affected and 804 unaffected carriers of European ancestry. Associations were evaluated using a survival-based score test adjusted for familial correlations and stratified by country of the study and BRCA2*6174delT mutation status. The genomic inflation factor (λ was 1.011. The stage 1 association analysis revealed multiple variants associated with breast cancer risk: 3 SNPs had p-values<10(-5 and 39 SNPs had p-values<10(-4. These variants included several previously associated with sporadic breast cancer risk and two novel loci on chromosome 20 (rs311499 and chromosome 10 (rs16917302. The chromosome 10 locus was in ZNF365, which contains another variant that has recently been associated with breast cancer in an independent study of unselected cases. In stage 2, the top 85 loci from stage 1 were genotyped in 1,264 cases and 1,222 controls. Hazard ratios (HR and 95% confidence intervals (CI for stage 1 and 2 were combined and estimated using a retrospective likelihood approach, stratified by country of residence and the most common mutation, BRCA2*6174delT. The combined per allele HR of the minor allele for the novel loci rs16917302 was 0.75 (95% CI 0.66-0.86, and for rs311499 was 0.72 (95% CI 0.61-0.85, . FGFR2 rs2981575 had the strongest association with breast cancer risk (per allele HR = 1.28, 95% CI 1.18-1.39, . These results indicate that SNPs that modify BRCA2 penetrance identified by an agnostic approach thus far are limited to variants that also modify risk of sporadic BRCA2 wild-type breast cancer.

  1. Doublecortin-like kinase 1 expression associates with breast cancer with neuroendocrine differentiation.

    Science.gov (United States)

    Liu, Yu-Hong; Tsang, Julia Y S; Ni, Yun-Bi; Hlaing, Thazin; Chan, Siu-Ki; Chan, Kui-Fat; Ko, Chun-Wai; Mujtaba, S Shafaq; Tse, Gary M

    2016-01-12

    Doublecortin-like kinase 1 (DCLK1), a microtubule associated kinase, has recently been proposed to be a putative marker for stemness and adverse prognosis in gastrointestinal cancers. However, it is not clear whether the protein also plays similar roles in breast cancer. Here, the expression of DCLK1 was analyzed in a large cohort of invasive breast cancers (IBC) by immunohistochemistry. DCKL1 was associated with favorable clinico-pathologic features, namely lower histologic grade, absence of lymphovascular invasion, fibrotic focus, necrosis and lower pN stage (p≤0.045). Additionally, independent significant correlations were found with estrogen receptor and neuroendocrine markers (p ≤0.019), implicating its relationship with IBC with neuroendocrine differentiation (IBC-NED). In the current cohort, IBC-NED showed worse outcome than luminal cancers without NED (hazard ratio=1.756, p=0.041). Interestingly, within the IBC-NED group, DCLK1 was found to be a good prognostic factor (hazard ratio =0.288, p=0.011). These findings were in contrast to those in gastrointestinal cancers, suggesting different functional roles of DCLK1 in different types of cancers. In clinical practice, NED is not routinely assessed; thus IBC-NED are not well studied. Its poor outcome and significant heterogeneity warrants more attention. DCLK1 expression could aid in the prognostication and management of this special cancer subtype. PMID:26621833

  2. Associations of persistent organic pollutants in serum and adipose tissue with breast cancer prognostic markers.

    Science.gov (United States)

    Arrebola, J P; Fernández-Rodríguez, M; Artacho-Cordón, F; Garde, C; Perez-Carrascosa, F; Linares, I; Tovar, I; González-Alzaga, B; Expósito, J; Torne, P; Fernández, M F; Olea, N

    2016-10-01

    This study aimed to evaluate associations between exposure to a group of persistent organic pollutants, measured in both adipose tissue and serum samples from breast cancer patients, and a set of tumor prognostic markers. The study population comprised 103 breast cancer patients recruited in Granada, Southern Spain. Data for tumor prognostic markers were retrieved from hospital clinical records and socio-demographic information was gathered by questionnaire. Persistent organic pollutants were quantified by gas chromatography with electron capture detection. Exposure levels were categorized in quartiles, and associations were evaluated using unconditional logistic regression. Adipose tissue HCB concentrations were associated positively with ER and PR expression (p-trends=0.044 and 0.005, respectively) and negatively with E-Cadherin and p53 expression (p-trends=0.012 and 0.027, respectively). PCB-180 adipose tissue concentrations were positively associated with HER2 expression (p-trend=0.036). Serum PCB-138 concentrations were positively associated with ER and PR expression (p-trends=0.052 and 0.042, respectively). The risk of p53 expression was higher among women in the lowest quartile of serum PCB-138 concentrations, but no significant trend was observed (p-trend=0.161). These findings indicate that human exposure to certain persistent organic pollutants might be related to breast cancer aggressiveness. We also highlight the influence on exposure assessment of the biological matrix selected, given that both serum and adipose tissue might yield relevant information on breast cancer prognosis. PMID:27213669

  3. Associations between Medical Conditions and Breast Cancer Risk in Asians: A Nationwide Population-Based Study in Taiwan.

    Directory of Open Access Journals (Sweden)

    Shu-Chun Chuang

    Full Text Available The breast cancer incidence in Asia is rising. To explore whether the etiology of breast cancer is different from the known risk factors from studies in Western countries, we conducted a nested case-control study using data from the Taiwan National Health Insurance Research Database (NHIRD.All medical conditions based on the first three digits of the ICD-9 and a list of medical conditions based on literature review were retrieved for each case and control. The odds ratios (OR and 95% confidence intervals (CI of the associations between medical conditions and breast cancer risks were estimated using conditional logistic regression and adjusted for occupation, number of breast cancer screening, and the average number of outpatient visits prior the diagnosis. The associations were also estimated for younger (<50 years old and older subjects separately.The analyses included 4,884 breast cancer cases and 19,536 age-matched controls. Prior breast diseases (OR, 95% CI: 2.47, 2.26-2.71, obesity (1.43, 1.04-1.96, endometriosis (1.44, 1.15-1.80, uterine leiomyoma (1.20, 1.03-1.40, hypertensive diseases (1.14, 1.05-1.25, and disorders in lipid metabolism (1.13, 1.04-1.24 were associated with increased breast cancer risk. No heterogeneity was observed between age groups (<50 and ≥50 years old.In addition to benign breast diseases, obesity, endometriosis, uterine leiomyoma, hypertensive diseases, and disorders of lipid metabolism were associated with a subsequent breast cancer risk.Our results suggest that estrogen related factors may play an important role in breast cancer risks in the Taiwanese female population.

  4. Lipid raft association restricts CD44-ezrin interaction and promotion of breast cancer cell migration.

    LENUS (Irish Health Repository)

    Donatello, Simona

    2012-12-01

    Cancer cell migration is an early event in metastasis, the main cause of breast cancer-related deaths. Cholesterol-enriched membrane domains called lipid rafts influence the function of many molecules, including the raft-associated protein CD44. We describe a novel mechanism whereby rafts regulate interactions between CD44 and its binding partner ezrin in migrating breast cancer cells. Specifically, in nonmigrating cells, CD44 and ezrin localized to different membranous compartments: CD44 predominantly in rafts, and ezrin in nonraft compartments. After the induction of migration (either nonspecific or CD44-driven), CD44 affiliation with lipid rafts was decreased. This was accompanied by increased coprecipitation of CD44 and active (threonine-phosphorylated) ezrin-radixin-moesin (ERM) proteins in nonraft compartments and increased colocalization of CD44 with the nonraft protein, transferrin receptor. Pharmacological raft disruption using methyl-β-cyclodextrin also increased CD44-ezrin coprecipitation and colocalization, further suggesting that CD44 interacts with ezrin outside rafts during migration. Conversely, promoting CD44 retention inside lipid rafts by pharmacological inhibition of depalmitoylation virtually abolished CD44-ezrin interactions. However, transient single or double knockdown of flotillin-1 or caveolin-1 was not sufficient to increase cell migration over a short time course, suggesting complex crosstalk mechanisms. We propose a new model for CD44-dependent breast cancer cell migration, where CD44 must relocalize outside lipid rafts to drive cell migration. This could have implications for rafts as pharmacological targets to down-regulate cancer cell migration.

  5. DNA repair gene ERCC2 polymorphisms and associations with breast and ovarian cancer risk

    Directory of Open Access Journals (Sweden)

    Rabiau Nadège

    2008-05-01

    Full Text Available Abstract Breast and ovarian cancers increased in the last decades. Except rare cases with a genetic predisposition and high penetrance, these pathologies are viewed as a polygenic disease. In this concept, association studies look for genetic variations such as polymorphisms in low penetrance genes, i.e. genes in interaction with environmental factors. DNA repair systems that protect the genome from deleterious endogenous and exogenous damages have been shown to have significantly reduced. In particular, enzymes of the nucleotide excision repair pathway are suspected to be implicated in cancer. In this study, 2 functional polymorphisms in a DNA repair gene ERCC2 were analyzed. The population included 911 breast cancer cases, 51 ovarian cancer cases and 1000 controls. The genotyping of 2 SNP (Single Nucleotide Polymorphism was carried out on the population with the MGB (Minor Groove Binder probe technique which consists of the use of the allelic discrimination with the Taqman® method. This study enabled us to show an increase in risk of breast cancer with no oral contraceptive users and with women exhibiting a waist-to-hip ratio (WHR > 0.85 for Asn homozygous for ERCC2 312.

  6. Expression of regulators of mitotic fidelity are associated with intercellular heterogeneity and chromosomal instability in primary breast cancer

    DEFF Research Database (Denmark)

    Roylance, Rebecca; Endesfelder, David; Jamal-Hanjani, Mariam; Burrell, Rebecca A.; Gorman, Patricia; Sander, Jil; Murphy, Niamh; Birkbak, Nicolai Juul; Hanby, Andrew M.; Speirs, Valerie; Johnston, Stephen R. D.; Kschischo, Maik; Swanton, Charles

    2014-01-01

    SURVIVIN increased expression were significantly associated with breast cancer grade. There was a significant association between increased CIN and both increased AURKA and SURVIVIN expression. AURKA gene amplification was also associated with increased CIN. To our knowledge this is the largest study...... quantified CIN, and their prognostic utility in breast cancer. The expression of SURVIVIN and AURKA was determined by immunohistochemistry in a cohort of 426 patients with primary breast cancer. The association between protein expression and histopathological characteristics, clinical outcome and CIN status......, as determined by centromeric FISH and defined by modal centromere deviation, was analysed. Significantly poorer clinical outcome was observed in patients with high AURKA expression levels. Expression of SURVIVIN was elevated in ER-negative relative to ER-positive breast cancer. Both AURKA and...

  7. Global characterization of signalling networks associated with tamoxifen resistance in breast cancer

    DEFF Research Database (Denmark)

    Browne, Brigid C.; Hochgräfe, Falko; Wu, Jianmin;

    2013-01-01

    Acquired resistance to the anti‐estrogen tamoxifen remains a significant challenge in breast cancer management. In this study, we used an integrative approach to characterize global protein expression and tyrosine phosphorylation events in tamoxifen‐resistant MCF7 breast cancer cells (Tam...... perturbed in TamR cells, together with pathways enriched for proteins associated with growth factor, cell–cell and cell matrix‐initiated signalling. Consistent with known roles for Ras/MAPK and PI3‐kinase signalling in tamoxifen resistance, tyrosine‐phosphorylated MAPK1, SHC1 and PIK3R2 were elevated in Tam...... molecular alterations associated with the tamoxifen‐resistant phenotype, and identify MARCKS as a potential biomarker of therapeutic responsiveness that may assist in stratification of patients for optimal therapy....

  8. HER-2 positive and p53 negative breast cancers are associated with poor prognosis.

    LENUS (Irish Health Repository)

    2011-06-01

    p53 and HER-2 coexpression in breast cancer has been controversial. These markers were tested using immunohistochemistry and HercepTest. HER-2 expression is related to reduced breast cancer survival (p = .02) . p53 expression relates to HER-2 expression (p = .029). Coexpression between p53 and HER-2 has no relation to prognosis. On univariate and multivariate analysis, combination of HER-2 positive and p53 negative expression was associated with a poor prognosis (p = .018 and p = .027, respectively), while the combination of HER-2 negative and p53 positive expression was associated with a favorable prognosis (p = .022 and p = .010, respectively). Therefore the expression of these markers should be considered collectively.

  9. HER-2 positive and p53 negative breast cancers are associated with poor prognosis.

    LENUS (Irish Health Repository)

    2012-02-01

    p53 and HER-2 coexpression in breast cancer has been controversial. These markers were tested using immunohistochemistry and HercepTest. HER-2 expression is related to reduced breast cancer survival (p = .02) . p53 expression relates to HER-2 expression (p = .029). Coexpression between p53 and HER-2 has no relation to prognosis. On univariate and multivariate analysis, combination of HER-2 positive and p53 negative expression was associated with a poor prognosis (p = .018 and p = .027, respectively), while the combination of HER-2 negative and p53 positive expression was associated with a favorable prognosis (p = .022 and p = .010, respectively). Therefore the expression of these markers should be considered collectively.

  10. The Use of Complementary and Alternative Medicine by Korean Breast Cancer Women: Is It Associated with Severity of Symptoms?

    Directory of Open Access Journals (Sweden)

    Jung Hye Hwang

    2015-01-01

    Full Text Available Background. Use of complementary and alternative medicine (CAM among patients with breast cancer could be associated with severity of the cancer symptoms experienced, but there is little evidence to prove this. This study tried to investigate any difference in the severity of breast cancer symptoms between CAM users and nonusers. Methods. The study followed cross-sectional design using structured survey questionnaire. Survey participants were recruited from four different healthcare settings in Seoul, South Korea. The survey instrument comprised 39 items including questions on demographics, use of CAM, and six main symptoms associated with breast cancer and cancer treatment. Results. Out of 288 participants, 67% stated using one or more modalities of CAM. Age, education, and time duration since diagnosis of cancer were significantly associated with use of CAM. About 90% of the CAM users experienced side effects of cancer treatment. CAM users reported more severe anxiety and skin/hair changes than nonusers. Conclusions. CAM was used by those breast cancer patients who experience more severe symptoms to alleviate the conditions associated with breast cancer and cancer treatment. Our findings revealed motivation behind the CAM use, which has profound implications for clinicians to recognize patient-perceived needs.

  11. Frequency of her-2/neu receptor positivity and its association with other features of breast cancer

    International Nuclear Information System (INIS)

    Carcinoma breast is the commonest malignancy of females all over the world and second leading cause of death due to cancer among females. In Pakistan it is more common at a young age contrary to the West where it is more common in old age (after 60 years). The objectives of this cross sectional study were to determine the frequency of HER-2/neu receptor over-expression and its association with some of the features of breast cancer like patient age, ER/PR status, tumour size, histological grade and axillary lymph node involvement. This study was conducted at Surgical C Unit, Postgraduate Medical Institute of Lady Reading Hospital, Peshawar, from January 2007 to December 2007. Study included all patients with breast cancer admitted in Surgical 'C' unit LRH, Peshawar for Modified Radical Mastectomy (MRM). The resected specimens were sent to histopathologist for immunohistochemical (IHC) studies (HER-2/neu receptor and ER/PR) and detailed histopathological analysis including tumour subtype, size, histological grade and involvement of axillary lymph nodes. Patients refusing HER-2/neu receptor immunohistochemistry were excluded from the study. Name, age, sex, other relevant data, detailed history and clinical examination findings and results of investigation were recorded. Data was analyzed with SPSS version 10. This study included 24 female patients of breast cancer having modified radical mastectomy (MRM). Age distribution ranged from 32-75 years with a Mean+-SD of age 48.3+-18.2 years. Fifteen out of 24 patients (62.5%) were >40 years, while nine patients out of 24 (37.5%) were =40 years of age. The HER-2/neu receptor status was found positive in 11 patients (45.9%) and negative in 13 patients (54%) of the total cases. HER-2/neu receptor positivity was not significantly associated with histopathological sub-type (p>0.05), number of axillary lymph nodes involved (p>0.05) and histological grade (p>0.05). While, it was significantly associated with tumour size (p<0

  12. Association of COMT Val158Met polymorphism and breast cancer risk: an updated meta-analysis

    OpenAIRE

    Qin Xue; Peng Qiliu; Qin Aiping; Chen Zhiping; Lin Liwen; Deng Yan; Xie Li; Xu Juanjuan; Li Haiwei; Li Taijie; Li Shan; Zhao Jinmin

    2012-01-01

    Abstract Background Catechol-O-methyltransferase (COMT) is one of the most important enzymes involved in estrogen metabolism and its functional genetic polymorphisms may be associated with breast cancer (BC) risk. Many epidemiological studies have been conducted to explore the association between the COMT Val158Met polymorphism and breast cancer risk. However, the results remain inconclusive. In order to derive a more precise estimation of this relationship, a large meta-analysis was performe...

  13. Breast cancer staging

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000911.htm Breast cancer staging To use the sharing features on this ... Once your health care team knows you have breast cancer , they will do more tests to stage it. ...

  14. Types of Breast Cancers

    Science.gov (United States)

    ... about this condition, see Inflammatory Breast Cancer . Paget disease of the nipple This type of breast cancer ... carcinoma (this is a type of metaplastic carcinoma) Medullary carcinoma Mucinous (or colloid) carcinoma Papillary carcinoma Tubular ...

  15. Associations between GPX1 Pro198Leu polymorphism, erythrocyte GPX activity, alcohol consumption and breast cancer risk in a prospective cohort study

    DEFF Research Database (Denmark)

    Ravn-Haren, Gitte; Olsen, A.; Tjonneland, A.;

    2006-01-01

    -control study was to determine whether GPX1 Pro198Leu and glutathione peroxidase (GPX) activity in prospectively collected blood samples are associated with breast cancer risk among postmenopausal women and whether GPX activity levels are associated with other known breast cancer risk factors. We matched 377...... female breast cancer cases with 377 controls all nested within the prospective 'Diet, Cancer and Health' study of 57 000 Danes. Carriers of the variant T-allele of GPX1 Pro198Leu were at 1.43-fold higher risk of breast cancer compared with non-carriers (95% CI = 1.07-1.92). Pre-diagnostic GPX activity......Breast cancer may be related to oxidative stress. Breast cancer patients have been reported to have lower antioxidant enzyme activity than healthy controls and the polymorphism GPX1 Pro198Leu has been associated with risk of lung and breast cancer. The purpose of the present nested case...

  16. ICOS gene polymorphisms are associated with sporadic breast cancer: a case-control study

    International Nuclear Information System (INIS)

    Inducible costimulator (ICOS), a costimulatory molecular of the CD28 family, provides positive signal to enhance T cell proliferation. Its abnormal expression can disturb the immune response and entail an increased risk of cancer. To investigate whether single nucleotide polymorphisms (SNPs) in the ICOS gene are associated with sporadic breast cancer susceptibility and progression in Chinese women, a case-control study was conducted. In the study cohort, we genotyped five SNPs (rs11889031, rs10932029, rs4675374, rs10183087 and rs10932037) in ICOS gene among 609 breast cancer patients and 665 age-matched healthy controls. Furthermore, the positive results were replicated in an independent validation cohort of 619 patients and 682 age-matched healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotypes. In rs10932029, compared with TT genotype and T allele, the CT genotype and C allele showed a significantly increased risk of breast cancer (P = 0.030, OR = 1.467, 95% CI 1.037-2.077; P = 0.017, OR = 1.481, 95% CI 1.070-2.049, respectively), and the associations were also significant in the validation cohort (P = 0.002, OR = 1.693, 95% CI 1.211-2.357; P = 0.003, OR = 1.607, 95% CI 1.171-2.204, respectively). Haplotype analysis showed that CTCAC haplotype containing rs10932029 T allele had a lower frequency in cases than in controls (P = 0.015), whereas haplotype CCCAC containing rs10932029 C allele was more common in cases than in controls (P = 0.013). In the analysis of clinicopathologic features, rs11889031 CT genotype and T allele were associated with progesterone receptor (PR) status and lymph node metastasis, which were further supported by our validation cohort. Moreover, some haplotypes were associated with estrogen receptor (ER) and PR statuses. These results indicate that ICOS gene polymorphisms may affect the risk of breast cancer and show that some SNPs are associated with breast cancer

  17. Epidemiology of male breast cancer.

    Science.gov (United States)

    Weiss, Joli R; Moysich, Kirsten B; Swede, Helen

    2005-01-01

    Breast cancer in men is a rare disease, accounting for approximately 1% of all breast cancer cases. Although the epidemiologic literature regarding female breast cancer is extensive, relatively little is known about the etiology of male breast cancer (MBC). This review is intended to summarize the existing body of evidence on genetic and epidemiologic risk factors for breast cancer in men. Overall, the epidemiology of MBC presents similarities with the epidemiology of female breast cancer. Major genetic factors associated with an increased risk of breast cancer for men include BRCA2 mutations, which are believed to account for the majority of inherited breast cancer in men, Klinefelter syndrome, and a positive family history. Suspected genetic factors include AR gene mutations, CYP17 polymorphism, Cowden syndrome, and CHEK2. Epidemiologic risk factors for MBC include disorders relating to hormonal imbalances, such as obesity, testicular disorders (e.g., cryptorchidism, mumps orchitis, and orchiectomy), and radiation exposure. Suspected epidemiologic risk factors include prostate cancer,prostate cancer treatment, gynecomastia, occupational exposures (e.g., electromagnetic fields, polycyclic aromatic hydrocarbons, and high temperatures), dietary factors (e.g., meat intake and fruit and vegetable consumption), and alcohol intake. PMID:15668471

  18. Breast Cancer (For Kids)

    Science.gov (United States)

    ... With Breast Cancer Breast Cancer Prevention en español Cáncer de mama You may have heard about special events, like walks or races, to raise money for breast cancer research. Or maybe you've seen people wear ...

  19. Identification of a putative protein profile associating with tamoxifen therapy resistance in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Umar, Arzu; Kang, Hyuk; Timmermans, A. M.; Look, Maxime P.; Meijer-van Gelder, M. E.; den Bakker, Michael A.; Jaitly, Navdeep; Martens, John W.; Luider, Theo M.; Foekens, John A.; Pasa-Tolic, Ljiljana

    2009-06-01

    Tamoxifen-resistance is a major cause of death in patients with recurrent breast cancer. Current clinical factors can correctly predict therapy response in only half of the treated patients. Identification of proteins that associate with tamoxifen-resistance is a first step towards better response prediction and tailored treatment of patients. In the present study we intended to identify putative protein biomarkers indicative of tamoxifen therapy-resistance in breast cancer, using nanoLC coupled with FTICR MS. Comparative proteome analysis was performed on ~5,500 pooled tumor cells (corresponding to ~550 ng protein lysate/analysis) obtained through laser capture microdissection (LCM) from two independently processed data sets (n=24 and n=27) containing both tamoxifen therapy-sensitive and therapy-resistant tumors. Peptides and proteins were identified by matching mass and elution time of newly acquired LC-MS features to information in previously generated accurate mass and time tag (AMT) reference databases.

  20. 9q31.2-rs865686 as a Susceptibility Locus for Estrogen Receptor-Positive Breast Cancer: Evidence from the Breast Cancer Association Consortium

    Science.gov (United States)

    Warren, Helen; Dudbridge, Frank; Fletcher, Olivia; Orr, Nick; Johnson, Nichola; Hopper, John L.; Apicella, Carmel; Southey, Melissa C.; Mahmoodi, Maryam; Schmidt, Marjanka K.; Broeks, Annegien; Cornelissen, Sten; Braaf, Linda M.; Muir, Kenneth R.; Lophatananon, Artitaya; Chaiwerawattana, Arkom; Wiangnon, Surapon; Fasching, Peter A.; Beckmann, Matthias W.; Ekici, Arif B.; Schulz-Wendtland, Ruediger; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael; Burwinkel, Barbara; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Mulot, Claire; Bojesen, Stig E; Nielsen, Sune F.; Flyger, Henrik; Nordestgaard, Børge G; Milne, Roger L.; Benítez, Javier; Arias-Pérez, José-Ignacio; Zamora, M. Pilar; Anton-Culver, Hoda; Ziogas, Argyrios; Bernstein, Leslie; Dur, Christina Clarke; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Langheinz, Anne; Meindl, Alfons; Golatta, Michael; Bartram, Claus R.; Schmutzler, Rita K.; Brauch, Hiltrud; Justenhoven, Christina; Brüning, Thomas; Chang-Claude, Jenny; Wang-Gohrke, Shan; Eilber, Ursula; Dörk, Thilo; Schürmann, Peter; Bremer, Michael; Hillemanns, Peter; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia; Antonenkova, Natalia; Rogov, Yuriy; Bermisheva, Marina; Prokofyeva, Darya; Zinnatullina, Guzel; Khusnutdinova, Elza; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.; Kataja, Vesa; Chenevix-Trench, Georgia; Beesley, Jonathan; Chen, Xiaoqing; Lambrechts, Diether; Smeets, Ann; Paridaens, Robert; Weltens, Caroline; Flesch-Janys, Dieter; Buck, Katharina; Behrens, Sabine; Peterlongo, Paolo; Bernard, Loris; Manoukian, Siranoush; Radice, Paolo; Couch, Fergus J.; Vachon, Celine; Wang, Xianshu; Olson, Janet; Giles, Graham; Baglietto, Laura; McLean, Cariona A.; Severi, Gianluca; John, Esther M.; Miron, Alexander; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Andrulis, Irene L.; Knight, Julia A.; Mulligan, Anna Marie; Weerasooriya, Nayana; Devilee, Peter; Tollenaar, Robert A.E.M.; Martens, John W.M.; Seynaeve, Caroline M.; Hooning, Maartje J.; Hollestelle, Antoinette; Jager, Agnes; Tilanus-Linthorst, Madeleine M.A.; Hall, Per; Czene, Kamila; Liu, Jianjun; Li, Jingmei; Cox, Angela; Cross, Simon S.; Brock, Ian W.; Reed, Malcolm W.R.; Pharoah, Paul; Blows, Fiona M.; Dunning, Alison M.; Ghoussaini, Maya; Ashworth, Alan; Swerdlow, Anthony; Jones, Michael; Schoemaker, Minouk; Easton, Douglas F.; Humphreys, Manjeet; Wang, Qin; Peto, Julian; dos-Santos-Silva, Isabel

    2013-01-01

    Background Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686). Methods To further investigate the rs865686–breast cancer association, we conducted a replication study within the Breast Cancer Association Consortium, which comprises 37 case–control studies (48,394 cases, 50,836 controls). Results This replication study provides additional strong evidence of an inverse association between rs865686 and breast cancer risk [study-adjusted per G-allele OR, 0.90; 95% confidence interval (CI), 0.88; 0.91, P = 2.01 × 10–29] among women of European ancestry. There were ethnic differences in the estimated minor (G)-allele frequency among controls [0.09, 0.30, and 0.38 among, respectively, Asians, Eastern Europeans, and other Europeans; P for heterogeneity (Phet) = 1.3 × 10–143], but no evidence of ethnic differences in per allele OR (Phet = 0.43). rs865686 was associated with estrogen receptor–positive (ER+) disease (per G-allele OR, 0.89; 95% CI, 0.86–0.91; P = 3.13 × 10–22) but less strongly, if at all, with ER-negative (ER–) disease (OR, 0.98; 95% CI, 0.94–1.02; P = 0.26; Phet = 1.16 × 10–6), with no evidence of independent heterogeneity by progesterone receptor or HER2 status. The strength of the breast cancer association decreased with increasing age at diagnosis, with case-only analysis showing a trend in the number of copies of the G allele with increasing age at diagnosis (P for linear trend = 0.0095), but only among women with ER+ tumors. Conclusions This study is the first to show that rs865686 is a susceptibility marker for ER+ breast cancer. Impact The findings further support the view that genetic susceptibility varies according to tumor subtype. PMID:22859399

  1. Paternal overweight is associated with increased breast cancer risk in daughters in a mouse model

    Science.gov (United States)

    Fontelles, Camile Castilho; Carney, Elissa; Clarke, Johan; Nguyen, Nguyen M.; Yin, Chao; Jin, Lu; Cruz, M. Idalia; Ong, Thomas Prates; Hilakivi-Clarke, Leena; de Assis, Sonia

    2016-01-01

    While many studies have shown that maternal weight and nutrition in pregnancy affects offspring’s breast cancer risk, no studies have investigated the impact of paternal body weight on daughters’ risk of this disease. Here, we show that diet-induced paternal overweight around the time of conception can epigenetically reprogram father’s germ-line and modulate their daughters’ birth weight and likelihood of developing breast cancer, using a mouse model. Increased body weight was associated with changes in the miRNA expression profile in paternal sperm. Daughters of overweight fathers had higher rates of carcinogen-induced mammary tumors which were associated with delayed mammary gland development and alterations in mammary miRNA expression. The hypoxia signaling pathway, targeted by miRNAs down-regulated in daughters of overweight fathers, was activated in their mammary tissues and tumors. This study provides evidence that paternal peri-conceptional body weight may affect daughters’ mammary development and breast cancer risk and warrants further studies in other animal models and humans. PMID:27339599

  2. RAD51B in Familial Breast Cancer

    OpenAIRE

    Pelttari, Liisa M.

    2016-01-01

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

  3. Radiotherapy for breast cancer is not associated with increased risk of cied implantation

    DEFF Research Database (Denmark)

    Johansen, J. B.; Rehammar, J. C.; Jorgensen, O. D.; Jensen, Mai-Britt; Videbaek, L. M.; Ewertz, M.

    . Methods: From the database of the Danish Breast Cancer Collaborative Group, we identified women treated with radiotherapy for early-stage breast cancer in Denmark from 1982 to 2005. By record linkage to the Danish Pacemaker and ICD Registry information was retrieved on CIED implants subsequent to...... radiotherapy. The rate ratios (RR) of CIED implantation were estimated by Poisson regression for left- versus right sided breast cancer with stratification for calendar year of breast cancer diagnosis, age at diagnosis and time since diagnosis (all in five-year groups). 95% confidence intervals (CI) and two...

  4. Phosphorylation of p90RSK is associated with increased response to neoadjuvant chemotherapy in ER-positive breast cancer

    International Nuclear Information System (INIS)

    The clinical implication of Ras/Raf/ERK pathway activity in breast cancer tissue and its association with response to chemotherapy is controversial. We aimed to explore the value of p90RSK phosphorylation, a downstram molecule of the pathway, in predicting chemotherapy response in breast cancer. The expression of phosphorylated p90RSK (phospho-p90RSK) and chemotherapy response was measured in 11 breast cancer cell lines and 21 breast cancer tissues. The predictive value of phospho-p90RSK was validated in core needle biopsy specimens of 112 locally advanced breast cancer patients who received anthracycline and taxane-based neoadjuvant chemotherapy. In 11 breast cancer cell lines, the relative expression of phospho-p90RSK was inversely correlated with cell survival after doxorubicin treatment (p = 0.021). Similar association was observed in fresh tissues from 21 breast cancer patients in terms of clinical response. In paraffin-embedded, formalin-fixed tissues from core needle biopsy tissues from 112 patients, positive phospho-p90RSK expression was associated with greater tumor shrinkage and smaller post-chemotherapy tumor size. The association between phospho-p90RSK expression and chemotherapy response was more evident in estrogen receptor(ER)-positive tumors. The expression of phosphor-p90RSK did not show a significant relationship with the incidence of pCR. P90RSK silencing using siRNA did not affect the cancer cell’s response to doxorubicin, and the expression of phospho-p90RSK was highly correlated with other Ras/Raf/ERK pathway activation. Our results suggest that phospho-p90RSK expression, which reflects the tumor’s Ras/Raf/ERK/p90RSK pathway activation can be a potential predictive marker for chemotherapy response in ER-positive breast cancer which needs further independent validation

  5. Association of the germline TP53 R337H mutation with breast cancer in southern Brazil

    International Nuclear Information System (INIS)

    The germline TP53-R337H mutation is strongly associated with pediatric adrenocortical tumors (ACT) in southern Brazil; it has low penetrance and limited tissue specificity in most families and therefore is not associated with Li-Fraumeni syndrome. However, other tumor types, mainly breast cancer, have been observed in carriers of several unrelated kindreds, raising the possibility that the R337H mutation may also contribute to breast tumorigenesis in a genetic background-specific context. We conducted a case-control study to determine the prevalence of the R337H mutation by sequencing TP53 exon 10 in 123 women with breast cancer and 223 age- and sex-matched control subjects from southern Brazil. Fisher's test was used to compare the prevalence of the R337H. The R337H mutation was found in three patients but in none of the controls (p = 0.0442). Among the carriers, two had familial history of cancer meeting the Li-Fraumeni-like criteria. Remarkably, tumors in each of these three cases underwent loss of heterozygosity by eliminating the mutant TP53 allele rather than the wild-type allele. Polymorphisms were identified within the TP53 (R72P and Ins16) and MDM2 (SNP309) genes that may further diminish TP53 tumor suppressor activity. These results demonstrate that the R337H mutation can significantly increase the risk of breast cancer in carriers, which likely depends on additional cooperating genetic factors. These findings are also important for understanding how low-penetrant mutant TP53 alleles can differentially influence tumor susceptibility

  6. Association of the germline TP53 R337H mutation with breast cancer in southern Brazil

    Directory of Open Access Journals (Sweden)

    Srivastava Kumar

    2008-12-01

    Full Text Available Abstract Background The germline TP53-R337H mutation is strongly associated with pediatric adrenocortical tumors (ACT in southern Brazil; it has low penetrance and limited tissue specificity in most families and therefore is not associated with Li-Fraumeni syndrome. However, other tumor types, mainly breast cancer, have been observed in carriers of several unrelated kindreds, raising the possibility that the R337H mutation may also contribute to breast tumorigenesis in a genetic background-specific context. Methods We conducted a case-control study to determine the prevalence of the R337H mutation by sequencing TP53 exon 10 in 123 women with breast cancer and 223 age- and sex-matched control subjects from southern Brazil. Fisher's test was used to compare the prevalence of the R337H. Results The R337H mutation was found in three patients but in none of the controls (p = 0.0442. Among the carriers, two had familial history of cancer meeting the Li-Fraumeni-like criteria. Remarkably, tumors in each of these three cases underwent loss of heterozygosity by eliminating the mutant TP53 allele rather than the wild-type allele. Polymorphisms were identified within the TP53 (R72P and Ins16 and MDM2 (SNP309 genes that may further diminish TP53 tumor suppressor activity. Conclusion These results demonstrate that the R337H mutation can significantly increase the risk of breast cancer in carriers, which likely depends on additional cooperating genetic factors. These findings are also important for understanding how low-penetrant mutant TP53 alleles can differentially influence tumor susceptibility.

  7. Hereditary breast cancer

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  8. Associations of intakes of magnesium and calcium and survival among women with breast cancer: results from Western New York Exposures and Breast Cancer (WEB) Study.

    Science.gov (United States)

    Tao, Meng-Hua; Dai, Qi; Millen, Amy E; Nie, Jing; Edge, Stephen B; Trevisan, Maurizio; Shields, Peter G; Freudenheim, Jo L

    2016-01-01

    Magnesium (Mg) and calcium (Ca) antagonizes each other in (re) absorption, cell cycle regulation, inflammation, and many other physiologic activities. However, few studies have investigated the association between magnesium and calcium intakes and breast cancer survival, and the interaction between calcium and magnesium intake. In a cohort of 1,170 women with primary, incident, and histologically confirmed breast cancer from Western New York State, we examined the relationship between intakes of these two minerals and survival. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). Mean follow-up time was 87.4 months after breast cancer diagnosis; there were 170 deaths identified. After adjustment for known prognostic factors, and intakes of energy, total vitamin D and total calcium, higher dietary intake of magnesium was inversely associated with risk of all-cause mortality (HR = 0.50, 95% CI, 0.28-0.90 for highest vs. lowest tertile; p trend = 0.02). Likewise, a marginal association was found for total Magnesium intake from foods and supplements combined (HR = 0.58, 95% CI, 0.31-1.08; p trend = 0.09). The inverse association of higher total magnesium intake with all-cause mortality was primarily presented among postmenopausal women and was stronger among women who had a high Ca:Mg intake ratio (>2.59). There were no clear associations for prognosis with intake of calcium. We found that magnesium intake alone may improve overall survival following breast cancer, and the association may be stronger among those with high Ca:Mg intake ratio. PMID:27073728

  9. Association of Type 2 Diabetes Genetic Variants with Breast Cancer Survival among Chinese Women

    Science.gov (United States)

    Gao, Yu-Tang; Zheng, Ying; Zhang, Ben; Cai, Hui; Zheng, Wei; Shu, Xiao-Ou; Lu, Wei

    2015-01-01

    Objective To evaluate whether the genetic susceptibility of T2D was associated with overall survival (OS) and disease-free survival (DFS) outcomes for breast cancer (BC). Methods Included in the study were 6346 BC patients who participated in three population-based epidemiological studies of BC and were genotyped with either GWAS or Exome-chip. We constructed a genetic risk score (GRS) for diabetes using risk variants identified from the GWAS catalog (http://genome.gov/gwastudies) that were associated with T2D risk at a minimum significance level of P ≤ 5.0E-8 among Asian population and evaluated its associations with BC outcomes with Cox proportional hazards models. Results During a median follow-up of 8.08 years (range, 0.01–16.95 years), 1208 deaths were documented in 6346 BC patients. Overall, the diabetes GRS was not associated with OS and DFS. Analyses stratified by estrogen receptor status (ER) showed that the diabetes GRS was inversely associated with OS among women with ER- but not in women with ER+ breast cancer; the multivariable adjusted HR was 1.38 (95% CI: 1.05–1.82) when comparing the highest to the lowest GRS quartiles. The association of diabetes GRS with OS varied by diabetes status (P for interaction <0.01). In women with history of diabetes, higher diabetes GRS was significantly associated with worse OS, with HR of 2.22 (95% CI: 1.28–3.88) for the highest vs. lowest quartile, particularly among women with an ER- breast cancer, with corresponding HR being 4.59 (95% CI: 1.04–20.28). No significant association between the diabetes GRS and OS was observed across different BMI and PR groups. Conclusions Our study suggested that genetic susceptibility of T2D was positively associated with total mortality among women with ER- breast cancer, particularly among subjects with a history of diabetes. Additional studies are warranted to verify the associations and elucidate the underlying biological mechanism. PMID:25679392

  10. Breast cancer stem cells: implications for therapy of breast cancer

    OpenAIRE

    Morrison, Brian J.; Schmidt, Chris W.; Lakhani, Sunil R; Reynolds, Brent A.; Lopez, J. Alejandro

    2008-01-01

    The concept of cancer stem cells responsible for tumour origin, maintenance, and resistance to treatment has gained prominence in the field of breast cancer research. The therapeutic targeting of these cells has the potential to eliminate residual disease and may become an important component of a multimodality treatment. Recent improvements in immunotherapy targeting of tumour-associated antigens have advanced the prospect of targeting breast cancer stem cells, an approach that might lead to...

