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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. 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...... stratification might help in the identification and characterization of novel risk factors for breast cancer subtypes. This may eventually result in further improvements in prevention, early detection and treatment.......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...... 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...

  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...

  8. 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.

  9. 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...

  10. 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....

  11. 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

  12. "Targeting" triple-negative breast cancer: the lessons learned from BRCA1-associated breast cancers.

    Science.gov (United States)

    Nanda, Rita

    2011-04-01

    Breast cancer has long been recognized as a heterogeneous entity, with distinct subsets characterized by differences in tumor biology and response to therapy. With the advent of molecular profiling, we have gained a further appreciation of the heterogeneity of this complex disease. While the last decade has seen advances in the treatment of hormone receptor (HR) and human epidermal growth factor receptor 2/erb-B2 (HER2)-positive breast cancers, outcomes for women with estrogen receptor (ER)-, progesterone receptor (PR)-, and HER2-negative-or "triple-negative"-breast cancer (TNBC) remain poor. A better understanding of the shared biology of BRCA1-associated breast cancer and sporadic TNBC holds much promise for changing the outlook for women with this aggressive disease. This review focuses on our current understanding of the clinicopathological features of TNBC, therapeutic options and ongoing research efforts.

  13. 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.

  14. 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 invasiv...

  15. 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.

  16. 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...

  17. Alcohol consumption before and after breast cancer diagnosis: associations with survival from breast cancer, cardiovascular disease, and other causes

    NARCIS (Netherlands)

    Newcomb, P.A.; Kampman, E.; Trentham-Dietz, A.; Egan, K.M.; Titus, L.J.; Baron, J.A.; Hampton, J.M.; Passarelli, M.N.; Willett, W.C.

    2013-01-01

    Purpose Alcohol intake is associated with increased risk of breast cancer. In contrast, the relation between alcohol consumption and breast cancer survival is less clear. Patients and Methods We assessed pre- and postdiagnostic alcohol intake in a cohort of 22,890 women with incident invasive breast

  18. 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

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

    NARCIS (Netherlands)

    A. Pirie (Ailith); Q. Guo (Qi); P. Kraft (Peter); S. Canisius (Sander); D. Eccles (Diana); N. Rahman (Nazneen); H. Nevanlinna (Heli); C. Chen (Constance); S. Khan (Sofia); J.P. Tyrer (Jonathan); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); K. Michailidou (Kyriaki); M. Lush (Michael); A.M. Dunning (Alison); M. Shah (Mitul); K. Czene (Kamila); H. Darabi (Hatef); M. Eriksson (Mats); D. Lambrechts (Diether); C. Weltens (Caroline); K. Leunen; C. van Ongeval (Chantal); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune); H. Flyger (Henrik); A. Rudolph (Anja); P. Seibold (Petra); D. Flesch-Janys (Dieter); C. Blomqvist (Carl); K. Aittomäki (Kristiina); R. Fagerholm (Rainer); T.A. Muranen (Taru); J.E. Olsen (Janet E.); B. Hallberg (Boubou); C. Vachon (Celine); J.A. Knight (Julia); G. Glendon (Gord); A.M. Mulligan (Anna Marie); A. Broeks (Annegien); S. Cornelissen (Sten); C.A. Haiman (Christopher); B.E. Henderson (Brian); F. Schumacher (Frederick); L. Le Marchand (Loic); J.L. Hopper (John); H. Tsimiklis (Helen); C. Apicella (Carmel); M.C. Southey (Melissa); S.S. Cross (Simon); M.W.R. Reed (Malcolm); G.G. Giles (Graham); R.L. Milne (Roger); C.A. McLean (Catriona Ann); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); M. Grip (Mervi); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); J.W.M. Martens (John); A.M.W. van den Ouweland (Ans); F. Marme (Federick); A. Schneeweiss (Andreas); R. Yang (Rongxi); B. Burwinkel (Barbara); J.D. Figueroa (Jonine); S.J. Chanock (Stephen); J. Lissowska (Jolanta); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); H. Brenner (Hermann); K. Butterbach (Katja); B. Holleczek (B.); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); J. Li (Jingmei); J.S. Brand (Judith S.); M.K. Humphreys (Manjeet); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); P. Radice (Paolo); P. Peterlongo (Paolo); S. Manoukian (Siranoush); F. Ficarazzi (Filomena); M.W. Beckmann (Matthias); R. Hein (Rebecca); A.B. Ekici (Arif); R. Balleine (Rosemary); K.-A. Phillips (Kelly-Anne); J. Benítez (Javier); M.P. Zamora (Pilar); J.I.A. Perez (Jose Ignacio Arias); P. Menéndez (Primitiva); A. Jakubowska (Anna); J. Lubinski (Jan); J. Gronwald (Jacek); K. Durda (Katarzyna); U. Hamann (Ute); M. Kabisch (Maria); H.U. Ulmer (Hans); T. Rud̈iger (Thomas); S. Margolin (Sara); V. Kristensen (Vessela); S. Nord (Siljie); D.G. Evans (Gareth); J. Abraham (Jean); H. Earl (Helena); C.J. Poole (Christopher J.); L. Hiller (Louise); J.A. Dunn (J.); S. Bowden (Sarah); R. Yang (Rose); D. Campa (Daniele); W.R. Diver (Ryan); S.M. Gapstur (Susan M.); M.M. Gaudet (Mia); S.E. Hankinson (Susan); R.N. Hoover (Robert); A. Hüsing (Anika); R. Kaaks (Rudolf); M.J. Machiela (Mitchell J.); W.C. Willett (Walter C.); M. Barrdahl (Myrto); F. Canzian (Federico); S.-F. Chin (Suet-Feung); C. Caldas (Carlos); D. Hunter (David); S. Lindstrom (Stephen); M. García-Closas (Montserrat); F.J. Couch (Fergus); G. Chenevix-Trench (Georgia); A. Mannermaa (Arto); I.L. Andrulis (Irene); P. Hall (Per); J. Chang-Claude (Jenny); D.F. Easton (Douglas); S.E. Bojesen (Stig); A. Cox (Angela); P.A. Fasching (Peter); P.D.P. Pharoah (Paul); M.K. Schmidt (Marjanka)

    2015-01-01

    textabstractIntroduction: 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 brea

  20. 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 ...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsS...