  11. Risk-Association of Five SNPs in TOX3/LOC643714 with Breast Cancer in Southern China

    Directory of Open Access Journals (Sweden)

    Xuanqiu He

    2014-01-01

    Full Text Available The specific mechanism by which low-risk genetic variants confer breast cancer risk is currently unclear, with contradictory evidence on the role of single nucleotide polymorphisms (SNPs in TOX3/LOC643714 as a breast cancer susceptibility locus. Investigations of this locus using a Chinese population may indicate whether the findings initially identified in a European population are generalizable to other populations, and may provide new insight into the role of genetic variants in the etiology of breast cancer. In this case-control study, 623 Chinese female breast cancer patients and 620 cancer-free controls were recruited to investigate the role of five SNPs in TOX3/LOC643714 (rs8051542, rs12443621, rs3803662, rs4784227, and rs3112612; Linkage disequilibrium (LD pattern analysis was performed. Additionally, we evaluated how these common SNPs influence the risk of specific types of breast cancer, as defined by estrogen receptor (ER status, progesterone receptor (PR status and human epidermal growth factor receptor 2 (HER2 status. Significant associations with breast cancer risk were observed for rs4784227 and rs8051542 with odds ratios (OR of 1.31 ((95% confidence intervals (CI, 1.10–1.57 and 1.26 (95% CI, 1.02–1.56, respectively, per T allele. The T-rs8051542 allele was significantly associated with ER-positive and HER2-negative carriers. No significant association existed between rs12443621, rs3803662, and rs3112612 polymorphisms and risk of breast cancer. Our results support the hypothesis that the applicability of a common susceptibility locus must be confirmed among genetically different populations, which may together explain an appreciable fraction of the genetic etiology of breast cancer.

  12. Radiogenomic analysis of breast cancer: dynamic contrast enhanced - magnetic resonance imaging based features are associated with molecular subtypes

    Science.gov (United States)

    Wang, Shijian; Fan, Ming; Zhang, Juan; Zheng, Bin; Wang, Xiaojia; Li, Lihua

    2016-03-01

    Breast cancer is one of the most common malignant tumor with upgrading incidence in females. The key to decrease the mortality is early diagnosis and reasonable treatment. Molecular classification could provide better insights into patient-directed therapy and prognosis prediction of breast cancer. It is known that different molecular subtypes have different characteristics in magnetic resonance imaging (MRI) examination. Therefore, we assumed that imaging features can reflect molecular information in breast cancer. In this study, we investigated associations between dynamic contrasts enhanced MRI (DCE-MRI) features and molecular subtypes in breast cancer. Sixty patients with breast cancer were enrolled and the MR images were pre-processed for noise reduction, registration and segmentation. Sixty-five dimensional imaging features including statistical characteristics, morphology, texture and dynamic enhancement in breast lesion and background regions were semiautomatically extracted. The associations between imaging features and molecular subtypes were assessed by using statistical analyses, including univariate logistic regression and multivariate logistic regression. The results of multivariate regression showed that imaging features are significantly associated with molecular subtypes of Luminal A (p=0.00473), HER2-enriched (p=0.00277) and Basal like (p=0.0117), respectively. The results indicated that three molecular subtypes are correlated with DCE-MRI features in breast cancer. Specifically, patients with a higher level of compactness or lower level of skewness in breast lesion are more likely to be Luminal A subtype. Besides, the higher value of the dynamic enhancement at T1 time in normal side reflect higher possibility of HER2-enriched subtype in breast cancer.

  13. Your Body After Breast Cancer

    Science.gov (United States)

    ... Breast Cancer , Coping with Cancer Your Body After Breast Cancer Article date: September 28, 2012 By Melissa Weber ... age 24, she was diagnosed with stage 3 breast cancer in 2010. “I had no control over what ...

  14. Association of paternal age at birth and the risk of breast cancer in offspring: a case control study

    Directory of Open Access Journals (Sweden)

    Yoo Keun-Young

    2005-10-01

    Full Text Available Abstract Background Older paternal age may increase the germ cell mutation rate in the offspring. Maternal age may also mediate in utero exposure to pregnancy hormones in the offspring. To evaluate the association between paternal and maternal age at birth with the risk of breast cancer in female offspring, a case-control study was conducted in Korea. Methods Histologically confirmed breast cancer cases (n = 1,011 and controls (n = 1,011 with no present or previous history of cancer, matched on year of birth and menopausal status, were selected from several teaching hospitals and community in Seoul during 1995–2003. Information on paternal and maternal ages and other factors was collected by interviewed questionnaire. Odds ratio (OR and 95% confidence interval (95% CI were estimated by unconditional logistic regression model adjusting for family history of breast cancer in 1st or 2nd degree relatives, and lifetime estrogen exposure duration. Results The risk of breast cancer significantly increased as the paternal age increased (p for trend = 0.025. The association was stronger after controlling for maternal age; women whose fathers were aged ≥40 years at their birth had 1.6-fold increased risk of breast cancer compared with fathers aged Conclusion These findings suggest that older paternal age increases the risk of breast cancer in their female offspring.

  15. Breast cancers in elderly women

    International Nuclear Information System (INIS)

    Breast cancer is the most commonly diagnosed cancer and leading cause of cancer mortality in women worldwide. Nearly half of the global total of breast cancer cases occurs in patients > 65 years of age. Advanced age at the diagnosis of breast cancer is associated with more favorable tumor biology, as indicated by increased hormone sensitivity, attenuated HER- 2/neu overexpression, and lower grades and proliferative indices Elderly patients, however, are more likely to present with larger and more advanced tumors, and recent reports suggest that lymph node involvement increases with age. Elderly patients care less likely to be treated according to accepted treatment guidelines and under treatment can, as a consequence, have a strong negative impact on survival.Breast cancer in elderly patients represents a great social problem and is expected to remain one of the most common cancers in the next half century. (author)

  16. HAP1 gene expression is associated with radiosensitivity in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Jing [The Fourth Clinical School of Nanjing Medical University, Nanjing, Jiangsu (China); Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu (China); Zhang, Jun-ying [Research Center of Clinical Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu (China); Yin, Li [Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu (China); Research Center of Clinical Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu (China); Wu, Jian-zhong [Research Center of Clinical Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu (China); Guo, Wen-jie; Wu, Jian-feng [Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu (China); Chen, Meng; Xia, You-you [The Fourth Clinical School of Nanjing Medical University, Nanjing, Jiangsu (China); Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu (China); Tang, Jin-hai [Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu (China); Ma, Yong-chao [Department of Hematology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu (China); He, Xia, E-mail: hexiadoctor@163.com [Department of Radiation Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu (China)

    2015-01-02

    Highlights: • Overexpression of HAP1 gene promotes apoptosis in MCF-7 cells after irradiation. • HAP1 reduces tumor volume in nude mice xenograft models after irradiation. • HAP1 increases radiosensitivity of breast cancer cells in vitro and vivo. - Abstract: Objectives: The purpose of this study was to investigate the relationship between huntingtin-associated protein1 (HAP1) gene and radiation therapy of breast cancer cells. Methods: HAP1 gene was transfected into breast cancer MCF-7 cells, which was confirmed by quantitative reverse transcription-polymerase chain reaction analysis (qRT-PCR) and Western blot in vitro. The changes of cell radiosensitivity were assessed by colony formation assay. Apoptosis were examined by flow cytometry. The expressions of two radiation-induced genes were evaluated by Western blot. Tumor growth was investigated in nude mice xenograft models in vivo. Results: Our data showed that HAP1 gene expression was significantly increased in HAP1-transfected MCF-7 cells in comparison with the parental cells or negative control cells. The survival rate in MCF-7/HAP1 cells was significantly decreased after irradiation (0, 2, 4, 6, 8 Gy), compared to cells in MCF-7 and MCF-7/Pb groups in vitro. HAP1 gene increased apoptosis in MCF-7 cells after irradiation. Additionally, the tumor volume and weight in MCF-7/HAP1 + RT group were observably lower than in MCF-7/HAP1 group and MCF-7/Pb + RT group. Conclusion: The present study indicated that HAP1 gene expression was related to the radiosensitivity of breast cancer cells and may play an important role in the regulation of cellular radiosensitivity.

  17. Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease.

    Science.gov (United States)

    Dalotto-Moreno, Tomás; Croci, Diego O; Cerliani, Juan P; Martinez-Allo, Verónica C; Dergan-Dylon, Sebastián; Méndez-Huergo, Santiago P; Stupirski, Juan C; Mazal, Daniel; Osinaga, Eduardo; Toscano, Marta A; Sundblad, Victoria; Rabinovich, Gabriel A; Salatino, Mariana

    2013-02-01

    Galectin-1 (Gal1), an evolutionarily conserved glycan-binding protein, contributes to the creation of an immunosuppressed microenvironment at sites of tumor growth. In spite of considerable progress in elucidating its role in tumor-immune escape, the mechanisms underlying the inhibitory functions of Gal1 remain obscure. Here, we investigated the contribution of tumor Gal1 to tumor growth, metastasis, and immunosuppression in breast cancer. We found that the frequency of Gal1(+) cells in human breast cancer biopsies correlated positively with tumor grade, while specimens from patients with benign hyperplasia showed negative or limited Gal1 staining. To examine the pathophysiologic relevance of Gal1 in breast cancer, we used the metastatic mouse mammary tumor 4T1, which expresses and secretes substantial amounts of Gal1. Silencing Gal1 expression in this model induced a marked reduction in both tumor growth and the number of lung metastases. This effect was abrogated when mice were inoculated with wild-type 4T1 tumor cells in their contralateral flank, suggesting involvement of a systemic modulation of the immune response. Gal1 attenuation in 4T1 cells also reduced the frequency of CD4(+)CD25(+) Foxp3(+) regulatory T (T(reg)) cells within the tumor, draining lymph nodes, spleen, and lung metastases. Further, it abrogated the immunosuppressive function of T(reg) cells and selectively lowered the expression of the T-cell regulatory molecule LAT (linker for activation of T cells) on these cells, disarming their suppressive activity. Taken together, our results offer a preclinical proof of concept that therapeutic targeting of Gal1 can overcome breast cancer-associated immunosuppression and can prevent metastatic disease. PMID:23204230

  18. HAP1 gene expression is associated with radiosensitivity in breast cancer cells

    International Nuclear Information System (INIS)

    Highlights: • Overexpression of HAP1 gene promotes apoptosis in MCF-7 cells after irradiation. • HAP1 reduces tumor volume in nude mice xenograft models after irradiation. • HAP1 increases radiosensitivity of breast cancer cells in vitro and vivo. - Abstract: Objectives: The purpose of this study was to investigate the relationship between huntingtin-associated protein1 (HAP1) gene and radiation therapy of breast cancer cells. Methods: HAP1 gene was transfected into breast cancer MCF-7 cells, which was confirmed by quantitative reverse transcription-polymerase chain reaction analysis (qRT-PCR) and Western blot in vitro. The changes of cell radiosensitivity were assessed by colony formation assay. Apoptosis were examined by flow cytometry. The expressions of two radiation-induced genes were evaluated by Western blot. Tumor growth was investigated in nude mice xenograft models in vivo. Results: Our data showed that HAP1 gene expression was significantly increased in HAP1-transfected MCF-7 cells in comparison with the parental cells or negative control cells. The survival rate in MCF-7/HAP1 cells was significantly decreased after irradiation (0, 2, 4, 6, 8 Gy), compared to cells in MCF-7 and MCF-7/Pb groups in vitro. HAP1 gene increased apoptosis in MCF-7 cells after irradiation. Additionally, the tumor volume and weight in MCF-7/HAP1 + RT group were observably lower than in MCF-7/HAP1 group and MCF-7/Pb + RT group. Conclusion: The present study indicated that HAP1 gene expression was related to the radiosensitivity of breast cancer cells and may play an important role in the regulation of cellular radiosensitivity

  19. Statins and breast cancer prognosis

    DEFF Research Database (Denmark)

    Ahern, Thomas P; Lash, Timothy L; Damkier, Per;

    2014-01-01

    Much preclinical and epidemiological evidence supports the anticancer effects of statins. Epidemiological evidence does not suggest an association between statin use and reduced incidence of breast cancer, but does support a protective effect of statins-especially simvastatin-on breast cancer...... recurrence. Here, we argue that the existing evidence base is sufficient to justify a clinical trial of breast cancer adjuvant therapy with statins and we advocate for such a trial to be initiated without delay. If a protective effect of statins on breast cancer recurrence is supported by trial evidence......, then the indications for a safe, well tolerated, and inexpensive treatment can be expanded to improve outcomes for breast cancer survivors. We discuss several trial design opportunities-including candidate predictive biomarkers of statin safety and efficacy-and off er solutions to the key challenges...

  20. Exploring the structural requirements for inhibition of the ubiquitin E3 ligase breast cancer associated protein 2 (BCA2) as a treatment for breast cancer.

    Science.gov (United States)

    Brahemi, Ghali; Kona, Fathima R; Fiasella, Annalisa; Buac, Daniela; Soukupová, Jitka; Brancale, Andrea; Burger, Angelika M; Westwell, Andrew D

    2010-04-01

    The zinc-ejecting aldehyde dehydrogenase (ALDH) inhibitory drug disulfiram (DSF) was found to be a breast cancer-associated protein 2 (BCA2) inhibitor with potent antitumor activity. We herein describe our work in the synthesis and evaluation of new series of zinc-affinic molecules to explore the structural requirements for selective BCA2-inhibitory antitumor activity. An N(C=S)S-S motif was found to be required, based on selective activity in BCA2-expressing breast cancer cell lines and against recombinant BCA2 protein. Notably, the DSF analogs (3a and 3c) and dithio(peroxo)thioate compounds (5d and 5f) were found to have potent activity (submicromolar IC(50)) in BCA2 positive MCF-7 and T47D cells but were inactive (IC(50) > 10 microM) in BCA2 negative MDA-MB-231 breast cancer cells and the normal breast epithelial cell line MCF10A. Testing in the isogenic BCA2 +ve MDA-MB-231/ER cell line restored antitumor activity for compounds that were inactive in the BCA2 -ve MDA-MB-231 cell line. In contrast, structurally related dithiocarbamates and benzisothiazolones (lacking the disulfide bond) were all inactive. Compounds 5d and 5f were additionally found to lack ALDH-inhibitory activity, suggestive of selective E3 ligase-inhibitory activity and worthy of further development. PMID:20222671

  1. Association of cytochrome P450 genetic polymorphisms with neoadjuvant chemotherapy efficacy in breast cancer patients

    Directory of Open Access Journals (Sweden)

    Seredina Tatyana A

    2012-06-01

    Full Text Available Abstract Background The enzymes of the cytochrome P450 family (CYPs play an important role in the metabolism of a great variety of anticancer agents; therefore, polymorphisms in genes encoding for metabolizing enzymes and drugs transporters can affect drug efficacy and toxicity. Methods The genetic polymorphisms of cytochrome P450 were studied in 395 patients with breast cancer by RLFP analysis. Results Here, we studied the association of functionally significant variant alleles of CYP3A4, CYP3A5, CYP2B6, CYP2C8, CYP2C9 and CYP2C19 with the clinical response to neoadjuvant chemotherapy in breast cancer patients. A significant correlation was observed between the CYP2C9*2 polymorphism and chemotherapy resistance (OR = 4.64; CI 95% = 1.01 – 20.91, as well as between CYP2C9*2 heterozygotes and chemotherapy resistance in women with nodal forms of breast cancer and a cancer hereditary load (OR = 15.50; CI 95% = 1.08 – 826.12 when the potential combined effects were examined. No significant association between chemotherapy resistance and the other examined genotypes and the potential combined clinical and tumour-related parameters were discovered. Conclusion In conclusion, CYP2C9*2 was associated with neoadjuvant chemotherapy resistance (OR = 4.64; CI 95% = 1.01 – 20.91 in the population of interest.

  2. Association of a mammographic parenchymal pattern (MPP) descriptor with breast cancer risk: a case-control study

    Science.gov (United States)

    Wei, Jun; Chan, Heang-Ping; Zhou, Chuan; Helvie, Mark A.; Hadjiiski, Lubomir M.; Sahiner, Berkman

    2010-03-01

    We are investigating the feasibility of improving breast cancer risk prediction by computerized mammographic parenchymal pattern (MPP) analysis. A case-control study was conducted to investigate the association of the MPP measures with breast cancer risk. The case group included 168 contralateral CC-view mammograms of breast cancer patients dated at least one year prior to cancer diagnosis, and the control group included 522 CC-view mammograms from one breast of normal subjects. We extracted and compared four types of statistical texture feature spaces that included run length statistics and region size statistics (RLS/RSS) features, spatial gray level dependence (SGLD) features, gray level difference statistics (GLDS) features, and the feature space combining these three types of texture features. A linear discriminant analysis (LDA) classifier with stepwise feature selection was trained and tested with leave-one-case-out resampling to evaluate whether the breast parenchyma of future cancer patients could be distinguished from those of normal subjects in each feature space. The areas under ROC curves (Az) were 0.71, 0.72, 0.71 and 0.76 for the four feature spaces, respectively. The Az obtained from the combined feature space was significantly (pindividual feature spaces. Odd ratios (OR) were used to assess the association between breast cancer risk and four categories of MPP measures: 0.2 (C4) while patient age was treated as a confounding factor. The adjusted ORs of breast cancer for C2, C3 and C4 were 3.23, 7.77 and 25.43, respectively. The preliminary result indicated that our proposed computerized MPP measures were strongly associated with breast cancer risk.

  3. Estimation of breast doses and breast cancer risk associated with repeated fluoroscopic chest examinations of women with tuberculosis

    International Nuclear Information System (INIS)

    A methodology is presented to estimate cumulative breast dose and breast cancer risk for women exposed to repeated fluoroscopic chest examinations during air collapse therapy for pulmonary tuberculosis. Medical record abstraction, physician interview, patient contact, machine exposure measurements, and absorbed dose computations were combined to estimate average breast doses for 1047 Massachusetts women who were treated between 1930 and 1954. The methodology presented considers breast size and composition, patient orientation, x-ray field size and location, beam quality, type of examination, machine exposure rate, and exposure time during fluoroscopic examinations. The best estimate for the risk of radiation-induced cancer for the women living longer than 10 years after initial fluoroscopic exposure is 6.2 excess breast cancers per million woman-year-rad with 90% confidence limits of 2.8 and 10.7 cancers/106 WY-rad. When breast cancer risk is considered as a function of absorbed dose in the breast, instead of as a function of the number of fluoroscopic examinations, a linear dose--response relationship over the range of estimated doses is consistent with the data. However, because of the uncertainty due to small-sample variability and because of the wide range of assumptions regarding certain fluoroscopy conditions, other dose--response relationships are compatible with the data

  4. Downregulation of serine protease HTRA1 is associated with poor survival in breast cancer

    NARCIS (Netherlands)

    Lehner, A.; Magdolen, V.; Schuster, T.; Kotzsch, M.; Kiechle, M.; Meindl, A.; Sweep, F.C.; Span, P.N.; Gross, E.

    2013-01-01

    HTRA1 is a highly conserved serine protease which has been implicated in suppression of epithelial-to-mesenchymal-transition (EMT) and cell motility in breast cancer. Its prognostic relevance for breast cancer is unclear so far. Therefore, we evaluated the impact of HTRA1 mRNA expression on patient

  5. Energy Balance and Breast Cancer Risk

    OpenAIRE

    Malin, Alecia; Matthews, Charles E.; Shu, Xiao-Ou; Cai, Hui; Dai, Qi; Jin, Fan; Gao, Yu-Tang; Zheng, Wei

    2005-01-01

    We evaluated the hypothesis that a pattern of behavioral exposures indicating positive energy balance [i.e., less exercise/sport activity, high body mass index (BMI), or high energy intake] would be associated with an increased breast cancer risk in the Shanghai Breast Cancer Study, a population-based study of 1,459 incident breast cancer cases and 1,556 age frequency-matched controls. Participants completed in-person interviews that collected information on breast cancer risk factors, usual ...

  6. Association of sulfotransferase SULT1A1 with breast cancer risk: a meta-analysis of case-control studies with subgroups of ethnic and menopausal statue

    OpenAIRE

    Shao Zhimin; Shen Zhenzhou; Yan Tingting; Zhou Liheng; Jiang Yiwei; Lu Jinsong

    2010-01-01

    Abstract Background Sulfotransferase (SULT) plays an important role in the formation of estrogen which is usually conferred as a risk factor for breast cancer. Polymorphism of the SULT1A1 may be closely associated with breast cancer. However, studies on the association between polymorphism and breast cancer have yielded inconsistent results. We performed a meta-analysis including ethnic subgroup and menopausal statue subgroup to investigate the association of SULT1A1 Arg213His polymorphism wi...

  7. NOTCH2 in breast cancer: association of SNP rs11249433 with gene expression in ER-positive breast tumors without TP53 mutations

    Directory of Open Access Journals (Sweden)

    Ambs Stefan

    2010-05-01

    Full Text Available Abstract Background A recent genome-wide association study (GWAS has identified a single nucleotide polymorphism (SNP rs11249433 in the 1p11.2 region as a novel genetic risk factor for breast cancer, and this association was stronger in patients with estrogen receptor (ER+ versus ER- cancer. Results We found association between SNP rs11249433 and expression of the NOTCH2 gene located in the 1p11.2 region. Examined in 180 breast tumors, the expression of NOTCH2 was found to be lowest in tumors with TP53 mutations and highest in TP53 wild-type/ER+ tumors (p = 0.0059. In the latter group, the NOTCH2 expression was particularly increased in carriers of the risk genotypes (AG/GG of rs11249433 when compared to the non-risk AA genotype (p = 0.0062. Similar association between NOTCH2 expression and rs11249433 was observed in 60 samples of purified monocytes from healthy controls (p = 0.015, but not in total blood samples from 302 breast cancer patients and 76 normal breast tissue samples. We also identified the first possible dominant-negative form of NOTCH2, a truncated version of NOTCH2 consisting of only the extracellular domain. Conclusion This is the first study to show that the expression of NOTCH2 differs in subgroups of breast tumors and by genotypes of the breast cancer-associated SNP rs11249433. The NOTCH pathway has key functions in stem cell differentiation of ER+ luminal cells in the breast. Therefore, increased expression of NOTCH2 in carriers of rs11249433 may promote development of ER+ luminal tumors. Further studies are needed to investigate possible mechanisms of regulation of NOTCH2 expression by rs11249433 and the role of NOTCH2 splicing forms in breast cancer development.

  8. 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

    OpenAIRE

    Tomohiro Okuda; Sakura Yamamoto; Seiki Matsuo; Hisashi Kataoka; Jo Kitawaki

    2016-01-01

    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 ...

  9. Activated FXR Inhibits Leptin Signaling and Counteracts Tumor-promoting Activities of Cancer-Associated Fibroblasts in Breast Malignancy.

    Science.gov (United States)

    Giordano, Cinzia; Barone, Ines; Vircillo, Valentina; Panza, Salvatore; Malivindi, Rocco; Gelsomino, Luca; Pellegrino, Michele; Rago, Vittoria; Mauro, Loredana; Lanzino, Marilena; Panno, Maria Luisa; Bonofiglio, Daniela; Catalano, Stefania; Andò, Sebastiano

    2016-01-01

    Cancer-associated fibroblasts (CAFs), the principal components of the tumor stroma, play a central role in cancer development and progression. As an important regulator of the crosstalk between breast cancer cells and CAFs, the cytokine leptin has been associated to breast carcinogenesis. The nuclear Farnesoid X Receptor-(FXR) seems to exert an oncosuppressive role in different tumors, including breast cancer. Herein, we demonstrated, for the first time, that the synthetic FXR agonist GW4064, inhibiting leptin signaling, affects the tumor-promoting activities of CAFs in breast malignancy. GW4064 inhibited growth, motility and invasiveness induced by leptin as well as by CAF-conditioned media in different breast cancer cell lines. These effects rely on the ability of activated FXR to increase the expression of the suppressor of the cytokine signaling 3 (SOCS3) leading to inhibition of leptin-activated signaling and downregulation of leptin-target genes. In vivo xenograft studies, using MCF-7 cells alone or co-injected with CAFs, showed that GW4064 administration markedly reduced tumor growth. Interestingly, GW4064-treated tumors exhibited decreased levels of leptin-regulated proteins along with a strong staining intensity for SOCS3. Thus, FXR ligands might represent an emerging potential anti-cancer therapy able to block the tumor supportive role of activated fibroblasts within the breast microenvironment. PMID:26899873

  10. TRIB3 protein denotes a good prognosis in breast cancer patients and is associated with hypoxia sensitivity

    International Nuclear Information System (INIS)

    Background: Tribbles homolog 3 (TRIB3) is a pseudokinase involved in the regulation of several signaling pathways involved in cell survival and/or cell stress. Here, we determined the correlation between breast cancer prognosis and TRIB3 protein levels and established the role of TRIB3 in cell survival after hypoxia and/or radiotherapy. Material and methods: TRIB3 mRNA and protein were quantified in a new independent breast cancer patient cohort using QPCR and a new specific avian antibody against TRIB3. In addition, we used siRNA-mediated knockdown of TRIB3 in a colony-forming assay after hypoxia and radiotherapy. Results: TRIB3 mRNA and protein levels did not correlate in breast cancer cell lines or human breast cancer material. We validated our earlier finding that high TRIB3 mRNA denotes a poor prognosis, but found that high TRIB3 protein levels were associated with a good prognosis in breast cancer patients. We also show that knockdown of TRIB3 resulted in an increased survival under hypoxic conditions. Conclusion: Whereas mRNA levels of TRIB3 are related with a poor prognosis, TRIB3 protein is associated with a good prognosis in human breast cancer patients, possibly due to the fact that TRIB3 is involved in hypoxia tolerance.

  11. Breast cancer laterality among Egyptian patients and its association with treatments and survival

    International Nuclear Information System (INIS)

    Background and aim: Breast cancers (BCs) involve the left side (LS) more than the right side (RS). Among the Egyptians, neither BC laterality nor its association with demographic factors, tumor locations, treatments and outcomes were previously reported. Patients and methods: Laterality was analyzed among 5459 BCs from the Gharbiah population- based cancer registry covering > 5% of the Egyptian population. Cox proportional model was used to assess the independent effect of stage, ER, and laterality on overall survival (OS). Results: In Egypt, BCs involve LS more than RS with LS-to-RS ratio (LRR) of 1.16. LS predominance was evident among men and women and both younger (< 45 years) and older patients. HER2 over-expression and ductal cancers were significantly more in RSBCs while lobular cancers were significantly more in LSBCs. There were no significant differences in localization within the breast between LSBCs and RSBCs (p = 0.51). LS predominance was noticed across all subgroups except in patients with HER2 positive tumors (LRR = 0.63; p = 0.02). OS was significantly better in stage II and ER positive tumors than stage III and ER negative tumors. Despite OS of LSBCs being generally lower than RSBCs, this was not statistically significant. The significant impact of stage on OS was lost in LSBCs. ConclTusions: Among Egyptian patients, the left breast is at greater risk of cancer than the right one. Despite right-sided tumors seemed more aggressive, Left-sided ones tend to confer worse survival than right-sided tumors.

  12. Associations of polymorphisms in histidine decarboxylase, histamine N-methyltransferase and histamine receptor H3 genes with breast cancer.

    Directory of Open Access Journals (Sweden)

    Gong-Hao He

    Full Text Available We previously found that genetic polymorphisms in gene coding for histamine H4 receptors were related to the risk and malignant degree of breast cancer. The roles of polymorphisms in other histamine-related genes, such as histidine decarboxylase (HDC, histamine N-methyltransferase (HNMT and histamine H3 receptor (HRH3, remain unexplored. The aim of this study is to analyze the clinical associations of polymorphisms in HDC, HNMT and HRH3 with breast cancer. Two hundred and one unrelated Chinese Han breast cancer patients and 205 ethnicity-matched health controls were recruited for case-control investigation. Genomic DNA from the participants was extracted and 5 single nucleotide polymorphisms (SNPs in HDC, HNMT and HRH3 were genotyped. We found that polymorphisms of HNMT and HRH3 were irrelevant with breast cancer in the present study. However, the T allele of rs7164386 in HDC significantly decreased the risk of breast cancer (adjusted odds ratios [ORs], 0.387; 95% confidence intervals [CIs], 0.208-0.720; P = 0.003. Furthermore, for HDC haplotypes, the CG haplotype of rs7164386-rs7182203 was more frequent among breast cancer patients (adjusted OR, 1.828; 95% CI, 1.218-2.744; P = 0.004 while the TG haplotype was more frequent among health controls (adjusted OR, 0.351; 95% CI, 0.182-0.678; P = 0.002. These findings indicated that polymorphisms of HDC gene were significantly associated with breast cancer in Chinese Han population and may be novel diagnostic or therapeutic targets for breast cancer. Further studies with larger participants worldwide are still needed for conclusion validation.

  13. Common non-synonymous SNPs associated with breast cancer susceptibility

    DEFF Research Database (Denmark)

    Milne, Roger L; Burwinkel, Barbara; Michailidou, Kyriaki;

    2014-01-01

    SNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04-1.10, P = 2.9 × 10(-6)], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03-1.07, P = 1.7 × 10(-6)) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07-1.12, P = 5.1 × 10(-17)). The first two...... associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05-1.10, P = 1.0 × 10(-8)); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04-1.07, P = 2.0 × 10...

  14. Mitochondrial DNA A10398G Mutation is not Associated with Breast Cancer Risk in a Sample of Iraqi Women

    Directory of Open Access Journals (Sweden)

    Rawaa A. Zahid

    2013-05-01

    Full Text Available The aim of this study was to investigate if there is a relationship between mtDNA polymorphism (A10398G and breast cancer in a sample of 59 Iraqi women. Breast cancer is the second most common diagnosed cause of cancer death in the developed countries and accounts for 23% of the total cancers. Different studies reported that breast cancer accounts for 14% of all cancer deaths in females. It is well documented that the different factors such as genetics and environment factors are involved in tumorigenesis. Mutations in the mitochondrial DNA D-loop region and somatic mutations are emerging as early genetic markers of cancer. Identification of such markers for breast cancer would prevent late detection and increase the chance of recovery and survival rate. In breast cancer different mtDNA alterations were reported. The A10398G mutation in NADH Dehyrogenase (ND3 a subunit of complex I of the Oxidative Phosphorylation process (OXPHOS is perhaps one of the most studied mutations with conflicting reports of its association with breast cancer. Genomic DNA was extracted from 21 unrelated women with malignant tumors, 22 women with benign tumors and 16 healthy women blood donors. Subsequently, PCR amplification was performed using specific primers, PCR products were subjected to a suitable restriction enzyme. No genetic variants were identified in mtDNA among malignant tumoral group and controls while 9% of benign tumor cases exhibited the variant. Our finding indicated that A10398G polymorphism cannot be used as a biomarker for breast cancer detection in Iraqi women.

  15. Estrogens and breast cancer

    Directory of Open Access Journals (Sweden)

    HANKINSON SUSAN E

    1997-01-01

    Full Text Available In this review, we summarize the epidemiologic evidence for the associations of oral contraceptives and postmenopausal hormones with risk of breast cancer. We also describe the biologic plausibility of these relationships. Overall, there appears to be little, if any, increase in risk with oral contraceptive use in general, even among users for 10 or more years. However, compared to never users, current oral contraceptive users appear to have a modest elevation in risk that subsides within about 10 years after cessation of use. For postmenopausal hormones, the weight of the evidence suggests little or no increase in risk among users of short duration, or for use in the past. However, current longer term use is associated with an increased risk of breast cancer that increases with duration. This increase in risk is large enough, and well enough supported, to be considered along with the other risks and benefits of postmenopausal hormone therapy.

  16. PROFILES OF GENE EXPRESSION ASSOCIATED WITH TETRACYCLINE OVER EXPRESSION OF HSP70 IN MCF-7 BREAST CANCER CELLS

    Science.gov (United States)

    Profiles of gene expression associated with tetracycline over expression of HSP70 in MCF-7 breast cancer cells. Heat shock proteins (HSPs) protect cells from damage through their function as molecular chaperones. Some cancers reveal high levels of HSP70 expression in asso...

  17. 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 E; 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 an...

  18. Association between manganese superoxide dismutase gene polymorphism and breast cancer risk: a meta-analysis of 17,842 subjects.

    Science.gov (United States)

    Liu, Geling; Sun, Guogui; Wang, Yadi; Wang, Dan; Hu, Wanning; Zhang, Jun

    2012-10-01

    The aim of this meta-analysis was to explore the association between the manganese superoxide dismutase (MnSOD) gene polymorphism and breast cancer risk, and to investigate the interaction of this gene polymorphism with known risk factors for breast cancer. Crude odds ratios (ORs) with 95% confidence intervals (CIs) for breast cancer risk associated with co-dominant models [valine/alanine (Val/Ala) vs. Val/Val, Ala/Ala vs. Val/Val], a dominant model (Val/Ala + Ala/Ala vs. Val/Val) and a recessive model (Ala/Ala vs. Val/Ala + Val/Val) were statistically estimated. This meta‑analysis included 8,102 breast cancer cases and 9,740 controls from 14 published case-control studies. The data revealed no significant association between the MnSOD polymorphism and the risk of developing breast cancer. However, upon subgroup analyses, the risk was significantly increased in premenopausal women with the dominant model of the MnSOD gene polymorphism (OR, 1.15; 95% CI, 1.01-1.31). Statistically significant increased risks were also identified in women with the MnSOD genotypes containing the Ala allele who had a tobacco smoking history (OR, 1.17; 95% CI, 1.02-1.34), a higher body mass index (OR, 1.26; 95% CI, 1.02-1.56) or who used oral contraceptives (OR, 1.98; 95% CI, 1.34-2.93). By contrast, there was no significant association between breast cancer risk and alcohol consumption and ethnicity. This meta‑analysis demonstrated no statistically significant association between the MnSOD gene polymorphism and breast cancer susceptibility, except in premenopausal women with certain unhealthy lifestyle habbits. PMID:22825700

  19. FGFR2 and other loci identified in genome-wide association studies are associated with breast cancer in African-American and younger women

    OpenAIRE

    Barnholtz-Sloan, Jill S; Shetty, Priya B; Guan, Xiaowei; Nyante, Sarah J; Luo, Jingchun; Brennan, Donal J.; Millikan, Robert C.

    2010-01-01

    Twenty-nine single-nucleotide polymorphisms (SNPs) from previously published genome-wide association studies (GWAS) and multiple ancestry informative markers were genotyped in the Carolina Breast Cancer Study (CBCS) (742 African-American (AA) cases, 1230 White cases; 658 AA controls, 1118 White controls). In the entire study population, 9/10 SNPs in fibroblast growth factor receptor 2 (FGFR2) were significantly associated with breast cancer after adjusting for age, race and European ancestry ...

  20. Compliance of patients concerning recommended radiotherapy in breast cancer. Association with recurrence, age, and hormonal therapy

    International Nuclear Information System (INIS)

    Background and purpose: In this study, we investigated how often guidelines for radiation therapy in patients with breast cancer are not complied with, which patient group is mostly affected, and how this influences local recurrence. Patients and methods: All patients (n = 1,903) diagnosed between November 2003 and December 2008 with primary invasive or intraductal breast cancer in the interdisciplinary breast center of the Charite Hospital Berlin were included and followed for a median 2.18 years. Results: Patients who, in contrast to the recommendation of the interdisciplinary tumor board, did not undergo postoperative radiation experienced a fivefold higher local recurrence rate (p < 0.0005), corresponding to a 5-year locoregional recurrence-free survival of 74.5% in this group. The 5-year locoregional recurrence-free survival of patients following the recommendations was 93.3%. Guideline compliance was dependent on age of patients, acceptance of adjuvant hormonal treatment or chemotherapy, and increased diameter of the primary tumor. Multiple logistic regression analysis showed an association between compliance and age or hormonal therapy. Conclusion: In order to avoid local recurrence patients should be motivated to comply with guideline driven therapy. Since a higher number of local recurrences is observed in health services research compared to clinical research, studies on the value of adjuvant treatment following local recurrence should be performed. (orig.)

  1. Association of tissue inhibitor of metalloproteinases-1 and Ki67 in estrogen receptor positive breast cancer

    DEFF Research Database (Denmark)

    Bjerre, Christina Annette; Knoop, Ann; Bjerre, Karsten;

    2013-01-01

    Background. The role of tissue inhibitor of metalloproteinases-1 (TIMP-1) in estrogen receptor (ER) positive breast cancer remains to be fully elucidated. We evaluated TIMP-1 as a prognostic marker in patients treated with adjuvant tamoxifen and investigated TIMP-1s association with Ki67 and ER...... differences in disease free survival (HR 0.98; 95% CI 0.63-1.53; p = 0.92) and overall survival (HR 0.94; 95% CI 0.63-1.43; p = 0.79) were observed according to TIMP-1 status. A significant negative association between TIMP-1 and Ki67 was identified (p = 0.015). TIMP-1 expression did not differ significantly...... = 0.48; OR 0.68; 95% CI 0.23-1.99). Conclusion. TIMP-1 does not appear to be prognostic in breast cancer patients receiving adjuvant tamoxifen. We identified a negative association between TIMP-1 and Ki67. We did not confirm our previous in vitro findings of a negative association between TIMP-1 and...