  2. 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...

  3. Management of pregnancy associated breast cancer with chemotherapy in a developing country

    OpenAIRE

    Emmanuel A. Sule; Festus Ewemade

    2015-01-01

    Context: Although breast cancer is a common cancer, Pregnancy associated breast cancer is uncommon. Adjuvant chemotherapy administered intrapartum has been resolved to be safe from the second trimester. Objective: To review cases of pregnancy associated breast cancer managed with adjuvant intrapartum chemotherapy. Patients and method: Gravid patients diagnosed with breast cancer had chemotherapy administered by a slow infusion protocol at 3 weekly interval from the second trimester till...

  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. 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.

  6. 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 ...

  7. 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...

  8. 9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer: Evidence from the Breast Cancer Association Consortium

    NARCIS (Netherlands)

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

    2012-01-01

    textabstractBackground: 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

  9. Association of Telomere Length with Breast Cancer Prognostic Factors

    Science.gov (United States)

    Têtu, Bernard; Maunsell, Elizabeth; Poirier, Brigitte; Montoni, Alicia; Rochette, Patrick J.; Diorio, Caroline

    2016-01-01

    Introduction Telomere length, a marker of cell aging, seems to be affected by the same factors thought to be associated with breast cancer prognosis. Objective To examine associations of peripheral blood cell-measured telomere length with traditional and potential prognostic factors in breast cancer patients. Methods We conducted a cross-sectional analysis of data collected before surgery from 162 breast cancer patients recruited consecutively between 01/2011 and 05/2012, at a breast cancer reference center. Data on the main lifestyle factors (smoking, alcohol consumption, physical activity) were collected using standardized questionnaires. Anthropometric factors were measured. Tumor biological characteristics were extracted from pathology reports. Telomere length was measured using a highly reproducible quantitative PCR method in peripheral white blood cells. Spearman partial rank-order correlations and multivariate general linear models were used to evaluate relationships between telomere length and prognostic factors. Results Telomere length was positively associated with total physical activity (rs = 0.17, P = 0.033; Ptrend = 0.069), occupational physical activity (rs = 0.15, P = 0.054; Ptrend = 0.054) and transportation-related physical activity (rs = 0.19, P = 0.019; P = 0.005). Among post-menopausal women, telomere length remained positively associated with total physical activity (rs = 0.27, P = 0.016; Ptrend = 0.054) and occupational physical activity (rs = 0.26, P = 0.021; Ptrend = 0.056) and was only associated with transportation-related physical activity among pre-menopausal women (rs = 0.27, P = 0.015; P = 0.004). No association was observed between telomere length and recreational or household activities, other lifestyle factors or traditional prognostic factors. Conclusions Telomeres are longer in more active breast cancer patients. Since white blood cells are involved in anticancer immune responses, these findings suggest that even regular low

  10. Distinct microbiological signatures associated with triple negative breast cancer.

    Science.gov (United States)

    Banerjee, Sagarika; Wei, Zhi; Tan, Fei; Peck, Kristen N; Shih, Natalie; Feldman, Michael; Rebbeck, Timothy R; Alwine, James C; Robertson, Erle S

    2015-10-15

    Infectious agents are the third highest human cancer risk factor and may have a greater role in the origin and/or progression of cancers, and related pathogenesis. Thus, knowing the specific viruses and microbial agents associated with a cancer type may provide insights into cause, diagnosis and treatment. We utilized a pan-pathogen array technology to identify the microbial signatures associated with triple negative breast cancer (TNBC). This technology detects low copy number and fragmented genomes extracted from formalin-fixed paraffin embedded archival tissues. The results, validated by PCR and sequencing, define a microbial signature present in TNBC tissue which was underrepresented in normal tissue. Hierarchical clustering analysis displayed two broad microbial signatures, one prevalent in bacteria and parasites and one prevalent in viruses. These signatures demonstrate a new paradigm in our understanding of the link between microorganisms and cancer, as causative or commensal in the tumor microenvironment and provide new diagnostic potential.

  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. 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...

  13. 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.

  14. 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.

  15. 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 ... the risk. Women who have family members with breast or ovarian cancer may wish to be tested ...

  16. Common variants associated with breast cancer in genome-wide association studies are modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers.

    NARCIS (Netherlands)

    Wang, X.; Pankratz, V.S.; Fredericksen, Z.; Tarrell, R.; Karaus, M.; McGuffog, L.; Pharaoh, P.D.; Ponder, B.A.J.; Dunning, A.M.; Peock, S.; Cook, M.; Oliver, C.; Frost, D.; Sinilnikova, O.M.; Stoppa-Lyonnet, D.; Mazoyer, S.; Houdayer, C.; Hogervorst, F.B.L.; Hooning, M.J.; Ligtenberg, M.J.L.; Spurdle, A.; Chenevix-Trench, G.; Schmutzler, R.K.; Wappenschmidt, B.; Engel, C.; Meindl, A.; Domchek, S.M.; Nathanson, K.L.; Rebbeck, T.R.; Singer, C.F.; Gschwantler-Kaulich, D.; Dressler, C.; Fink, A.; Szabo, C.I.; Zikan, M.; Foretova, L.; Claes, K.; Thomas, G.; Hoover, R.N.; Hunter, D.J.; Chanock, S.J.; Easton, D.F.; Antoniou, A.C.; Couch, F.J.

    2010-01-01

    Recent studies have identified single nucleotide polymorphisms (SNPs) that significantly modify breast cancer risk in BRCA1 and BRCA2 mutation carriers. Since these risk modifiers were originally identified as genetic risk factors for breast cancer in genome-wide association studies (GWASs), additio

  17. Common variants associated with breast cancer in genome-wide association studies are modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers

    NARCIS (Netherlands)

    Wang, Xianshu; Pankratz, V. Shane; Fredericksen, Zachary; Tarrell, Robert; Karaus, Mary; McGuffog, Lesley; Pharaoh, Paul D. P.; Ponder, Bruce A. J.; Dunning, Alison M.; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Sinilnikova, Olga M.; Stoppa-Lyonnet, Dominique; Mazoyer, Sylvie; Houdayer, Claude; Hogervorst, Frans B. L.; Hooning, Maartje J.; Ligtenberg, Marjolijn J.; Spurdle, Amanda; Chenevix-Trench, Georgia; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Singer, Christian F.; Gschwantler-Kaulich, Daphne; Dressler, Catherina; Fink, Anneliese; Szabo, Csilla I.; Zikan, Michal; Foretova, Lenka; Claes, Kathleen; Thomas, Gilles; Hoover, Robert N.; Hunter, David J.; Chanock, Stephen J.; Easton, Douglas F.; Antoniou, Antonis C.; Couch, Fergus J.

    2010-01-01

    Recent studies have identified single nucleotide polymorphisms (SNPs) that significantly modify breast cancer risk in BRCA1 and BRCA2 mutation carriers. Since these risk modifiers were originally identified as genetic risk factors for breast cancer in genome-wide association studies (GWASs), additio

  18. 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 ...

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

    NARCIS (Netherlands)

    Ghoussaini, M.; Fletcher, O.; Michailidou, K.; Turnbull, C.; Schmidt, M.K.; Dicks, E.; Dennis, J.; Wang, Q.; Humphreys, M.K.; Luccarini, C.; Baynes, C.; Conroy, D.; Maranian, M.; Ahmed, S.; Driver, K.; Johnson, N.; Orr, N.; dos Santos Silva, I.; Waisfisz, Q.; Meijers-Heijboer, H.; Uitterlinden, A.G.; Rivadeneira, F.; Hall, P.; Czene, K.; Irwanto, A.; Liu, J.; Nevanlinna, H.; Aittomaki, K.; Blomqvist, C.; Meindl, A.; Schmutzler, R.K.; Muller-Myhsok, B.; Lichtner, P.; Chang-Claude, J.; Hein, R.; Nickels, S.; Flesch-Janys, D.; Tsimiklis, H.; Makalic, E.; Schmidt, D.; Bui, M.; Hopper, J.L.; Apicella, C.; Park, D.J.; Southey, M.; Hunter, D.J.; Chanock, S.J.; Broeks, A.; Verhoef, S.; Hogervorst, F.B.; Fasching, P.A.; Lux, M.P.; Beckmann, M.W.; Ekici, A.B.; Sawyer, E.; Tomlinson, I.; Kerin, M.; Marme, F.; Schneeweiss, A.; Sohn, C.; Burwinkel, B.; Guenel, P.; Truong, T.; Cordina-Duverger, E.; Menegaux, F.; Bojesen, S.E.; Nordestgaard, B.G.; Nielsen, S.F.; Flyger, H.; Milne, R.L.; Alonso, M.R.; Gonzalez-Neira, A.; Benitez, J.; Anton-Culver, H.; Ziogas, A.; Bernstein, L.; Dur, C.C.; Brenner, H.; Muller, H.; Arndt, V.; Stegmaier, C.; Justenhoven, C.; Brauch, H.; Bruning, T.; Wang-Gohrke, S.; Eilber, U.; Dork, T.; Schurmann, P.; Bremer, M.; Hillemanns, P.; Bogdanova, N.V.; Antonenkova, N.N.; Rogov, Y.I.; Karstens, J.H.; Bermisheva, M.; Prokofieva, D.; Ligtenberg, M.J.

    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 approximately 8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies

  20. 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...

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

    Science.gov (United States)