  2. Association of single nucleotide polymorphism rs3803662 with the risk of breast cancer.

    Science.gov (United States)

    Yang, Yuan; Wang, Wenjing; Liu, Guiyou; Yu, Yingcui; Liao, Mingzhi

    2016-01-01

    Large scale association studies have identified the single nucleotide polymorphism rs3803662 associated with breast cancer risk. However, the sample size of most studies is too small. Here, we performed this meta-analysis to make the result more convincing. Relevant articles published up to 2016 were identified by searching the PubMed database. 13 studies, involving a total of 29405 participants, were included in the meta-analysis. Odds Ratios (ORs) with 95% confidence intervals (CIs) was calculated with random or fixed effects model. All data analyses were analyzed by Review Manger 5.3 software. In Caucasian subgroup: Dominant model (TT + CT vs CC): OR = 1.17 (1.06, 1.29), Recessive model (TT vs CT + CC): OR = 1.25 (1.13, 1.39) and Allele frequency (T vs C): OR = 1.15 (1.08, 1.22). The present meta-analysis suggests that rs3803662 polymorphism is significantly associated with breast cancer risk in Caucasian women, and we did not find the association in Asian women. PMID:27350156

  3. Fine-scale mapping of the 4q24 locus identifies & pr two Independent loci associated with breast cancer risk

    NARCIS (Netherlands)

    X. Guo (Xingyi); J. Long (Jirong); C. Zeng (Chenjie); K. Michailidou (Kyriaki); M. Ghoussaini (Maya); M.K. Bolla (Manjeet); Q. Wang (Qing); R.L. Milne (Roger L.); X.-O. Shu (Xiao-Ou); Q. Cai (Qiuyin); J. Beesley (Jonathan); S. Kar (Siddhartha); I.L. Andrulis (Irene); H. Anton-Culver (Hoda); V. Arndt (Volker); M.W. Beckmann (Matthias W.); A. Beeghly-Fadiel (Alicia); J. Benítez (Javier); W.J. Blot (William); N.V. Bogdanova (Natalia); S.E. Bojesen (Stig); H. Brauch (Hiltrud); H. Brenner (Hermann); L.A. Brinton (Louise); A. Broekss (Annegien); T. Brüning (Thomas); B. Burwinkel (Barbara); H. Cai (Hui); S. Canisius (Sander); J. Chang-Claude (Jenny); J.-Y. Choi (J.); F.J. Couch (Fergus); A. Cox (Angela); S.S. Cross (Simon); K. Czene (Kamila); H. Darabi (Hatef); P. Devilee (Peter); A. Droit (Arnaud); T. Dörk (Thilo); P.A. Fasching (Peter); O. Fletcher (Olivia); H. Flyger (Henrik); F. Fostira (Florentia); V. Gaborieau (Valerie); M. García-Closas (Montserrat); G.G. Giles (Graham G.); M. Grip (Mervi); P. Guénel (Pascal); C.A. Haiman (Christopher A.); U. Hamann (Ute); J.M. Hartman (Joost); A. Hollestelle (Antoinette); J.L. Hopper (John L.); C.-N. Hsiung (Chia-Ni); H. Ito (Hidemi); A. Jakubowska (Anna); N. Johnson (Nichola); M. Kabisch (Maria); D. Kang (Daehee); S. Khan (Sofia); J.A. Knight (Julia); V-M. Kosma (Veli-Matti); D. Lambrechts (Diether); L. Le Marchand (Loic); J. Li (Jingmei); A. Lindblom (Annika); A. Lophatananon (Artitaya); J. Lubinski (Jan); A. Mannermaa (Arto); S. Manoukian (Siranoush); S. Margolin (Sara); F. Marme (Federick); K. Matsuo (Keitaro); C.A. McLean (Catriona Ann); A. Meindl (Alfons); K. Muir (Kenneth); S.L. Neuhausen (Susan); H. Nevanlinna (Heli); S. Nord (Silje); J.E. Olson (Janet); N. Orr (Nick); P. Peterlongo (Paolo); T.C. Putti (Thomas Choudary); A. Rudolph (Anja); S. Sangrajrang (Suleeporn); E.J. Sawyer (Elinor); M.K. Schmidt (Marjanka); R.K. Schmutzler (Rita); C-Y. Shen (Chen-Yang); J. Shi (Jiajun); M. Shrubsole (Martha); M.C. Southey (Melissa); A.J. Swerdlow (Anthony ); S.H. Teo (Soo Hwang); B. Thienpont (Bernard); A.E. Toland (Amanda); R.A.E.M. Tollenaar (Rob); I. Tomlinson (Ian); T. Truong (Thérèse); C.-C. Tseng (Chiu-chen); A.M.W. van den Ouweland (Ans); W. Wen (Wanqing); R. Winqvist (Robert); A. Wu (Anna); C.H. Yip (Cheng Har); M.P. Zamora (Pilar); Y. Zheng (Ying); P. Hall (Per); P.D.P. Pharoah (Paul); J. Simard (Jacques); G. Chenevix-Trench (Georgia); A.M. Dunning (Alison); D.F. Easton (Douglas F.); W. Zheng (Wei); R. Eeles (Rosalind); A.A. Al Olama (Ali Amin); Z. Kote-Jarai; S. Benlloch (Sara); A.C. Antoniou (Antonis C.); L. McGuffog (Lesley); K. Offit (Kenneth); A. Lee (Andrew); E. Dicks (Ed); C. Luccarini (Craig); D.C. Tessier (Daniel C.); F. Bacot (Francois); D. Vincent (Daniel); S. La Boissière (Sylvie); F. Robidoux (Frederic); S.F. Nielsen (Sune); J.M. Cunningham (Julie); S.A. Windebank (Sharon A.); C.A. Hilker (Christopher A.); J. Meyer (Jeffrey); M. Angelakos (Maggie); J. Maskiell (Judi); E.J. Rutgers (Emiel J.); S. Verhoef; F.B.L. Hogervorst (Frans); P. Boonyawongviroj (Prat); P. Siriwanarungsan (Pornthep); A. Schrauder (André); M. Rübner (Matthias); S. Oeser (Sonja); S. Landrith (Silke); E. Williams (Eileen); E. Ryder-Mills (Elaine); K. Sargus (Kara); N. McInerney (Niall); G. Colleran (Gabrielle); A. Rowan (Andrew); A. Jones (Angela); C. Sohn (Christof); A. Schneeweiß (Andeas); P. Bugert (Peter); N. Álvarez (Nuria); L. Bernstein (Leslie); J. Lacey (James); S. Wang (Sophia); H. Ma (Huiyan); Y. Lu (Yani); J. Clague De Hart (Jessica); D. Deapen (Dennis); R. Pinder (Rich); E. Lee (Eunjung); F.R. Schumacher (Fredrick); P. Horn-Ross (Pam); P. Reynolds (Peggy); D. Nelson (David); H. Park (Hannah); H. Ziegler (Hartwig); S. Wolf (Sonja); V. Hermann (Volker); W.-Y. Lo (Wing-Yee); C. Justenhoven (Christina); Y.-D. Ko (Yon-Dschun); C. Baisch (Christian); H.-P. Fischer (Hans-Peter); B. Pesch (Beate); S. Rabstein (Sylvia); A. Lotz (Anne); V. Harth (Volker); T. Heikkinen (Tuomas); I. Erkkilä (Irja); K. Aaltonen (Kirsimari); K. von Smitten (Karl); N.N. Antonenkova (Natalia); P. Hillemanns (Peter); H. Christiansen (Hans); E. Myöhänen (Eija); H. Kemiläinen (Helena); H. Thorne (Heather); E. Niedermayr (Eveline); D. Bowtell; G. Chenevix-Trench (Georgia); A. De Fazio (Anna); D. Gertig; A. Green; P. Webb (Penny); A. Green; P. Parsons; N. Hayward; P.M. Webb (P.); D. Whiteman; A. Fung (Annie); J. Yashiki (June); G. Peuteman (Gilian); D. Smeets (Dominiek); T. Van Brussel (Thomas); K. Corthouts (Kathleen); N. Obi (Nadia); J. Heinz (Judith); T.W. Behrens (Timothy); U. Eilber (Ursula); M. Celik (Muhabbet); T. Olchers (Til); B. Peissel (Bernard); G. Scuvera (Giulietta); D. Zaffaroni (Daniela); B. Bonnani (Bernardo); I. Feroce (Irene); A. Maniscalco (Angela); A. Rossi (Alessandra); L. Bernard (Loris); M. Tranchant (Martine); M.-F. Valois (Marie-France); A. Turgeon (Annie); L. Heguy (Lea); P.S. Yee (Phuah Sze); P. Kang (Peter); K.I. Nee (Kang In); S. Mariapun (Shivaani); Y. Sook-Yee (Yoon); D.S.C. Lee (Daphne S.C.); T.Y. Ching (Teh Yew); N.A.M. Taib (Nur Aishah Mohd); M. Otsukka (Meeri); K. Mononen (Kari); T. Selander (Teresa); N. Weerasooriya (Nayana); E.M.M. Krol-Warmerdam (Elly); J. Molenaar; J. Blom; N. Szeszenia-Dabrowska (Neonilia); B. Peplonska (Beata); W. Zatonski (Witold); P. Chao (Pei); M. Stagner (Michael); P. Bos (Petra); J. Blom (Jannet); E. Crepin (Ellen); A. Nieuwlaat (Anja); A. Heemskerk (Annette); S. Higham (Sue); H.E. Cramp (Helen); D. Connley (Daniel); S. Balasubramanian (Sabapathy); I.W. Brock (Ian); M. Kerin (Michael); N. Miller (Nicola); P. Kerbrat (Pierre); P. Arveux (Patrick); R. Le Scodan (Romuald); Y. Raoul (Yves); P. Laurent-Puig (Pierre); C. Mulot (Claire); C. Stegmaier (Christa); K. Butterbach (Katja); J.H. Karstens (Johann); D. Flesch-Janys (Dieter); P. Seibold (Petra); A. Vrieling (Alina); S. Nickels (Stefan); P. Radice (Paolo); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); S. Kauppila (Saila); D. Conroy (Don); C. Baynes (Caroline); K. Chua (Kimberley); R. Pilarski (Robert)

    2015-01-01

    textabstractBackground: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540

  4. Breast Cancer Immunotherapy

    Institute of Scientific and Technical Information of China (English)

    JuhuaZhou; YinZhong

    2004-01-01

    Breast cancer is a leading cause of cancer-related deaths in women worldwide. Although tumorectomy, radiotherapy, chemotherapy and hormone replacement therapy have been used for the treatment of breast cancer, there is no effective therapy for patients with invasive and metastatic breast cancer. Immunotherapy may be proved effective in treating patients with advanced breast cancer. Breast cancer immunotherapy includes antibody based immunotherapy, cancer vaccine immunotherapy, adoptive T cell transfer immunotherapy and T cell receptor gene transfer immunotherapy. Antibody based immunotherapy such as the monoclonal antibody against HER-2/neu (trastuzumab) is successfully used in the treatment of breast cancer patients with over-expressed HER-2/neu, however, HER-2/neu is over-expressed only in 25-30% of breast cancer patients. Cancer vaccine immunotherapy is a promising method to treat cancer patients. Cancer vaccines can be used to induce specific anti-tumor immunity in breast cancer patients, but cannot induce objective tumor regression. Adoptive T cell transfer immunotherapy is an effective method in the treatment of melanoma patients. Recent advances in anti-tumor T cell generation ex vivo and limited clinical trial data have made the feasibility of adoptive T cell transfer immunotherapy in the treatment of breast cancer patients. T cell receptor gene transfer can redirect the specificity of T cells. Chimeric receptor, scFv(anti-HER-2/neu)/zeta receptor, was successfully used to redirect cytotoxic T lymphocyte hybridoma cells to obtain anti-HER-2/neu positive tumor cells, suggesting the feasibility of treatment of breast cancer patients with T cell receptor gene transfer immunotherapy. Clinical trials will approve that immunotherapy is an effective method to cure breast cancer disease in the near future. Cellular & Molecular Immunology.

  5. Breast Cancer Immunotherapy

    Institute of Scientific and Technical Information of China (English)

    Juhua Zhou; Yin Zhong

    2004-01-01

    Breast cancer is a leading cause of cancer-related deaths in women worldwide. Although tumorectomy,radiotherapy, chemotherapy and hormone replacement therapy have been used for the treatment of breast cancer, there is no effective therapy for patients with invasive and metastatic breast cancer. Immunotherapy may be proved effective in treating patients with advanced breast cancer. Breast cancer immunotherapy includes antibody based immunotherapy, cancer vaccine immunotherapy, adoptive T cell transfer immunotherapy and T cell receptor gene transfer immunotherapy. Antibody based immunotherapy such as the monoclonal antibody against HER-2/neu (trastuzumab) is successfully used in the treatment of breast cancer patients with over-expressed HER-2/neu, however, HER-2/neu is over-expressed only in 25-30% of breast cancer patients. Cancer vaccine immunotherapy is a promising method to treat cancer patients. Cancer vaccines can be used to induce specific anti-tumor immunity in breast cancer patients, but cannot induce objective tumor regression. Adoptive T cell transfer immunotherapy is an effective method in the treatment of melanoma patients. Recent advances in anti-tumor T cell generation ex vivo and limited clinical trial data have made the feasibility of adoptive T cell transfer immunotherapy in the treatment of breast cancer patients. T cell receptor gene transfer can redirect the specificity of T cells. Chimeric receptor, scFv(anti-HER-2/neu)/zeta receptor, was successfully used to redirect cytotoxic T lymphocyte hybridoma cells to obtain anti-HER-2/neu positive tumor cells, suggesting the feasibility of treatment of breast cancer patients with T cell receptor gene transfer immunotherapy. Clinical trials will approve that immunotherapy is an effective method to cure breast cancer disease in the near future.

  6. Risk of treatment-related esophageal cancer among breast cancer survivors

    DEFF Research Database (Denmark)

    Morton, L M; Gilbert, E S; Hall, P;

    2012-01-01

    Radiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy use.......Radiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy use....

  7. Association between vitamin D receptor gene polymorphisms and breast cancer risk: a meta-analysis of 39 studies.

    Directory of Open Access Journals (Sweden)

    Kai Zhang

    Full Text Available BACKGROUND: The associations between vitamin D receptor (VDR gene polymorphisms and breast cancer risk were comprehensively investigated to clarify issues that remain controversial. METHODOLOGY/PRINCIPAL FINDINGS: An electronic search was conducted of several databases, including PubMed, the Cochrane library, Web of Science, EMBASE, CBM and CNKI, for papers that describe the association between Fok1, poly-A repeat, Bsm1, Taq1 or Apa1 polymorphisms of the VDR gene and breast cancer risk. Summary odds ratios and 95% confidence intervals (CI were estimated based on a fixed-effect model (FEM or random-effect model (REM, depending on the absence or presence of significant heterogeneity. A total of 39 studies met the inclusion criteria. A meta-analysis of high-quality studies showed that the Fok1 polymorphism of the VDR gene was associated with an increased risk of breast cancer (ff vs. Ff+FF, OR: 1.09, 95%CI: 1.02 to 1.16, p = 0.007. No significant associations were observed between the other polymorphisms and breast cancer risk. No positive results were detected by pooling the results of all relevant studies. CONCLUSION: A meta-analysis of high-quality studies demonstrated that the Fok1 polymorphism of the VDR gene was closely associated with breast cancer risk.

  8. Early breast cancer

    International Nuclear Information System (INIS)

    Breast cancer remains a common disease throughout the world. Here we review new knowledge about early breast cancer obtained during the past 5 years. The prognosis of early breast cancer is generally favorable. Especially, ductal carcinoma in situ has been regarded as a non-life-threatening disease. Therefore, early diagnosis and early onset of the treatment has been important. Early age at menarche, late age at first birth, and late age at menopause are related to breast cancer risk. Examination by mammography and ultrasonography is still the most effective means of detection for premenopausal and postmenopausal women, respectively. Additionally, there have been important advances in MRI, sentinel lymph node biopsy, breast-conserving surgery, partial breast irradiation, neoadjuvant systemic therapy, and adjuvant systemic therapy. Another approach to keeping the disease under control is the elucidation of breast cancer's molecular biological features. Assessment of potential molecular targets can lead to early diagnosis and molecular targeted treatment. (author)

  9. High DRC Levels Are Associated with Let-7b Overexpression in Women with Breast Cancer

    OpenAIRE

    Jarline Encarnación; Carmen Ortiz; Ralphdy Vergne; Wanda Vargas; Domenico Coppola; Matta, Jaime L.

    2016-01-01

    Nucleotide Excision Repair (NER) is a critical pathway involved in breast cancer (BC). We have previously published that a low DNA repair capacity (DRC) is associated with a higher risk of BC in Puerto Rican women. Let-7b belongs to a miRNA family with tumor suppressor activity that targets oncogenes. We isolated miRNAs from plasma of 153 Puerto Rican women with and without BC. DRC was measured in lymphocytes by means of a host cell reactivation assay. These women were divided into four group...

  10. Association Between Vascular Endothelial Growth Factor Gene Polymorphisms with Breast Cancer Risk in an Iranian Population

    OpenAIRE

    Rezaei, Maryam; Hashemi, Mohammad; Sanaei, Sara; Mashhadi, Mohammad Ali; Taheri, Mohsen

    2016-01-01

    Breast cancer (BC) is one of the most causes of death in women worldwide. It affects Iranian female population approximately a decade earlier than those in other parts of the world. Previous studies have shown that vascular endothelial growth factor (VEGF) gene variants were associated with BC risk. The current study aimed to evaluate the impact of VEGF rs3025039 (+936C>T), rs2010963 (+405C>G), rs833061 (-460T>C), rs699947 (-2578C>A), and rs35569394 (18-bp I/D) polymorphisms on BC risk in an ...

  11. Identification of microRNAs associated with tamoxifen resistance in breast cancer

    OpenAIRE

    Lau, Lai-yee.; 劉麗儀.

    2011-01-01

    Tamoxifen is the most widely used endocrine therapy for both early and advanced estrogen receptor (ER) positive breast cancer patients. About half of the patients that initially respond to the antiestrogen become estrogen-independent and ultimately develop resistance to the treatment. The precise molecular mechanisms of tamoxifen resistance remain poorly understood. Dysregulation of microRNAs (miRNAs) has been frequently reported in breast cancer and linked to cancer development, progression...

  12. Associations of two common genetic variants with breast cancer risk in a chinese population: a stratified interaction analysis.

    Directory of Open Access Journals (Sweden)

    Yuxiang Lin

    Full Text Available Recent genome-wide association studies (GWAS have identified a series of new genetic susceptibility loci for breast cancer (BC. However, the correlations between these variants and breast cancer are still not clear. In order to explore the role of breast cancer susceptibility variants in a Southeast Chinese population, we genotyped two common SNPs at chromosome 6q25 (rs2046210 and in TOX3 (rs4784227 in a case-control study with a total of 702 breast cancer cases and 794 healthy-controls. In addition, we also evaluated the multiple interactions among genetic variants, risk factors, and tumor subtypes. Associations of genotypes with breast cancer risk was evaluated using multivariate logistic regression to estimate odds ratios (OR and their 95% confidence intervals (95% CI. The results indicated that both polymorphisms were significantly associated with the risk of breast cancer, with per allele OR = 1.35, (95%CI = 1.17-1.57 for rs2046210 and per allele OR = 1.24 (95%CI = 1.06-1.45 for rs4784227. Furthermore, in subgroup stratified analyses, we observed that the T allele of rs4784227 was significantly associated with elevated OR among postmenopausal populations (OR = 1.44, 95%CI 1.11-1.87 but not in premenopausal populations, with the heterogeneity P value of P = 0.064. These findings suggest that the genetic variants at chromosome 6q25 and in the TOX3 gene may play important roles in breast cancer development in a Chinese population and the underlying biological mechanisms need to be further elucidated.

  13. Breast cancer risk associated with different HRT formulations: a register-based case-control study

    Directory of Open Access Journals (Sweden)

    Thai Do

    2006-09-01

    Full Text Available Abstract Background Previous epidemiological studies have inconsistently shown a modestly increased breast cancer risk associated with hormone replacement therapy (HRT. Limited information is available about different formulations – particularly concerning different progestins. Methods A case-control study was performed within Germany in collaboration with regional cancer registries and tumor centers. Up to 5 controls were matched breast cancer cases. Conditional logistic regression analysis was applied to estimate crude and adjusted odds ratios (OR and 95% confidence intervals (95% CI. Stratified analyses were performed to compare the risk of different estrogens, progestins, and combinations. Results A total of 3593 cases of breast cancer were identified and compared with 9098 controls. The adjusted overall risk estimate for breast cancer (BC associated with current or past use of HRT was 1.2 (1.1–1.3, and almost identical for lag times from 6 months to 6 years prior to diagnosis. No significant trend of increasing BC risk was found with increasing duration of HRT use, or time since first or last use in aggregate. Many established BC risk factors significantly modified the effect of HRT on BC risk, particularly first-degree family history of BC, higher age, lower education, higher body mass index (BMI, and never having used oral contraceptives (OCs during lifetime. Whereas the overall risk estimates were stable, the numbers in many of the sub-analyses of HRT formulation groups (estrogens, progestins, and combinations were too small for strong conclusions. Nevertheless, the BC risk seems not to vary much across HRT formulation subgroups. In particular, no substantial difference in BC risk was observed between HRT containing conjugated equine estrogens (CEE or medroxyprogesterone acetate (MPA and other formulations more common in Europe. Conclusion The BC risk of HRT use is rather small. Low risk estimates for BC and a high potential for

  14. Association between CLN3 (Neuronal Ceroid Lipofuscinosis, CLN3 type gene expression and clinical characteristics of breast cancer patients

    Directory of Open Access Journals (Sweden)

    Rose-Mary eBoustany

    2015-10-01

    Full Text Available Breast cancer is the most common cancer in women worldwide. Elucidation of underlying biology and molecular pathways is necessary for improving therapeutic options and clinical outcomes. CLN3 protein (CLN3p, deficient in neurodegenerative CLN3 disease is anti-apoptotic, and defects in the CLN3 gene cause accelerated apoptosis of neurons in CLN3 disease and upregulation of ceramide. Dysregulated apoptotic pathways are often implicated in the development of the oncogenic phenotype. Predictably, CLN3 mRNA expression and CLN3 protein were upregulated in a number of human and murine breast cancer cell lines. Here, we determine CLN3 expression in non-tumor vs. tumor samples from fresh and formalin-fixed/paraffin-embedded (FFPE breast tissue and analyze the association between CLN3 overexpression and different clinicopathological characteristics of breast cancer patients. Additionally, gene expression of 28 enzymes involved in sphingolipid metabolism was determined. CLN3 mRNA is overexpressed in tumor vs. non-tumor breast tissue from FFPE and fresh samples, as well as in mouse MCF7 breast cancer compared to MCF10A normal cells. Of the clinicopathological characteristics of tumor grade, age, menopause status, estrogen receptor (ER, progesterone receptor (PR, and human epidermal growth factor receptor 2 (HER2, only absence of HER2 expression correlated with CLN3 overexpression. Sphingolipid genes for ceramide synthases 2 and 6 (CerS2; CerS6, delta(4-desaturase sphingolipid 2 (DEGS2 and acidic sphingomyelinase (SMPD1 displayed higher expression levels in breast cancer vs. control tissue, whereas, ceramide galactosyltransferase (UGT8 was underexpressed in breast cancer samples. CLN3 may be a novel molecular target for cancer drug discovery with the goal of modulation of ceramide pathways.

  15. Loss of membranous VEGFR1 expression is associated with an adverse phenotype and shortened survival in breast cancer.

    Science.gov (United States)

    Lebok, Patrick; Huber, Julia; Burandt, Eike-Christian; Lebeau, Annette; Marx, Andreas Holger; Terracciano, Luigi; Heilenkötter, Uwe; Jänicke, Fritz; Müller, Volkmar; Paluchowski, Peter; Geist, Stefan; Wilke, Christian; Simon, Ronald; Sauter, Guido; Quaas, Alexander

    2016-08-01

    Angiogenesis is a key process in tumor growth and progression, which is controlled by vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs). In order to better understand the prevalence and prognostic value of VEGFR1 expression in breast cancer, a tissue microarray containing >2,100 breast cancer specimens, with clinical follow‑up data, was analyzed by immunohistochemistry using an antibody directed against the membrane‑bound full‑length receptor protein. The results demonstrated that membranous VEGFR1 staining was detected in all (5 of 5) normal breast specimens. In carcinoma specimens, membranous staining was negative in 3.1%, weak in 6.3%, moderate in 10.9%, and strong in 79.7% of the 1,630 interpretable tissues. Strong staining was significantly associated with estrogen receptor and progesterone receptor expression, but was inversely associated with advanced tumor stage (P=0.0431), high Bloom-Richardson-Ellis Score for Breast Cancer grade and low Ki67 labeling index (both Ptamoxifen as the sole therapy (P=0.001). In conclusion, these data indicated that membrane‑bound VEGFR1 is frequently expressed in normal and cancerous breast epithelium. In addition, reduced or lost VEGFR1 expression may serve as a marker for poor prognosis in patients with breast cancer, who might not optimally benefit from endocrine therapy. PMID:27357606

  16. Nestin expression associates with poor prognosis and triple negative phenotype in locally advanced (T4 breast cancer

    Directory of Open Access Journals (Sweden)

    F. Piras

    2011-11-01

    Full Text Available Nestin, an intermediate filament protein, has traditionally been noted for its importance as a neural stem cell marker. However, in recent years, expression of nestin has shown to be associated with general proliferation of progenitor cell populations within neoplasms. There is no reported study addressing nestin expression in T4 breast cancer patients. Thus, the aim of the present study was to investigate, through immunohistochemistry, the expression and distribution of nestin in T4 breast cancer, in order to determine its association with clinical and pathological parameters as well as with patients’ outcome. Nestin was detectable in tumoral cells and in endothelial cells of blood microvessels, and it is significantly expressed in triple-negative and in inflammatory breast cancer (IBC subgroups of T4 breast tumours. The Kaplan-Meier analysis showed that the presence of nestin in tumoral cells significantly predicted poor prognosis at 5-years survival (P=0.02 and with borderline significance at 10-years of survival (P=0.05 in T4 breast cancer patients. On the basis of these observations, we speculate that nestin expression may characterize tumours with an aggressive clinical behavior, suggesting that the presence of nestin in tumoral cells and vessels may be considered an important factor that leads to a poor prognosis. Further studies are awaited to define the biological role of nestin in the etiology of these subgroups of breast cancers.

  17. Breast Cancer Risk in American Women

    Science.gov (United States)

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Risk in American Women On This Page What ... risk of developing the disease. Personal history of breast cancer : Women who have had breast cancer are more ...

  18. Cyclooxygenase-2 in tumor-associated macrophages promotes breast cancer cell survival by triggering a positive-feedback loop between macrophages and cancer cells

    OpenAIRE

    Li, Hongzhong; Yang, Bing; Huang, Jing; Lin, Yong; Xiang, Tingxiu; Wan, Jingyuan; Li, Hongyuan; Chouaib, Salem; Ren, Guosheng

    2015-01-01

    Tumor-associated macrophages (TAMs) play an important role in cancer cell survival, however, the mechanism of which remains elusive. In this study, we found that COX-2 was abundantly expressed in breast TAMs, which was correlated to poor prognosis in breast cancer patients. Ectopic over-expression of COX-2 in TAMs enhanced breast cancer cell survival both in vitro and in vivo. COX-2 in TAMs was determined to be essential for the induction and maintenance of M2-phenotype macrophage polarity. C...

  19. COX-2 activation is associated with Akt phosphorylation and poor survival in ER-negative, HER2-positive breast cancer

    Directory of Open Access Journals (Sweden)

    Goodman Julie E

    2010-11-01

    Full Text Available Abstract Background Inducible cyclooxgenase-2 (COX-2 is commonly overexpressed in breast tumors and is a target for cancer therapy. Here, we studied the association of COX-2 with breast cancer survival and how this association is influenced by tumor estrogen and HER2 receptor status and Akt pathway activation. Methods Tumor COX-2, HER2 and estrogen receptor α (ER expression and phosphorylation of Akt, BAD, and caspase-9 were analyzed immunohistochemically in 248 cases of breast cancer. Spearman's correlation and multivariable logistic regression analyses were used to examine the relationship between COX-2 and tumor characteristics. Kaplan-Meier survival and multivariable Cox proportional hazards regression analyses were used to examine the relationship between COX-2 and disease-specific survival. Results COX-2 was significantly associated with breast cancer outcome in ER-negative [Hazard ratio (HR = 2.72; 95% confidence interval (CI, 1.36-5.41; comparing high versus low COX-2] and HER2 overexpressing breast cancer (HR = 2.84; 95% CI, 1.07-7.52. However, the hazard of poor survival associated with increased COX-2 was highest among patients who were both ER-negative and HER2-positive (HR = 5.95; 95% CI, 1.01-34.9. Notably, COX-2 expression in the ER-negative and HER2-positive tumors correlated significantly with increased phosphorylation of Akt and of the two Akt targets, BAD at Ser136 and caspase-9 at Ser196. Conclusions Up-regulation of COX-2 in ER-negative and HER2-positive breast tumors is associated with Akt pathway activation and is a marker of poor outcome. The findings suggest that COX-2-specific inhibitors and inhibitors of the Akt pathway may act synergistically as anticancer drugs in the ER-negative and HER2-positive breast cancer subtype.

  20. Association between urinary prostaglandin E2 metabolite and breast cancer risk: a prospective, case-cohort study of postmenopausal women.

    Science.gov (United States)

    Kim, Sangmi; Taylor, Jack A; Milne, Ginger L; Sandler, Dale P

    2013-06-01

    Overweight or obese women are at increased risk of developing and dying from breast cancer. Obesity-driven inflammation may stimulate prostaglandin E2 (PGE2)-mediated aromatase activation and estrogen biosynthesis in breast tissues. We hypothesized that increased production of PGE2 would contribute to elevated breast cancer risk in postmenopausal women. We carried out a case-cohort study with 307 incident breast cancer cases and 300 subcohort members from the Sister Study cohort. HRs and 95% confidence intervals (CI) were estimated for the association between urinary levels of a major PGE2 metabolite (PGE-M) and breast cancer risk using Prentice's pseudo-likelihood approach. Several lifestyle factors were associated with urinary levels of PGE-M: smoking, high-saturated fat diet, and obesity increased urinary PGE-M, and use of nonsteroidal antiinflammatory drugs (NSAID) decreased urinary PGE-M. Although there was no association between urinary PGE-M and postmenopausal breast cancer risk in the overall analysis or among regular users of NSAIDs, there was a positive association among postmenopausal women who did not regularly use NSAIDs with HRs of 2.1 [95% confidence interval (CI): 1.0-4.3]; 2.0 (95% CI: 1.0-3.9); and 2.2 (95% CI: 1.1-4.3) for the second, third, and highest quartiles of PGE-M. Our findings suggest a link between systemic PGE2 formation and postmenopausal breast cancer, and a possible modification of the association by lifestyle and pharmacologic interventions. If confirmed in larger studies, these results may have useful implications for the development of preventive strategies. PMID:23636050

  1. Do adipokines underlie the association between known risk factors and breast cancer among a cohort of U.S. women?

    Science.gov (United States)

    Gaudet, Mia M.; Falk, Roni T.; Gierach, Gretchen L.; Lacey, James V.; Graubard, Barry I.; Dorgan, Joanne F.; Brinton, Louise A.

    2010-01-01

    Obesity is a well-established risk factor for postmenopausal breast cancer, but mechanisms underlying the association are unclear. Adipocyte-derived, cytokine-like adipokines have been suggested as contributory factors. To evaluate their association with breast cancer risk factors and breast cancer risk, we conducted a nested case-control study of 234 postmenopausal breast cancer cases and 234 controls in a cohort of U.S. women with prospectively-collected serum samples obtained in the mid 1970’s and followed for up to 25 years. Adiponectin, absolute plasminogen activator inhibitor-1 (aPAI-1), and resistin were measured by a multiplex immunoassay. Sex hormones were available for 67 cases and 67 controls. Among controls, we found that lower levels of adiponectin and higher levels of aPAI-1 were correlated with increasing levels of estradiol (Spearman r=−0.26, p-value=0.033; r=0.42, p=0.0003), decreasing levels of sex hormone binding globulin (r=0.38, p=0.0013; r=−0.32, p=0.0076), and increasing body mass index (BMI) (r=−0.31, p=0.05). The lack of association with risk may be due to measurement error of the laboratory assays. In conclusion, lower levels of adiponectin and higher levels of aPAI-1 measured in prospectively-collected serum from postmenopausal women were associated with increasing BMI but not breast cancer risk. PMID:20579950

  2. Association between genomic recurrence risk and well-being among breast cancer patients

    International Nuclear Information System (INIS)

    Gene expression profiling (GEP) is increasingly used in the rapidly evolving field of personalized medicine. We sought to evaluate the association between GEP-assessed of breast cancer recurrence risk and patients’ well-being. Participants were Dutch women from 10 hospitals being treated for early stage breast cancer who were enrolled in the MINDACT trial (Microarray In Node-negative and 1 to 3 positive lymph node Disease may Avoid ChemoTherapy). As part of the trial, they received a disease recurrence risk estimate based on a 70-gene signature and on standard clinical criteria as scored via a modified version of Adjuvant! Online. /Women completed a questionnaire 6–8 weeks after surgery and after their decision regarding adjuvant chemotherapy. The questionnaire assessed perceived understanding, knowledge, risk perception, satisfaction, distress, cancer worry and health-related quality of life (HRQoL), 6–8 weeks after surgery and decision regarding adjuvant chemotherapy. Women (n = 347, response rate 62%) reported high satisfaction with and a good understanding of the GEP information they received. Women with low risk estimates from both the standard and genomic tests reported the lowest distress levels. Distress was higher predominately among patients who had received high genomic risk estimates, who did not receive genomic risk estimates, or who received conflicting estimates based on genomic and clinical criteria. Cancer worry was highest for patients with higher risk perceptions and lower satisfaction. Patients with concordant high-risk profiles and those for whom such profiles were not available reported lower quality of life. Patients were generally satisfied with the information they received about recurrence risk based on genomic testing. Some types of genomic test results were associated with greater distress levels, but not with cancer worry or HRQoL. ISRCTN: http://www.controlled-trials.com/ISRCTN18543567/MINDACT

  3. Oxalate induces breast cancer

    OpenAIRE

    Castellaro, Andrés M.; Tonda, Alfredo; Cejas, Hugo H.; Ferreyra, Héctor; Caputto, Beatriz L.; Pucci, Oscar A.; Gil, German A.

    2015-01-01

    Background Microcalcifications can be the early and only presenting sign of breast cancer. One shared characteristic of breast cancer is the appearance of mammographic mammary microcalcifications that can routinely be used to detect breast cancer in its initial stages, which is of key importance due to the possibility that early detection allows the application of more conservative therapies for a better patient outcome. The mechanism by which mammary microcalcifications are formed is still l...

  4. Depression is associated with some patient-perceived cosmetic changes, but not with radiotherapy-induced late toxicity, in long-term breast cancer survivors. : Depression-associated factors in long-term breast cancer survivors

    OpenAIRE

    Brunault, Paul; Suzanne, Isabelle; Trzepidur-Edom, Magdalena; Garaud, Pascal; Calais, Gilles; Toledano, Alain; Camus, Vincent

    2013-01-01

    OBJECTIVE: Although depression is prevalent in long-term breast cancer survivors (LTBCS; ≥5 years since diagnosis), it is underdiagnosed and undertreated. A better understanding of factors associated with depression could improve depression screening, treatment, and prevention in this population. Our study aimed to assess the link between patient and doctor ratings of breast cosmetic outcomes, late radiotherapy toxicity, and depression in LTBCS. METHODS: In all, 214 patients recruited from th...

  5. Digit ratio (2D:4D) is associated with breast cancer

    OpenAIRE

    Patrícia Helena Costa Mendes; Ana Carolina de Campos Gomes; Priscila Bernadina Miranda Soares; Eduardo Gonçalves; Clayton Paraíso Macedo; Marise Fagundes Silveira; Daniella Reis Barbosa Martelli; Lívia Máris Ribeiro Paranaíba; Hercílio Martelli-Júnior

    2016-01-01

    Purpose: Digit ratio (2D:4D) has been considered as a proxy biomarker for prenatal hormonal exposure and may represent an individual’s predisposition to breast cancer. The purpose of the present study is to investigate whether there is a link between digit ratio and breast cancer in a Brazilian population.Methods: Digital measurements of the lengths of the index and ring fingers of both hands were obtained from women with breast cancer (n = 100) and age-matched controls (n = 100) using a digi...

  6. Bra wearing not associated with breast cancer risk: a population based case-control study

    OpenAIRE

    Chen, Lu; Malone, Kathleen E.; Li, Christopher I.

    2014-01-01

    Despite the widespread use of bras among U.S. women and concerns in the lay media that bra wearing may increase breast cancer risk, there is a scarcity of credible scientific studies addressing this issue. The goal of the study was to evaluate the relationship between various bra wearing habits and breast cancer risk among postmenopausal women. We conducted a population-based case-control study of breast cancer in the Seattle-Puget Sound metropolitan area that compared 454 invasive ductal car...

  7. Breast cancer stem cells

    OpenAIRE

    Owens, Thomas W.; Naylor, Matthew J.

    2013-01-01

    Cancer metastasis, resistance to therapies and disease recurrence are significant hurdles to successful treatment of breast cancer. Identifying mechanisms by which cancer spreads, survives treatment regimes and regenerates more aggressive tumors are critical to improving patient survival. Substantial evidence gathered over the last 10 years suggests that breast cancer progression and recurrence is supported by cancer stem cells (CSCs). Understanding how CSCs form and how they contribute to th...

  8. Dietary fat and risk of breast cancer

    Directory of Open Access Journals (Sweden)

    Mathew Aleyamma

    2005-07-01

    Full Text Available Abstract Background Breast cancer is one of the major public health problems among women worldwide. A number of epidemiological studies have been carried out to find the role of dietary fat and the risk of breast cancer. The main objective of the present communication is to summarize the evidence from various case-control and cohort studies on the consumption of fat and its subtypes and their effect on the development of breast cancer. Methods A Pubmed search for literature on the consumption of dietary fat and risk of breast cancer published from January 1990 through December 2003 was carried out. Results Increased consumption of total fat and saturated fat were found to be positively associated with the development of breast cancer. Even though an equivocal association was observed for the consumption of total monounsaturated fatty acids (MUFA and the risk of breast cancer, there exists an inverse association in the case of oleic acid, the most abundant MUFA. A moderate inverse association between consumption of n-3 fatty acids and breast cancer risk and a moderate positive association between n-6 fatty acids and breast cancer risk were observed. Conclusion Even though all epidemiological studies do not provide a strong positive association between the consumption of certain types of dietary fat and breast cancer risk, at least a moderate association does seem to exist and this has a number of implications in view of the fact that breast cancer is an increasing public health concern.

  9. Human Papillomavirus Is Associated with Breast Cancer in the North Part of Iran

    Directory of Open Access Journals (Sweden)

    Afsaneh Sigaroodi

    2012-01-01

    Full Text Available We have analyzed the possible relevance of HPV infection for breast cancer risk among Iranian women from north part of Iran. Among women with breast cancer, 25.9% had positive test results for HPV DNA in breast tumor samples in contrast to 2.4% of women with noncancer status (P=0.002. The infection of HPV has increased the risk of breast cancer (OR 14.247; 95% CI 1.558–130.284, P=0.019. The high-risk HPV genotypes (types 16 and 18 in samples of breast cancer patients were the predominant types (53.34%. Other genotypes detected in breast cancer were HPV-6, HPV-11, HPV-15, HPV-23, and HPV-124, and one isolate could not be genotyped compared to HPV reference sequences. While the sole detected HPV in control specimens was HPV-124. Our study reveals that HPV infection and age are the risk factors in breast cancer development in the north part of Iran.

  10. Association between tumor tissue TIMP-1 levels and objective response to first-line chemotherapy in metastatic breast cancer

    DEFF Research Database (Denmark)

    Klintman, Marie; Würtz, Sidse Ørnbjerg; Christensen, Ib Jarle;

    2010-01-01

    In a previous study from our laboratory, high tumor levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) have been associated with an adverse response to chemotherapy in metastatic breast cancer suggesting that TIMP-1, which is known to inhibit apoptosis, may be a new predictive marker in...... this disease. The purpose of this study was to investigate the association between TIMP-1 and objective response to chemotherapy in an independent patient population consisting of patients with metastatic breast cancer from Sweden and Denmark. TIMP-1 was measured using ELISA in 162 primary tumor...... extracts from patients who later developed metastatic breast cancer and these levels were related to the objective response to first-line chemotherapy. Increasing levels of TIMP-1 were associated with a decreasing probability of response to treatment, reaching borderline significance (OR = 1.59, 95% CI: 0...

  11. Low Expression of Slit2 and Robo1 is Associated with Poor Prognosis and Brain-specific Metastasis of Breast Cancer Patients

    OpenAIRE

    Fengxia Qin; Huikun Zhang; Li Ma; Xiaoli Liu; Kun Dai; Wenliang Li; Feng Gu; Li Fu; Yongjie Ma

    2015-01-01

    Brain metastasis is a significant unmet clinical problem in breast cancer treatment. It is always associated with poor prognosis and high morbidity. Recently, Slit2/Robo1 pathway has been demonstrated to be involved in the progression of breast carcinoma. However, until present, there are no convincing reports that suggest whether the Slit2/Robo1 axis has any role in brain metastasis of breast cancer. In this study, we investigated the correlation between Slit2/Robo1 signaling and breast canc...