    Milne, Roger L.; Burwinkel, Barbara; Michailidou, Kyriaki; Arias-Perez, Jose-Ignacio; Zamora, M. Pilar; Menéndez-Rodríguez, Primitiva; Hardisson, David; Mendiola, Marta; González-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Dennis, Joe; Wang, Qin; Bolla, Manjeet K.; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk; Ko, Yon-Dschun; Brauch, Hiltrud; Hamann, Ute; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Tchatchou, Sandrine; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Li, Jingmei; Brand, Judith S.; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Lambrechts, Diether; Peuteman, Gilian; Christiaens, Marie-Rose; Smeets, Ann; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katazyna; Hartman, Mikael; Hui, Miao; Yen Lim, Wei; Wan Chan, Ching; Marme, Federick; Yang, Rongxi; Bugert, Peter; Lindblom, Annika; Margolin, Sara; García-Closas, Montserrat; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Bojesen, Stig E.; Nordestgaard, Børge G.; Flyger, Henrik; Hooning, Maartje J.; Kriege, Mieke; van den Ouweland, Ans M.W.; Koppert, Linetta B.; Fletcher, Olivia; Johnson, Nichola; dos-Santos-Silva, Isabel; Peto, Julian; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha J.; Long, Jirong; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Cox, Angela; Cross, Simon S.; Reed, Malcolm W.R.; Schmidt, Marjanka K.; Broeks, Annegien; Cornelissen, Sten; Braaf, Linde; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K.; Noh, Dong-Young; Simard, Jacques; Dumont, Martine; Goldberg, Mark S.; Labrèche, France; Fasching, Peter A.; Hein, Alexander; Ekici, Arif B.; Beckmann, Matthias W.; Radice, Paolo; Peterlongo, Paolo; Azzollini, Jacopo; Barile, Monica; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael; Miller, Nicola; Hopper, John L.; Schmidt, Daniel F.; Makalic, Enes; Southey, Melissa C.; Hwang Teo, Soo; Har Yip, Cheng; Sivanandan, Kavitta; Tay, Wan-Ting; Shen, Chen-Yang; Hsiung, Chia-Ni; Yu, Jyh-Cherng; Hou, Ming-Feng; Guénel, Pascal; Truong, Therese; Sanchez, Marie; Mulot, Claire; Blot, William; Cai, Qiuyin; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Wu, Anna H.; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O.; Bogdanova, Natalia; Dörk, Thilo; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Zhang, Ben; Couch, Fergus J.; Toland, Amanda E.; Yannoukakos, Drakoulis; Sangrajrang, Suleeporn; McKay, James; Wang, Xianshu; Olson, Janet E.; Vachon, Celine; Purrington, Kristen; Severi, Gianluca; Baglietto, Laura; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Devilee, Peter; Tollenaar, Robert A.E.M.; Seynaeve, Caroline; Czene, Kamila; Eriksson, Mikael; Humphreys, Keith; Darabi, Hatef; Ahmed, Shahana; Shah, Mitul; Pharoah, Paul D.P.; Hall, Per; Giles, Graham G.; Benítez, Javier; Dunning, Alison M.; Chenevix-Trench, Georgia; Easton, Douglas F.; Berchuck, Andrew; Eeles, Rosalind A.; Olama, Ali Amin Al; Kote-Jarai, Zsofia; Benlloch, Sara; Antoniou, Antonis; McGuffog, Lesley; Offit, Ken; Lee, Andrew; Dicks, Ed; Luccarini, Craig; Tessier, Daniel C.; Bacot, Francois; Vincent, Daniel; LaBoissière, Sylvie; Robidoux, Frederic; Nielsen, Sune F.; Cunningham, Julie M.; Windebank, Sharon A.; Hilker, Christopher A.; Meyer, Jeffrey; Angelakos, Maggie; Maskiell, Judi; van der Schoot, Ellen; Rutgers, Emiel; Verhoef, Senno; Hogervorst, Frans; Boonyawongviroj, Prat; Siriwanarungsan, Pornthep; Schrauder, Michael; Rübner, Matthias; Oeser, Sonja; Landrith, Silke; Williams, Eileen; Ryder-Mills, Elaine; Sargus, Kara; McInerney, Niall; Colleran, Gabrielle; Rowan, Andrew; Jones, Angela; Sohn, Christof; Schneeweiß, Andeas; Bugert, Peter; Álvarez, Núria; Lacey, James; Wang, Sophia; Ma, Huiyan; Lu, Yani; Deapen, Dennis; Pinder, Rich; Lee, Eunjung; Schumacher, Fred; Horn-Ross, Pam; Reynolds, Peggy; Nelson, David; Ziegler, Hartwig; Wolf, Sonja; Hermann, Volker; Lo, Wing-Yee; Justenhoven, Christina; Baisch, Christian; Fischer, Hans-Peter; Brüning, Thomas; Pesch, Beate; Rabstein, Sylvia; Lotz, Anne; Harth, Volker; Heikkinen, Tuomas; Erkkilä, Irja; Aaltonen, Kirsimari; von Smitten, Karl; Antonenkova, Natalia; Hillemanns, Peter; Christiansen, Hans; Myöhänen, Eija; Kemiläinen, Helena; Thorne, Heather; Niedermayr, Eveline; Bowtell, D; Chenevix-Trench, G; deFazio, A; Gertig, D; Green, A; Webb, P; Green, A.; Parsons, P.; Hayward, N.; Webb, P.; Whiteman, D.; Fung, Annie; Yashiki, June; Peuteman, Gilian; Smeets, Dominiek; Brussel, Thomas Van; Corthouts, Kathleen; Obi, Nadia; Heinz, Judith; Behrens, Sabine; Eilber, Ursula; Celik, Muhabbet; Olchers, Til; Manoukian, Siranoush; Peissel, Bernard; Scuvera, Giulietta; Zaffaroni, Daniela; Bonanni, Bernardo; Feroce, Irene; Maniscalco, Angela; Rossi, Alessandra; Bernard, Loris; Tranchant, Martine; Valois, Marie-France; Turgeon, Annie; Heguy, Lea; Sze Yee, Phuah; Kang, Peter; Nee, Kang In; Mariapun, Shivaani; Sook-Yee, Yoon; Lee, Daphne; Ching, Teh Yew; Taib, Nur Aishah Mohd; Otsukka, Meeri; Mononen, Kari; Selander, Teresa; Weerasooriya, Nayana; staff, OFBCR; Krol-Warmerdam, E.; Molenaar, J.; Blom, J.; Brinton, Louise; Szeszenia-Dabrowska, Neonila; Peplonska, Beata; Zatonski, Witold; Chao, Pei; Stagner, Michael; Bos, Petra; Blom, Jannet; Crepin, Ellen; Nieuwlaat, Anja; Heemskerk, Annette; Higham, Sue; Cross, Simon; Cramp, Helen; Connley, Dan; Balasubramanian, Sabapathy; Brock, Ian; Luccarini, Craig; Conroy, Don; Baynes, Caroline; Chua, Kimberley

    2014-01-01

    Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: 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 × 10−10). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act

  2. 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.

  3. 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...

  4. 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 ...

  5. 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...

  6. 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...

  7. 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...... 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.-93C...... are associated with increased breast cancer risk. In accordance with previous results, these data link decreased DMBT1 levels to breast cancer risk....

  8. c-Ski activates cancer-associated fibroblasts to regulate breast cancer cell invasion.

    Science.gov (United States)

    Wang, Liyang; Hou, Yixuan; Sun, Yan; Zhao, Liuyang; Tang, Xi; Hu, Ping; Yang, Jiajia; Zeng, Zongyue; Yang, Guanglun; Cui, Xiaojiang; Liu, Manran

    2013-12-01

    Aberrant expression of c-Ski oncoprotein in some tumor cells has been shown to be associated with cancer development. However, the role of c-Ski in cancer-associated fibroblasts (CAFs) of tumor microenvironment has not been characterized. In the current study, we found that c-Ski is highly expressed in CAFs derived from breast carcinoma microenvironment and this CAF-associated c-Ski expression is associated with invasion and metastasis of human breast tumors. We showed that c-Ski overexpression in immortalized breast normal fibroblasts (NFs) induces conversion to breast CAFs by repressing p53 and thereby upregulating SDF-1 in NFs. SDF-1 treatment or p53 knockdown in NFs had similar effects on the activation of NFs as c-Ski overexpression. The c-Ski-activated CAFs show increased proliferation, migration, invasion and contraction compared with NFs. Furthermore, c-Ski-activated CAFs facilitated the migration and invasion of MDA-MB-231 breast cancer cells. Our data suggest that c-Ski is an important regulator in the activation of CAFs and may serve as a potential therapeutic target to block breast cancer progression.

  9. 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

  10. 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.

  11. 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...

  12. 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

  13. 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...

  14. [Sentinel lymph node biopsy in pregnancy-associated breast cancer].

    Science.gov (United States)

    Mátrai, Zoltán; Bánhidy, Ferenc; Téglás, Melinda; Kovács, Eszter; Sávolt, Akos; Udvarhelyi, Nóra; Bartal, Alexandra; Kásler, Miklós

    2013-12-01

    The incidence of pregnancy-associated breast cancer is rising. Sentinel lymph node biopsy is the method of choice in clinically node negative cases as the indicated minimally invasive regional staging procedure. Some reports have linked radioisotope and blue dye required for lymphatic mapping to teratogenic effects, the idea of which has become a generalized statement and, until recently, contraindication for these agents was considered during pregnancy. Today, there are many published reports of successful interventions with low-dose 99mTc-labeled human albumin nanocolloid, based on dosimetric modeling demonstrating a negligible radiation exposure of the fetus. These results contributed to the seemingly safe and successful use of sentinel lymph node biopsy during pregnancy, though generally it can not replace axillary lymphadenectomy in the absence of high-quality evidence. The possibility of sentinel lymph node biopsy should be offered to pregnancy-associated early breast cancer patients with clinically negative axilla, and patients should be involved in the decision making following extensive counselling. This paper presents the successful use of sentinel lymph node biopsy with low-dose tracer during two pregnancies (in the first and third trimesters) and, for the first time in Hungarian language, it offers a comprehensive literature review on this topic. Orv. Hetil., 154(50), 1991-1997. PMID:24317358

  15. 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

  16. Genetic polymorphisms in DPF3 associated with risk of breast cancer and lymph node metastases

    Directory of Open Access Journals (Sweden)

    Hoyal Carolyn R

    2005-08-01

    Full Text Available Abstract Background Several studies have identified rare genetic variations responsible for many cases of familial breast cancer but their contribution to total breast cancer incidence is relatively small. More common genetic variations with low penetrance have been postulated to account for a higher proportion of the population risk of breast cancer. Methods and Results In an effort to identify genes that influence non-familial breast cancer risk, we tested over 25,000 single nucleotide polymorphisms (SNPs located within approximately 14,000 genes in a large-scale case-control study in 254 German women with breast cancer and 268 age-matched women without malignant disease. We identified a marker on chromosome 14q24.3-q31.1 that was marginally associated with breast cancer status (OR = 1.5, P = 0.07. Genotypes for this SNP were also significantly associated with indicators of breast cancer severity, including presence of lymph node metastases (P = 0.006 and earlier age of onset (P = 0.01. The association with breast cancer status was replicated in two independent samples (OR = 1.35, P = 0.05. High-density association fine mapping showed that the association spanned about 80 kb of the zinc-finger gene DPF3 (also known as CERD4. One SNP in intron 1 was found to be more strongly associated with breast cancer status in all three sample collections (OR = 1.6, P = 0.003 as well as with increased lymph node metastases (P = 0.01 and tumor size (P = 0.01. Conclusion Polymorphisms in the 5' region of DPF3 were associated with increased risk of breast cancer development, lymph node metastases, age of onset, and tumor size in women of European ancestry. This large-scale association study suggests that genetic variation in DPF3 contributes to breast cancer susceptibility and severity.

  17. Association of ESR1 gene tagging SNPs with breast cancer risk

    DEFF Research Database (Denmark)

    Dunning, Alison M; Healey, Catherine S; Baynes, Caroline;

    2009-01-01

    We have conducted a three-stage, comprehensive single nucleotide polymorphism (SNP)-tagging association study of ESR1 gene variants (SNPs) in more than 55,000 breast cancer cases and controls from studies within the Breast Cancer Association Consortium (BCAC). No large risks or highly significant...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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

  3. 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 polymorp...

  4. 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....