  12. Association of CTLA-4 gene polymorphisms with sporadic breast cancer in Chinese Han population

    International Nuclear Information System (INIS)

    The host immunogenetic background plays an important role in the development of breast cancer. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a molecule expressed predominantly on activated T cells and is important during the down-regulation of T-cell activation. To evaluate the potential influences of CTLA-4 gene polymorphisms on breast cancer risk, a case-control study was conducted in Han women of Northeast China. We genotyped CTLA-4 variants (-1661 G/A, -658 T/C, -318 T/C, +49 G/A and CT60 G/A) to tag all common haplotypes (≥ 1% frequency) in 117 Chinese breast cancer cases and 148 age/sex matched healthy individuals. Genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Data was analyzed using the Chi-square test and Haploview software. The frequency of CTLA-4 -1661G allele, -318T allele and CT60G allele carriers was significantly higher in patients than in controls (P = 0.0057, OR 1.91, 95% CI 1.21–3.02; P = 0.0031, OR 2.39, 95% CI 1.34–4.27; P = 0.023, OR 1.52, 95% CI 1.06–2.17, respectively). The -658T allele carrier frequency was significantly lower than in controls (P = 0.0000082, OR 0.17, 95% CI 0.08–0.37), whereas the +49A allele was significantly associated with tumor size in patients (P = 0.0033). Two common CTLA-4 haplotypes, ATCGA and ATCAG, were higher in healthy controls than patients (P = 0.0026, OR 0.17, 95% CI 0.05–0.54; P = 0.034, OR 0.12, 95% CI 0.02–0.92, respectively). A strong association was observed between tumor size and the ACCAA, ACCAG and ACCGA haplotypes (P = 0.0032, P = 0.0000031 and P = 0.017). These results suggest that polymorphisms of the CTLA-4 gene may modify individual susceptibility to and progression of breast cancer in Chinese Han women

  13. Leptomeningeal metastases in breast cancer

    OpenAIRE

    Scott, Brian J.; Kesari, Santosh

    2013-01-01

    Central nervous system (CNS) metastasis from breast cancer may be characterized as either parenchymal brain metastasis (BM) or leptomeningeal (LM) metastasis. BM are much more common (about 80% of all CNS metastases), and have been more extensively studied than LM. CNS metastasis in breast cancer has been associated with reduced overall survival, with the shortest survival generally observed in cases of LM. Here, we review the epidemiology, prognostic factors, diagnostic tools, currently avai...

  14. AT1-IR-beta Association: A New Mechanism for the Inhibition of Insulin Receptor Function in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Lakshmi Pulakat

    2008-01-01

    Full Text Available Epidemiological evidence show that increased mortality in breast cancer is linked to hypertension and insulin resistance. Because Angiotensin II (Ang II, a hormone implicated in hypertension and insulin resistance, is a normal mitogen for breast tissue and elevated expression of the Ang II receptor AT1 is seen in breast cancer, we analyzed the effects of Ang II exposure on the functions of IR in human breast cancer cell line MCF-7. Exposure of MCF-7 to Ang II for 2 hours a significantly reduced 125I-insulin binding to IR, and b induced co-immuno-precipitation of the AT1 with IR-beta subunit. These Ang II-mediated effects on IR were inhibited by the AT1 antagonist losartan, and were not observed when exposure time was below 1-hour. These observations suggest extended exposure to Ang II have detrimental effects on insulin binding to IR that were not discovered in the previous studies where Ang II-exposure of insulin responsive cells was performed for periods less than one hour. In addition, they suggest a novel mechanism that involves AT1-IR-beta association for the inhibition of insulin binding to IR in response to extended exposure (2-hours of breast cancer cells to elevated levels of Ang II (as seen in hypertensive patients, and provides a molecular link for the inhibition of normal IR signaling by Ang II in breast cancer.

  15. Melatonin decreases breast cancer metastasis by modulating Rho-associated kinase protein-1 expression

    Science.gov (United States)

    Borin, Thaiz Ferraz; Arbab, Ali Syed; Gelaleti, Gabriela Bottaro; Ferreira, Lívia Carvalho; Moschetta, Marina Gobbe; Jardim-Perassi, Bruna Victorasso; Iskander, ASM; Varma, Nadimpalli Ravi S.; Shankar, Adarsh; Coimbra, Verena Benedick; Fabri, Vanessa Alves; de Oliveira, Juliana Garcia; de Campos Zuccari, Debora Aparecida Pires

    2016-01-01

    The occurrence of metastasis, an important breast cancer prognostic factor, depends on cell migration/invasion mechanisms, which can be controlled by regulatory and effector molecules such as Rho-associated kinase protein (ROCK-1). Increased expression of this protein promotes tumor growth and metastasis, which can be restricted by ROCK-1 inhibitors. Melatonin has shown oncostatic, antimetastatic, and anti-angiogenic effects and can modulate ROCK-1 expression. Metastatic and nonmetastatic breast cancer cell lines were treated with melatonin as well as with specific ROCK-1 inhibitor (Y27632). Cell viability, cell migration/invasion, and ROCK-1 gene expression and protein expression were determined in vitro. In vivo lung metastasis study was performed using female athymic nude mice treated with either melatonin or Y27832 for 2 and 5 wk. The metastases were evaluated by X-ray computed tomography and single photon emission computed tomography (SPECT) and by immunohistochemistry for ROCK-1 and cytokeratin proteins. Melatonin and Y27632 treatments reduced cell viability and invasion/migration of both cell lines and decreased ROCK-1 gene expression in metastatic cells and protein expression in nonmetastatic cell line. The numbers of ‘hot’ spots (lung metastasis) identified by SPECT images were significantly lower in treated groups. ROCK-1 protein expression also was decreased in metastatic foci of treated groups. Melatonin has shown to be effective in controlling metastatic breast cancer in vitro and in vivo, not only via inhibition of the proliferation of tumor cells but also through direct antagonism of metastatic mechanism of cells rendered by ROCK-1 inhibition. When Y27632 was used, the effects were similar to those found with melatonin treatment. PMID:26292662

  16. Overexpression of centromere protein H is significantly associated with breast cancer progression and overall patient survival

    Institute of Scientific and Technical Information of China (English)

    Wen-Ting Liao; Yan Feng; Men-Lin Li; Guang-Lin Liu; Man-Zhi Li; Mu-Sheng Zeng; Li-Bing Song

    2011-01-01

    Breast cancer is one of the leading causes of cancer death worldwide.This study aimed to analyze the expression of centromere protein H (CENP-H) in breast cancer and to correlate it with clinicopathologic data,including patient survival.Using reverse transcription-polymerase chain reaction and Westem blotting to detect the expression of CENP-H in normal mammary epithelial cells,immortalized mammary epithelial cell lines,and breast cancer cell lines,we observed that the mRNA and protein levels of CENP-H were higher in breast cancer cell lines and in immortalized mammary epithelial cells than in normal mammary epithelial cells.We next examined CENP-H expression in 307 paraffin-embedded archived samples of clinicopathologically characterized breast cancer using immunohistochemistry,and detected high CENP-H expression in 134 (43.6%) samples.Statistical analysis showed that CENP-H expression was related with clinical stage (P = 0.001),T classification (P = 0.032),N classification (P =0.018),and Ki-67 (P<0.001).Patients with high CENP-H expression had short overall survival.Multivariate analysis showed that CENP-H expression was an independent prognostic indicator for patient survival.Our results suggest that CENP-H protein is a valuable marker of breast cancer progression and prognosis.

  17. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer

    DEFF Research Database (Denmark)

    Michailidou, Kyriaki; Beesley, Jonathan; Lindstrom, Sara;

    2015-01-01

    Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748...

  18. Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility: a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium.

    Science.gov (United States)

    Lei, Jieping; Rudolph, Anja; Moysich, Kirsten B; Behrens, Sabine; Goode, Ellen L; Bolla, Manjeet K; Dennis, Joe; Dunning, Alison M; Easton, Douglas F; Wang, Qin; Benitez, Javier; Hopper, John L; Southey, Melissa C; Schmidt, Marjanka K; Broeks, Annegien; Fasching, Peter A; Haeberle, Lothar; Peto, Julian; Dos-Santos-Silva, Isabel; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Marmé, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Flyger, Henrik; Nielsen, Sune F; Nordestgaard, Børge G; González-Neira, Anna; Menéndez, Primitiva; Anton-Culver, Hoda; Neuhausen, Susan L; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Hamann, Ute; Nevanlinna, Heli; Fagerholm, Rainer; Dörk, Thilo; Bogdanova, Natalia V; Mannermaa, Arto; Hartikainen, Jaana M; Van Dijck, Laurien; Smeets, Ann; Flesch-Janys, Dieter; Eilber, Ursula; Radice, Paolo; Peterlongo, Paolo; Couch, Fergus J; Hallberg, Emily; Giles, Graham G; Milne, Roger L; Haiman, Christopher A; Schumacher, Fredrick; Simard, Jacques; Goldberg, Mark S; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Zheng, Wei; Beeghly-Fadiel, Alicia; Winqvist, Robert; Grip, Mervi; Andrulis, Irene L; Glendon, Gord; García-Closas, Montserrat; Figueroa, Jonine; Czene, Kamila; Brand, Judith S; Darabi, Hatef; Eriksson, Mikael; Hall, Per; Li, Jingmei; Cox, Angela; Cross, Simon S; Pharoah, Paul D P; Shah, Mitul; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Ademuyiwa, Foluso; Ambrosone, Christine B; Swerdlow, Anthony; Jones, Michael; Chang-Claude, Jenny

    2016-01-01

    Immunosuppression plays a pivotal role in assisting tumors to evade immune destruction and promoting tumor development. We hypothesized that genetic variation in the immunosuppression pathway genes may be implicated in breast cancer tumorigenesis. We included 42,510 female breast cancer cases and 40,577 controls of European ancestry from 37 studies in the Breast Cancer Association Consortium (2015) with available genotype data for 3595 single nucleotide polymorphisms (SNPs) in 133 candidate genes. Associations between genotyped SNPs and overall breast cancer risk, and secondarily according to estrogen receptor (ER) status, were assessed using multiple logistic regression models. Gene-level associations were assessed based on principal component analysis. Gene expression analyses were conducted using RNA sequencing level 3 data from The Cancer Genome Atlas for 989 breast tumor samples and 113 matched normal tissue samples. SNP rs1905339 (A>G) in the STAT3 region was associated with an increased breast cancer risk (per allele odds ratio 1.05, 95 % confidence interval 1.03-1.08; p value = 1.4 × 10(-6)). The association did not differ significantly by ER status. On the gene level, in addition to TGFBR2 and CCND1, IL5 and GM-CSF showed the strongest associations with overall breast cancer risk (p value = 1.0 × 10(-3) and 7.0 × 10(-3), respectively). Furthermore, STAT3 and IL5 but not GM-CSF were differentially expressed between breast tumor tissue and normal tissue (p value = 2.5 × 10(-3), 4.5 × 10(-4) and 0.63, respectively). Our data provide evidence that the immunosuppression pathway genes STAT3, IL5, and GM-CSF may be novel susceptibility loci for breast cancer in women of European ancestry. PMID:26621531

  19. Association between the BsmI Polymorphism in the Vitamin D Receptor Gene and Breast Cancer Risk: Results from a Pakistani Case-Control Study.

    Directory of Open Access Journals (Sweden)

    Muhammad Usman Rashid

    Full Text Available Vitamin D is postulated to decrease the risk of breast cancer by inhibiting cell proliferation via the vitamin D receptor (VDR. Two common single nucleotide polymorphisms (SNPs in the VDR gene, rs1544410 (BsmI and rs2228570 (FokI, are inconsistently associated with breast cancer risk in Caucasian populations, while data for Asians are scarce. Here, we investigated the possible contribution of these SNPs to breast cancer risk in Pakistani breast cancer patients and in controls participating in a hospital-based breast cancer case-control study (PAK-BCCC.Genotyping of the BsmI and FokI SNPs was performed by PCR-based restriction fragment length polymorphism (RFLP analysis of 463 genetically enriched female breast cancer cases with known BRCA1/2 status and in 1,012 controls from Pakistan. The association between SNP genotypes and breast cancer risk was investigated by logistic regression adjusted for potential breast cancer risk factors and stratified by BRCA1/2 status and family history. Odds ratios (ORs and 95% confidence intervals (CIs were reported.The b allele of the BsmI was associated with an increased breast cancer risk (per b allele OR 1.28, 95% CI 1.09-1.49, P = 0.003. Subgroup analysis revealed that this effect was restricted to BRCA1/2 non-carriers (per b allele OR 1.33, 95% CI 1.11-1.59, P = 0.002 and was stronger in those who reported a positive family history of breast and/or ovarian cancer (per b allele OR 1.64, 95% CI 1.20-2.22, P = 0.002. No association with breast cancer risk was detected for the FokI SNP.The BsmI polymorphism in the VDR gene may be associated with an increased breast cancer risk in Pakistani women negative for BRCA1/2 germline mutations.

  20. Breast Cancer In Women Infographic

    Science.gov (United States)

    This infographic shows the Breast Cancer Subtypes in Women. It’s important for guiding treatment and predicting survival. Know the Science: HR = Hormone receptor. HR+ means tumor cells have receptors for the hormones estrogen or progesterone, which can promote the growth of HR+ tumors. Hormone therapies like tamoxifen can be used to treat HR+ tumors. HER2 = Human epidermal growth Factor receptor, HER2+ means tumor cells overexpress (make high levels of) a protein, called HE2/neu, which has been shown to be associated with certain aggressive types of breast cancer. Trastuzumab and some other therapies can target cells that overexpress HER2. HR+/HER2, aka “LuminalA”. 73% of all breast cancer cases: best prognosis, most common subtype for every race, age, and poverty level. HR-/HER2, aka “Triple Negative”: 13% of all breast cancer cases, Worst prognosis, Non-Hispanic blacks have the highest rate of this subtype at every age and poverty level. HR+/HER2+, aka “Luminal B”, 10% of all breast cancer cases, little geographic variation by state. HR-/HER2+, aka”HER2-enriched”, 5% of all breast cancer cases, lowest rates for all races and ethnicities. www.cancer.gov Source: Special section of the Annual Report to the Nation on the Status of Cancer, 1975-2011.

  1. PARP-1 inhibitors: are they the long-sought genetically specific drugs for BRCA1/2-associated breast cancers?

    OpenAIRE

    De Soto, Joseph A.; Deng, Chu-Xia

    2006-01-01

    Recent studies demonstrated that PARP-1 [poly(ADP-ribose) polymerase-1] inhibitors kill breast cancer associated gene-1 and –2 (BRCA1/2) deficient cells with extremely high efficiency while BRCA+/- and BRCA+/+ cells are relatively non-responsive to the treatment. It was therefore proposed that PARP-1 inhibitors might be the long-sought genetically specific drugs that are both safe and effective for treating BRCA1/2-associated breast cancers. However, a report published in a recent issue of th...

  2. Germline HVR-II mitochondrial polymorphisms associated with breast cancer in Tunisian women.

    Science.gov (United States)

    Yacoubi Loueslati, B; Troudi, W; Cherni, L; Rhomdhane, K B; Mota-Vieira, L

    2010-01-01

    A high incidence of somatic mtDNA polymorphisms has been reported in a wide variety of human cancers; some of them have been proposed as markers for the early detection of breast cancer. However, little attention has been paid to the potential of germline mitochondrial sequence variations as genetic risk factors for cancer. We performed a case-control study of 70 unrelated Tunisian women with breast cancer and 80 healthy age- and gender-matched blood donors, taking into account clinicopathological data, to evaluate germline polymorphism of mitochondrial HVR-II region as a genetic risk factor for breast cancer. Through direct sequencing, we detected 351 polymorphisms in controls and 248 variants in patients, with 47 and 39 segregating sites, respectively. In both groups, more than 50% of the polymorphisms were due to four variants: 315 ins C, 309 ins C, 263 A>G, and 73 A>G. The HVR-II sequences were also classified into haplotypes on the basis of the polymorphisms. Fifty-nine different haplotypes were found, 20 of them shared between patients and controls. Both groups had specific haplotypes, 18 in breast cancer patients and 21 in controls. Statistical analysis revealed a weak protective effect against breast cancer risk for two mitochondrial polymorphisms - 152 T>C (odds ratio (OR) = 0.33, 95% confidence interval (CI) = 0.12-0.91) and 263 A>G (OR = 0.17, 95%CI = 0.06-0.47). In contrast, an increased risk of breast cancer was detected for the 315+C haplotype (OR = 11.66, 95%CI = 1.44-252.23). We conclude that mitochondrial variants can affect breast cancer risk. More extensive studies, involving different types of cancer and patients with different genetic makeup, will be required to improve our understanding of the effects of germline mtDNA polymorphisms on carcinogenesis. PMID:20812191

  3. Decreased expression of SOX17 is associated with tumor progression and poor prognosis in breast cancer.

    Science.gov (United States)

    Fu, De-Yuan; Tan, Hao-Sheng; Wei, Jin-Li; Zhu, Chang-Ren; Jiang, Ji-Xin; Zhu, Yu-Xiang; Cai, Feng-Lin; Chong, Mei-Hong; Ren, Chuan-Li

    2015-09-01

    The SOX17 (SRY-related HMG-box) transcription factor is involved in a variety of biological processes and is related to the tumorigenesis and progression of multiple tumors. However, the clinical application of SOX17 for breast cancer prognosis is currently limited. The aim of this study was to investigate the clinicopathologic and prognostic significance of SOX17 expression in human breast cancer. qPCR and western blot assays were performed to measure the expression of SOX17 in breast cancer cell lines and 30 matched pairs of breast cancer and corresponding noncancerous tissues. A SOX17 overexpression cell model was used to examine changes in cell growth in vitro. Immunohistochemical analyses were performed to retrospectively examine the prognostic impact of SOX17 expression in 187 additional breast cancer patients. Our results showed that SOX17 expression was decreased at both the messenger RNA (mRNA) and protein levels in the breast cancer cell lines and tissues, and that SOX17 overexpression could strongly suppress cell growth in vitro. Furthermore, the lack of SOX17 protein expression was strongly correlated with higher tumor grade (P = 0.002), lymph node metastasis (P SOX17 expression (P = 0.002 and 0.001, respectively). Univariate and multivariate analyses indicated that lower SOX17 expression was an independent prognostic factor for DFS (P = 0.007; HR = 2.854; 95 % CI 1.326-6.147) and OS (P = 0.005; HR = 5.035; 95 % CI 1.648-15.385) for breast cancer. Our findings indicate that SOX17 expression is a useful prognostic biomarker for breast cancer. PMID:25971583

  4. Breast cancer risk factors.

    Science.gov (United States)

    Kamińska, Marzena; Ciszewski, Tomasz; Łopacka-Szatan, Karolina; Miotła, Paweł; Starosławska, Elżbieta

    2015-09-01

    Breast cancer is the most frequently diagnosed neoplastic disease in women around menopause often leading to a significant reduction of these women's ability to function normally in everyday life. The increased breast cancer incidence observed in epidemiological studies in a group of women actively participating in social and professional life implicates the necessity of conducting multidirectional studies in order to identify risk factors associated with the occurrence of this type of neoplasm. Taking the possibility of influencing the neoplastic transformation process in individuals as a criterion, all the risk factors initiating the process can be divided into two groups. The first group would include inherent factors such as age, sex, race, genetic makeup promoting familial occurrence of the neoplastic disease or the occurrence of benign proliferative lesions of the mammary gland. They all constitute independent parameters and do not undergo simple modification in the course of an individual's life. The second group would include extrinsic factors conditioned by lifestyle, diet or long-term medical intervention such as using oral hormonal contraceptives or hormonal replacement therapy and their influence on the neoplastic process may be modified to a certain degree. Identification of modifiable factors may contribute to development of prevention strategies decreasing breast cancer incidence. PMID:26528110

  5. Breast cancer risk factors

    Directory of Open Access Journals (Sweden)

    Marzena Kamińska

    2015-09-01

    Full Text Available Breast cancer is the most frequently diagnosed neoplastic disease in women around menopause often leading to a significant reduction of these women’s ability to function normally in everyday life. The increased breast cancer incidence observed in epidemiological studies in a group of women actively participating in social and professional life implicates the necessity of conducting multidirectional studies in order to identify risk factors associated with the occurrence of this type of neoplasm. Taking the possibility of influencing the neoplastic transformation process in individuals as a criterion, all the risk factors initiating the process can be divided into two groups. The first group would include inherent factors such as age, sex, race, genetic makeup promoting familial occurrence of the neoplastic disease or the occurrence of benign proliferative lesions of the mammary gland. They all constitute independent parameters and do not undergo simple modification in the course of an individual’s life. The second group would include extrinsic factors conditioned by lifestyle, diet or long-term medical intervention such as using oral hormonal contraceptives or hormonal replacement therapy and their influence on the neoplastic process may be modified to a certain degree. Identification of modifiable factors may contribute to development of prevention strategies decreasing breast cancer incidence.

  6. Breast cancer (metastatic)

    OpenAIRE

    Stebbing, Justin; Slater, Sarah; Slevin, Maurice

    2007-01-01

    Median survival from metastatic breast cancer is 12 months without treatment, but young people can survive up to 20 years with the disease, whereas in other metastatic cancers this would be considered very unusual.

  7. Is telomerase reactivation associated with the down-regulation of TGF β receptor-II expression in human breast cancer?

    Directory of Open Access Journals (Sweden)

    Thomas Valene

    2003-07-01

    Full Text Available Abstract Background Telomerase is a ribonucleoprotein that synthesizes telomeres and plays an important role in chromosomal stability and cellular immortalisation. Telomerase activity is detectable in most human cancers but not in normal somatic cells. TGF beta (transforming growth factor beta is a member of a family of cytokines that are essential for cell survival and seems to be down-regulated in human cancer. Recent in vitro work using human breast cancer cell lines has suggested that TGF beta down-regulates the expression of hTERT (human telomerase reverse transcriptase : the catalytic subunit of telomerase. We have therefore hypothesised that telomerase reactivation is associated with reduced immunohisto-chemical expression of TGF beta type II receptor (RII in human breast cancer. Methods TGF beta RII immunohistochemical expression was determined in 24 infiltrating breast carcinomas with known telomerase activity (17 telomerase-positive and 7 telomerase-negative. Immunohistochemical expression of TGF beta RII was determined by a breast pathologist who was blinded to telomerase data. Results TGF beta RII was detected in all lesions. The percentage of stained cells ranged from 1–100%. The difference in TGF beta RII expression between telomerase positive and negative tumours was not statistically significant (p = 1.0. Conclusion The results of this pilot study suggest that there is no significant association between telomerase reactivation and TGF-beta RII down-regulation in human breast cancer.

  8. Does the association of education with breast cancer replicate within twin pairs? A register-based study on Danish female twins

    DEFF Research Database (Denmark)

    Madsen, M; Andersen, Per Kragh; Gerster, M;

    2011-01-01

    A positive association between socio-economic position and breast cancer has been widely observed, but not hitherto within twin pairs, where shared familial factors were adjusted for.......A positive association between socio-economic position and breast cancer has been widely observed, but not hitherto within twin pairs, where shared familial factors were adjusted for....

  9. Intraductal papilloma of the breast in association with preoncogenic gene of breast cancer

    Institute of Scientific and Technical Information of China (English)

    Tuenchit Khammapirad; Jenjeera Prueksadee; Concepcion Diaz-Arrastia; Shaleen K Botting; Morton Leonard; Louisea Bonoan-Deomampo; Mahmoud A Eltorky

    2011-01-01

    We reported a case of an African American woman who went to the hospital with palpable right breast lump with bloody nipple discharge at University of Texas Medical Branct at Galvestion. The modalities of breast imagings included mammography and ultrasongraphy. The method used for viral identification was Linear ArrayHPV genotyping test. Intraductal papilloma revealed as high density tubular or rounded lobular masses with partially circumscribed, obscured margins and clustered punctate microcalcifications on mammograms. Ultrasound showed as intraductal masses with dilated ducts. The core biopsy demonstrated duct filled with papillary lesion and post excision revealed intraductal papilloma.HPV DNA types16, 33, 58 and71 were detected after use of Linear ArrayHPV genotyping test.

  10. Stiffening and unfolding of early deposited-fibronectin increase proangiogenic factor secretion by breast cancer-associated stromal cells

    OpenAIRE

    Wang, Karin; Andresen Eguiluz, Roberto C.; Wu, Fei; Seo, Bo Ri; Fischbach, Claudia; Gourdon, Delphine

    2015-01-01

    Fibronectin (Fn) forms a fibrillar network that controls cell behavior in both physiological and diseased conditions including cancer. Indeed, breast cancer-associated stromal cells not only increase the quantity of deposited Fn but also modify its conformation. However, (i) the interplay between mechanical and conformational properties of early tumor-associated Fn networks and (ii) its effect on tumor vascularization remain unclear. Here, we first used the Surface Forces Apparatus to reveal ...

  11. Carboplatin and Eribulin Mesylate in Triple Negative Breast Cancer Patients

    Science.gov (United States)

    2015-06-23

    Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer

  12. Cancer associated fibroblasts promote tumor growth and metastasis by modulating the tumor immune microenvironment in a 4T1 murine breast cancer model.

    Directory of Open Access Journals (Sweden)

    Debbie Liao

    Full Text Available BACKGROUND: Local inflammation associated with solid tumors commonly results from factors released by tumor cells and the tumor stroma, and promotes tumor progression. Cancer associated fibroblasts comprise a majority of the cells found in tumor stroma and are appealing targets for cancer therapy. Here, our aim was to determine the efficacy of targeting cancer associated fibroblasts for the treatment of metastatic breast cancer. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate that cancer associated fibroblasts are key modulators of immune polarization in the tumor microenvironment of a 4T1 murine model of metastatic breast cancer. Elimination of cancer associated fibroblasts in vivo by a DNA vaccine targeted to fibroblast activation protein results in a shift of the immune microenvironment from a Th2 to Th1 polarization. This shift is characterized by increased protein expression of IL-2 and IL-7, suppressed recruitment of tumor-associated macrophages, myeloid derived suppressor cells, T regulatory cells, and decreased tumor angiogenesis and lymphangiogenesis. Additionally, the vaccine improved anti-metastatic effects of doxorubicin chemotherapy and enhanced suppression of IL-6 and IL-4 protein expression while increasing recruitment of dendritic cells and CD8(+ T cells. Treatment with the combination therapy also reduced tumor-associated Vegf, Pdgfc, and GM-CSF mRNA and protein expression. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that cancer associated fibroblasts promote tumor growth and metastasis through their role as key modulators of immune polarization in the tumor microenvironment and are valid targets for therapy of metastatic breast cancer.

  13. Neuroendocrine breast cancer

    OpenAIRE

    Graça, Susana; Esteves, Joana; Costa, Sílvia; Vale, Sílvio; Maciel, Jorge

    2012-01-01

    Neuroendocrine breast cancer is thought to account for about 1% of all breast cancers. This rare type of breast malignancy is more common in older women and presents as a low-grade, slow-growing cancer. The most definitive markers that indicate neuroendocrine carcinoma are the presence of chromogranin, synaptophysin or neuron-specific enolase, in at least 50% of malignant tumour cells. The authors present a case report of an 83-year-old woman, admitted to their institution with right breast l...

  14. The association of DNA Repair with breast cancer risk in women. A comparative observational study

    Directory of Open Access Journals (Sweden)

    Matta Jaime

    2012-10-01

    Full Text Available Abstract Background Previous studies have found a link between a low DNA repair capacity (DRC level and increased cancer risk. Our aim was to assess the statistical association of DRC level and breast cancer (BC using a case–control epidemiological study in a Hispanic community. Methods We conducted a comparative observational study to assess the validity of DRC in detecting BC in 824 women throughout Puerto Rico. Over a 6-year period, we compared 285 women newly diagnosed with BC to 539 without BC. DRC levels were measured in lymphocytes by means of a host-cell reactivation assay. We assessed the sensitivity, specificity, and association using the receiver operating characteristic curve analysis. Multiple logistic regression-adjusted odds ratios were estimated with 95% confidence level to measure the strength of the association of DRC and BC after adjusting for all confounders simultaneously. Results Compared to women without cancer, women with BC showed an average decrease of 60% in their DRC levels (p p Conclusions Our results support the usefulness of DRC level as a measure of BC risk. Additional studies in other populations are needed to further verify its usefulness.

  15. Contralateral breast cancer risk

    International Nuclear Information System (INIS)

    The use of breast-conserving treatment approaches for breast cancer has now become a standard option for early stage disease. Numerous randomized studies have shown medical equivalence when mastectomy is compared to lumpectomy followed by radiotherapy for the local management of this common problem. With an increased emphasis on patient involvement in the therapeutic decision making process, it is important to identify and quantify any unforeseen risks of the conservation approach. One concern that has been raised is the question of radiation- related contralateral breast cancer after breast radiotherapy. Although most studies do not show statistically significant evidence that patients treated with breast radiotherapy are at increased risk of developing contralateral breast cancer when compared to control groups treated with mastectomy alone, there are clear data showing the amount of scattered radiation absorbed by the contralateral breast during a routine course of breast radiotherapy is considerable (several Gy) and is therefore within the range where one might be concerned about radiogenic contralateral tumors. While radiation related risks of contralateral breast cancer appear to be small enough to be statistically insignificant for the majority of patients, there may exist a smaller subset which, for genetic or environmental reasons, is at special risk for scatter related second tumors. If such a group could be predicted, it would seem appropriate to offer either special counselling or special prevention procedures aimed at mitigating this second tumor risk. The use of genetic testing, detailed analysis of breast cancer family history, and the identification of patients who acquired their first breast cancer at a very early age may all be candidate screening procedures useful in identifying such at- risk groups. Since some risk mitigation strategies are convenient and easy to utilize, it makes sense to follow the classic 'ALARA' (as low as reasonably

  16. The association between polymorphisms in the leptin receptor gene and risk of breast cancer: a systematic review and pooled analysis.

    Science.gov (United States)

    Wang, Li-qiang; Shen, Wei; Xu, Lan; Chen, Min-Bin; Gong, Ting; Lu, Pei-Hua; Tao, Guo-Qing

    2012-11-01

    Many epidemiological studies have found that leptin correlates to body fat extent and breast cancer. Leptin exerts its physiological action through the leptin receptor (LEPR). However, published data on the association between LEPR alleles and breast cancer occurrence have led to in contradictory results. A total of 10 studies were identified to the meta-analysis, including 4,644 cases and 5,485 controls for LEPR rs1137101 polymorphism, 5 studies with 2,759 cases and 4,464 controls for rs1137100 polymorphism, and 2 studies for rs8051542, rs8051542, and rs8051542 polymorphisms. The pooled odds ratios (OR) with 95 % confidence intervals (CI) for breast cancer risk associated with LEPR genotypes were estimated. Elevated breast cancer risk was associated with LEPR rs1137101 polymorphism when all studies were pooled in the meta-analysis (allele contrast model: OR = 0.71, 95 % CI = 0.551-0.997). In the stratified analysis by ethnicity, significantly increased risks were also found among Asians for allele contrast model (OR 0.414, 95 % CI 0.312-0.550) and dominant model (OR 0.537, 95 % CI 0.370-0.781); for Africans, significantly increased risks were also found for allele contrast model (OR 0.716, 95 % CI 0.595-0.861), homozygote codominant (OR 0.537, 95 % CI 0.370-0.781) and dominant model (OR 1.595, 95 % CI 1.207-2.108). And significantly elevated breast cancer risk was associated with LEPR rs1137100 polymorphism for allele contrast (OR = 0.666, 95 % CI = 0.603-0.720) and homozygote codominant models (OR = 0.344, 95 % CI = 0.282-0.421). For LEPR rs8179183, rs4655537, and rs3762274 polymorphisms, no significant associations were detected in all comparison models. This pooled analysis suggested that rs1137101 and rs1137100 polymorphisms were significantly correlated with breast cancer risk and the A allele of LEPR rs1137101 variant and the G allele of LEPR rs1137100 variant were low-penetrant risk factors for developing breast cancer. Further, no

  17. n-3 Polyunsaturated Fatty Acids and Mechanisms to Mitigate Inflammatory Paracrine Signaling in Obesity-Associated Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jennifer M. Monk

    2014-10-01

    Full Text Available Globally, the prevalence of obesity is increasing which subsequently increases the risk of the development of obesity-related chronic diseases. Low-grade chronic inflammation and dysregulated adipose tissue inflammatory mediator/adipokine secretion are well-established in obesity, and these factors increase the risk of developing inflammation-associated cancer. Breast cancer is of particular interest given that increased inflammation within the subcutaneous mammary adipose tissue depot can alter the local tissue inflammatory microenvironment such that it resembles that of obese visceral adipose tissue. Therefore, in obese women with breast cancer, increased inflammatory mediators both locally and systemically can perpetuate inflammation-associated pro-carcinogenic signaling pathways, thereby increasing disease severity. Herein, we discuss some of these inflammation-associated pro-carcinogenic mechanisms of the combined obese breast cancer phenotype and offer evidence that dietary long chain n-3 polyunsaturated fatty acids (PUFA may have utility in mitigating the severity of obesity-associated inflammation and breast cancer.

  18. Inflammatory Breast Cancer

    Science.gov (United States)

    ... breast cancer: consensus statement for standardized diagnosis and treatment. Annals of Oncology 2011; 22(3):515-523. [PubMed Abstract] Fouad TM, Kogawa T, Reuben JM, Ueno NT. The role of inflammation in inflammatory breast cancer. Advances in Experimental Medicine and Biology 2014; 816:53-73. [PubMed ...

  19. Sense-antisense gene-pairs in breast cancer and associated pathological pathways

    Science.gov (United States)

    Grinchuk, Oleg V.; Motakis, Efthymios; Yenamandra, Surya Pavan; Ow, Ghim Siong; Jenjaroenpun, Piroon; Tang, Zhiqun; Yarmishyn, Aliaksandr A.; Ivshina, Anna V.; Kuznetsov, Vladimir A.

    2015-01-01

    More than 30% of human protein-coding genes form hereditary complex genome architectures composed of sense-antisense (SA) gene pairs (SAGPs) transcribing their RNAs from both strands of a given locus. Such architectures represent important novel components of genome complexity contributing to gene expression deregulation in cancer cells. Therefore, the architectures might be involved in cancer pathways and, in turn, be used for novel drug targets discovery. However, the global roles of SAGPs in cancer pathways has not been studied. Here we investigated SAGPs associated with breast cancer (BC)-related pathways using systems biology, prognostic survival and experimental methods. Gene expression analysis identified 73 BC-relevant SAGPs that are highly correlated in BC. Survival modelling and metadata analysis of the 1161 BC patients allowed us to develop a novel patient prognostic grouping method selecting the 12 survival-significant SAGPs. The qRT-PCR-validated 12-SAGP prognostic signature reproducibly stratified BC patients into low- and high-risk prognostic subgroups. The 1381 SAGP-defined differentially expressed genes common across three studied cohorts were identified. The functional enrichment analysis of these genes revealed the GABPA gene network, including BC-relevant SAGPs, specific gene sets involved in cell cycle, spliceosomal and proteasomal pathways. The co-regulatory function of GABPA in BC cells was supported using siRNA knockdown studies. Thus, we demonstrated SAGPs as the synergistically functional genome architectures interconnected with cancer-related pathways and associated with BC patient clinical outcomes. Taken together, SAGPs represent an important component of genome complexity which can be used to identify novel aspects of coordinated pathological gene networks in cancers. PMID:26517092

  20. Promoter methylation-associated loss of ID4 expression is a marker of tumour recurrence in human breast cancer

    International Nuclear Information System (INIS)

    Inhibitor of DNA binding/Inhibitor of differentiation 4 (ID4) is a critical factor for cell proliferation and differentiation in normal vertebrate development. ID4 has regulative functions for differentiation and growth of the developing brain. The role of ID1, ID2 and ID3 are expected to be oncogenic due to their overexpression in pancreatic cancer and colorectal adenocarcinomas, respectively. Aside from these findings, loss of ID3 expression was demonstrated in ovarian cancer. The aim of the present study was to reveal the factual role of ID4 in carcinogenesis in more detail, since its role for the pathogenesis of human breast cancer has been discussed controversially, assigning both oncogenic and tumour suppressive functions. ID4 promoter methylation, ID4 mRNA expression and ID4 protein expression were analysed in primary human breast cancer specimens using methylation-specific PCR (MSP) (n=170), semiquantitative realtime RT-PCR (n=46) and immunhistochemistry (n=3), respectively. In order to demonstrate a functional association of ID4 promoter methylation with its gene silencing, we performed DNA demethylation analysis with four human breast cell lines using MSP and semiquantitative realtime RT-PCR. In addition, we performed correlations of ID4 promoter methylation with ID4 mRNA and ID4 protein expression in matched samples of breast tumour and corresponding normal tissue. We carried out statistical analyses in order to find correlations between ID4 promoter methylation and clinicopathological parameters. Frequent ID4 promoter methylation was observed in primary breast cancer samples (69%, 117/170). We found a tight correlation (P<0.0001) between ID4 promoter methylation and loss of ID4 expression in primary breast cancer 3 specimens. Demethylating treatment with breast cancer cell lines was associated with clear ID4 mRNA re-expression. Tumours with ID4 promoter methylation showed distinct loss of ID4 expression on both transcription and protein level

  1. Possible association of β2- and β3-adrenergic receptor gene polymorphisms with susceptibility to breast cancer

    International Nuclear Information System (INIS)

    The involvement of β2-adrenergic receptor (ADRB2) and β3-adrenergic receptor (ADRB3) in both adipocyte lipolysis and thermogenic activity suggests that polymorphisms in the encoding genes might be linked with interindividual variation in obesity, an important risk factor for postmenopausal breast cancer. In order to examine the hypothesis that genetic variations in ADRB2 and ADRB3 represent interindividual susceptibility factors for obesity and breast cancer, we conducted a hospital-based, case-control study in the Aichi Cancer Center, Japan. A self-administered questionnaire was given to 200 breast cancer patients and 182 control individuals, and pertinent information on lifestyle, family history and reproduction was collected. ADRB2 and ADRB3 genotypes were determined by polymerase chain reaction (PCR) restriction fragment length polymorphism assessment. Twenty-five (12.4%) breast cancer patients and 32 (17.6%) control individuals were found to bear a glutamic acid (Glu) allele for the ADRB2 gene (odds ratio [OR] 0.67, 95% confidence interval [CI] 0.38-1.18), and 60 (30.0%) breast cancer patients and 61 (33.5%) control individuals were found to bear an Arg allele for the ADRB3 gene (OR 0.85, 95% CI 0.55-1.31). A significantly lower risk was observed in those who carried the Glu ADRB2 allele and who reported first childbirth when they were younger than 25 years (OR 0.35; 95% CI 0.13-0.99). A potential association may exist between risk of breast cancer and polymorphisms in the ADRB2 and ADRB3 genes; further studies in larger samples and/or in different ethnic groups are warranted to investigate this potential association

  2. A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor–negative breast cancer in the general population

    Science.gov (United States)

    Antoniou, Antonis C; Wang, Xianshu; Fredericksen, Zachary S; McGuffog, Lesley; Tarrell, Robert; Sinilnikova, Olga M; Healey, Sue; Morrison, Jonathan; Kartsonaki, Christiana; Lesnick, Timothy; Ghoussaini, Maya; Barrowdale, Daniel; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Eccles, Diana; Evans, D Gareth; Eeles, Ros; Izatt, Louise; Chu, Carol; Douglas, Fiona; Paterson, Joan; Stoppa-Lyonnet, Dominique; Houdayer, Claude; Mazoyer, Sylvie; Giraud, Sophie; Lasset, Christine; Remenieras, Audrey; Caron, Olivier; Hardouin, Agnès; Berthet, Pascaline; Hogervorst, Frans B L; Rookus, Matti A; Jager, Agnes; van den Ouweland, Ans; Hoogerbrugge, Nicoline; van der Luijt, Rob B; Meijers-Heijboer, Hanne; García, Encarna B Gómez; Devilee, Peter; Vreeswijk, Maaike P G; Lubinski, Jan; Jakubowska, Anna; Gronwald, Jacek; Huzarski, Tomasz; Byrski, Tomasz; Górski, Bohdan; Cybulski, Cezary; Spurdle, Amanda B; Holland, Helene; Goldgar, David E; John, Esther M; Hopper, John L; Southey, Melissa; Buys, Saundra S; Daly, Mary B; Terry, Mary-Beth; Schmutzler, Rita K; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Preisler-Adams, Sabine; Arnold, Norbert; Niederacher, Dieter; Sutter, Christian; Domchek, Susan M; Nathanson, Katherine L; Rebbeck, Timothy; Blum, Joanne L; Piedmonte, Marion; Rodriguez, Gustavo C; Wakeley, Katie; Boggess, John F; Basil, Jack; Blank, Stephanie V; Friedman, Eitan; Kaufman, Bella; Laitman, Yael; Milgrom, Roni; Andrulis, Irene L; Glendon, Gord; Ozcelik, Hilmi; Kirchhoff, Tomas; Vijai, Joseph; Gaudet, Mia M; Altshuler, David; Guiducci, Candace; Loman, Niklas; Harbst, Katja; Rantala, Johanna; Ehrencrona, Hans; Gerdes, Anne-Marie; Thomassen, Mads; Sunde, Lone; Peterlongo, Paolo; Manoukian, Siranoush; Bonanni, Bernardo; Viel, Alessandra; Radice, Paolo; Caldes, Trinidad; de la Hoya, Miguel; Singer, Christian F; Fink-Retter, Anneliese; Greene, Mark H; Mai, Phuong L; Loud, Jennifer T; Guidugli, Lucia; Lindor, Noralane M; Hansen, Thomas V O; Nielsen, Finn C; Blanco, Ignacio; Lazaro, Conxi; Garber, Judy; Ramus, Susan J; Gayther, Simon A; Phelan, Catherine; Narod, Stephen; Szabo, Csilla I; Benitez, Javier; Osorio, Ana; Nevanlinna, Heli; Heikkinen, Tuomas; Caligo, Maria A; Beattie, Mary S; Hamann, Ute; Godwin, Andrew K; Montagna, Marco; Casella, Cinzia; Neuhausen, Susan L; Karlan, Beth Y; Tung, Nadine; Toland, Amanda E; Weitzel, Jeffrey; Olopade, Olofunmilayo; Simard, Jacques; Soucy, Penny; Rubinstein, Wendy S; Arason, Adalgeir; Rennert, Gad; Martin, Nicholas G; Montgomery, Grant W; Chang-Claude, Jenny; Flesch-Janys, Dieter; Brauch, Hiltrud; Severi, Gianluca; Baglietto, Laura; Cox, Angela; Cross, Simon S; Miron, Penelope; Gerty, Sue M; Tapper, William; Yannoukakos, Drakoulis; Fountzilas, George; Fasching, Peter A; Beckmann, Matthias W; Silva, Isabel dos Santos; Peto, Julian; Lambrechts, Diether; Paridaens, Robert; Rüdiger, Thomas; Försti, Asta; Winqvist, Robert; Pylkäs, Katri; Diasio, Robert B; Lee, Adam M; Eckel-Passow, Jeanette; Vachon, Celine; Blows, Fiona; Driver, Kristy; Dunning, Alison; Pharoah, Paul P D; Offit, Kenneth; Pankratz, V Shane; Hakonarson, Hakon; Chenevix-Trench, Georgia; Easton, Douglas F; Couch, Fergus J

    2011-01-01

    Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (Ptrend = 2.3 × 10−9 to Ptrend = 3.9 × 10−7), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17–1.35; rs2363956 HR = 0.84, 95% CI 0.80–0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor–negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75–0.92, Ptrend = 0.0003) and an association with estrogen receptor–positive disease in the opposite direction (OR = 1.07, 95% CI 1.01–1.14, Ptrend = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (Ptrend = 1 × 10−7 to Ptrend = 8 × 10−5; rs2363956 per-allele OR = 0.80, 95% CI 0.74–0.87, Ptrend = 1.1 × 10−7). PMID:20852631

  3. The VEGF_936_C>T 3'UTR polymorphism reduces BRCA1-associated breast cancer risk in Polish women.

    Science.gov (United States)

    Jakubowska, Anna; Gronwald, Jacek; Menkiszak, Janusz; Górski, Bohdan; Huzarski, Tomasz; Byrski, Tomasz; Edler, Lutz; Lubiński, Jan; Scott, Rodney J; Hamann, Ute

    2008-04-01

    The vascular endothelial growth factor (VEGF) plays a crucial role in the initiation of angiogenesis, which is an important stage in tumor development. A functional 936_C>T polymorphism in the VEGF gene and its association with sporadic breast cancer risk has been analyzed in various studies yielding conflicting results. To analyze the role of this polymorphism in modifying hereditary breast and ovarian cancer risks, we conducted a case-control study and genotyped 755 Polish BRCA1 carriers, including 319 breast cancer cases, 146 ovarian cancer cases, and 290 unaffected controls. The results revealed an association of the CT+TT genotypes with a reduced breast cancer risk (OR(adj) 0.63, 95% CI, 0.41-0.98; OR(clustered) 0.63, 95% CI, 0.48-0.83), and a potential effect on ovarian cancer risk (OR(adj) 0.62, 95% CI, 0.33-1.18; OR(clustered) 0.62, 95% CI, 0.47-0.83). Thus, the 936_C>T polymorphism appears to modify disease risks in BRCA1 carriers. PMID:18171601

  4. Fatigue and depression in disease-free breast cancer survivors: prevalence, correlates, and association with quality of life.