  5. Cancer-associated adipocytes promotes breast tumor radioresistance

    Energy Technology Data Exchange (ETDEWEB)

    Bochet, Ludivine; Meulle, Aline [Universite de Toulouse, UPS, F-31077 Toulouse Cedex (France); CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, BP 64182, F-31077 Toulouse Cedex (France); Institut National de la Sante et de la Recherche Medicale, INSERM U1048, 1 Avenue du Pr Jean Poulhes, BP 84225, F-31432 Toulouse Cedex (France); Imbert, Sandrine [CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, BP 64182, F-31077 Toulouse Cedex (France); Salles, Bernard [Universite de Toulouse, UPS, F-31077 Toulouse Cedex (France); CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, BP 64182, F-31077 Toulouse Cedex (France); Valet, Philippe [Universite de Toulouse, UPS, F-31077 Toulouse Cedex (France); Institut National de la Sante et de la Recherche Medicale, INSERM U1048, 1 Avenue du Pr Jean Poulhes, BP 84225, F-31432 Toulouse Cedex (France); Muller, Catherine, E-mail: muller@ipbs.fr [Universite de Toulouse, UPS, F-31077 Toulouse Cedex (France); CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 route de Narbonne, BP 64182, F-31077 Toulouse Cedex (France)

    2011-07-22

    Highlights: {yields} Tumor-surrounding adipocytes contribute to breast cancer progression. {yields} Breast tumor cells previously co-cultivated with mature adipocytes exhibit radioresistance. {yields} Increased in Chk1 phosphorylation is observed in irradiated co-cultivated tumor cells. {yields} IL-6 is over-expressed in tumor cells co-cultivated with adipocytes. {yields} IL-6 exposure confers increased Chk1 phosphorylation and radioresistance in tumor cells. -- Abstract: Mature adipocytes are excellent candidates to influence tumor behavior through heterotypic signaling processes since these cells produce hormones, growth factors, cytokines and other molecules, a heterogeneous group of molecules named adipokines. Using a 2D coculture system, we demonstrate that breast tumor cells previously co-cultivated with mature adipocytes exhibit radioresistance and an earlier and higher increase in the effector kinase Chk1, a phenotype that was associated with decreased cell death as compared to tumor cells grown alone. Interestingly, the adipocytes-induced tumor changes taking place during the coculture time preceding the exposure to IR were sufficient to confer the radioresistant effect. Notorious among the changes brought by adipocytes was the significant increase of IL-6 expression in tumor cells, whose activity may well account for the observed tumor cell protection from IR toxicity. Indeed, our data confirmed the protective role of this cytokine as tumor cells incubated after irradiation with recombinant IL-6 exhibit an increased in Chk1 phosphorylation and a radioresistant phenotype, thus far recapitulating the effects observed in the presence of adipocytes. Our current study sheds light on a new role of tumor-surrounding adipocytes in fostering a radioresistant phenotype in breast tumors, a finding that might have important clinical implications in obese patients that frequently exhibit aggressive diseases.

  6. 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 ...

  7. 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 ...

  8. 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

  9. Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

    NARCIS (Netherlands)

    Couch, Fergus J.; Wang, Xianshu; McGuffog, Lesley; Lee, Andrew; Olswold, Curtis; Kuchenbaecker, Karoline B.; Soucy, Penny; Fredericksen, Zachary; Barrowdale, Daniel; Dennis, Joe; Gaudet, Mia M.; Dicks, Ed; Kosel, Matthew; Healey, Sue; Sinilnikova, Olga M.; Lee, Adam; Bacot, Francois; Vincent, Daniel; Hogervorst, Frans B. L.; Peock, Susan; Stoppa-Lyonnet, Dominique; Jakubowska, Anna; Radice, Paolo; Schmutzler, Rita Katharina; Domchek, Susan M.; Piedmonte, Marion; Singer, Christian F.; Friedman, Eitan; Thomassen, Mads; Hansen, Thomas V. O.; Neuhausen, Susan L.; Szabo, Csilla I.; Blanco, Ignacio; Greene, Mark H.; Karlan, Beth Y.; Garber, Judy; Phelan, Catherine M.; Weitzel, Jeffrey N.; Montagna, Marco; Olah, Edith; Andrulis, Irene L.; Godwin, Andrew K.; Yannoukakos, Drakoulis; Goldgar, David E.; Caldes, Trinidad; Nevanlinna, Heli; Osorio, Ana; Terry, Mary Beth; Daly, Mary B.; van Rensburg, Elizabeth J.; Hamann, Ute; Ramus, Susan J.; Toland, Amanda Ewart; Caligo, Maria A.; Olopade, Olufunmilayo I.; Tung, Nadine; Claes, Kathleen; Beattie, Mary S.; Southey, Melissa C.; Imyanitov, Evgeny N.; Tischkowitz, Marc; Janavicius, Ramunas; John, Esther M.; Kwong, Ava; Diez, Orland; Balmana, 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; Garcia, Encarna B. Gomez; 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, Agnes; 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; Leone, Melanie; Pujol, Pascal; Mazoyer, Sylvie; Bignon, Yves-Jean; Zlowocka-Perlowska, Elzbieta; 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; Paluch, Shani Shimon; 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.; Jonson, Lars; Andersen, Mette K.; Ding, Yuan Chun; Steele, Linda; Foretova, Lenka; Teule, Alex; Lazaro, Conxi; Brunet, Joan; Angel Pujana, Miquel; 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; Aittomaki, 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.

    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 furthe

  10. Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

    NARCIS (Netherlands)

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

    2013-01-01

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

  11. Association study of prostate cancer susceptibility variants with risks of invasive ovarian, breast, and colorectal cancer

    DEFF Research Database (Denmark)

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

    2008-01-01

    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...

  12. 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 ...

  13. 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.

  14. 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)

  15. 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 ...

  16. 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

  17. 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.

  18. Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers

    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...

  19. 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

  20. 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

  1. 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).

  2. 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.

  3. 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...

  4. Tamoxifen-associated vasculitis in a breast cancer patient

    Directory of Open Access Journals (Sweden)

    Vargas-Viveros Pablo

    2007-01-01

    Full Text Available Abstract Background Estrogen plays a critical role in breast cancer. Thereafter, endocrine therapy is a standard of care in patients with breast carcinoma, expressing ER or PR. Case presentation Herein we report the case of a 53-year old patient, who developed cholestasis and vasculitis during the treatment with tamoxifen. This toxicity was reversable after the removal of the drug. Thereafter she continued adjuvant treatment for breast carcinoma with anastrazole. Since tamoxifen has been widely indicated for patients with breast carcinoma, we did a literature review, looking for other cases with this type of toxicity. Conclusion This case is the third with vasculitis informed in the literature, but the first one that additionally developed cholestasis and arthritis. Although it is rare, we discuss the indication of this drug in the actual era, where aromatase inhibitors offer a better security profile.

  5. 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 ...

  6. 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

  7. 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 ...

  8. 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, ...

  9. 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 ...

  10. 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....

  11. 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 ...

  12. Microarray analysis of genes associated with cell surface NIS protein levels in breast cancer

    Directory of Open Access Journals (Sweden)

    Richardson Andrea L

    2011-10-01

    Full Text Available Abstract Background Na+/I- symporter (NIS-mediated iodide uptake allows radioiodine therapy for thyroid cancer. NIS is also expressed in breast tumors, raising potential for radionuclide therapy of breast cancer. However, NIS expression in most breast cancers is low and may not be sufficient for radionuclide therapy. We aimed to identify biomarkers associated with NIS expression such that mechanisms underlying NIS modulation in human breast tumors may be elucidated. Methods Published oligonucleotide microarray data within the National Center for Biotechnology Information Gene Expression Omnibus database were analyzed to identify gene expression tightly correlated with NIS mRNA level among human breast tumors. NIS immunostaining was performed in a tissue microarray composed of 28 human breast tumors which had corresponding oligonucleotide microarray data available for each tumor such that gene expression associated with cell surface NIS protein level could be identified. Results and Discussion NIS mRNA levels do not vary among breast tumors or when compared to normal breast tissues when detected by Affymetrix oligonucleotide microarray platforms. Cell surface NIS protein levels are much more variable than their corresponding NIS mRNA levels. Despite a limited number of breast tumors examined, our analysis identified cysteinyl-tRNA synthetase as a biomarker that is highly associated with cell surface NIS protein levels in the ER-positive breast cancer subtype. Conclusions Further investigation on genes associated with cell surface NIS protein levels within each breast cancer molecular subtype may lead to novel targets for selectively increasing NIS expression/function in a subset of breast cancers patients.

  13. Dietary Associations with a Breast Cancer Risk Biomarker Depend on Menopause Status.

    Science.gov (United States)

    Hidaka, Brandon H; Carlson, Susan E; Kimler, Bruce F; Fabian, Carol J

    2016-10-01

    We investigated how timing influences the role of diet in breast cancer risk with a cross-sectional study of pre-malignant change in breast tissue. Women with an elevated risk of developing breast cancer (33 premenopausal and 32 postmenopausal) completed the National Cancer Institute's food frequency questionnaire and underwent random periareolar fine-needle aspiration for evaluation of cytologic atypia, an established risk biomarker. Fatty acid composition of breast adipose was measured in 32 (49%) subjects. We found that premenopausal and postmenopausal women had similar diets, but the associations between atypia and intake of total n-3 polyunsaturated fatty acids (PUFA) and soy differed by menopause status (both P interaction soy (P = 0.0003 and P = 0.48, respectively). This pattern of dietary interaction with menopause was mirrored in tissue fatty acids (P interaction 0.37). Dietary associations with breast cancer risk are stronger prior to menopause. PMID:27618149

  14. 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 ...

  15. Comparison of 6q25 Breast Cancer Hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC)

    NARCIS (Netherlands)

    Hein, Rebecca; Maranian, Melanie; Hopper, John L.; Kapuscinski, Miroslaw K.; Southey, Melissa C.; Park, Daniel J.; Schmidt, Marjanka K.; Broeks, Annegien; Hogervorst, Frans B. L.; Bueno-de-Mesquit, H. Bas; Muir, Kenneth R.; Lophatananon, Artitaya; Rattanamongkongul, Suthee; Puttawibul, Puttisak; Fasching, Peter A.; Hein, Alexander; Ekici, Arif B.; Beckmann, Matthias W.; Fletcher, Olivia; Johnson, Nichola; Silva, Isabel dos Santos; Peto, Julian; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael; Miller, Nicola; Marmee, Frederick; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Guenel, Pascal; Cordina-Duverger, Emilie; Menegaux, Florence; Truong, Therese; Bojesen, Stig E.; Nordestgaard, Borge G.; Flyger, Henrik; Milne, Roger L.; Arias Perez, Jose Ignacio; Pilar Zamora, M.; Benitez, Javier; Anton-Culver, Hoda; Ziogas, Argyrios; Bernstein, Leslie; Clarke, Christina A.; Brenner, Hermann; Mueller, Heiko; Arndt, Volker; Stegmaier, Christa; Rahman, Nazneen; Seal, Sheila; Turnbull, Clare; Renwick, Anthony; Meindl, Alfons; Schott, Sarah; Bartram, Claus R.; Schmutzler, Rita K.; Brauch, Hiltrud; Hamann, Ute; Ko, Yon-Dschun; Wang-Gohrke, Shan; Doerk, Thilo; Schuermann, Peter; Karstens, Johann H.; Hillemanns, Peter; Nevanlinna, Heli; Heikkinen, Tuomas; Aittomaki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia V.; Zalutsky, Iosif V.; Antonenkova, Natalia N.; Bermisheva, Marina; Prokovieva, Darya; Farahtdinova, Albina; Khusnutdinova, Elza; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana; Chen, Xiaoqing; Beesley, Jonathan; Lambrechts, Diether; Zhao, Hui; Neven, Patrick; Wildiers, Hans; Nickels, Stefan; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Barile, Monica; Couch, Fergus J.; Olson, Janet E.; Wang, Xianshu; Fredericksen, Zachary; Giles, Graham G.; Baglietto, Laura; McLean, Catriona A.; Severi, Gianluca; Offit, Kenneth; Robson, Mark; Gaudet, Mia M.; Vijai, Joseph; Alnaes, Grethe Grenaker; Kristensen, Vessela; Borresen-Dale, Anne-Lise; John, Esther M.; Miron, Alexander; Winqvist, Robert; Pylkas, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Figueroa, Jonine D.; Garcia-Closas, Montserrat; Lissowska, Jolanta; Sherman, Mark E.; Hooning, Maartje; Martens, John W. M.; Seynaeve, Caroline; Collee, Margriet; Hall, Per; Humpreys, Keith; Czene, Kamila; Liu, Jianjun; Cox, Angela; Brock, Ian W.; Cross, Simon S.; Reed, Malcolm W. R.; Ahmed, Shahana; Ghoussaini, Maya; Pharoah, Paul D. P.; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Zlowocka, Elzbieta; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Shen, Chen-Yang; Yu, Jyh-Cherng; Hsu, Huan-Ming; Hou, Ming-Feng; Orr, Nick; Schoemaker, Minouk; Ashworth, Alan; Swerdlow, Anthony; Trentham-Dietz, Amy; Newcomb, Polly A.; Titus, Linda; Egan, Kathleen M.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Humphreys, Manjeet K.; Morrison, Jonathan; Chang-Claude, Jenny; Easton, Douglas F.; Dunning, Alison M.