    Science.gov (United States)

    Kim, Soo Hyun; Son, Byung Ho; Hwang, Sook Yeon; Han, Wonshik; Yang, Jung-Hyun; Lee, Seeyoun; Yun, Young Ho

    2008-06-01

    We performed this study to examine the prevalence and correlates of fatigue and depression, and their relevance to health-related quality of life in disease-free breast cancer survivors. A total of 1,933 breast cancer survivors recruited from five large hospitals in Korea completed a mailed survey, which included the Brief Fatigue Inventory, Beck Depression Inventory, European Organization for Research and Treatment of Cancer QLQ-C30, and QLQ-BR23. With a framework that included sociodemographic, clinical, and symptom characteristics, multivariate logistic regression models were used to identify factors associated with fatigue and depression. Among breast cancer survivors, 66.1% reported moderate to severe fatigue and 24.9% reported moderate to severe depression. Risk factors common to both fatigue and depression were lower income, dyspnea, insomnia, appetite loss, constipation, and arm symptoms. Risk factors for fatigue only included younger age, employment, presence of gastrointestinal disease, and pain. Having a musculoskeletal disease was identified as a risk factor for depression only. Both fatigue and depression were influenced by sociodemographic factors, comorbidity and symptom characteristics rather than cancer or treatment-related factors. Both fatigue and depression were negatively associated with survivors' health-related quality of life. However, the patterns of differences in health-related quality of life according to severity of fatigue or depression were similar. This concurrent examination of risk factors for fatigue and depression may be helpful in the development of clinical management strategies in disease-free breast cancer survivors. PMID:18358687

  5. Exploring miRNA-Associated Signatures with Diagnostic Relevance in Glioblastoma Multiforme and Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Véronique C. LeBlanc

    2015-08-01

    Full Text Available The growing attention that non-coding RNAs have attracted in the field of cancer research in recent years is undeniable. Whether investigated as prospective therapeutic targets or prognostic indicators or diagnostic biomarkers, the clinical relevance of these molecules is starting to emerge. In addition, identification of non-coding RNAs in a plethora of body fluids has further positioned these molecules as attractive non-invasive biomarkers. This review will first provide an overview of the synthetic cascade that leads to the production of the small non-coding RNAs microRNAs (miRNAs and presents their strengths as biomarkers of disease. Our interest will next be directed at exploring the diagnostic utility of miRNAs in two types of cancer: the brain tumor glioblastoma multiforme (GBM and breast cancer. Finally, we will discuss additional clinical implications associated with miRNA detection as well as introduce other non-coding RNAs that have generated recent interest in the cancer research community.

  6. CDC Vital Signs: Breast Cancer

    Science.gov (United States)

    ... 2.65 MB] Read the MMWR Science Clips Breast Cancer Black Women Have Higher Death Rates from Breast ... of Page U.S. State Info Number of Additional Breast Cancer Deaths Among Black Women, By State SOURCE: National ...

  7. Alteration of Topoisomerase II–Alpha Gene in Human Breast Cancer: Association With Responsiveness to Anthracycline-Based Chemotherapy

    Science.gov (United States)

    Press, Michael F.; Sauter, Guido; Buyse, Marc; Bernstein, Leslie; Guzman, Roberta; Santiago, Angela; Villalobos, Ivonne E.; Eiermann, Wolfgang; Pienkowski, Tadeusz; Martin, Miguel; Robert, Nicholas; Crown, John; Bee, Valerie; Taupin, Henry; Flom, Kerry J.; Tabah-Fisch, Isabelle; Pauletti, Giovanni; Lindsay, Mary-Ann; Riva, Alessandro; Slamon, Dennis J.

    2011-01-01

    Purpose Approximately 35% of HER2-amplified breast cancers have coamplification of the topoisomerase II-alpha (TOP2A) gene encoding an enzyme that is a major target of anthracyclines. This study was designed to evaluate whether TOP2A gene alterations may predict incremental responsiveness to anthracyclines in some breast cancers. Methods A total of 4,943 breast cancers were analyzed for alterations in TOP2A and HER2. Primary tumor tissues from patients with metastatic breast cancer treated in a trial of chemotherapy plus/minus trastuzumab were studied for amplification/deletion of TOP2A and HER2 as a test set followed by evaluation of malignancies from two separate, large trials for changes in these same genes as a validation set. Association between these alterations and clinical outcomes was determined. Results Test set cases containing HER2 amplification treated with doxorubicin and cyclophosphamide (AC) plus trastuzumab, demonstrated longer progression-free survival compared to those treated with AC alone (P = .0002). However, patients treated with AC alone whose tumors contain HER2/TOP2A coamplification experienced a similar improvement in survival (P = .004). Conversely, for patients treated with paclitaxel, HER2/TOP2A coamplification was not associated with improved outcomes. These observations were confirmed in a larger validation set, where HER2/TOP2A coamplification was again associated with longer survival when only anthracycline-containing chemotherapy was used for treatment compared with outcome in HER2-positive cancers lacking TOP2A coamplification. Conclusion In a study involving nearly 5,000 breast malignancies, both test set and validation set demonstrate that TOP2A coamplification, not HER2 amplification, is the clinically useful predictive marker of an incremental response to anthracycline-based chemotherapy. Absence of HER2/TOP2A coamplification may indicate a more restricted efficacy advantage for breast cancers than previously thought. PMID

  8. Regulation of DNA Damage Response by Estrogen Receptor β-Mediated Inhibition of Breast Cancer Associated Gene 2

    Directory of Open Access Journals (Sweden)

    Yuan-Hao Lee

    2015-04-01

    Full Text Available Accumulating evidence suggests that ubiquitin E3 ligases are involved in cancer development as their mutations correlate with genomic instability and genetic susceptibility to cancer. Despite significant findings of cancer-driving mutations in the BRCA1 gene, estrogen receptor (ER-positive breast cancers progress upon treatment with DNA damaging-cytotoxic therapies. In order to understand the underlying mechanism by which ER-positive breast cancer cells develop resistance to DNA damaging agents, we employed an estrogen receptor agonist, Erb-041, to increase the activity of ERβ and negatively regulate the expression and function of the estrogen receptor α (ERα in MCF-7 breast cancer cells. Upon Erb-041-mediated ERα down-regulation, the transcription of an ERα downstream effector, BCA2 (Breast Cancer Associated gene 2, correspondingly decreased. The ubiquitination of chromatin-bound BCA2 was induced by ultraviolet C (UVC irradiation but suppressed by Erb-041 pretreatment, resulting in a blunted DNA damage response. Upon BCA2 silencing, DNA double-stranded breaks increased with Rad51 up-regulation and ataxia telangiectasia mutated (ATM activation. Mechanistically, UV-induced BCA2 ubiquitination and chromatin binding were found to promote DNA damage response and repair via the interaction of BCA2 with ATM, γH2AX and Rad51. Taken together, this study suggests that Erb-041 potentiates BCA2 dissociation from chromatin and co-localization with Rad51, resulting in inhibition of homologous recombination repair.

  9. Loss of miR-133a expression associated with poor survival of breast cancer and restoration of miR-133a expression inhibited breast cancer cell growth and invasion

    International Nuclear Information System (INIS)

    miRNAs, endogenous oligonucleotide RNAs, play an important role in mammary gland carcinogenesis and tumor progression. Detection of their expression and investigation of their functions could lead to discovery of novel biomarkers for breast cancer. In situ hybridization was used to detect miR-133a expression in formalin-fixed paraffin-embedded breast surgical specimens from 26 benign, 34 pericancerously normal and 90 cancerous tissues. qRT-PCR was performed to assess miR-133a levels in 6 breast cell lines and 10 benign and 18 cancerous fresh breast tissue specimens. Cell viability, migration, and invasion assays were used to determine the role of miR-133a in regulation of breast cancer cell growth, migration, and invasion, respectively. Luciferase assay was performed to assess miR-133a binding to FSCN1 gene. Expression of miR-133a was reduced from normal through benign to cancerous breast tissues. Expression of miR-133a was also low in breast cancer cell lines. The reduced miR-133a expression was associated with lymph nodes metastasis, high clinical stages, and shorter relapse-free survivals of patients with breast cancer. Furthermore, transfection of miR-133a oligonucleotides slightly inhibited growth but significantly decreased migration and invasion capacity of breast cancer cells, compared with negative controls, whereas knockdown of miR-133a expression induced breast cancer cell migration and invasion. In addition, we identified a putative miR-133a binding site in the 3'-untranslated region (UTR) of Fascin1 (FSCN1) gene using an online bioinformatical tool. We found that miR-133a transfection significantly reduced expression of FSCN1 mRNA and protein. The luciferase reporter assay confirmed that FSCN1 was the direct target gene of miR-133a. miR-133a expression was lost in breast cancer tissues, loss of which was associated with lymph nodes metastasis, high clinical stages and shorter relapse-free survivals of patients with breast cancer. Functionally, mi

  10. Variants in estrogen-biosynthesis genes CYP17 and CYP19 and breast cancer risk: a family-based genetic association study

    International Nuclear Information System (INIS)

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

  11. Breast Cancer and Bone Loss

    Science.gov (United States)

    ... Balance › Breast Cancer and Bone Loss Fact Sheet Breast Cancer and Bone Loss July, 2010 Download PDFs English ... JoAnn Pinkerton, MD What is the link between breast cancer and bone loss? Certain treatments for breast cancer ...

  12. Soy intake in association with menopausal symptoms during the first 6 and 36 months after breast cancer diagnosis

    OpenAIRE

    Dorjgochoo, Tsogzolmaa; Gu, Kai; Zheng, Ying; Kallianpur, Asha; Chen, Zhi; Zheng, Wei; Lu, Wei; Shu, Xiao Ou

    2010-01-01

    It has been suggested that soy food and its components may relieve menopausal symptoms (MPS) including hot flashes, night sweats, and vaginal dryness in healthy women. However, little is known about the effect of soy food intake on MPS in women with breast cancer. We examined associations of occurrence of MPS with soy food intake in 4,842 Chinese women aged 20–75 years who had non-metastatic breast cancer and had not used hormone replacement therapy. MPS were assessed at 6 and 36 months after...

  13. A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor–negative breast cancer

    OpenAIRE

    Haiman, Christopher A.; Chen, Gary K.; Vachon, Celine M.; Canzian, Federico; Dunning, Alison; Millikan, Robert C.; Wang, Xianshu; Ademuyiwa, Foluso; Ahmed, Shahana; Ambrosone, Christine B.; Baglietto, Laura; Balleine, Rosemary; Bandera, Elisa V.; Beckmann, Matthias W; Berg, Christine D

    2011-01-01

    Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls...

  14. Clinical and morphological characteristics and prognosis of BRCA-associated breast cancer in women of the reproductive age

    Directory of Open Access Journals (Sweden)

    D. E. Avtomonov

    2014-07-01

    Full Text Available During last years one should note an unstoppable increase of the breast cancer incidence among patients of reproductive age. A group of pa- tients of young age with the breast cancer whose disease is associated with the BRCA1/2 genes is of particular scientific interest. However, until now no single opinion on survival results in the given group of oncological patients has been evolved yet. In this article, preliminary data on general and non-recurrence survival of patients of the reproductive age are given, depending on BRCA1 gene status.

  15. Estimating the alcohol-breast cancer association: a comparison of diet diaries, FFQs and combined measurements.

    Science.gov (United States)

    Keogh, Ruth H; Park, Jin Young; White, Ian R; Lentjes, Marleen A H; McTaggart, Alison; Bhaniani, Amit; Cairns, Benjamin J; Key, Timothy J; Greenwood, Darren C; Burley, Victoria J; Cade, Janet E; Dahm, Christina C; Pot, Gerda K; Stephen, Alison M; Masset, Gabriel; Brunner, Eric J; Khaw, Kay-Tee

    2012-07-01

    The alcohol-breast cancer association has been established using alcohol intake measurements from Food Frequency Questionnaires (FFQ). For some nutrients diet diary measurements are more highly correlated with true intake compared with FFQ measurements, but it is unknown whether this is true for alcohol. A case-control study (656 breast cancer cases, 1905 matched controls) was sampled from four cohorts in the UK Dietary Cohort Consortium. Alcohol intake was measured prospectively using FFQs and 4- or 7-day diet diaries. Both relied on fixed portion sizes allocated to given beverage types, but those used to obtain FFQ measurements were lower. FFQ measurements were therefore on average lower and to enable fair comparison the FFQ was "calibrated" using diet diary portion sizes. Diet diaries gave more zero measurements, demonstrating the challenge of distinguishing never-from episodic-consumers using short term instruments. To use all information, two combined measurements were calculated. The first is an average of the two measurements with special treatment of zeros. The second is the expected true intake given both measurements, calculated using a measurement error model. After confounder adjustment the odds ratio (OR) per 10 g/day of alcohol intake was 1.05 (95 % CI 0.98, 1.13) using diet diaries, and 1.13 (1.02, 1.24) using FFQs. The calibrated FFQ measurement and combined measurements 1 and 2 gave ORs 1.10 (1.03, 1.18), 1.09 (1.01, 1.18), 1.09 (0.99,1.20), respectively. The association was modified by HRT use, being stronger among users versus non-users. In summary, using an alcohol measurement from a diet diary at one time point gave attenuated associations compared with FFQ. PMID:22644108

  16. Breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    MatthewJNaylor

    2013-08-01

    Full Text Available Cancer metastasis, resistance to therapies and disease recurrence are significant hurdles to successful treatment of breast cancer. Identifying mechanisms by which cancer spreads, survives treatment regimes and regenerates more aggressive tumours are critical to improving patient survival. Substantial evidence gathered over the last 10 years suggests that breast cancer progression and recurrence is supported by cancer stem cells (CSCs. Understanding how CSCs form and how they contribute to the pathology of breast cancer will greatly aid the pursuit of novel therapies targeted at eliminating these cells. This review will summarise what is currently known about the origins of breast CSCs, their role in disease progression and ways in which they may be targeted therapeutically.

  17. Tumour-associated endothelial-FAK correlated with molecular sub-type and prognostic factors in invasive breast cancer

    International Nuclear Information System (INIS)

    Breast cancer is a heterogeneous disease that can be classified into one of 4 main molecular sub-types: luminal A, luminal B, Her2 over-expressing and basal-like (BL). These tumour sub-types require different treatments and have different risks of disease progression. BL cancers can be considered a sub-group of Triple negative (TN) cancers since they lack estrogen (ER), progesterone (PR) and Her2 expression. No targeted treatment currently exists for TN/BL cancers. Thus it is important to identify potential therapeutic targets and describe their relationship with established prognostic factors. Focal adhesion kinase (FAK) is upregulated in several human cancers and also plays a functional role in tumour angiogenesis. However, the association between breast cancer sub-types and tumour endothelial-FAK expression is unknown. Using immunofluorescence, we quantified FAK expression in tumour endothelial and tumour cell compartments in 149 invasive breast carcinomas and correlated expression with clinical, pathological and molecular parameters. Low endothelial-FAK expression was independently associated with luminal A tumours at univariate (p < 0.001) and multivariate (p = 0.001) analysis. There was a positive correlation between FAK expression in the vascular and tumour cell compartments (Spearman’s correlation co-efficient = 0.394, p < 0.001). Additionally, endothelial and tumour cell FAK expression were significantly increased in TN tumours (p = 0.043 and p = 0.033 respectively), in tumours with negative ER and PR status, and in high grade tumours at univariate analysis. Our findings establish a relationship between endothelial-FAK expression levels and the molecular sub-type of invasive breast cancer, and suggest that endothelial-FAK expression is potentially more clinically relevant than tumour cell FAK expression in breast cancer

  18. Autoantibodies to aberrantly glycosylated MUC1 in early stage breast cancer are associated with a better prognosis

    DEFF Research Database (Denmark)

    Blixt, Ola; Bueti, Deanna; Burford, Brian; Allen, Diane; Julien, Sylvain; Hollingsworth, Michael; Gammerman, Alex; Fentiman, Ian; Taylor-Papadimitriou, Joyce; Burchell, Joy M

    2011-01-01

    associated glycoforms of MUC1 in a proportion of early breast cancer patients (54/198). Five positive sera were selected for detailed definition of the reactive epitopes using on chip glycosylation technology and a panel of glycopeptides based on a single MUC1 tandem repeat carrying specific glycans at...

  19. Invasive breast cancer in Argentine women: association between risk and prognostic factors with antigens of a peptidic and carbohydrate nature

    Directory of Open Access Journals (Sweden)

    Croce MV

    2011-12-01

    Full Text Available Sandra O Demichelis, Marina T Isla-Larrain, Luciano Cermignani, Cecilio G Alberdi, Amada Segal-Eiras, María Virginia CroceCentre of Basic and Applied Immunological Research, Faculty of Medical Sciences, National University of La Plata, La Plata, ArgentinaObjective: In breast cancer, several tumor markers have been identified. The marker most extensively associated with breast cancer is MUC1. The objective of the study was to analyze prognostic and risk factors in relation to tumor markers in order to clarify breast cancer biology. A total of 349 primary tumor samples and lymph nodes from breast cancer patients were studied. Risk and prognostic factors were considered. An immunohistochemical approach was applied and an extensive statistical analysis was performed, including frequency analysis and analysis of variance. Correlation among variables was performed with principal component analysis.Results: All the antigens showed an increased expression according to tumor size increment; moreover, sialyl Lewis x expression showed a significant increase in relation to disease stage, whereas Tn and TF presented a positive tendency. Vascular invasion was related to sialyl Lewis x expression and number of metastatic lymph nodes. Taking into account risk factors, when a patient had at least one child, Lewis antigens diminished their expression. In relation to breastfeeding, sialyl Lewis x expression diminished, although its apical expression increased.Conclusion: Associations between MUC1 and carbohydrate antigens and risk and prognostic factors show the complexity of the cellular biological behavior that these antigens modulate in breast cancer.Keywords: breast cancer, Argentine women, risk factors, prognostic factors, antigenic expression

  20. 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...

  1. Technical factors associated with radiation pneumonitis after local ± regional radiation therapy for breast cancer

    International Nuclear Information System (INIS)

    Purpose: To assess the incidence of, and clinical factors associated with, symptomatic radiation pneumonitis (RP) after tangential breast/chest wall irradiation with or without regional lymph node treatment. Methods and Materials: The records of 613 patients irradiated with tangential photon fields for breast cancer with >6 months follow-up were reviewed. Clinically significant RP was defined as the presence of new pulmonary symptoms requiring steroids. Data on clinical factors previously reported to be associated with RP were collected, e.g., tamoxifen or chemotherapy exposure and age. The central lung distance (CLD) and the average of the superior and inferior mid lung distance (ALD) in the lateral tangential field were measured on simulator films as a surrogate for irradiated lung volume. Many patients were treated with partly wide tangential fields that included a heart block shielding a part of the lower lung. Results: RP developed in 15/613 (2.4%) patients. In the univariate analysis, there was an increased incidence of RP among patients treated with local-regional radiotherapy (RT) (4.1%) vs. those receiving local RT only (0.9%) (p=0.02), and among patients receiving chemotherapy (3.9%) vs. those not treated with chemotherapy (1.4%) (p=0.06). According to multivariate analysis, only the use of nodal RT remained independently associated with RP (p=0.03). There was no statistically significant association between ranked CLD or ALD measurements and RP among patients treated with nodal irradiation with tangential beams. However, there was a statistically nonsignificant trend for increasing rates of RP with grouped ALD values: below 2 cm (4% RP rate), between 2 and 3 cm (6%), and above 3 cm (14%). Conclusions: RP was an uncommon complication, both with local and local-regional RT. The addition of regional lymph node irradiation slightly increased the incidence of RP among patients treated with the partly wide tangential field technique. Concern for RP should

  2. Differential expression of cancer associated proteins in breast milk based on age at first full term pregnancy

    International Nuclear Information System (INIS)

    First full term pregnancy (FFTP) completed at a young age has been linked to low long term breast cancer risk, whereas late FFTP pregnancy age confers high long term risk, compared to nulliparity. Our hypothesis was that proteins linked to breast cancer would be differentially expressed in human milk collected at three time points during lactation based on age at FFTP. We analyzed breast milk from 72 lactating women. Samples were collected within 10 days of the onset of lactation (baseline-BL), two months after lactation started and during breast weaning (W). We measured 16 proteins (11 kallikreins (KLKs), basic fibroblast growth factor, YKL-40, neutrophil gelatinase-associated lipocalin and transforming growth factor (TGF) β-1 and -2) associated with breast cancer, most known to be secreted into milk. During lactation there was a significant change in the expression of 14 proteins in women < 26 years old and 9 proteins in women > = 26 at FFTP. The most significant (p < .001) changes from BL to W in women divided by FFTP age (< 26 vs. > = 26) were in KLK3,6, 8, and TGFβ2 in women < 26; and KLK6, 8, and TGFβ2 in women > = 26. There was a significant increase (p = .022) in KLK8 expression from BL to W depending on FFTP age. Examination of DNA methylation in the promoter region of KLK6 revealed high levels of methylation that did not explain the observed changes in protein levels. On the other hand, KLK6 and TGFβ1 expression were significantly associated (r2 = .43, p = .0050). The expression profile of milk proteins linked to breast cancer is influenced by age at FFTP. These proteins may play a role in future cancer risk

  3. Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

    Directory of Open Access Journals (Sweden)

    Mirco Pistelli

    2014-06-01

    Full Text Available Background: Triple-negative breast cancers (TNBC are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001 and a lympho-vascular invasion (p = 0.01, but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72 or overall survival (p = 0.93. Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target.

  4. Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

    Energy Technology Data Exchange (ETDEWEB)

    Pistelli, Mirco, E-mail: mirco.pistelli@alice.it; Caramanti, Miriam [Clinica di Oncologia Medica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona 60020 (Italy); Biscotti, Tommasina; Santinelli, Alfredo [Anatomia Patologica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona 60020 (Italy); Pagliacci, Alessandra; De Lisa, Mariagrazia; Ballatore, Zelmira; Ridolfi, Francesca; Maccaroni, Elena; Bracci, Raffaella; Berardi, Rossana; Battelli, Nicola; Cascinu, Stefano [Clinica di Oncologia Medica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona 60020 (Italy)

    2014-06-27

    Background: Triple-negative breast cancers (TNBC) are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR) is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001) and a lympho-vascular invasion (p = 0.01), but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72) or overall survival (p = 0.93). Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target.

  5. Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

    International Nuclear Information System (INIS)

    Background: Triple-negative breast cancers (TNBC) are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR) is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001) and a lympho-vascular invasion (p = 0.01), but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72) or overall survival (p = 0.93). Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target

  6. Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers

    DEFF Research Database (Denmark)

    Antoniou, Antonis C; Kartsonaki, Christiana; Sinilnikova, Olga M;

    2011-01-01

    Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs...

  7. Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers

    NARCIS (Netherlands)

    Antoniou, Antonis C.; Kartsonaki, Christiana; Sinilnikova, Olga M.; Soucy, Penny; McGuffog, Lesley; Healey, Sue; Lee, Andrew; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Cattaneo, Elisa; Barile, Monica; Pensotti, Valeria; Pasini, Barbara; Dolcetti, Riccardo; Giannini, Giuseppe; Putignano, Anna Laura; Varesco, Liliana; Radice, Paolo; Mai, Phuong L.; Greene, Mark H.; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Thomassen, Mads; Gerdes, Anne-Marie; Kruse, Torben A.; Jensen, Uffe Birk; Crueger, Dorthe G.; Caligo, Maria A.; Laitman, Yael; Milgrom, Roni; Kaufman, Bella; Paluch-Shimon, Shani; Friedman, Eitan; Loman, Niklas; Harbst, Katja; Lindblom, Annika; Arver, Brita; Ehrencrona, Hans; Melin, Beatrice; Nathanson, Katherine L.; Domchek, Susan M.; Rebbeck, Timothy; Jakubowska, Ania; Lubinski, Jan; Gronwald, Jacek; Huzarski, Tomasz; Byrski, Tomasz; Cybulski, Cezary; Gorski, Bohdan; Osorio, Ana; Ramon y Cajal, Teresa; Fostira, Florentia; Andres, Raquel; Benitez, Javier; Hamann, Ute; Hogervorst, Frans B.; Rookus, Matti A.; Hooning, Maartje J.; Nelen, Marcel R.; van der Luijt, Rob B.; van Os, Theo A. M.; van Asperen, Christi J.; Devilee, Peter; Meijers-Heijboer, Hanne E. J.; Garcia, Encarna B. Gomez; Peock, Susan; Cook, Margaret; Frost, Debra; Platte, Radka; Leyland, Jean; Evans, D. Gareth; Lalloo, Fiona; Eeles, Ros; Izatt, Louise; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Ong, Kai-ren; Cook, Jackie; Douglas, Fiona; Paterson, Joan; Kennedy, M. John; Miedzybrodzka, Zosia; Godwin, Andrew; Stoppa-Lyonnet, Dominique; Buecher, Bruno; Belotti, Muriel; Tirapo, Carole; Mazoyer, Sylvie; Barjhoux, Laure; Lasset, Christine; Leroux, Dominique; Faivre, Laurence; Bronner, Myriam; Prieur, Fabienne; Nogues, Catherine; Rouleau, Etienne; Pujol, Pascal; Coupier, Isabelle; Frenay, Marc; Hopper, John L.; Daly, Mary B.; Terry, Mary B.; John, Esther M.; Buys, Saundra S.; Yassin, Yosuf; Miron, Alexander; Goldgar, David; Singer, Christian F.; Tea, Muy-Kheng; Pfeiler, Georg; Dressler, Anne Catharina; Hansen, Thomas v. O.; Jonson, Lars; Ejlertsen, Bent; Barkardottir, Rosa Bjork; Kirchhoff, Tomas; Offit, Kenneth; Piedmonte, Marion; Rodriguez, Gustavo; Small, Laurie; Boggess, John; Blank, Stephanie; Basil, Jack; Azodi, Masoud; Toland, Amanda Ewart; Montagna, Marco; Tognazzo, Silvia; Agata, Simona; Imyanitov, Evgeny; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Ignacio; Pharoah, Paul D. P.; Sucheston, Lara; Karlan, Beth Y.; Walsh, Christine S.; Olah, Edith; Bozsik, Aniko; Teo, Soo-Hwang; Seldon, Joyce L.; Beattie, Mary S.; van Rensburg, Elizabeth J.; Sluiter, Michelle D.; Diez, Orland; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ruehl, Ina; Varon-Mateeva, Raymonda; Kast, Karin; Deissler, Helmut; Niederacher, Dieter; Arnold, Norbert; Gadzicki, Dorothea; Schoenbuchner, Ines; Caldes, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomaki, Kristiina; Dumont, Martine; Chiquette, Jocelyne; Tischkowitz, Marc; Chen, Xiaoqing; Beesley, Jonathan; Spurdle, Amanda B.; Neuhausen, Susan L.; Ding, Yuan Chun; Fredericksen, Zachary; Wang, Xianshu; Pankratz, Vernon S.; Couch, Fergus; Simard, Jacques; Easton, Douglas F.; Chenevix-Trench, Georgia

    2011-01-01

    Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs112

  8. Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers

    NARCIS (Netherlands)

    A.C. Antoniou (Antonis); C. Kartsonaki (Christiana); O. Sinilnikova (Olga); P. Soucy (Penny); L. McGuffog (Lesley); S. Healey (Sue); A. Lee (Andrew); P. Peterlongo (Paolo); S. Manoukian (Siranoush); B. Peissel (Bernard); D. Zaffaroni (D.); E. Cattaneo (Elisa); M. Barile (Monica); V. Pensotti (Valeria); B. Pasini (Barbara); R. Dolcetti (Riccardo); G. Giannini (Giuseppe); A.L. Putignano; L. Varesco (Liliana); P. Radice (Paolo); P.L. Mai (Phuong); M.H. Greene (Mark); I.L. Andrulis (Irene); G. Glendon (Gord); H. Ozcelik (Hilmi); M. Thomassen (Mads); A-M. Gerdes (Anne-Marie); T.A. Kruse (Torben); U.B. Jensen; D. Cruger (Dorthe); M.A. Caligo (Maria); Y. Laitman (Yael); R. Milgrom (Roni); B. Kaufman (Bella); S. Paluch-Shimon (Shani); E. Friedman (Eitan); N. Loman (Niklas); K. Harbst (Katja); A. Lindblom (Annika); B. Melin (Beatrice); K.L. Nathanson (Katherine); S.M. Domchek (Susan); R. Rebbeck (Timothy); A. Jakubowska (Anna); J. Lubinski (Jan); J. Gronwald (Jacek); T. Huzarski (Tomasz); T. Byrski (Tomasz); C. Cybulski (Cezary); B. Górski (Bohdan); A. Osorio (Ana); T.R. Cajal; F. Fostira (Florentia); R. Andres (Raquel); J. Benitez (Javier); U. Hamann (Ute); F.B.L. Hogervorst (Frans); M.A. Rookus (Matti); M.J. Hooning (Maartje); M.R. Nelen (Marcel); R.B. van der Luijt (Rob); T.A.M. van Os (Theo); C.J. van Asperen (Christi); P. Devilee (Peter); H. Meijers-Heijboer (Hanne); E.B.G. Garcia; S. Peock (Susan); M. Cook (Margaret); D. Frost; R. Platte (Radka); J. Leyland (Jean); D.G. Evans (Gareth); F. Lalloo (Fiona); R. Eeles (Rosalind); L. Izatt (Louise); R. Davidson (Rosemarie); D. Eccles (Diana); K.-R. Ong; F. Douglas (Fiona); J. Paterson (Joan); M.J. Kennedy (John); Z. Miedzybrodzka (Zosia); A.K. Godwin (Andrew); D. Stoppa-Lyonnet (Dominique); B. Buecher (Bruno); M. Belotti (Muriel); C. Tirapo (Carole); S. Mazoyer (Sylvie); L. Barjhoux (Laure); C. Lasset (Christine); D. Leroux (Dominique); L. Faivre (Laurence); M. Bronner (Myriam); F. Prieur (Fabienne); C. Nogues (Catherine); E. Rouleau (Etienne); P. Pujol (Pascal); I. Coupier (Isabelle); M. Frenay (Marc); J. Hopper (John); M.J. Daly (Mark); M-B. Terry (Mary-beth); E.M. John (Esther); S.S. Buys (Saundra); Y. Yassin (Yosuf); A. Miron (Alexander); D. Goldgar (David); C.F. Singer (Christian); M.-K. Tea; G. Pfeiler (Georg); C. Dressler (Catherina); T.V.O. Hansen (Thomas); L. Jønson (Lars); B. Ejlertsen (Bent); R.B. Barkardottir (Rosa); T. Kircchoff (Tomas); K. Offit (Kenneth); M. Piedmonte (Marion); G.C. Rodriguez (Gustavo); L. Small (Laurie); J.F. Boggess (John); S.V. Blank (Stephanie); J. Basil (Jack); M. Azodi (Masoud); A.E. Toland (Amanda); M. Montagna (Marco); S. Tognazzo (Silvia); S. Agata (Simona); E.N. Imyanitov (Evgeny); R. Janavicius (Ramunas); C. Lazaro (Conxi); I. Blanco (Ignacio); P.D.P. Pharoah (Paul); L. Sucheston (Lara); B.Y. Karlan (Beth); C.S. Walsh (Christine); E. Olah (Edith); A. Bozsik (Aniko); S.-H. Teo; J.L. Seldon (Joyce); M.S. Beattie (Mary); E.J. van Rensburg (Elizabeth); M.D. Sluiter (Michelle); O. Diez (Orland); R.K. Schmutzler (Rita); B. Wapenschmidt (Barbara); C. Engel (Christoph); A. Meindl (Alfons); I. Ruehl (Ina); R. Varon-Mateeva (Raymonda); K. Kast (Karin); H. Deissler (Helmut); D. Niederacher (Dieter); N. Arnold (Norbert); D. Gadzicki (Dorothea); I. Schönbuchner (Ines); T. Caldes (Trinidad); M. de La Hoya (Miguel); H. Nevanlinna (Heli); K. Aittomäki (Kristiina); M. Dumont (Martine); J. Chiquette (Jocelyne); M. Tischkowitz (Marc); G. Chenevix-Trench (Georgia); J. Beesley (Jonathan); A.B. Spurdle (Amanda); S.L. Neuhausen (Susan); Y.C. Ding (Yuan); Z. Fredericksen (Zachary); X. Wang (Xing); V.S. Pankratz (Shane); F.J. Couch (Fergus); J. Simard (Jacques); D.F. Easton (Douglas); G. Chenevix-Trench (Georgia); P. Karlsson (Per); M. Nordling (Margareta); A. Bergman (Annika); Z. Einbeigi (Zakaria); M. Stenmark-Askmalm (M.); S. Liedgren (Sigrun); Å. Borg (Åke); H. Olsson (Hans); U. Kristoffersson (Ulf); H. Jernström (H.); K. Henriksson (Karin); A. von Wachenfeldt (Anna); A. Liljegren (Annelie); G. Barbany-Bustinza (Gisela); J. Rantala (Johanna); H. Grönberg (Henrik); E.-L. Stattin; M. Emanuelsson (Monica); R.R. Brandell; N. Dahl (Niklas); S. Verhoef; M. Verheus (Martijn); L.v. Veer; F.E. van Leeuwen; J.M. Collee (Margriet); A.M.W. van den Ouweland (Ans); A. Jager; M.M.A. Tilanus-Linthorst (Madeleine); C.M. Seynaeve (Caroline); J.T. Wijnen (Juul); M.P. Vreeswijk (Maaike); R.A.E.M. Tollenaar (Rob); M.J. Ligtenberg (Marjolijn); N. Hoogerbrugge (Nicoline); M.G.E.M. Ausems (Margreet); C.M. Aalfs (Cora); J.J.P. Gille (Jan); Q. Waisfisz (Quinten); E.B. Gómez García (Encarna); C.E. van Roozendaal (Cees); M.J. Blok (Marinus); B. Caanen; J.C. Oosterwijk; A.H. van der Hout (Annemarie); M.J. Mourits; H.F. Vasen (Hans); H. Gregory (Helen); P.J. Morrison (Patrick); L. Jeffers (Lisa); T.J. Cole (Trevor); C. McKeown (Carole); J. Hoffman (Jonathan); A. Donaldson (Alan); S. Downing (Sarah); A. Taylor (Amy); A. Murray (Alexandra); M.T. Rogers (Mark); E. McCann (Emma); M.E. Porteous (Mary); S. Drummond (Sarah); C. Brewer (Carole); E. Kivuva (Emma); A. Searle (Anne); S. Goodman (Selina); K. Hill (Kathryn); 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); C. Jacobs (Chris); C. Langman (Caroline); A. Whaite (Anna); H. Dorkins (Huw); J. Barwell (Julian); C. Chu (Chengbin); J. Miller (Julie); I.O. Ellis (Ian); C. Houghton (Catherine); L. Side (Lucy); A. Male (Alison); C. Berlin (Cheryl); J. Eason (Jacqueline); R. Collier (Rebecca); O. Claber (Oonagh); I. Jobson (Irene); L.J. Walker (Lisa); D. McLeod (Diane); D. Halliday (Dorothy); S. Durell (Sarah); B. Stayner (Barbara); S. Shanley; N. Rahman (Nazneen); R. Houlston (Richard); E. Bancroft (Elizabeth); L. D'Mello (Lucia); E. Page (Elizabeth); A. Ardern-Jones (Audrey); K. Kohut (Kelly); J. Wiggins (Jennifer); E. Castro (Elena); A. Mitra (Anita); L. Robertson (Lisa); O. Quarrell (Oliver); C. Bardsley (Cathryn); H. Ehrencrona (Hans); S.V. Hodgson (Shirley); D.E. Barton (David); S. Goff (Sheila); G. Brice (Glen); L. Winchester (Lizzie); C. Eddy (Charlotte); V. Tripathi (Vishakha); V. Attard (Virginia); A. Lucassen (Anneke); G. Crawford (Gillian); D. McBride (Donna); S. Smalley (Sarah); J.W. Adlard (Julian); B. Arver (Brita Wasteson)

    2011-01-01

    textabstractTwo single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility var

  9. Activation of VCAM-1 and Its Associated Molecule CD44 Leads to Increased Malignant Potential of Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Pei-Chen Wang

    2014-02-01

    Full Text Available VCAM-1 (CD106, a transmembrane glycoprotein, was first reported to play an important role in leukocyte adhesion, leukocyte transendothelial migration and cell activation by binding to integrin VLA-1 (α4β1. In the present study, we observed that VCAM-1 expression can be induced in many breast cancer epithelial cells by cytokine stimulation in vitro and its up-regulation directly correlated with advanced clinical breast cancer stage. We found that VCAM-1 over-expression in the NMuMG breast epithelial cells controls the epithelial and mesenchymal transition (EMT program to increase cell motility rates and promote chemoresistance to doxorubicin and cisplatin in vitro. Conversely, in the established MDAMB231 metastatic breast cancer cell line, we confirmed that knockdown of endogenous VCAM-1 expression reduced cell proliferation and inhibited TGFβ1 or IL-6 mediated cell migration, and increased chemosensitivity. Furthermore, we demonstrated that knockdown of endogenous VCAM-1 expression in MDAMB231 cells reduced tumor formation in a SCID xenograft mouse model. Signaling studies showed that VCAM-1 physically associates with CD44 and enhances CD44 and ABCG2 expression. Our findings uncover the possible mechanism of VCAM-1 activation facilitating breast cancer progression, and suggest that targeting VCAM-1 is an attractive strategy for therapeutic intervention.

  10. Common breast cancer susceptibility alleles are associated with tumor subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2

    DEFF Research Database (Denmark)

    Mulligan, Anna Marie; Couch, Fergus J; Barrowdale, Daniel;

    2011-01-01

    ABSTRACT: INTRODUCTION: Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtype...... subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers....

  11. miR-21 Expression in Pregnancy-Associated Breast Cancer: A Possible Marker of Poor Prognosis

    Directory of Open Access Journals (Sweden)

    Beatriz A. Walter, Gabriela Gómez-Macias, Vladimir A. Valera, Mark Sobel, Maria J. Merino

    2011-01-01

    Full Text Available Aims: microRNAs (miRNAs are a class of small noncoding RNAs that can act as key modulators in tumorigenesis-related genes. Specifically, it has been suggested that miR-21 overexpression plays a role in the development and progression of breast cancer. So far, the role of miRNAs in pregnancy-associated breast cancer (PABC has not been investigated.Methods and Results: We evaluated miR-21 expression by quantitative RT-PCR in 35 patients, 25 with PABC and 10 control breast cancer cases not pregnancy-associated with similar clinicopathological features. We then analyzed protein expression for PTEN, BCL2 and PDCD4 as miR-21 target genes by IHC, and finally correlated the results with patients' clinicopathological features.Significant overexpression of miR-21 in PABC tumors compared to normal adjacent tissue was found. Overexpression of miR-21 was frequently found in high grade tumors with loss of hormone receptor expression and was significantly associated with positive lymph nodes (p=0.025. In PABC patients, PTEN, BCL2 and PDCD4 target protein expression was decreased in 80%, 76% and 40% respectively.Conclusion: Our study supports the involvement of miR-21 in breast cancer progression and metastasis formation in PABC implying a role of this miRNA as a marker for poor prognosis in PABC patients.

  12. Profile of thyroid hormones in breast cancer patients

    OpenAIRE

    Saraiva P.P.; Figueiredo N.B.; Padovani C.R.; Brentani M.M.; Nogueira C.R.

    2005-01-01

    Estrogen involvement in breast cancer has been established; however, the association between breast cancer and thyroid diseases is controversial. Estrogen-like effects of thyroid hormone on breast cancer cell growth in culture have been reported. The objective of the present study was to determine the profile of thyroid hormones in breast cancer patients. Serum aliquots from 26 patients with breast cancer ranging in age from 30 to 85 years and age-matched normal controls (N = 22) were analyze...

  13. Molecular mechanisms associated with breast cancer based on integrated gene expression profiling by bioinformatics analysis.

    Science.gov (United States)

    Wu, Di; Han, Bing; Guo, Liang; Fan, Zhimin

    2016-07-01

    In this study, we aimed to gain more insights into the underlying molecular mechanisms responsible for breast cancer (BC) progression. Three gene expression profiles of human BC were integrated and used to screen the differentially expressed genes (DEGs) between healthy breast samples and BC samples. Protein-protein interaction (PPI) network of DEGs was constructed by mapping DEGs into the Search Tool for the Retrieval of Interacting Genes (STRING) database; then the subnetworks of PPI were constructed with plug-in, MCODE and DEGs in Subnetwork 1 were analysed based on Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway database ( http://www.genome.jp/kegg /). In addition, co-expression network of DEGs was established using the Cytoscape. Totalally 931 DEGs were selected, including 340 up-regulated genes and 591 down-regulated genes. KEGG pathway analysis for DEGs in Subnetwork 1 showed that the pathogenesis of BC was associated with cell cycle, oocyte meiosis, progesterone-mediated oocyte maturation and p53 signalling pathways. Meanwhile, the most significant-related DEGs were found by co-expression network analysis of DEGs. In conclusion, CCNG1 might be involved in the progression of BC via inhibiting cell proliferation, and ADAMTS1 might play a crucial role in BC development through the regulation of angiogenesis. PMID:26804550

  14. Pregnancy After Breast Cancer.

    Science.gov (United States)

    Gemignani; Petrek

    1999-05-01

    BACKGROUND: The issue of pregnancy following the diagnosis and treatment of breast cancer is important because the incidence of breast cancer is increasing in women of childbearing age. The fact that many women are delaying childbearing, whether for educational, professional, or personal reasons, increases the number of women who will undergo breast cancer treatment before completing childbearing. METHODS: Data on pregnancy in breast cancer survivors are limited and consist only of retrospective data. This paper reviews the published literature on the influence of subsequent pregnancy on breast cancer, including three recent large-scale population-based studies. RESULTS: The survival of women with breast carcinoma who subsequently become pregnant is not reported to be decreased in any of the published series. However, several biases may be present that justify the concern regarding the conclusions. CONCLUSIONS: Further research on the safety of subsequent pregnancy after breast carcinoma treatment is needed. To address these issues, patients are currently being accrued for a large, prospective, multicenter study of young breast carcinoma patients. PMID:10758557

  15. Arsenic methylation capacity is associated with breast cancer in northern Mexico

    Energy Technology Data Exchange (ETDEWEB)

    López-Carrillo, Lizbeth; Hernández-Ramírez, Raúl Ulises [Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México (Mexico); Gandolfi, A. Jay [Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ (United States); Ornelas-Aguirre, José Manuel [Unidad de Investigación en Epidemiología Clínica del Hospital de Especialidades No. 2, Unidad Médica de Alta Especialidad, Instituto Mexicano del Seguro Social, Ciudad Obregón, Sonora, México (Mexico); Torres-Sánchez, Luisa [Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México (Mexico); Cebrian, Mariano E., E-mail: mcebrian@cinvestav.mx [Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del IPN, México City, México (Mexico)

    2014-10-01

    Exposure to environmental contaminants, dietary factors and lifestyles may explain worldwide different breast cancer (BC) incidence. Inorganic arsenic (iAs) in the drinking water is a concern in many regions, such as northern Mexico. Studies in several countries have associated the proportion of urinary monomethylarsenic (%MMA) with increased risks for many As-related diseases, including cancer. To investigate the potential relationships between the risk of BC and the capacity to methylate iAs, a hospital-based case–control study (1016 cases/1028 controls) was performed in northern Mexico. Women were directly interviewed about their reproductive histories. The profile of As metabolites in urine was determined by HPLC-ICP-MS and methylation capacity was assessed by metabolite percentages and indexes. Total urinary As, excluding arsenobetaine (TAs-AsB), ranged from 0.26 to 303.29 μg/L. Most women (86%) had TAs-AsB levels below As biological exposure index (35 μg/L). Women with higher %MMA and/or primary methylation index (PMI) had an increased BC risk (%MMA OR{sub Q5vs.Q1} = 2.63; 95%CI 1.89,3.66; p for trend < 0.001; PMI OR{sub Q5vs.Q1} = 1.90; 95%CI 1.39,2.59, p for trend < 0.001). In contrast, women with higher proportion of urinary dimethylarsenic (%DMA) and/or secondary methylation index (SMI) had a reduced BC risk (%DMA OR{sub Q5vs.Q1} = 0.63; 95%CI 0.45,0.87, p for trend 0.006; SMI OR{sub Q5vsQ1} = 0.42, 95%CI 0.31,0.59, p for trend < 0.001). Neither %iAs nor total methylation index was associated to BC risk. Inter-individual variations in iAs metabolism may play a role in BC carcinogenesis. Women with higher capacity to methylate iAs to MMA and/or a lower capacity to further methylate MMA to DMA were at higher BC risk. - Highlights: • Arsenic methylation capacity is associated to an increased breast cancer (BC) risk. • Women with higher capacity to methylate arsenic to MMA were at higher BC risk. • Women with higher capacity to methylate arsenic to

  16. Arsenic methylation capacity is associated with breast cancer in northern Mexico

    International Nuclear Information System (INIS)

    Exposure to environmental contaminants, dietary factors and lifestyles may explain worldwide different breast cancer (BC) incidence. Inorganic arsenic (iAs) in the drinking water is a concern in many regions, such as northern Mexico. Studies in several countries have associated the proportion of urinary monomethylarsenic (%MMA) with increased risks for many As-related diseases, including cancer. To investigate the potential relationships between the risk of BC and the capacity to methylate iAs, a hospital-based case–control study (1016 cases/1028 controls) was performed in northern Mexico. Women were directly interviewed about their reproductive histories. The profile of As metabolites in urine was determined by HPLC-ICP-MS and methylation capacity was assessed by metabolite percentages and indexes. Total urinary As, excluding arsenobetaine (TAs-AsB), ranged from 0.26 to 303.29 μg/L. Most women (86%) had TAs-AsB levels below As biological exposure index (35 μg/L). Women with higher %MMA and/or primary methylation index (PMI) had an increased BC risk (%MMA ORQ5vs.Q1 = 2.63; 95%CI 1.89,3.66; p for trend < 0.001; PMI ORQ5vs.Q1 = 1.90; 95%CI 1.39,2.59, p for trend < 0.001). In contrast, women with higher proportion of urinary dimethylarsenic (%DMA) and/or secondary methylation index (SMI) had a reduced BC risk (%DMA ORQ5vs.Q1 = 0.63; 95%CI 0.45,0.87, p for trend 0.006; SMI ORQ5vsQ1 = 0.42, 95%CI 0.31,0.59, p for trend < 0.001). Neither %iAs nor total methylation index was associated to BC risk. Inter-individual variations in iAs metabolism may play a role in BC carcinogenesis. Women with higher capacity to methylate iAs to MMA and/or a lower capacity to further methylate MMA to DMA were at higher BC risk. - Highlights: • Arsenic methylation capacity is associated to an increased breast cancer (BC) risk. • Women with higher capacity to methylate arsenic to MMA were at higher BC risk. • Women with higher capacity to methylate arsenic to DMA were at lower BC

  17. Diet and risk of breast cancer.

    Science.gov (United States)

    Kotepui, Manas

    2016-01-01

    Diet may play a role in both promoting and inhibiting human breast cancer development. In this review, nutritional risk factors such as consumption of dietary fat, meat, fiber, and alcohol, and intake of phytoestrogen, vitamin D, iron, and folate associated with breast cancer are reviewed. These nutritional factors have a variety of associations with breast cancer risk. Type of fat consumed has different effects on risk of breast cancer: consumption of meat is associated with heterocyclic amine (HCA) exposure; different types of plant fiber have various effects on breast cancer risk; alcohol consumption may increase the risk of breast cancer by producing acetaldehyde and reactive oxygen species (ROS); intake of phytoestrogen may reduce risk of breast cancer through genomic and non-genomic action; vitamin D can reduce the risk of breast cancer by inhibiting the process of cancer invasion and metastasis; intake of dietary iron may lead to oxidative stress, DNA damage, and lipid peroxidation; and lower intake of folate may be linked to a higher risk of breast cancer. PMID:27095934

  18. Associations between body mass index and molecular subtypes as well as other clinical characteristics of breast cancer in Chinese women

    Directory of Open Access Journals (Sweden)

    Chen FY

    2013-03-01

    Full Text Available Fei-Yu Chen, Hui-Ying Ou, Shou-Man Wang, Yu-Hui Wu, Guo-Jiao Yan, Li-Li Tang Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha City, Hunan Province, People's Republic of China Background: Several studies have shown a positive association between body mass index (BMI and the development of hormone receptor-positive breast cancer in postmenopausal women; however, the associations between BMI groups and molecular subtypes have yet to be well defined in premenopausal breast cancer patients. Methods: A total of 2465 female breast cancer patients diagnosed at our institution were recruited for this study. Clinicopathologic information (including age, body height and weight, as well as tumor subtypes and stages was collected; analyses of these characteristics and the associations between them were performed. Results: A total of 1951 cases were included in the study. The mean age was 47.3 years, the majority of patients were of normal weight, premenopausal, had stage 2 cancer, and did not present with positive nodes. The prevalence of the luminal A, luminal B, human epidermal growth factor receptor 2+, and triple-negative subtypes were 57.8%, 11.6%, 6.1%, and 24.5%, respectively. There were significant differences in the clinicopathologic features among BMI groups in premenopausal patients. The case-only odds ratio (OR analysis revealed that normal weight patients tended to have luminal B cancer (OR = 1.4, P = 0.206, and overweight and obese patients tended to have triple-negative cancer in premenopausal patients (OR = 2.8, OR = 3.7, respectively; P < 0.001. Conclusion: In Chinese women, breast cancer came with these characteristics: young mean age (premenopause, luminal A subtype, and the majority of them were within a normal weight range. In premenopausal patients, underweight patients tended to have luminal A, lower human epidermal growth factor receptor 2+ expression, stage 1 and no positive node cancer. However

  19. Docosahexaenoic Acid in Preventing Recurrence in Breast Cancer Survivors

    Science.gov (United States)

    2016-06-20

    Benign Breast Neoplasm; Ductal Breast Carcinoma In Situ; Invasive Breast Carcinoma; Lobular Breast Carcinoma In Situ; Paget Disease of the Breast; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  20. Breast Cancers Between Mammograms Have Aggressive Features

    Science.gov (United States)

    Breast cancers that are discovered in the period between regular screening mammograms—known as interval cancers—are more likely to have features associated with aggressive behavior and a poor prognosis than cancers found via screening mammograms.

  1. The p53 pathway in breast cancer

    OpenAIRE

    Gasco, Milena; Shami, Shukri; Crook, Tim

    2002-01-01

    p53 mutation remains the most common genetic change identified in human neoplasia. In breast cancer, p53 mutation is associated with more aggressive disease and worse overall survival. The frequency of mutation in p53 is, however, lower in breast cancer than in other solid tumours. Changes, both genetic and epigenetic, have been identified in regulators of p53 activity and in some downstream transcriptional targets of p53 in breast cancers that express wild-type p53. Molecular pathological an...

  2. Targeted Next-Generation Sequencing Identifies a Recurrent Mutation in MCPH1 Associating with Hereditary Breast Cancer Susceptibility.

    Directory of Open Access Journals (Sweden)

    Tuomo Mantere

    2016-01-01

    Full Text Available Breast cancer is strongly influenced by hereditary risk factors, a majority of which still remain unknown. Here, we performed a targeted next-generation sequencing of 796 genes implicated in DNA repair in 189 Finnish breast cancer cases with indication of hereditary disease susceptibility and focused the analysis on protein truncating mutations. A recurrent heterozygous mutation (c.904_916del, p.Arg304ValfsTer3 was identified in early DNA damage response gene, MCPH1, significantly associating with breast cancer susceptibility both in familial (5/145, 3.4%, P = 0.003, OR 8.3 and unselected cases (16/1150, 1.4%, P = 0.016, OR 3.3. A total of 21 mutation positive families were identified, of which one-third exhibited also brain tumors and/or sarcomas (P = 0.0007. Mutation carriers exhibited significant increase in genomic instability assessed by cytogenetic analysis for spontaneous chromosomal rearrangements in peripheral blood lymphocytes (P = 0.0007, suggesting an effect for MCPH1 haploinsufficiency on cancer susceptibility. Furthermore, 40% of the mutation carrier tumors exhibited loss of the wild-type allele. These findings collectively provide strong evidence for MCHP1 being a novel breast cancer susceptibility gene, which warrants further investigations in other populations.

  3. Targeted Next-Generation Sequencing Identifies a Recurrent Mutation in MCPH1 Associating with Hereditary Breast Cancer Susceptibility

    Science.gov (United States)

    Mantere, Tuomo; Winqvist, Robert; Kauppila, Saila; Grip, Mervi; Jukkola-Vuorinen, Arja; Tervasmäki, Anna; Rapakko, Katrin; Pylkäs, Katri

    2016-01-01

    Breast cancer is strongly influenced by hereditary risk factors, a majority of which still remain unknown. Here, we performed a targeted next-generation sequencing of 796 genes implicated in DNA repair in 189 Finnish breast cancer cases with indication of hereditary disease susceptibility and focused the analysis on protein truncating mutations. A recurrent heterozygous mutation (c.904_916del, p.Arg304ValfsTer3) was identified in early DNA damage response gene, MCPH1, significantly associating with breast cancer susceptibility both in familial (5/145, 3.4%, P = 0.003, OR 8.3) and unselected cases (16/1150, 1.4%, P = 0.016, OR 3.3). A total of 21 mutation positive families were identified, of which one-third exhibited also brain tumors and/or sarcomas (P = 0.0007). Mutation carriers exhibited significant increase in genomic instability assessed by cytogenetic analysis for spontaneous chromosomal rearrangements in peripheral blood lymphocytes (P = 0.0007), suggesting an effect for MCPH1 haploinsufficiency on cancer susceptibility. Furthermore, 40% of the mutation carrier tumors exhibited loss of the wild-type allele. These findings collectively provide strong evidence for MCHP1 being a novel breast cancer susceptibility gene, which warrants further investigations in other populations. PMID:26820313

  4. B7-H4 gene polymorphisms are associated with sporadic breast cancer in a Chinese Han population

    International Nuclear Information System (INIS)

    B7-H4, a co-inhibitory molecule of the B7 family, can restrain T cell proliferation, cytokine secretion and the development of cytotoxicity. B7-H4 is expressed in tumor tissues at a higher level than in normal tissues, and has a potential effect to protect tumors from anti-tumor immune responses. This case-control study was carried out to determine the potential influences of B7-H4 gene polymorphisms on the susceptibility and progression of breast cancer in Han women of Northeast China. We genotyped three B7-H4 variants (rs10754339, rs10801935 and rs3738414) and tagged all common haplotypes (frequency greater than or equal to 1%) in a Chinese population consisting of 500 breast cancer cases and 504 control individuals matched for age. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to determine the genotypes. Our data indicated that, compared with the common genotype and allele of each SNP, the rs10754339 AG genotype and G allele showed a significantly increased risk of breast cancer (OR = 1.455, 95% CI 1.119-1.892; OR = 1.325, 95% CI 1.073-1.637, respectively). The rs10801935 CC genotype, the rs3738414 AA genotype and the rs3738414 A allele were associated with a significantly decreased risk of breast cancer (OR = 0.328, 95% CI 0.145-0.739; OR = 0.412, 95% CI 0.203-0.835; OR = 0.698, 95% CI 0.564-0.864, respectively). Additionally, the rs10754339 GG genotype was significantly associated with lymph node metastasis and PR status, and the G allele and the AG genotype were respectively associated with lymph node metastasis and ER status. In haplotype analysis, we observed that compared with the AAG haplotype, the AAA haplotype showed a significantly decreased risk of breast cancer (OR = 0.689, 95% CI 0.539-0.881), but the GAG haplotype was associated with a significantly increased risk of breast cancer (OR = 1.511, 95% CI 1.125-2.031). And the AAA and the GCG haplotypes also respectively have significant influences on

  5. Broccoli Sprout Extract in Treating Patients With Breast Cancer

    Science.gov (United States)

    2016-02-18

    Ductal Breast Carcinoma; Ductal Breast Carcinoma In Situ; Estrogen Receptor Negative; Estrogen Receptor Positive; Invasive Breast Carcinoma; Lobular Breast Carcinoma; Postmenopausal; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

  6. 2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy

    Science.gov (United States)

    Li, Jingmei; Lindström, Linda S.; Foo, Jia N.; Rafiq, Sajjad; Schmidt, Marjanka K.; Pharoah, Paul D. P.; Michailidou, Kyriaki; Dennis, Joe; Bolla, Manjeet K.; Wang, Qin; Van ‘t Veer, Laura J.; Cornelissen, Sten; Rutgers, Emiel; Southey, Melissa C.; Apicella, Carmel; Dite, Gillian S.; Hopper, John L.; Fasching, Peter A.; Haeberle, Lothar; Ekici, Arif B.; Beckmann, Matthias W.; Blomqvist, Carl; Muranen, Taru A.; Aittomäki, Kristiina; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.; Kataja, Vesa; Chenevix-Trench, Georgia; Investigators, kConFab; Phillips, Kelly-Anne; McLachlan, Sue-Anne; Lambrechts, Diether; Thienpont, Bernard; Smeets, Ann; Wildiers, Hans; Chang-Claude, Jenny; Flesch-Janys, Dieter; Seibold, Petra; Rudolph, Anja; Giles, Graham G.; Baglietto, Laura; Severi, Gianluca; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Kristensen, Vessela; Alnæs, Grethe I. Grenaker; Borresen-Dale, Anne-Lise; Nord, Silje; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert; Seynaeve, Caroline; Hooning, Maartje; Kriege, Mieke; Hollestelle, Antoinette; van den Ouweland, Ans; Li, Yi; Hamann, Ute; Torres, Diana; Ulmer, Hans U.; Rüdiger, Thomas; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Chen, Shou-Tung; Teo, Soo Hwang; Taib, Nur Aishah Mohd; Har Yip, Cheng; Fuang Ho, Gwo; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K.; Yoo, Keun-Young; Maishman, Tom; Tapper, William J.; Dunning, Alison; Shah, Mitul; Luben, Robert; Brown, Judith; Chuen Khor, Chiea; Eccles, Diana M.; Nevanlinna, Heli; Easton, Douglas; Humphreys, Keith; Liu, Jianjun; Hall, Per; Czene, Kamila

    2014-01-01

    Large population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oestrogen receptor (ER)-negative patients treated with chemotherapy (279 events) from 14 European studies in a prior large-scale genotyping experiment, which is part of the Collaborative Oncological Gene-environment Study (COGS) initiative. We carry out replication using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events). Rs4458204_A near CCL20 (2q36.3) is found to be associated with breast cancer-specific death at a genome-wide significant level (n=2,641, 440 events, combined allelic hazard ratio (HR)=1.81 (1.49–2.19); P for trend=1.90 × 10−9). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities. PMID:24937182

  7. Anterior gradient protein 3 is associated with less aggressive tumors and better outcome of breast cancer patients

    Directory of Open Access Journals (Sweden)

    Obacz J

    2015-06-01

    Full Text Available Joanna Obacz,1 Veronika Brychtova,1 Jan Podhorec,1 Pavel Fabian,2 Petr Dobes,1 Borivoj Vojtesek,1 Roman Hrstka1 1Regional Centre for Applied Molecular Oncology (RECAMO, 2Department of Pathology, Masaryk Memorial Cancer Institute, Brno, Czech Republic Abstract: Anterior gradient protein (AGR 3 is a highly related homologue of pro-oncogenic AGR2 and belongs to the family of protein disulfide isomerases. Although AGR3 was found in breast, ovary, prostate, and liver cancer, it remains of yet poorly defined function in tumo-rigenesis. This study aimed to determine AGR3 expression in a cohort of 129 primary breast carcinomas and evaluate the clinical and prognostic significance of AGR3 in these tumors. The immunohistochemical analysis revealed the presence of AGR3 staining to varying degrees in 80% of analyzed specimens. The percentage of AGR3-positive cells significantly correlated with estrogen receptor, progesterone receptor (both P<0.0001 as well as low histological grade (P=0.003, and inversely correlated with the level of Ki-67 expression (P<0.0001. In the whole cohort, AGR3 expression was associated with longer progression-free survival (PFS, whereas AGR3-positive subgroup of low-histological grade tumors showed both significantly longer PFS and overall survival. In conclusion, AGR3 is associated with the level of differentiation, slowly proliferating tumors, and more favorable prognosis of breast cancer patients. Keywords: AGR3, patient survival, protein disulfide isomerase, ER-positive breast cancer, immuno­histochemistry

  8. Results based on 124 cases of breast cancer and 97 controls from Taiwan suggest that the single nucleotide polymorphism (SNP309) in the MDM2 gene promoter is associated with earlier onset and increased risk of breast cancer

    International Nuclear Information System (INIS)

    It has been suggested that the single nucleotide polymorphism 309 (SNP309, T -> G) in the promoter region of the MDM2 gene is important for tumor development; however, with regards to breast cancer, inconsistent associations have been reported worldwide. It is speculated that these conflicting results may have arisen due to different patient subgroups and ethnicities studied. For the first time, this study explores the effect of the MDM2 SNP309 genotype on Taiwanese breast cancer patients. Genomic DNA was obtained from the whole blood of 124 breast cancer patients and 97 cancer-free healthy women living in Taiwan. MDM2 SNP309 genotyping was carried out by restriction fragment length polymorphism (RFLP) assay. The multivariate logistic regression and the Kaplan-Meier method were used for analyzing the risk association and significance of age at diagnosis among different MDM2 SNP309 genotypes, respectively. Compared to the TT genotype, an increased risk association with breast cancer was apparent for the GG genotype (OR = 3.05, 95% CI = 1.04 to 8.95), and for the TG genotype (OR = 2.12, 95% CI = 0.90 to 5.00) after adjusting for age, cardiovascular disease/diabetes, oral contraceptive usage, and body mass index, which exhibits significant difference between cases and controls. Furthermore, the average ages at diagnosis for breast cancer patients were 53.6, 52 and 47 years for those harboring TT, TG and GG genotypes, respectively. A significant difference in median age of onset for breast cancer between GG and TT+TG genotypes was obtained by the log-rank test (p = 0.0067). Findings based on the current sample size suggest that the MDM2 SNP309 GG genotype may be associated with both the risk of breast cancer and an earlier age of onset in Taiwanese women

  9. Early breast cancer

    International Nuclear Information System (INIS)

    The therapy of early breast cancer has been changing during the last decennium. It requires a multi-disciplinary approach and in each of these disciplines improvements have been implemented. The result is that treatment schedules can now be adapted to specific subgroups. In this review early breast cancer is defined as operable disease, using the criteria set out by Haagensen. Emphasis is given to describing the new developments in prognostic criteria, since these form the basis for creating subgroups for specific treatment schedules. Distinction is made between the factors relating to growth rate and those relating to metastatic potential. Data on screening promises a beneficial effect of the implementation of screening in national health care programs. Important shifts are seen in treatment schedules; the place of postoperative radiotherapy after classic ablative treatment is being challenged, whereas it plays a major role in the new breast conserving therapy schedules. The data mentioned in the review suggest that a large proportion of 'operable' cases can be treated with breast conservation but details in the technique of breast conserving therapy are still under investigation. They form a major part of the coming prospective studies in breast cancer. Improvements in reconstruction techniques, creating better cosmetic results, make reconstruction more competitive with breast conserving therapy. The use of chemotherapy and endocrine manipulation in early breast cancer has now been clearly confirmed by the overview technique by the Peto-group, thanks to all efforts of individual trialists together. (orig.)

  10. Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

    DEFF Research Database (Denmark)

    Antoniou, Antonis C; Kuchenbaecker, Karoline B; Soucy, Penny;

    2012-01-01

    Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 ...

  11. Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

    NARCIS (Netherlands)

    Antoniou, A.C.; Kuchenbaecker, K.B.; Soucy, P.; Beesley, J.; Chen, X.; McGuffog, L.; Lee, A.; Barrowdale, D.; Healey, S.; Sinilnikova, O.M.; Caligo, M.A.; Loman, N.; Harbst, K.; Lindblom, A.; Arver, B.; Rosenquist, R.; Karlsson, P.; Nathanson, K.; Domchek, S.; Rebbeck, T.; Jakubowska, A.; Lubinski, J.; Jaworska, K.; Durda, K.; Zlowowcka-Perlowska, E.; Osorio, A.; Duran, M.; Andres, R.; Benitez, J.; Hamann, U.; Hogervorst, F.B.; Os, T.A. van; Verhoef, S.; Meijers-Heijboer, H.E.; Wijnen, J.; Gomez Garcia, E.B.; Ligtenberg, M.J.L.; Kriege, M.; Collee, J.M.; Ausems, M.G.; Oosterwijk, J.C.; Peock, S.; Frost, D.; Ellis, S.D.; Platte, R.; Fineberg, E.; Evans, D.G.; Lalloo, F.; Jacobs, C.; Eeles, R.; Adlard, J.; Davidson, R.; Cole, T.; Cook, J.; Paterson, J.; Douglas, F.; Brewer, C.; Hodgson, S.; Morrison, P.J.; Walker, L.; Rogers, M.T.; Donaldson, A.; Dorkins, H.; Godwin, A.K.; Bove, B.; Stoppa-Lyonnet, D.; Houdayer, C.; Buecher, B.; Pauw, A. de; Mazoyer, S.; Calender, A.; Leone, M.; Bressac-de Paillerets, B.; Caron, O.; Sobol, H.; Frenay, M.; Prieur, F.; Ferrer, S.U.; Mortemousque, I.; Buys, S.; Daly, M.; Miron, A.; Terry, M.U.; Hopper, J.L.; John, E.M.; Southey, M.; Goldgar, D.; Singer, C.F.; Fink-Retter, A.; Tea, M.K.; Kaulich, D.U.; Hansen, T.V.; Nielsen, F.C.; Barkardottir, R.B.; Gaudet, M.; Kirchhoff, T.; Joseph, V.; Dutra-Clarke, A.; Offit, K.; Piedmonte, M., et al.

    2012-01-01

    INTRODUCTION: Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B),

  12. Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

    NARCIS (Netherlands)

    Antoniou, Antonis C.; Kuchenbaecker, Karoline B.; Soucy, Penny; Beesley, Jonathan; Chen, Xiaoqing; McGuffog, Lesley; Lee, Andrew; Barrowdale, Daniel; Healey, Sue; Sinilnikova, Olga M.; Caligo, Maria A.; Loman, Niklas; Harbst, Katja; Lindblom, Annika; Arver, Brita; Rosenquist, Richard; Karlsson, Per; Nathanson, Kate; Domchek, Susan; Rebbeck, Tim; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Zlowowcka-Perlowska, Elzbieta; Osorio, Ana; Duran, Mercedes; Andres, Raquel; Benitez, Javier; Hamann, Ute; Hogervorst, Frans B.; van Os, Theo A.; Verhoef, Senno; Meijers-Heijboer, Hanne E. J.; Wijnen, Juul; Garcia, Encarna B. Gomez; Ligtenberg, Marjolijn J.; Kriege, Mieke; Collee, Margriet; Ausems, Margreet G. E. M.; Oosterwijk, Jan C.; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Evans, D. Gareth; Lalloo, Fiona; Jacobs, Chris; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Cole, Trevor; Cook, Jackie; Paterson, Joan; Douglas, Fiona; Brewer, Carole; Hodgson, Shirley; Morrison, Patrick J.; Walker, Lisa; Rogers, Mark T.; Donaldson, Alan; Dorkins, Huw; Godwin, Andrew K.; Bove, Betsy; Stoppa-Lyonnet, Dominique; Houdayer, Claude; Buecher, Bruno; de Pauw, Antoine; Mazoyer, Sylvie; Calender, Alain; Leone, Melanie; Bressac-de Paillerets, Brigitte; Caron, Olivier; Sobol, Hagay; Frenay, Marc; Prieur, Fabienne; Ferrer, Sandra Fert; Mortemousque, Isabelle; Buys, Saundra; Daly, Mary; Miron, Alexander; Terry, Mary Beth; Hopper, John L.; John, Esther M.; Southey, Melissa; Goldgar, David; Singer, Christian F.; Fink-Retter, Anneliese; Tea, Muy-Kheng; Kaulich, Daphne Geschwantler; Hansen, Thomas V. O.; Nielsen, Finn C.; Barkardottir, Rosa B.; Gaudet, Mia; Kirchhoff, Tomas; Joseph, Vijai; Dutra-Clarke, Ana; Offit, Kenneth; Piedmonte, Marion; Kirk, Judy; Cohn, David; Hurteau, Jean; Byron, John; Fiorica, James; Toland, Amanda E.; Montagna, Marco; Oliani, Cristina; Imyanitov, Evgeny; Isaacs, Claudine; Tihomirova, Laima; Blanco, Ignacio; Lazaro, Conxi; Teule, Alex; Del Valle, J.; Gayther, Simon A.; Odunsi, Kunle; Gross, Jenny; Karlan, Beth Y.; Olah, Edith; Teo, Soo-Hwang; Ganz, Patricia A.; Beattie, Mary S.; Dorfling, Cecelia M.; van Rensburg, Elizabeth Jansen; 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; Schaefer, Dieter; Caldes, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Muranen, Taru A.; Lesperance, Bernard; Spurdle, Amanda B.; Neuhausen, Susan L.; Ding, Yuan C.; Wang, Xianshu; Fredericksen, Zachary; Pankratz, Vernon S.; Lindor, Noralane M.; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Bonanni, Bernardo; Bernard, Loris; Dolcetti, Riccardo; Papi, Laura; Ottini, Laura; Radice, Paolo; Greene, Mark H.; Loud, Jennifer T.; Andrulis, Irene L.; Ozcelik, Hilmi; Mulligan, Anna Marie; Glendon, Gord; Thomassen, Mads; Gerdes, Anne-Marie; Jensen, Uffe B.; Skytte, Anne-Bine; Kruse, Torben A.; Chenevix-Trench, Georgia; Couch, Fergus J.; Simard, Jacques; Easton, Douglas F.

    2012-01-01

    Introduction: Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B),

  13. Common breast cancer susceptibility alleles are associated with tumor subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2

    DEFF Research Database (Denmark)

    Mulligan, Anna Marie; Couch, Fergus J; Barrowdale, Daniel;

    2011-01-01

    ABSTRACT: INTRODUCTION: Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtype...

  14. Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2

    NARCIS (Netherlands)

    Mulligan, A.M.; Couch, F.J.; Barrowdale, D.; Domchek, S.M.; Eccles, D.; Nevanlinna, H.; Ramus, S.J.; Robson, M.; Sherman, M.; Spurdle, A.B.; Wappenschmidt, B.; Lee, A.; McGuffog, L.; Healey, S.; Sinilnikova, O.M.; Janavicius, R.; Hansen, T.V.; Nielsen, F.C.; Ejlertsen, B.; Osorio, A.; Munoz-Repeto, I.; Duran, M.; Godino, J.; Pertesi, M.; Benitez, J.; Peterlongo, P.; Manoukian, S.; Peissel, B.; Zaffaroni, D.; Cattaneo, E.; Bonanni, B.; Viel, A.; Pasini, B.; Papi, L.; Ottini, L.; Savarese, A.; Bernard, L.; Radice, P.; Hamann, U.; Verheus, M.; Meijers-Heijboer, H.E.; Wijnen, J.; Gomez Garcia, E.B.; Nelen, M.R.; Kets, C.M.; Seynaeve, C.; Tilanus-Linthorst, M.M.; Luijt, R.B. van der; Os, T.V.; Rookus, M.; Frost, D.; Jones, J.L.; Evans, D.G.; Lalloo, F.; Eeles, R.; Izatt, L.; Adlard, J.; Davidson, R.; Cook, J.; Donaldson, A.; Dorkins, H.; Gregory, H.; Eason, J.; Houghton, C.; Barwell, J.; Side, L.E.; McCann, E.; Murray, A.; Peock, S.; Godwin, A.K.; Schmutzler, R.K.; Rhiem, K.; Engel, C.; Meindl, A.; Ruehl, I.; Arnold, N.; Niederacher, D.; Sutter, C.; Deissler, H.; Gadzicki, D.; Kast, K.; Preisler-Adams, S.; Varon-Mateeva, R.; Schoenbuchner, I.; Fiebig, B.; Heinritz, W.; Schafer, D.; Gevensleben, H.; Caux-Moncoutier, V.; Fassy-Colcombet, M.; Cornelis, F.; Mazoyer, S.; Leone, M.; Boutry-Kryza, N.; Hardouin, A.; Berthet, P.; Muller, D.; Fricker, J.P.; Mortemousque, I.; Pujol, P.

    2011-01-01

    ABSTRACT: INTRODUCTION: Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes i

  15. Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers : results from the Consortium of Investigators of Modifiers of BRCA1/2

    NARCIS (Netherlands)

    Mulligan, Anna Marie; Couch, Fergus J.; Barrowdale, Daniel; Domchek, Susan M.; Eccles, Diana; Nevanlinna, Heli; Ramus, Susan J.; Robson, Mark; Sherman, Mark; Spurdle, Amanda B.; Wappenschmidt, Barbara; Lee, Andrew; McGuffog, Lesley; Healey, Sue; Sinilnikova, Olga M.; Janavicius, Ramunas; Hansen, Thomas V. O.; Nielsen, Finn C.; Ejlertsen, Bent; Osorio, Ana; Munoz-Repeto, Ivan; Duran, Mercedes; Godino, Javier; Pertesi, Maroulio; Benitez, Javier; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Cattaneo, Elisa; Bonanni, Bernardo; Viel, Alessandra; Pasini, Barbara; Papi, Laura; Ottini, Laura; Savarese, Antonella; Bernard, Loris; Radice, Paolo; Hamann, Ute; Verheus, Martijn; Meijers-Heijboer, Hanne E. J.; Wijnen, Juul; Garcia, Encarna B. Gomez; Nelen, Marcel R.; Kets, C. Marleen; Seynaeve, Caroline; Tilanus-Linthorst, Madeleine M. A.; van der Luijt, Rob B.; van Os, Theo; Rookus, Matti; Frost, Debra; Jones, J. Louise; Evans, D. Gareth; Lalloo, Fiona; Eeles, Ros; Izatt, Louise; Adlard, Julian; Davidson, Rosemarie; Cook, Jackie; Donaldson, Alan; Dorkins, Huw; Gregory, Helen; Eason, Jacqueline; Houghton, Catherine; Barwell, Julian; Side, Lucy E.; McCann, Emma; Murray, Alex; Peock, Susan; Godwin, Andrew K.; Schmutzler, Rita K.; Rhiem, Kerstin; Engel, Christoph; Meindl, Alfons; Ruehl, Ina; Arnold, Norbert; Niederacher, Dieter; Sutter, Christian; Deissler, Helmut; Gadzicki, Dorothea; Kast, Karin; Preisler-Adams, Sabine; Varon-Mateeva, Raymonda; Schoenbuchner, Ines; Fiebig, Britta; Heinritz, Wolfram; Schaefer, Dieter; Gevensleben, Heidrun; Caux-Moncoutier, Virginie; Fassy-Colcombet, Marion; Cornelis, Francois; Mazoyer, Sylvie; Leone, Melanie; Boutry-Kryza, Nadia; Hardouin, Agnes; Berthet, Pascaline; Muller, Daniele; Fricker, Jean-Pierre; Mortemousque, Isabelle; Pujol, Pascal; Coupier, Isabelle; Lebrun, Marine; Kientz, Caroline; Longy, Michel; Sevenet, Nicolas; Stoppa-Lyonnet, Dominique; Isaacs, Claudine; Caldes, Trinidad; de la Hoya, Miguel; Heikkinen, Tuomas; Aittomaki, Kristiina; Blanco, Ignacio; Lazaro, Conxi; Barkardottir, Rosa B.; Soucy, Penny; Dumont, Martine; Simard, Jacques; Montagna, Marco; Tognazzo, Silvia; D'Andrea, Emma; Fox, Stephen; Yan, Max; Rebbeck, Tim; Olopade, Olufunmilayo I.; Weitzel, Jeffrey N.; Lynch, Henry T.; Ganz, Patricia A.; Tomlinson, Gail E.; Wang, Xianshu; Fredericksen, Zachary; Pankratz, Vernon S.; Lindor, Noralane M.; Szabo, Csilla; Offit, Kenneth; Sakr, Rita; Gaudet, Mia; Bhatia, Jasmine; Kauff, Noah; Singer, Christian F.; Tea, Muy-Kheng; Gschwantler-Kaulich, Daphne; Fink-Retter, Anneliese; Mai, Phuong L.; Greene, Mark H.; Imyanitov, Evgeny; O'Malley, Frances P.; Ozcelik, Hilmi; Glendon, Gordon; Toland, Amanda E.; Gerdes, Anne-Marie; Thomassen, Mads; Kruse, Torben A.; Jensen, Uffe Birk; Skytte, Anne-Bine; Caligo, Maria A.; Soller, Maria; Henriksson, Karin; Wachenfeldt, von Anna; Arver, Brita; Stenmark-Askmalm, Marie; Karlsson, Per; Ding, Yuan Chun; Neuhausen, Susan L.; Beattie, Mary; Pharoah, Paul D. P.; Moysich, Kirsten B.; Nathanson, Katherine L.; Karlan, Beth Y.; Gross, Jenny; John, Esther M.; Daly, Mary B.; Buys, Saundra M.; Southey, Melissa C.; Hopper, John L.; Terry, Mary Beth; Chung, Wendy; Miron, Alexander F.; Goldgar, David; Chenevix-Trench, Georgia; Easton, Douglas F.; Andrulis, Irene L.; Antoniou, Antonis C.

    2011-01-01

    Introduction: Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 an

  16. Mammographic casting-type calcification associated with small screen-detected invasive breast cancers: is this a reliable prognostic indicator?

    International Nuclear Information System (INIS)

    AIM: The aim of the present study was to establish whether mammographic casting-type calcification associated with small screen-detected invasive breast cancers is a reliable prognostic indicator. METHODS AND MATERIALS: We retrospectively identified 50 consecutive women diagnosed with an invasive cancer less than 15 mm who showed associated casting calcification on their screening mammograms. Controls were identified that showed no microcalcification and were matched for tumour size, histological type and lymph node status. A minimum of 5 years follow-up was obtained, noting recurrence and outcome. Conditional and unconditional logistic regression, depending on the outcome variable, were used to analyse the data, taking the matched design into account in both cases. Where small numbers prohibited the use of logistic regression, Fisher's exact test was used. RESULTS: Five deaths from breast cancer occurred out of the 50 cases, of which three were lymph node positive, two were lymph node negative and none were grade 3. None of the 78 control cases died from breast cancer. The difference in breast cancer death rates was significant by Fisher's exact test (p=0.02). Risk of recurrence was also significantly increased in the casting cases (OR=3.55, 95% CI 1.02-12.33, p=0.046). CONCLUSION: Although the overall outcome for small screen-detected breast cancers is good, our study suggests that casting calcification is a poorer prognostic factor. The advantage of a mammographic feature as an independent prognostic indicator lies in early identification of high-risk patients, allowing optimization of management

  17. [Immunotherapy opportunities in breast cancer].

    Science.gov (United States)

    Pusztai, Lajos; Ladányi, Andrea; Székely, Borbála; Dank, Magdolna

    2016-03-01

    The prognostic value of tumor infiltrating lymphocytes in breast cancer has long been recognized by histopathologists. These observations were reaffirmed by recent immunohistochemistry and gene expression profiling studies that also revealed an association between greater chemotherapy sensitivity and extensive lymphocytic infiltration in early stage breast cancers treated with neoadjuvant chemotherapy. These results suggest that local anti-tumor immune response can at least partially control cancer growth and may mediate the antitumor effects of chemotherapy. However, until recently, there was no direct clinical evidence to demonstrate that enhancing anti-tumor immune response could lead to clinical benefit in breast cancer patients. The recent development of clinically effective immune checkpoint inhibitors made it possible to test the therapeutic impact of augmenting the local anti-tumor immune response. Two Phase I clinical trials using single agent anti-PD-1 (MK-3475, pembrolizumab) and anti-PD-L1 (MPDL3280A, atezolizumab) antibodies demonstrated close to 20% tumor response rates in heavily pretreated, metastatic, triple negative breast cancers. The most remarkable feature of the responses was their long duration. Several patients had disease control close to a year, or longer, which has not previously been seen with chemotherapy regimens in this patient population. A large number of clinical trials are currently underway with these and similar drugs in the neoadjuvant, adjuvant and metastatic settings to define the role of this new treatment modality in breast cancer. PMID:26934349

  18. Living Beyond Breast Cancer

    Science.gov (United States)

    ... Prosthesis Complementary Therapy Types of Complementary Therapy Acupuncture Art Therapy Diet, Nutrition and Exercise Expressive Writing Guided ... SIGN UP FOR OUR MAILING LIST SIGN UP Facebook Twitter Instagram YouTube Living Beyond Breast Cancer Conference ...

  19. Breast Cancer Prevention

    Science.gov (United States)

    ... the risk of breast cancer: Having an abortion. Making diet changes such as eating less fat or more ... does not give formal guidelines or recommendations for making decisions about health care. Reviewers and Updates Editorial Boards ...

  20. Women and breast cancer.

    OpenAIRE

    Lippman, M E

    1987-01-01

    One in every 12 women will develop breast cancer; the incidence increases with age, dietary fat intake, caloric intake, height, and weight. The 10-year survival rate of breast cancer patients who refuse therapy is virtually zero. Segmental mastectomy plus radiation and lumpectomy, combined with systemic (adjuvant)chemotherapy, are alternatives under investigation at the National Institutes of Health that may increase the survival rate by decreasing metastatic complications.

  1. 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; Hilda A Pickett; Shen, Howard C.; Chanel E. Smart; 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...

  2. Association of shared decision-making with type of breast cancer surgery: a cross-sectional study

    OpenAIRE

    Lee Eun; Park Byeong; Ahn Se; Nam Seok; Noh Dong; Lee Myung; Yun Young

    2010-01-01

    Abstract Background Although some studies examined the association between shared decision-making (SDM) and type of breast cancer surgery received, it is little known how treatment decisions might be shaped by the information provided by physicians. The purpose of this study was to identify the associations between shared decision making (SDM) and surgical treatment received. Methods Questionnaires on SDM were administered to 1,893 women undergoing primary curative surgery for newly diagnosed...

  3. Association Between a Germline OCA2 Polymorphism at Chromosome 15q13.1 and Estrogen Receptor-Negative Breast Cancer Survival

    DEFF Research Database (Denmark)

    Azzato, E.M.; Tyrer, J.; Fasching, P.A.;

    2010-01-01

    Epidemiology and Risk factors in Cancer Heredity [SEARCH]) to investigate associations between variation in germline DNA and overall survival. We evaluated possible associations between overall survival after a breast cancer diagnosis and 10 621 germline single-nucleotide polymorphisms (SNPs) from up to 3761......Traditional prognostic factors for survival and treatment response of patients with breast cancer do not fully account for observed survival variation. We used available genotype data from a previously conducted two-stage, breast cancer susceptibility genome-wide association study (ie, Studies of...... patients with invasive breast cancer (including 647 deaths and 26 978 person-years at risk) that were genotyped previously in the SEARCH study with high-density oligonucleotide microarrays (ie, hypothesis-generating set). Associations with all-cause mortality were assessed for each SNP by use of Cox...

  4. Association Between a Germline OCA2 Polymorphism at Chromosome 15q13.1 and Estrogen Receptor-Negative Breast Cancer Survival

    DEFF Research Database (Denmark)

    Azzato, E.M.; Tyrer, J.; Fasching, P.A.;

    2010-01-01

    Traditional prognostic factors for survival and treatment response of patients with breast cancer do not fully account for observed survival variation. We used available genotype data from a previously conducted two-stage, breast cancer susceptibility genome-wide association study (ie, Studies of...... Epidemiology and Risk factors in Cancer Heredity [SEARCH]) to investigate associations between variation in germline DNA and overall survival. We evaluated possible associations between overall survival after a breast cancer diagnosis and 10 621 germline single-nucleotide polymorphisms (SNPs) from up to 3761...... regression analysis, generating a per rare allele hazard ratio (HR). To validate putative associations, we used patient genotype information that had been obtained with 5' nuclease assay or mass spectrometry and overall survival information for up to 14 096 patients with invasive breast cancer (including...

  5. Association between urinary prostaglandin E2 metabolite and breast cancer risk: a prospective, case-cohort study of postmenopausal women

    OpenAIRE

    Kim, Sangmi; Taylor, Jack A.; Milne, Ginger L.; Sandler, Dale P.

    2013-01-01

    Overweight or obese women are at increased risk of developing and dying from breast cancer. Obesity-driven inflammation may stimulate prostaglandin E2 (PGE2)-mediated aromatase activation and estrogen biosynthesis in breast tissues. We hypothesized that increased production of PGE2 would contribute to elevated breast cancer risk in postmenopausal women. We carried out a case-cohort study with 307 incident breast cancer cases and 300 subcohort members from the Sister Study cohort. Hazard ratio...

  6. Simultaneous Expression of Cancer Stem Cell-Like Properties and Cancer-Associated Fibroblast-Like Properties in a Primary Culture of Breast Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Ishikawa, Mami; Inoue, Takahiro; Shirai, Takuma; Takamatsu, Kazuhiko; Kunihiro, Shiori; Ishii, Hirokazu [Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, Kobe 650-0047 (Japan); Nishikata, Takahito, E-mail: nisikata@konan-u.ac.jp [Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, Kobe 650-0047 (Japan); Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, Kobe 650-0047 (Japan)

    2014-07-31

    The importance of cancer-associated fibroblasts (CAFs) in cancer biology has been recently highlighted owing to their critical roles in cancer growth, progression, metastasis, and therapeutic resistance. We have previously established a primary culture of breast cancer cells, which showed epithelial-mesenchymal transition and cancer stem cell-like properties. In this study, we found that the primary culture also showed CAF-like properties. For example, hypoxia inducible factor 1α (HIF1A) and its downstream genes, nuclear factor-kappa B2 (NF-κB2) and BCL2/adenovirus E1B 19 kd-interacting protein 3 (BNIP3), and many enzymes involved in glycolysis, such as GAPDH, LDH, PGAM1, and PKM2, were highly overexpressed in the primary culture. Moreover, media conditioned with the primary culture cells enhanced the growth of breast cancer cells. Similar to previous CAF studies, this enhancement suggested to be occurred through fibroblast growth factor signaling. This MCKH primary culture cell, which showed simultaneous expression of tumorigenic and CAF properties, offers a unique experimental system for studying the biology of CAFs.

  7. Simultaneous Expression of Cancer Stem Cell-Like Properties and Cancer-Associated Fibroblast-Like Properties in a Primary Culture of Breast Cancer Cells

    International Nuclear Information System (INIS)

    The importance of cancer-associated fibroblasts (CAFs) in cancer biology has been recently highlighted owing to their critical roles in cancer growth, progression, metastasis, and therapeutic resistance. We have previously established a primary culture of breast cancer cells, which showed epithelial-mesenchymal transition and cancer stem cell-like properties. In this study, we found that the primary culture also showed CAF-like properties. For example, hypoxia inducible factor 1α (HIF1A) and its downstream genes, nuclear factor-kappa B2 (NF-κB2) and BCL2/adenovirus E1B 19 kd-interacting protein 3 (BNIP3), and many enzymes involved in glycolysis, such as GAPDH, LDH, PGAM1, and PKM2, were highly overexpressed in the primary culture. Moreover, media conditioned with the primary culture cells enhanced the growth of breast cancer cells. Similar to previous CAF studies, this enhancement suggested to be occurred through fibroblast growth factor signaling. This MCKH primary culture cell, which showed simultaneous expression of tumorigenic and CAF properties, offers a unique experimental system for studying the biology of CAFs

  8. Towards Evidence-Based Management of Inherited Breast and Breast-Ovarian Cancer

    OpenAIRE

    Møller Pål

    2004-01-01

    Abstract Inherited breast-ovarian cancer was described in 1866. The underlying genetic defects in BRCA1/2 were demonstrated 128 years later. We now have 10 years of experience with genetic testing in BRCA kindreds. The majority of breast cancer kindreds (familial breast cancer) do not demonstrate ovarian cancer and are not associated with BRCA mutations. The effect of early diagnosis and treatment is monitored through international collaborations. BRCA1-associated breast cancer is biologicall...

  9. THE MAMMOGRAPHIC CALCIFICATIONS IN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    Tang Ruiying; Liu Jingxian; Gaowen

    1998-01-01

    Objective: This study was performed to exam the relativeship between mammographic calcifications and breast cancer. Methods: All of the 184 patients with breast diseases underwent mammography before either an open biopsy or a mastectomy. The presence,morphology, and distribution of calcifications visualized on mammograms for breast cancer were compared with the controls who remained cancer free. Statistical comparisons were made by using the x2 test. Results:Of the 184 patients with breast diaeases, 93 malignant and 91 benign lesions were histologically confirmed.Calcifications were visualized on mammograms in 60(64%) of 93 breast cancers and 26 (28%) of 91 non breast cancers. The estimated odds ratio (OR) of breast cancer was 4.5 in women with calcifications seen on mammograms, compared with those having none (P<0.01). Of the 60 breast carcinomas having mammographic calcifications, 28 (47%) were infiltrating ductal carcinomas.There were only 8 (24%) cases with infiltrating ductal cancers in the group of without calcifications seen on the mammograms (P<0.05). Conclusion: Our finding suggests that mammographic calcification appears to be a risk factor for breast cancer. The granular and linear cast type calcification provide clues to the presence of breast cancer, especially when the carcinomas without associated masses were seen on mammograms.

  10. Epigenetic events associated with breast cancer and their prevention by dietary components targeting the epigenome

    Science.gov (United States)

    Aberrant epigenetic alterations in the genome such as DNA methylation and chromatin remodeling play a significant role in breast cancer development. Since epigenetic alterations are considered to be more easily reversible compared to genetic changes, epigenetic therapy is potentially very useful in ...

  11. The Association of Social Support and Education with Breast and Cervical Cancer Screening

    Science.gov (United States)

    Documet, Patricia; Bear, Todd M.; Flatt, Jason D.; Macia, Laura; Trauth, Jeanette; Ricci, Edmund M.

    2015-01-01

    Background: Disparities in breast and cervical cancer screening by socioeconomic status persist in the United States. It has been suggested that social support may facilitate screening, especially among women of low socioeconomic status. However, at present, it is unclear whether social support enables mammogram and Pap test compliance. Purpose:…

  12. Genome-wide association studies identify four ER negative-specific breast cancer risk loci

    DEFF Research Database (Denmark)

    Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara;

    2013-01-01

    Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including diff...

  13. Using hair to screen for breast cancer

    Science.gov (United States)

    James, Veronica; Kearsley, John; Irving, Tom; Amemiya, Yoshiyuki; Cookson, David

    1999-03-01

    We have studied hair using fibre X-ray diffraction studies with synchrotron radiation and find that hair from breast-cancer patients has a different intermolecular structure to hair from healthy subjects. These changes are seen in all samples of scalp and pubic hair taken from women diagnosed with breast cancer. All the hair samples from women who tested positive for a mutation of the BRCA1 gene, which is associated with a higher risk of breast cancer, also show these changes. Because our results are so consistent, we propose that such hair analyses may be used as a simple, non-invasive screening method for breast cancer.

  14. Diet and breast cancer

    Directory of Open Access Journals (Sweden)

    Isabelle Romieu

    2011-10-01

    Full Text Available Both diet and nutrition have been studied in relationship with breast cancer risk, as the great variation among different countries in breast cancer incidence could possibly be explained through the inflammatory and immune response, as well as antioxidant intake, among others.To date, no clear association with diet beyond overweight and weight gain has been found, except for alcohol consumption. Nonetheless, the small number of studies done in middle to low income countries where variability of food intake is wider,is beginning to show interesting results.Tanto la dieta como la nutrición han sido estudiadas en relación con el riesgo de cáncer de mama, dada la gran variación de incidencia de cáncer entre países, y la posibilidad de explicarla a través de la respuesta inflamatoria o inmune, así como ingesta de antioxidantes,entre otros.Hasta la fecha, ninguna asociación clara con la dieta ha sido encontrada, excepto para el consumo de alcohol, más allá del sobrepeso y del incremento de peso. Sin embargo, los estudios que se están realizando en países de mediano a bajo nivel de ingresos, con mayor variabilidad de ingesta de alimentos, comienzan a mostrar resultados interesantes.

  15. FGF receptor genes and breast cancer susceptibility

    DEFF Research Database (Denmark)

    Agarwal, D; Pineda, S; Michailidou, K;

    2014-01-01

    Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying......, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression.Results:Little evidence of association with breast cancer risk...... that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2....

  16. Breast cancer and the consumption of coffee.

    Science.gov (United States)

    Rosenberg, L; Miller, D R; Helmrich, S P; Kaufman, D W; Schottenfeld, D; Stolley, P D; Shapiro, S

    1985-09-01

    The hypothesis has been raised that coffee consumption may increase the incidence of breast cancer, based on the report that fibrocystic breast disease, a risk factor for breast cancer, regresses after abstention from coffee and other methylxanthines. The relation between recent coffee consumption and the risk of breast cancer was evaluated in a case-control study, based on interviews conducted 1975-1982 at several mainly eastern US teaching and community hospitals. The responses of 2,651 women with newly diagnosed breast cancer were compared with those of 1,501 controls with nonmalignant conditions and 385 controls with cancers at other sites. The relative risk estimates for levels of coffee drinking up to seven or more cups daily, relative to none, approximated 1.0 with narrow 95% confidence intervals. After allowance for confounding, the relative risk estimate for drinking at least five cups a day was 1.2 (95% confidence interval, 0.9-1.6) using the noncancer controls and 1.1 (0.7-1.6) using the cancer controls. Coffee consumption was not associated with an increase in the risk of breast cancer among women with a history of fibrocystic breast disease, nor were tea or decaffeinated coffee associated with an increase in the risk of breast cancer. The results suggest that the recent consumption of coffee does not influence the incidence of breast cancer. PMID:4025289

  17. MIR-9-1 ABERRANT METHYLATION IS A FREQUENT EVENT IN BREAST CANCER AND IS ASSOCIATED WITH BONE METASTASES

    Directory of Open Access Journals (Sweden)

    Anca Florescu

    2012-03-01

    Full Text Available Abstract:Background. Aberrant promoter methylation of classical tumor suppressor genes occurs frequently during carcinogenesis. Several lines of evidences suggest that this epigenetic change also regulates microRNAs expression and may represent a potential molecular marker for cancer.Methods. We examined the methylation status at the hsa-miR-9-1 gene promoter in a series of 66 breast cancer cases by methylation sensitive PCR (MSP analysis. For 43 of the 66 patients paired normal breast tissue and/or pre invasive (ADH, DCIS lesions were also available. As control methylation status was determined on 6 normal breast tissues obtained from reductive mammoplasty.  Results. Methylation at mir-9-1 gene was detected in 32 out of 66 breast tumours (49% and in none of the 6 normal breast tissues derived from reductive mammoplasty (P=0.02 χ2- Test. In all cases the same methylation status was demonstrated in tumour specimen, paired normal breast tissues and/or pre-invasive (ADH and DCIS lesions. An higher frequency of methylation was found in patients showing metastases at diagnosis as compared with non metastatic patients (P=0.03 χ2-Test. Moreover, methylation at mir-9-1 gene was more frequent in patients showing bone metastases as first metastatic sites (P=0.04 χ2-Test, and in the subgroup of patients developing only bone metastases as compared with patients developing metastases  to visceral organs (P=0.03 χ2-Test.Conclusions. This study give further evidence of epigenetic mechanisms as regulators of miR-9 expression in breast cancer. Moreover, our results suggest an association between hypermethylation  at the miR-9-1 gene and metastatic site.

  18. Association of adiposity, dysmetabolisms, and inflammation with aggressive breast cancer subtypes: a cross-sectional study.

    Science.gov (United States)

    Agresti, Roberto; Meneghini, Elisabetta; Baili, Paolo; Minicozzi, Pamela; Turco, Alberto; Cavallo, Ilaria; Funaro, Francesco; Amash, Hade; Berrino, Franco; Tagliabue, Elda; Sant, Milena

    2016-05-01

    Obesity and metabolic syndrome are risk and prognostic factors for breast cancer (BC) and are associated with chronic inflammation. We investigated the association between distinct BC subtypes and markers of adiposity, dysmetabolisms, and inflammation. We analyzed 1779 patients with primary invasive BC treated at a single institution, for whom anthropometric and clinical-pathological data were archived. BC subtypes were classified by immunohistochemical staining of ER, PR, HER2, and Ki67, and their relations with the study markers were assessed by multinomial logistic regression. Adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated taking luminal A as reference. All subtypes more aggressive than luminal A were significantly more frequent in younger (<45 years) than older women. Before menopause, luminal B HER2-negative tumors were positively associated with large waist (OR 2.55, 95 % CI 1.53-4.24) and insulin resistance (OR 1.90, 95 % CI 1.05-3.41); luminal B HER2-positive tumors with large waist (OR 2.11, 95 % CI 1.03-4.35) and triple-negative tumors with overweight (OR 3.04, 95 % CI 1.43-6.43) and high C-reactive protein (p trend = 0.026). In postmenopausal women aged <65, luminal B HER2-negative (OR 1.94, 95 % CI 1.16-3.24) and luminal B HER2-positive tumors (OR 2.48, 95 % CI 1.16-5.27) were positively related with metabolic syndrome. Dysmetabolisms and inflammation may be related to different BC subtypes. Before menopause, triple-negative cancers were related to obesity and chronic inflammation, and aggressive luminal subtypes to abdominal adiposity. After menopause, in women aged <65 these latter subtypes were related to metabolic syndrome. Control of adiposity and dysmetabolism can reduce the risk of aggressive BC subtypes, improving the prognosis. PMID:27117160

  19. Dataset for the proteomic inventory and quantitative analysis of the breast cancer hypoxic secretome associated with osteotropism

    Directory of Open Access Journals (Sweden)

    Thomas R. Cox

    2015-12-01

    Full Text Available The cancer secretome includes all of the macromolecules secreted by cells into their microenvironment. Cancer cell secretomes are significantly different to that of normal cells reflecting the changes that normal cells have undergone during their transition to malignancy. More importantly, cancer secretomes are known to be active mediators of both local and distant host cells and play an important role in the progression and dissemination of cancer. Here we have quantitatively profiled both the composition of breast cancer secretomes associated with osteotropism, and their modulation under normoxic and hypoxic conditions. We detect and quantify 162 secretome proteins across all conditions which show differential hypoxic induction and association with osteotropism. Mass Spectrometry proteomics data have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD000397 and the complete proteomic, bioinformatic and biological analyses are reported in Cox et al. (2015 [1].

  20. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer

    Science.gov (United States)

    Michailidou, Kyriaki; Beesley, Jonathan; Lindstrom, Sara; Canisius, Sander; Dennis, Joe; Lush, Michael; Maranian, Mel J; Bolla, Manjeet K; Wang, Qin; Shah, Mitul; Perkins, Barbara J; Czene, Kamila; Eriksson, Mikael; Darabi, Hatef; Brand, Judith S; Bojesen, Stig E; Nordestgaard, Børge G; Flyger, Henrik; Nielsen, Sune F; Rahman, Nazneen; Turnbull, Clare; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; dos-Santos-Silva, Isabel; Chang-Claude, Jenny; Flesch-Janys, Dieter; Rudolph, Anja; Eilber, Ursula; Behrens, Sabine; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Khan, Sofia; Aaltonen, Kirsimari; Ahsan, Habibul; Kibriya, Muhammad G; Whittemore, Alice S; John, Esther M; Malone, Kathleen E; Gammon, Marilie D; Santella, Regina M; Ursin, Giske; Makalic, Enes; Schmidt, Daniel F; Casey, Graham; Hunter, David J; Gapstur, Susan M; Gaudet, Mia M; Diver, W Ryan; Haiman, Christopher A; Schumacher, Fredrick; Henderson, Brian E; Le Marchand, Loic; Berg, Christine D; Chanock, Stephen; Figueroa, Jonine; Hoover, Robert N; Lambrechts, Diether; Neven, Patrick; Wildiers, Hans; van Limbergen, Erik; Schmidt, Marjanka K; Broeks, Annegien; Verhoef, Senno; Cornelissen, Sten; Couch, Fergus J; Olson, Janet E; Hallberg, Emily; Vachon, Celine; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel A; van der Luijt, Rob B; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K; Yoo, Keun-Young; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Guénel, Pascal; Truong, Thérèse; Mulot, Claire; Sanchez, Marie; Burwinkel, Barbara; Marme, Frederik; Surowy, Harald; Sohn, Christof; Wu, Anna H; Tseng, Chiu-chen; Van Den Berg, David; Stram, Daniel O; González-Neira, Anna; Benitez, Javier; Zamora, M Pilar; Perez, Jose Ignacio Arias; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cox, Angela; Cross, Simon S; Reed, Malcolm WR; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Lindblom, Annika; Margolin, Sara; Teo, Soo Hwang; Yip, Cheng Har; Taib, Nur Aishah Mohd; TAN, Gie-Hooi; Hooning, Maartje J; Hollestelle, Antoinette; Martens, John WM; Collée, J Margriet; Blot, William; Signorello, Lisa B; Cai, Qiuyin; Hopper, John L; Southey, Melissa C; Tsimiklis, Helen; Apicella, Carmel; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Hou, Ming-Feng; Kristensen, Vessela N; Nord, Silje; Alnaes, Grethe I Grenaker; Giles, Graham G; Milne, Roger L; McLean, Catriona; Canzian, Federico; Trichopoulos, Dmitrios; Peeters, Petra; Lund, Eiliv; Sund, Malin; Khaw, Kay-Tee; Gunter, Marc J; Palli, Domenico; Mortensen, Lotte Maxild; Dossus, Laure; Huerta, Jose-Maria; Meindl, Alfons; Schmutzler, Rita K; Sutter, Christian; Yang, Rongxi; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Hartman, Mikael; Miao, Hui; Chia, Kee Seng; Chan, Ching Wan; Fasching, Peter A; Hein, Alexander; Beckmann, Matthias W; Haeberle, Lothar; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J; Swerdlow, Anthony J; Brinton, Louise; Garcia-Closas, Montserrat; Zheng, Wei; Halverson, Sandra L; Shrubsole, Martha; Long, Jirong; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Brauch, Hiltrud; Hamann, Ute; Brüning, Thomas; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bernard, Loris; Bogdanova, Natalia V; Dörk, Thilo; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Devilee, Peter; Tollenaar, Robert AEM; Seynaeve, Caroline; Van Asperen, Christi J; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Huzarski, Tomasz; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Slager, Susan; Toland, Amanda E; Ambrosone, Christine B; Yannoukakos, Drakoulis; Kabisch, Maria; Torres, Diana; Neuhausen, Susan L; Anton-Culver, Hoda; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Healey, Catherine S; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Pita, Guillermo; Alonso, M Rosario; Álvarez, Nuria; Herrero, Daniel; Simard, Jacques; Pharoah, Paul PDP; Kraft, Peter; Dunning, Alison M; Chenevix-Trench, Georgia; Hall, Per; Easton, Douglas F

    2015-01-01

    Genome wide association studies (GWAS) and large scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ~14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS comprising of 15,748 breast cancer cases and 18,084 controls, and 46,785 cases and 42,892 controls from 41 studies genotyped on a 200K custom array (iCOGS). Analyses were restricted to women of European ancestry. Genotypes for more than 11M SNPs were generated by imputation using the 1000 Genomes Project reference panel. We identified 15 novel loci associated with breast cancer at P<5×10−8. Combining association analysis with ChIP-Seq data in mammary cell lines and ChIA-PET chromatin interaction data in ENCODE, we identified likely target genes in two regions: SETBP1 on 18q12.3 and RNF115 and PDZK1 on 1q21.1. One association appears to be driven by an amino-acid substitution in EXO1. PMID:25751625

  1. KRAS rs61764370 is associated with HER2-overexpressed and poorly-differentiated breast cancer in hormone replacement therapy users: a case control study

    International Nuclear Information System (INIS)

    A single nucleotide polymorphism located in the 3'-untranslated region of the KRAS oncogene (KRAS variant; rs61764370) disrupts a let-7 miRNA binding and was recently reported to act as a genetic marker for increased risk of developing human cancers. We aimed to investigate an association of the KRAS variant with sporadic and familial breast cancer and breast tumor characteristics. Genotyping was accomplished in 530 sporadic postmenopausal breast cancer cases, 165 familial breast cancer cases (including N = 29, who test positive for BRCA1/2 mutations) and 270 postmenopausal control women using the flurogenic 5' nuclease assay. Information on hormone replacement therapy (HRT) use and tumor characteristics in sporadic breast cancer cases was ascertained from a postal questionnaire and pathology reports, respectively. Associations between the KRAS genotype and breast cancer or breast tumor characteristics were assessed using chi-square test and logistic regression models. No evidence of association was observed between the KRAS variant and risk of sporadic and familial breast cancer - either among BRCA carriers or non-BRCA carriers. The KRAS variant was statistically significantly more often associated with human epidermal growth factor receptor 2 (HER2) - positive tumors and tumors of higher histopathologic grade. However, both associations were detected only in HRT users. Our data do not support the hypothesis that the KRAS variant rs61764370 is implicated in the aetiology of sporadic or of familial breast cancer. In postmenopausal women using HRT, the KRAS variant might lead to HER2 overexpressed and poorly-differentiated breast tumors, both indicators of a worse prognosis

  2. HPV-Associated Cancers Statistics

    Science.gov (United States)

    ... What CDC Is Doing Related Links Stay Informed Statistics for Other Kinds of Cancer Breast Cervical Colorectal ( ... Vaginal and Vulvar Cancer Home HPV-Associated Cancer Statistics Language: English Español (Spanish) Recommend on Facebook Tweet ...

  3. Quantitative detection of metastasis-associated1mRNA and protein expression in breast cancer%Quantitative detection of metastasis-associated 1 mRNA and protein expression in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Hiroko Yamashita; Tatsuya Toyama; Hiroshi Sugiura; Mei ZHANG; Shunzo Kobayashi; Yoshitaka Fujii; Hirotaka Iwase; Zhenhuan ZHANG

    2013-01-01

    Objective Understanding the mechanism of breast cancer metastasis will benefit those patients in need of aggressive treatment and avoid side effects caused by chemotherapy over treatment.Recently,a potential metastasis-associated gene and its product,the metastasis-associated 1 (MTA1),were identified; this gene has been found to be overexpressed in a variety of cancers.Methods In the present study,therefore,the level of expression of MTA1 mRNA has been assessed by LightCycler quantitative real-time RT-PCR in 160 cases of invasive carcinoma of the breast.MTA1 protein expression level was also detected by immunohistochemistry from available paired tissues of 154 cases.Associations between MTA1 mRNA and protein expression and clinicopathological factors were analyzed.Results It was found that MTA1 mRNA was expressed at significantly higher levels in patients with negative lymph node status,with ER and PgR positive and HER2 negative tumor.No difference was found between patient age,tumor size and histological grade groups.Patients with high levels of expression of MTA1 mRNA had a better prognosis than those with low expression.However,no difference was found between the protein level and clinicopathological factors.Univariate and multivariate prognostic analysis did not demonstrate that MTA1 mRNA was an independent prognostic factor for breast cancer.Conclusion In breast cancer,inconsistent with other tumor types,MTA1 gene expression is correlated with non-invasive clinicopathological factors and longer survival,which might suggest MTA1 gene is a tumor type specific metastasis associated gene.

  4. Manganese superoxide dismutase and breast cancer recurrence

    DEFF Research Database (Denmark)

    Cronin-Fenton, Deirdre; Christensen, Mariann; Lash, Timothy;

    2014-01-01

    BACKGROUND: Manganese superoxide dismutase (MnSOD) inhibits oxidative damage and cancer therapy effectiveness. A polymorphism in its encoding gene (SOD2: Val16Ala rs4880) may confer poorer breast cancer survival, but data are inconsistent. We examined the association of SOD2 genotype and breast......-metastatic breast cancer from 1990-2001, received adjuvant Cyclo, and were registered in the Danish Breast Cancer Cooperative Group. We identified 118 patients with BCR and 213 matched breast cancer controls. We genotyped SOD2 and used conditional logistic regression to compute the odds ratio (OR) and associated 95...... cancer recurrence (BCR) among patients treated with cyclophosphamide-based chemotherapy (Cyclo). We compared our findings with published studies using meta-analyses. METHODS: We conducted a population-based case-control study of BCR among women in Jutland, Denmark. Subjects were diagnosed with non...

  5. Factors associated with cancer-related fatigue in breast cancer patients undergoing endocrine therapy in an urban setting: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Huang Xu

    2010-08-01

    Full Text Available Abstract Background Fatigue is prevalent in breast cancer survivors and has profound effects on daily life. The interference of fatigue with endocrine therapy may be difficult to separate. This study investigates the prevalence and severity of fatigue and identifies the demographic, clinical, and lifestyle factors associated with cancer-related fatigue (CRF in breast cancer patients undergoing endocrine therapy in an urban area. Methods Women with stage I-IIIA breast cancer were recruited and asked to participate (n = 371 in the study. The 315 women who responded to the questionnaire (84.9%, 54 (17.1% had completed endocrine therapy and 261 (82.9% were still undergoing endocrine therapy. The patients had been diagnosed at an average of 31 months prior to recruitment (range, 7 to 60 months; the average age was 48 (range, 33 to 72 years. The 11-point scale and Visual Analog Scale (VAS were employed to quantify the level of fatigue experienced by the patients. Logistic regression analyses and a trend test method were performed to evaluate factors associated with CRF. Results Among the 315 patients, 189 (60% had experienced or were experiencing CRF during endocrine therapy. Logistic regression analysis was performed to identify factors associated with CRF, including BMI (body mass index, clinical stage, menopausal status, duration of endocrine therapy, physical activity, and diet. Factors unrelated to CRF were age, marital status, treatment, endocrine therapy drugs, alcohol intake, and smoking. The trend test method revealed an association between physical activity and dietary level and the intensity of CRF. Conclusions The present findings suggest that fatigue is an important problem in the majority of breast cancer patients during endocrine therapy. We found that BMI, clinical stage, menopausal status, duration of endocrine therapy, physical activity, and diet are associated with fatigue. Future research should focus on the impact factors of CRF

  6. The p53 codon 72 polymorphism is associated with risk and early onset of breast cancer among Saudi women

    OpenAIRE

    Al-Qasem, Abeer; Toulimat, Mohamed; Tulbah, Asma; Elkum, Naser; Al-Tweigeri, Taher; Aboussekhra, Abdelilah

    2012-01-01

    Breast cancer has a major impact on the health of women worldwide. In the Kingdom of Saudi Arabia (KSA), breast cancer incidence is on the increase and is characterized by early onset and aggressiveness. Owing to the importance of the TP53 gene in breast carcinogenesis, we analyzed the possible link between TP53 single nucleotide polymorphisms (SNPs) and the risk of breast cancer in Saudi women by direct sequencing of the TP53 gene exon 4 from 100 breast cancer tissues. The proportion of the ...

  7. P53 and P-glycoprotein are often coexpressed and are associated with poor prognosis in breast cancer

    OpenAIRE

    Linn, S. C.; Honkoop, A.H.; Hoekman, K.; De Valk; Pinedo, H. M.; Giaccone, G.

    1996-01-01

    Expression of both P-glycoprotein (P-gp) and mutant p53 have recently been reported to be associated with poor prognosis of breast cancer. The expression of P-gp is associated in vitro and in vivo with cross-resistance to several anti-cancer drugs. p53 plays a regulatory role in apoptosis, and mutant p53 has been suggested to be involved in drug resistance. Interestingly, in vitro experiments have shown that mutant p53 can activate the promoter of the MDR1 gene, which encodes P-gp. We investi...

  8. Breast cancer statistics and markers

    OpenAIRE

    Mallika Siva Donepudi; Kasturi Kondapalli; Seelam Jeevan Amos; Pavithra Venkanteshan

    2014-01-01

    Breast cancer is one of the familiar diseases in women. Incidence and mortality due to cancer, particularly breast cancer has been increasing for last 50 years, even though there is a lacuna in the diagnosis of breast cancer at early stages. According to World Health Organization (WHO) 2012 reports, breast cancer is the leading cause of death in women, accounting 23% of all cancer deaths. In Asia, one in every three women faces the risk of breast cancer in their lifetime as per reports of WHO...

  9. BDNF is associated with SFRP1 expression in luminal and basal-like breast cancer cell lines and primary breast cancer tissues: a novel role in tumor suppression?

    Directory of Open Access Journals (Sweden)

    Laura Huth

    Full Text Available Secreted frizzled related protein 1 (SFRP1 functions as an important inhibitor of the Wnt pathway and is a known tumor suppressor gene, which is epigenetically silenced in a variety of tumors e.g. in breast cancer. However, it is still unclear how SFRP1 exactly affects the Wnt pathway. Our aim was to decipher SFRP1 involvement in biochemical signaling in dependency of different breast cancer subtypes and to identify novel SFRP1-regulated genes. We generated SFRP1 over-expressing in vitro breast cancer models, reflecting the two major subtypes by using basal-like BT20 and luminal-like HER2-positive SKBR3 cells. DNA microarray expression profiling of these models revealed that SFRP1 expression potentially modulates Bone morphogenetic protein- and Smoothened signaling (p<0.01, in addition to the known impact on Wnt signaling. Importantly, further statistical analysis revealed that in dependency of the cancer subtype model SFRP1 may affect the canonical and non-canonical Wnt pathway (p<0.01, respectively. While SFRP1 re-expression generally mediated distinct patterns of transcriptionally induced or repressed genes in BT20 and SKBR3 cells, brain derived neurotrophic factor (BDNF was identified as a SFRP1 induced gene in both cell lines. Although BDNF has been postulated as a putative oncogene, the co-regulation with SFRP1 indicates a potential suppressive function in breast cancer. Indeed, a positive correlation between SFRP1 and BDNF protein expression could be shown (p<0.001 in primary breast cancer samples. Moreover, TCGA dataset based analysis clearly underscores that BDNF mRNA is down-regulated in primary breast cancer samples predicting a poor prognosis of these patients. In line, we functionally provide evidence that stable BDNF re-expression in basal-like BT20 breast cancer cells blocks tumor cell proliferation. Hence, our results suggest that BDNF might rather mediate suppressive than promoting function in human breast cancer whose mode of

  10. Haplotype-Based Analysis of Genes Associated With Risk of Adverse Skin Reactions After Radiotherapy in Breast Cancer Patients

    International Nuclear Information System (INIS)

    Purpose: To identify haplotypes of single nucleotide polymorphism markers associated with the risk of early adverse skin reactions (EASRs) after radiotherapy in breast cancer patients. Methods and Materials: DNA was sampled from 399 Japanese breast cancer patients who qualified for breast-conserving radiotherapy. Using the National Cancer Institute-Common Toxicity Criteria scoring system, version 2, the patients were grouped according to EASRs, defined as those occurring within 3 months of starting radiotherapy (Grade 1 or less, n = 290; Grade 2 or greater, n = 109). A total of 999 single nucleotide polymorphisms from 137 candidate genes for radiation susceptibility were genotyped, and the haplotype associations between groups were assessed. Results: The global haplotype association analysis (p < 0.05 and false discovery rate < 0.05) indicated that estimated haplotypes in six loci were associated with EASR risk. A comparison of the risk haplotype with the most frequent haplotype in each locus showed haplotype GGTT in CD44 (odds ratio [OR] = 2.17; 95% confidence interval [CI], 1.07-4.43) resulted in a significantly greater EASR risk. Five haplotypes, CG in MAD2L2 (OR = 0.55; 95% CI, 0.35-0.87), GTTG in PTTG1 (OR = 0.48; 95% CI, 0.24-0.96), TCC (OR = 0.48; 95% CI, 0.26-0.89) and CCG (OR = 0.50; 95% CI, 0.27-0.92) in RAD9A, and GCT in LIG3 (OR = 0.46; 95% CI, 0.22-0.93) were associated with a reduced EASR risk. No significant risk haplotype was observed in REV3L. Conclusion: Individual radiosensitivity can be partly determined by these haplotypes in multiple loci. Our findings may lead to a better understanding of the mechanisms underlying the genetic variation in radiation sensitivity and resistance among breast cancer patients

  11. Stereotactic Image-Guided Navigation During Breast Reconstruction in Patients With Breast Cancer

    Science.gov (United States)

    2015-08-27

    Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

  12. Peritumoral vascular invasion and NHERF1 expression define an immunophenotype of grade 2 invasive breast cancer associated with poor prognosis

    International Nuclear Information System (INIS)

    Traditional determinants proven to be of prognostic importance in breast cancer include the TNM staging, histological grade, proliferative activity, hormone receptor status and HER2 overexpression. One of the limitations of the histological grading scheme is that a high percentage of breast cancers are still classified as grade 2, a category with ambiguous clinical significance. The aim of this study was to best characterize tumors scored as grade 2. We investigated traditional prognostic factors and a panel of tumor markers not used in routine diagnosis, such as NHERF1, VEGFR1, HIF-1α and TWIST1, in 187 primary invasive breast cancers by immunohistochemistry, stratifying patients into good and poor prognostic groups by the Nottingham Prognostic Index. Grade 2 subgroup analysis showed that the PVI (p = 0.023) and the loss of membranous NHERF1 (p = 0.028) were adverse prognostic factors. Relevantly, 72% of grade 2 tumors were associated to PVI+/membranous NHERF1- expression phenotype, characterizing an adverse prognosis (p = 0.000). Multivariate logistic regression analysis in the whole series revealed poor prognosis correlated with PVI and MIB1 (p = 0.000 and p = 0.001, respectively). Furthermore, in the whole series of breast cancers we found cytoplasmic NHERF1 expression positively correlated to VEGFR1 (r = 0.382, p = 0.000), and in VEGFR1-overexpressing tumors the oncogenic receptor co-localized with NHERF1 at cytoplasmic level. The PVI+/membranous NHERF1- expression phenotype identifies a category of grade 2 tumors with the worst prognosis, including patient subgroup with a family history of breast cancer. These observations support the idea of the PVI+/membranous NHERF1- expression immunophenotype as a useful marker, which could improve the accuracy of predicting clinical outcome in grade 2 tumors

  13. Peritumoral vascular invasion and NHERF1 expression define an immunophenotype of grade 2 invasive breast cancer associated with poor prognosis

    Directory of Open Access Journals (Sweden)

    Malfettone Andrea

    2012-03-01

    Full Text Available Abstract Background Traditional determinants proven to be of prognostic importance in breast cancer include the TNM staging, histological grade, proliferative activity, hormone receptor status and HER2 overexpression. One of the limitations of the histological grading scheme is that a high percentage of breast cancers are still classified as grade 2, a category with ambiguous clinical significance. The aim of this study was to best characterize tumors scored as grade 2. Methods We investigated traditional prognostic factors and a panel of tumor markers not used in routine diagnosis, such as NHERF1, VEGFR1, HIF-1α and TWIST1, in 187 primary invasive breast cancers by immunohistochemistry, stratifying patients into good and poor prognostic groups by the Nottingham Prognostic Index. Results Grade 2 subgroup analysis showed that the PVI (p = 0.023 and the loss of membranous NHERF1 (p = 0.028 were adverse prognostic factors. Relevantly, 72% of grade 2 tumors were associated to PVI+/membranous NHERF1- expression phenotype, characterizing an adverse prognosis (p = 0.000. Multivariate logistic regression analysis in the whole series revealed poor prognosis correlated with PVI and MIB1 (p = 0.000 and p = 0.001, respectively. Furthermore, in the whole series of breast cancers we found cytoplasmic NHERF1 expression positively correlated to VEGFR1 (r = 0.382, p = 0.000, and in VEGFR1-overexpressing tumors the oncogenic receptor co-localized with NHERF1 at cytoplasmic level. Conclusions The PVI+/membranous NHERF1- expression phenotype identifies a category of grade 2 tumors with the worst prognosis, including patient subgroup with a family history of breast cancer. These observations support the idea of the PVI+/membranous NHERF1- expression immunophenotype as a useful marker, which could improve the accuracy of predicting clinical outcome in grade 2 tumors.

  14. Associations of CYP1A1 gene polymorphisms and risk of breast cancer in Indian women: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Eloisa Singian

    2015-10-01

    Full Text Available Reported associations of CYP1A1 polymorphisms with breast cancer have been inconsistent. In this meta-analysis examining breast cancer associations of three CYP1A1 polymorphisms (M1, M2 and M4 among Indian women may yield information that may be of clinical and epidemiological use for this particular demography. We searched MEDLINE using PubMed and Embase for association studies. From seven published case-control studies, we estimated overall associations and applied subgroup analysis to explore differential effects. All three polymorphisms exhibited overall increased risk, significant in M1 (OR 1.61-1.65, p = 0.04 and M4 (OR 2.02-3.92, p = 0.02-0.04. Differential effects were observed only in the M1 polymorphism where M1 effects were significant in South Indians (OR 2.20-4.34, p < 0.0001 but not the North population, who were at reduced risk (OR 0.64-0.77, p = 0.03-0.55. These populations were not materially different in regard to M2 and M4 as did the women stratified by menopausal status. In this meta-analysis, M1 and M4 effects may render Indian women susceptible, but may be limited by heterogeneity of the studies. Differential effects of the M1 polymorphism in breast cancer render South Indians susceptible compared to those in the North.

  15. Association between bilateral asymmetry of kinetic features computed from the DCE-MRI images and breast cancer

    Science.gov (United States)

    Yang, Qian; Li, Lihua; Zhang, Juan; Zhang, Chengjie; Zheng, Bin

    2013-03-01

    Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of breast yields high sensitivity but relatively lower specificity. To improve diagnostic accuracy of DCE-MRI, we investigated the association between bilateral asymmetry of kinetic features computed from the left and right breasts and breast cancer detection with the hypothesis that due to the growth of angiogenesis associated with malignant lesions, the average dynamic contrast enhancement computed from the breasts depicting malignant lesions should be higher than negative or benign breasts. To test this hypothesis, we assembled a database involving 130 DCE-MRI examinations including 81 malignant and 49 benign cases. We developed a computerized scheme that automatically segments breast areas depicted on MR images and computes kinetic features related to the bilateral asymmetry of contrast enhancement ratio between two breasts. An artificial neural network (ANN) was then used to classify between malignant and benign cases. To identify the optimal approach to compute the bilateral kinetic feature asymmetry, we tested 4 different thresholds to select the enhanced pixels (voxels) from DCE-MRI images and compute the kinetic features. Using the optimal threshold, the ANN had a classification performance measured by the area under the ROC curve of AUC=0.79+/-0.04. The positive and negative predictive values were 0.75 and 0.67, respectively. The study suggested that the bilateral asymmetry of kinetic features or contrast enhancement of breast background tissue could provide valuable supplementary information to distinguish between the malignant and benign cases, which can be fused into existing computer-aided detection schemes to improve classification performance.

  16. Breast cancer chemoprevention

    Directory of Open Access Journals (Sweden)

    Ivana Sestak

    2011-12-01

    Full Text Available Trials with tamoxifen have clearly shown that the risk of developing oestrogen receptor positive breast cancer can be reduced by at least 50% with prophylactic agents. The current challenge is to find new agents which achieve this or better efficacy, but with fewer side effects. Recent results indicate that the SERM raloxifene has similar efficacy to tamoxifen, but leads to fewer endometrial cancers, gynecological symptoms, and thromboembolic events. Results for contralateral tumors in adjuvant trials suggest that aromatase inhibitors may be able to prevent up to 70%–80% of ER-positive breast cancers, and this is currently being investigated in two large prevention trials, one using anastrozole (IBIS-II and the other exemestane (MAP.3. New agents are needed for receptor negative breast cancer and several possibilities are currently under investigation.

  17. Mitochondria and Familial Predisposition to Breast Cancer

    OpenAIRE

    Weigl, Stefania; Paradiso, Angelo; Tommasi, Stefania

    2013-01-01

    Mitochondrial genome and functional alterations are related to various diseases including cancer. In all cases, the role of these organelles is associated with defects in oxidative energy metabolism and control of tumor-induced oxidative stress. The present study examines the involvement of mitochondrial DNA in cancer and in particular in breast cancer. Furthermore, since mitochondrial DNA is maternally inherited, hereditary breast cancer has been focused on.

  18. Life After Breast Cancer Treatment

    Science.gov (United States)

    FACTS FOR LIFE Life After Breast Cancer Treatment Once breast cancer treatment ends, you may face a new set of issues and concerns. ... fear. If fear starts to disrupt your daily life, talk to your doctor. Getting the support and ...

  19. Vitamin D and Breast Cancer

    OpenAIRE

    Shao, Theresa; Klein, Paula; Grossbard, Michael L.

    2012-01-01

    Vitamin D metabolism and its mechanism of action, the current evidence on the relationship between vitamin D and breast cancer, and the optimal dosing of vitamin D for breast cancer prevention are summarized.

  20. Preventing Breast Cancer: Making Progress

    Science.gov (United States)

    ... Navigation Bar Home Current Issue Past Issues Preventing Breast Cancer: Making Progress Past Issues / Fall 2006 Table of ... 000 women will have been diagnosed with invasive breast cancer, and nearly 41,000 women will die from ...

  1. Association between adjuvant regional radiotherapy and cognitive function in breast cancer patients treated with conservation therapy

    International Nuclear Information System (INIS)

    Although protracted cognitive impairment has been reported to occur after radiotherapy even when such therapy is not directed to brain areas, the mechanism remains unclear. This study investigated whether breast cancer patients exposed to local radiotherapy showed lower cognitive function mediated by higher plasma interleukin (IL)-6 levels than those unexposed. We performed the Wechsler Memory Scale-Revised (WMS-R) and measured plasma IL-6 levels for 105 breast cancer surgical patients within 1 year after the initial therapy. The group differences in each of the indices of WMS-R were investigated between cancer patients exposed to adjuvant regional radiotherapy (n = 51) and those unexposed (n = 54) using analysis of covariance. We further investigated a mediation effect by plasma IL-6 levels on the relationship between radiotherapy and the indices of WMS-R using the bootstrapping method. The radiotherapy group showed significantly lower Immediate Verbal Memory Index and Delayed Recall Index (P = 0.001, P = 0.008, respectively). Radiotherapy exerted an indirect effect on the lower Delayed Recall Index of WMS-R through elevation of plasma IL-6 levels (bootstrap 95% confidence interval = −2.6626 to −0.0402). This study showed that breast cancer patients exposed to adjuvant regional radiotherapy in conservation therapy might have cognitive impairment even several months after their treatment. The relationship between the therapy and the cognitive impairment could be partially mediated by elevation of plasma IL-6 levels

  2. Comparison of radiation exposure and associated radiation-induced cancer risks from mammography and molecular imaging of the breast

    International Nuclear Information System (INIS)

    Purpose: Recent studies have raised concerns about exposure to low-dose ionizing radiation from medical imaging procedures. Little has been published regarding the relative exposure and risks associated with breast imaging techniques such as breast specific gamma imaging (BSGI), molecular breast imaging (MBI), or positron emission mammography (PEM). The purpose of this article was to estimate and compare the risks of radiation-induced cancer from mammography and techniques such as PEM, BSGI, and MBI in a screening environment. Methods: The authors used a common scheme for all estimates of cancer incidence and mortality based on the excess absolute risk model from the BEIR VII report. The lifetime attributable risk model was used to estimate the lifetime risk of radiation-induced breast cancer incidence and mortality. All estimates of cancer incidence and mortality were based on a population of 100 000 females followed from birth to age 80 and adjusted for the fraction that survives to various ages between 0 and 80. Assuming annual screening from ages 40 to 80 and from ages 50 to 80, the cumulative cancer incidence and mortality attributed to digital mammography, screen-film mammography, MBI, BSGI, and PEM was calculated. The corresponding cancer incidence and mortality from natural background radiation was calculated as a useful reference. Assuming a 15%-32% reduction in mortality from screening, the benefit/risk ratio for the different imaging modalities was evaluated. Results: Using conventional doses of 925 MBq Tc-99m sestamibi for MBI and BSGI and 370 MBq F-18 FDG for PEM, the cumulative cancer incidence and mortality were found to be 15-30 times higher than digital mammography. The benefit/risk ratio for annual digital mammography was >50:1 for both the 40-80 and 50-80 screening groups, but dropped to 3:1 for the 40-49 age group. If the primary use of MBI, BSGI, and PEM is in women with dense breast tissue, then the administered doses need to be in the range

  3. Low p53 Binding Protein 1 (53BP1) Expression Is Associated With Increased Local Recurrence in Breast Cancer Patients Treated With Breast-Conserving Surgery and Radiotherapy

    International Nuclear Information System (INIS)

    Purpose: To investigate whether the expression of p53 binding protein 1 (53BP1) has prognostic significance in a cohort of early-stage breast cancer patients treated with breast-conserving surgery and radiotherapy (BCS+RT). Methods and Materials: A tissue microarray of early-stage breast cancer treated with BCS+RT from a cohort of 514 women was assayed for 53BP1, estrogen receptor, progesterone receptor, and HER2 expression by immunohistochemistry. Through log–rank tests and univariate and multivariate models, the staining profile of each tumor was correlated with clinical endpoints, including ipsilateral breast recurrence–free survival (IBRFS), distant metastasis–free survival (DMFS), cause-specific survival (CSS), recurrence-free survival (RFS), and overall survival (OS). Results: Of the 477 (93%) evaluable tumors, 63 (13%) were scored as low. Low expression of 53BP1 was associated with worse outcomes for all endpoints studied, including 10-year IBRFS (76.8% vs. 90.5%; P=.01), OS (66.4% vs. 81.7%; P=.02), CSS (66.0% vs. 87.4%; P<.01), DMFS (55.9% vs. 87.0%; P<.01), and RFS (45.2% vs. 80.6%; P<.01). Multivariate analysis incorporating various clinico-pathologic markers and 53BP1 expression found that 53BP1 expression was again an independent predictor of all endpoints (IBRFS: P=.0254; OS: P=.0094; CSS: P=.0033; DMFS: P=.0006; RFS: P=.0002). Low 53BP1 expression was also found to correlate with triple-negative (TN) phenotype (P<.01). Furthermore, in subset analysis of all TN breast cancer, negative 53BP1 expression trended for lower IBRFS (72.3% vs. 93.9%; P=.0361) and was significant for worse DMFS (48.2% vs. 86.8%; P=.0035) and RFS (37.8% vs. 83.7%; P=.0014). Conclusion: Our data indicate that low 53BP1 expression is an independent prognostic indicator for local relapse among other endpoints in early-stage breast cancer and TN breast cancer patients treated with BCS+RT. These results should be verified in larger cohorts of patients to validate their

  4. Roles of micro RNA-140 in stem cell-associated early stage breast cancer

    Institute of Scientific and Technical Information of China (English)

    Benjamin; Wolfson; Gabriel; Eades; Qun; Zhou

    2014-01-01

    An increasing body of evidence supports a stepwise model for progression of breast cancer from ductal carcinoma in situ(DCIS) to invasive ductal carcinoma(IDC). Due to the high level of DCIS heterogeneity, we cannot currently predict which patients are at highest risk for disease recurrence or progression. The mechanisms of progression are still largely unknown, however cancer stem cell populations in DCIS lesions may serve as malignant precursor cells intimately involved in progression. While genetic and epigenetic alterations found in DCIS are often shared by IDC, m RNA and mi RNA expression profiles are significantly altered. Therapeutic targeting of cancer stem cell pathways and differentially expressed mi RNA could have significant clinical benefit. As tumor grade increases, mi RNA-140 is progressively downregulated. mi R-140 plays an important tumor suppressive role in the Wnt, SOX2 and SOX9 stem cell regulator pathways. Downregulation of mi R-140 removes inhibition of these pathways, leading to higher cancer stem cell populations and breast cancer progression. mi R-140 downregulation is mediated through both an estrogen response element in the mi R-140 promoter region and differential methylation of Cp G islands. These mechanisms are novel targets for epigenetic therapy to activate tumor suppressor signaling via mi R-140. Additionally, we briefly explored the emerging role of exosomes in mediating intercellular mi R-140 signaling. The purpose of this review is to examine the cancer stem cell signaling pathways involved in breast cancer progression, and the role of dysregulation of mi R-140 in regulating DCIS to IDC transition.

  5. Higher alcohol intake may modify the association between mammographic density and breast cancer: An analysis of three case-control studies

    OpenAIRE

    Conroy, Shannon M; Koga, Karin; Woolcott, Christy G.; Dahl, Timothy; Byrne, Celia; Nagata, Chisato; Ursin, Giske; Yaffe, Martin J.; Vachon, Celine M.; Maskarinec, Gertraud

    2012-01-01

    Alcohol consumption and mammographic density are established risk factors for breast cancer. This study examined whether the association of mammographic density with breast cancer varies by alcohol intake. Mammographic density was assessed in digitized images for 1,207 cases and 1,663 controls from three populations (Japan, Hawaii, California) using a computer-assisted method. Associations were estimated by logistic regression. When comparing ever to never drinking, mean density was similar a...

  6. Basal Subtype of Invasive Breast Cancer Is Associated With a Higher Risk of True Recurrence After Conventional Breast-Conserving Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hattangadi-Gluth, Jona A. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Wo, Jennifer Y. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Nguyen, Paul L. [Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women' s Hospital, Boston, Massachusetts (United States); Abi Raad, Rita F. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Sreedhara, Meera [Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women' s Hospital, Boston, Massachusetts (United States); Niemierko, Andrzej [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Freer, Phoebe E. [Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts (United States); Georgian-Smith, Dianne [Department of Radiology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Bellon, Jennifer R.; Wong, Julia S. [Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women' s Hospital, Boston, Massachusetts (United States); Smith, Barbara L. [Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts (United States); Harris, Jay R. [Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women' s Hospital, Boston, Massachusetts (United States); Taghian, Alphonse G., E-mail: ataghian@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2012-03-01

    Purpose: To determine whether breast cancer subtype is associated with patterns of ipsilateral breast tumor recurrence (IBTR), either true recurrence (TR) or elsewhere local recurrence (ELR), among women with pT1-T2 invasive breast cancer (IBC) who receive breast-conserving therapy (BCT). Methods and Materials: From Jan 1998 to Dec 2003, 1,223 women with pT1-T2N0-3 IBC were treated with BCT (lumpectomy plus whole-breast radiation). Ninety percent of patients received adjuvant systemic therapy, but none received trastuzumab. Biologic cancer subtypes were approximated by determining estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), and human epidermal growth factor receptor-2-positive (HER-2+) expression, classified as luminal A (ER+ or PR+ and HER-2 negative [HER-2-]), luminal B (ER+ or PR+ and HER-2+), HER-2 (ER- and PR- and HER-2+), and basal (ER- and PR- and HER-2- ) subtypes. Imaging, pathology, and operative reports were reviewed by two physicians independently, including an attending breast radiologist. Readers were blinded to subtype and outcome. TR was defined as IBTR within the same quadrant and within 3 cm of the primary tumor. All others were defined as ELR. Results: At a median follow-up of 70 months, 24 patients developed IBTR (5-year cumulative incidence of 1.6%), including 15 TR and 9 ELR patients. At 5 years, basal (4.4%) and HER-2 (9%) subtypes had a significantly higher incidence of TR than luminal B (1.2%) and luminal A (0.2%) subtypes (p < 0.0001). On multivariate analysis, basal subtype (hazard ratio [HR], 4.8, p = 0.01), younger age at diagnosis (HR, 0.97; p = 0.05), and increasing tumor size (HR, 2.1; p = 0.04) were independent predictors of TR. Only younger age (HR, 0.95; p = 0.01) significantly predicted for ELR. Conclusions: Basal and HER-2 subtypes are significantly associated with higher rates of TR among women with pT1-T2 IBC after BCT. Younger age predicts for both TR and ELR. Strategies to reduce TR in basal

  7. Basal Subtype of Invasive Breast Cancer Is Associated With a Higher Risk of True Recurrence After Conventional Breast-Conserving Therapy

    International Nuclear Information System (INIS)

    Purpose: To determine whether breast cancer subtype is associated with patterns of ipsilateral breast tumor recurrence (IBTR), either true recurrence (TR) or elsewhere local recurrence (ELR), among women with pT1–T2 invasive breast cancer (IBC) who receive breast-conserving therapy (BCT). Methods and Materials: From Jan 1998 to Dec 2003, 1,223 women with pT1–T2N0-3 IBC were treated with BCT (lumpectomy plus whole-breast radiation). Ninety percent of patients received adjuvant systemic therapy, but none received trastuzumab. Biologic cancer subtypes were approximated by determining estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), and human epidermal growth factor receptor-2-positive (HER-2+) expression, classified as luminal A (ER+ or PR+ and HER-2 negative [HER-2−]), luminal B (ER+ or PR+ and HER-2+), HER-2 (ER− and PR− and HER-2+), and basal (ER− and PR− and HER-2− ) subtypes. Imaging, pathology, and operative reports were reviewed by two physicians independently, including an attending breast radiologist. Readers were blinded to subtype and outcome. TR was defined as IBTR within the same quadrant and within 3 cm of the primary tumor. All others were defined as ELR. Results: At a median follow-up of 70 months, 24 patients developed IBTR (5-year cumulative incidence of 1.6%), including 15 TR and 9 ELR patients. At 5 years, basal (4.4%) and HER-2 (9%) subtypes had a significantly higher incidence of TR than luminal B (1.2%) and luminal A (0.2%) subtypes (p < 0.0001). On multivariate analysis, basal subtype (hazard ratio [HR], 4.8, p = 0.01), younger age at diagnosis (HR, 0.97; p = 0.05), and increasing tumor size (HR, 2.1; p = 0.04) were independent predictors of TR. Only younger age (HR, 0.95; p = 0.01) significantly predicted for ELR. Conclusions: Basal and HER-2 subtypes are significantly associated with higher rates of TR among women with pT1–T2 IBC after BCT. Younger age predicts for both TR and ELR. Strategies to reduce

  8. Plasma Protein Carbonyls and Breast Cancer Risk in Sisters Discordant for Breast Cancer from the New York Site of the Breast Cancer Family Registry

    OpenAIRE

    Zipprich, Jennifer; Terry, Mary Beth; Liao, Yuyan; Agrawal, Meenakshi; Gurvich, Irina; Senie, Ruby; Santella, Regina M.

    2009-01-01

    Reactive Oxygen Species (ROS) are important in the pathogenesis of many diseases, including breast cancer. Several population-based case-control studies have demonstrated that various biomarkers of oxidative stress are associated with an increase in breast cancer risk. We selected sisters discordant for breast cancer (n=645) from the New York site of the Breast Cancer Family Registry to explore factors that contribute to variation in plasma protein carbonyls, and to determine whether this bio...

  9. Association of estrogen receptor-α A908G (K303R) mutation with breast cancer risk

    OpenAIRE

    Abbasi, Sakineh; Rasouli, Mina; Nouri, Mehrnaz; Kalbasi, Samira

    2012-01-01

    Genetic mutations in premalignant breast lesions may have a role in malignancy progression or influence the behavior of subsequent disease. A point mutation in estrogen receptor-α (ER-α) as A908G (Lys303→Arg) was originally involved to hypersensitive to estrogen breast hyperplasia. We detected this mutation among Iranian women with invasive breast cancer. A population-based case-control study was conducted in 150 newly diagnosed invasive breast cancer and 147 healthy control individuals contr...

  10. Stromal cell derived factor-1: its influence on invasiveness and migration of breast cancer cells in vitro, and its association with prognosis and survival in human breast cancer

    International Nuclear Information System (INIS)

    Stromal cell-derived factor (SDF)-1 (CXC chemokine ligand-12) is a member of the CXC subfamily of chemokines, which, through its cognate receptor (CXC chemokine receptor [CXCR]4), plays an important role in chemotaxis of cancer cells and in tumour metastasis. We conducted the present study to evaluate the effect of SDF-1 on the invasiveness and migration of breast cancer cells, and we analyzed the expression of SDF-1 and its relation to clinicopathological features and clinical outcomes in human breast cancer. Expression of SDF-1 mRNA in breast cancer, endothelial (HECV) and fibroblast (MRC5) cell lines and in human breast tissues were studied using RT-PCR. MDA-MB-231 cells were transfected with a SDF-1 expression vector, and their invasiveness and migration was tested in vitro. In addition, the expression of SDF-1 was investigated using immunohistochemistry and quantitative RT-PCR in samples of normal human mammary tissue (n = 32) and mammary tumour (n = 120). SDF-1 expression was identified in MRC5, MDA-MB-435s and MDA-MB-436 cell lines, but CXCR4 expression was detected in all cell lines and breast tissues. An autocrine loop was created following transfection of MDA-MB-231 (which was CXCR4 positive and SDF-1 negative) with a mammalian expression cassette encoding SDF-1 (MDA-MB-231SDF1+/+) or with control plasmid pcDNA4/GFP (MDA-MB-231+/-). MDA-MB-231SDF1+/+ cells exhibited significantly greater invasion and migration potential (in transfected cells versus in wild type and empty MDA-MB-231+/-; P < 0.01). In mammary tissues SDF-1 staining was primarily seen in stromal cells and weakly in mammary epithelial cells. Significantly higher levels of SDF-1 were seen in node-positive than in node-negative tumours (P = 0.05), in tumours that metastasized (P = 0.05), and tumours from patients who died (P = 0.03) than in tumours from patients who were disease free. It was most notable that levels of SDF-1 correlated significantly with overall survival (P = 0.001) and

  11. S100A9 expressed in ER−PgR− breast cancers induces inflammatory cytokines and is associated with an impaired overall survival

    Science.gov (United States)

    Bergenfelz, Caroline; Gaber, Alexander; Allaoui, Roni; Mehmeti, Meliha; Jirström, Karin; Leanderson, Tomas; Leandersson, Karin

    2015-01-01

    Background: Breast cancer is the most common cancer form among women today. Depending on hormone receptor status, breast cancers are divided into different subtypes with vastly varying prognosis. S100A9 is a calcium-binding protein that is associated with inflammation and expressed not only in myeloid cells but also in some tumours. The role for S100A9 in the malignant cells is not well characterised; however, previous studies have shown that the protein could have important immune-modulating properties. Methods: Using a human breast cancer cohort consisting of 144 tumour samples and in vitro analysis of human breast cancer cell lines, we investigated the expression and function of S100A9 in human breast cancer. Results: We show that S100A9 expression in breast cancer correlated with the ER−PgR− breast tumour subtype (P<0.001) and with Ki67 (P=0.024) and was expressed both in the malignant cells and in the tumour-infiltrating anti-inflammatory CD163+ myeloid cells (P<0.001). Stromal expression of S100A9 also correlated to nodal stage, tumour size and Her2 positivity. Within the ER−PgR− subgroup, all Her2+ and EGFR+ tumours expressed S100A9 in the cytoplasm. Both cytoplasmic staining in the malignant cells as well as stromal S100A9 expression in myeloid cells correlated with a decreased overall survival in breast cancer patients. Furthermore, rS100A9 homodimers induced expression of pro-inflammatory cytokines (IL-6, IL-8 and IL-1β) in a TLR4- and EGFR-dependent manner in human breast cancer cells in vitro. Conclusion: We suggest that S100A9 could be viewed as a novel therapeutic target for patients with ER−PgR− breast cancers. PMID:26448179

  12. Breast cancer in women using digoxin

    DEFF Research Database (Denmark)

    Biggar, Robert J; Andersen, Louise Elisabeth; Kroman, Niels;

    2013-01-01

    INTRODUCTION: Digoxin use is associated with increased incidence of breast and uterus cancers. We postulated that digoxin use might affect tumor characteristics and increase relapse risk in women with breast cancer. METHODS: Incident breast cancer cases in Danish women (n = 49,312; 1995 to 2008...... Cox regression models. RESULTS: At diagnosis, tumors in digoxin users were more likely ER+ (85.4% vs. 78.6%: P = 0.002) and have grade 1 ductal histology (37.2% vs. 25.7%; P = 0.004), compared to non-users. 45 relapses occurred in women already using digoxin at breast cancer diagnosis (1,487 person...... cancers arising in digoxin-using women had better prognostic features. After adjustment for markers, overall breast cancer relapse risk in digoxin users was not increased significantly, although recurrence hazards for ER+ tumors were higher in the first year following diagnosis....

  13. Retinoic acid receptor alpha is associated with tamoxifen resistance in breast cancer

    OpenAIRE

    Johansson, Henrik J; Sanchez, Betzabe C.; Mundt, Filip; Forshed, Jenny; Kovacs, Aniko; Panizza, Elena; Hultin-Rosenberg, Lina; Lundgren, Bo; Martens, Ulf; Máthé, Gyöngyvér; Yakhini, Zohar; Helou, Khalil; Krawiec, Kamilla; Kanter, Lena; Hjerpe, Anders

    2013-01-01

    About one-third of oestrogen receptor alpha-positive breast cancer patients treated with tamoxifen relapse. Here we identify the nuclear receptor retinoic acid receptor alpha as a marker of tamoxifen resistance. Using quantitative mass spectrometry-based proteomics, we show that retinoic acid receptor alpha protein networks and levels differ in a tamoxifen-sensitive (MCF7) and a tamoxifen-resistant (LCC2) cell line. High intratumoural retinoic acid receptor alpha protein levels also correlate...

  14. Factors associated with the choice of surgery in breast cancer : a systematic review

    OpenAIRE

    Tam, Hin-pong; 譚顯邦

    2013-01-01

    Background: Patients with early stage breast cancer having more aggressive surgery have been reported by several studies. Some studies from US also reported that there is an increasing trend in the use of mastectomy. A study even showed that there is 150% increase in bilateral mastectomy rate using data from Surveillance, Epidemiology, and End Results registries (SEER). The increasing use of mastectomy leads to the concerns about reasons behind the decision of surgery type. The objective of t...

  15. Association of common ATM variants with familial breast cancer in a South American population

    International Nuclear Information System (INIS)

    The ATM gene has been frequently involved in hereditary breast cancer as a low-penetrance susceptibility gene but evidence regarding the role of ATM as a breast cancer susceptibility gene has been contradictory. In this study, a full mutation analysis of the ATM gene was carried out in patients from 137 Chilean breast cancer families, of which 126 were BRCA1/2 negatives and 11 BRCA1/2 positives. We further perform a case-control study between the subgroup of 126 cases BRCA1/2 negatives and 200 controls for the 5557G>A missense variant and the IVS38-8T>C and the IVS24-9delT polymorphisms. In the full mutation analysis we detected two missense variants and eight intronic polymorphisms. Carriers of the variant IVS24-9delT, or IVS38-8T>C, or 5557G>A showed an increase in breast cancer risk. The higher significance was observed in the carriers of IVS38-8T>C (OR = 3.09 [95%CI 1.11–8.59], p = 0.024). The IVS24-9 T/(-T), IVS38-8 T/C, 5557 G/A composite genotype confered a 3.19 fold increase in breast cancer risk (OR = 3.19 [95%CI 1.16–8.89], p = 0.021). The haplotype estimation suggested a strong linkage disequilibrium between the three markers (D' = 1). We detected only three haplotypes in the cases and control samples, some of these may be founder haplotypes in the Chilean population. The IVS24-9 T/(-T), IVS38-8 T/C, 5557 G/A composite genotype alone or in combination with certain genetic background and/or environmental factors, could modify the cancer risk by increasing genetic inestability or by altering the effect of the normal DNA damage response

  16. Evaluating genome-wide association study-identified breast cancer risk variants in African-American women.

    Directory of Open Access Journals (Sweden)

    Jirong Long

    Full Text Available Genome-wide association studies (GWAS, conducted mostly in European or Asian descendants, have identified approximately 67 genetic susceptibility loci for breast cancer. Given the large differences in genetic architecture between the African-ancestry genome and genomes of Asians and Europeans, it is important to investigate these loci in African-ancestry populations. We evaluated index SNPs in all 67 breast cancer susceptibility loci identified to date in our study including up to 3,300 African-American women (1,231 cases and 2,069 controls, recruited in the Southern Community Cohort Study (SCCS and the Nashville Breast Health Study (NBHS. Seven SNPs were statistically significant (P ≤ 0.05 with the risk of overall breast cancer in the same direction as previously reported: rs10069690 (5p15/TERT, rs999737 (14q24/RAD51L1, rs13387042 (2q35/TNP1, rs1219648 (10q26/FGFR2, rs8170 (19p13/BABAM1, rs17817449 (16q12/FTO, and rs13329835 (16q23/DYL2. A marginally significant association (P<0.10 was found for three additional SNPs: rs1045485 (2q33/CASP8, rs4849887 (2q14/INHBB, and rs4808801 (19p13/ELL. Three additional SNPs, including rs1011970 (9p21/CDKN2A/2B, rs941764 (14q32/CCDC88C, and rs17529111 (6q14/FAM46A, showed a significant association in analyses conducted by breast cancer subtype. The risk of breast cancer was elevated with an increasing number of risk variants, as measured by quintile of the genetic risk score, from 1.00 (reference, to 1.75 (1.30-2.37, 1.56 (1.15-2.11, 2.02 (1.50-2.74 and 2.63 (1.96-3.52, respectively, (P = 7.8 × 10(-10. Results from this study highlight the need for large genetic studies in AAs to identify risk variants impacting this population.

  17. Omega-3 Fatty Acid in Treating Patients With Stage I-III Breast Cancer

    Science.gov (United States)

    2016-03-17

    Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Male Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  18. 25-Hydroxy vitamin-D, obesity, and associated variables as predictors of breast cancer risk and tamoxifen benefit in NSABP-P1

    OpenAIRE

    Amir, Eitan; Cecchini, Reena S.; Ganz, Patricia A.; Costantino, Joseph P.; Beddows, Samantha; Hood, Nicola; Goodwin, Pamela J

    2012-01-01

    Observational studies suggest that host factors are associated with breast cancer risk. The influence of obesity, vitamin-D status, insulin resistance, inflammation, and elevated adipocytokines in women at high risk of breast cancer is unknown. The NSABP-P1 trial population was used for a nested case–control study. Cases were drawn from those who developed invasive breast cancer and controls selected from unaffected participants (≤4 per case) matched for age, race, 5 year Gail score, and geog...

  19. The Relationship Between Eight GWAS-Identified Single-Nucleotide Polymorphisms and Primary Breast Cancer Outcomes

    OpenAIRE

    Bayraktar, Soley; Thompson, Patricia A.; Yoo, Suk-Young; Do, Kim-Anh; Sahin, Aysegul A.; Arun, Banu K; Bondy, Melissa L.; Brewster, Abenaa M.

    2013-01-01

    Several single-nucleotide polymorphisms (SNPs) associated with breast cancer risk have been identified through genome-wide association studies. This study investigated the association of eight risk SNPs with breast cancer disease-free survival and overall survival rates. Results suggest that two previously identified breast cancer risk susceptibility loci may influence breast cancer prognosis or comorbid conditions associated with overall survival.

  20. Predictors for Reconstruction and Mood Disorder Associated With Reconstruction in Patients With Breast Cancer and Mastectomy: A Retrospective Cohort Study.

    Science.gov (United States)

    Pan, Hsueh-Hsing; Chu, Chun-Hui; Wu, Li-Fen; Hsieh, Pi-Ching; Chang, Kun-Chia; Li, Chung-Yi

    2016-01-01

    This study used Taiwan's National Health Insurance medical claims to investigate the predictors for operative modes chosen by early-stage breast cancer patients; as well as to assess whether operative modes are associated with risk of mood disorder. We included 36,377 patients with breast cancer who received surgery between 2000 and 2008, and were followed to the end of 2010; they were further classified into 3 groups: mastectomy alone (n = 34,900), along with early reconstruction (n = 1080), and along with delayed reconstruction (n = 397). The results showed that age, insurance premium, urbanization level, and postsurgery chemotherapy and radiotherapy were all significant predictors for the selection of operative modes. Breast cancer patients with mastectomy alone, early reconstruction, and delayed reconstruction showed a cumulative incidence rate of mood disorder of 36.90%, 41.56%, and 33.89%, respectively. The multiple cox proportional model further revealed that e