    2012-01-01

    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 Europea

  16. 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

  17. 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 ...

  18. 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...

  19. 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...

  20. Life history theory and breast cancer risk: methodological and theoretical challenges: Response to "Is estrogen receptor negative breast cancer risk associated with a fast life history strategy?".

    Science.gov (United States)

    Aktipis, Athena

    2016-01-01

    In a meta-analysis published by myself and co-authors, we report differences in the life history risk factors for estrogen receptor negative (ER-) and estrogen receptor positive (ER+) breast cancers. Our meta-analysis did not find the association of ER- breast cancer risk with fast life history characteristics that Hidaka and Boddy suggest in their response to our article. There are a number of possible explanations for the differences between their conclusions and the conclusions we drew from our meta-analysis, including limitations of our meta-analysis and methodological challenges in measuring and categorizing estrogen receptor status. These challenges, along with the association of ER+ breast cancer with slow life history characteristics, may make it challenging to find a clear signal of ER- breast cancer with fast life history characteristics, even if that relationship does exist. The contradictory results regarding breast cancer risk and life history characteristics illustrate a more general challenge in evolutionary medicine: often different sub-theories in evolutionary biology make contradictory predictions about disease risk. In this case, life history models predict that breast cancer risk should increase with faster life history characteristics, while the evolutionary mismatch hypothesis predicts that breast cancer risk should increase with delayed reproduction. Whether life history tradeoffs contribute to ER- breast cancer is still an open question, but current models and several lines of evidence suggest that it is a possibility.

  1. 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 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

  2. Genetic variants in interleukin genes are associated with breast cancer risk and survival in a genetically admixed population: the Breast Cancer Health Disparities Study.

    Science.gov (United States)

    Slattery, Martha L; Herrick, Jennifer S; Torres-Mejia, Gabriella; John, Esther M; Giuliano, Anna R; Hines, Lisa M; Stern, Mariana C; Baumgartner, Kathy B; Presson, Angela P; Wolff, Roger K

    2014-08-01

    Interleukins (ILs) are key regulators of immune response. Genetic variation in IL genes may influence breast cancer risk and mortality given their role in cell growth, angiogenesis and regulation of inflammatory process. We examined 16 IL genes with breast cancer risk and mortality in an admixed population of Hispanic/Native American (NA) (2111 cases and 2597 controls) and non-Hispanic white (NHW) (1481 cases and 1585 controls) women. Adaptive Rank Truncated Product (ARTP) analysis was conducted to determine gene significance and lasso (least absolute shrinkage and selection operator) was used to identify potential gene by gene and gene by lifestyle interactions. The pathway was statistically significant for breast cancer risk overall (P ARTP = 0.0006), for women with low NA ancestry (P(ARTP) = 0.01), for premenopausal women (P(ARTP) = 0.02), for estrogen receptor (ER)+/progesterone receptor (PR)+ tumors (P(ARTP) = 0.03) and ER-/PR- tumors (P(ARTP) = 0.02). Eight of the 16 genes evaluated were associated with breast cancer risk (IL1A, IL1B, IL1RN, IL2, IL2RA, IL4, IL6 and IL10); four genes were associated with breast cancer risk among women with low NA ancestry (IL1B, IL6, IL6R and IL10), two were associated with breast cancer risk among women with high NA ancestry (IL2 and IL2RA) and four genes were associated with premenopausal breast cancer risk (IL1A, IL1B, IL2 and IL3). IL4, IL6R, IL8 and IL17A were associated with breast cancer-specific mortality. We confirmed associations with several functional polymorphisms previously associated with breast cancer risk and provide support that their combined effect influences the carcinogenic process.

  3. 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...

  4. An estrogen-associated dietary pattern and breast cancer risk in the Swedish Mammography Cohort.

    Science.gov (United States)

    Harris, Holly R; Bergkvist, Leif; Wolk, Alicja

    2015-11-01

    High endogenous hormone levels have been associated with breast cancer and dietary factors have the potential to influence breast cancer risk through effects on hormone levels. Dietary patterns derived from reduced rank regression provide a way to identify food groups correlated with hormones and subsequently examine food patterns that may be associated with breast cancer risk. We investigated whether a dietary pattern previously correlated with estradiol and estrone sulfate was associated with breast cancer in the prospective Swedish Mammography Cohort. Among 37,004 primarily postmenopausal women diet was assessed with a food frequency questionnaire. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). During 15 years of follow-up 1,603 cases of breast cancer were identified. A higher estrogen dietary pattern score was associated with an increased risk of breast cancer. Women in the highest quartile of estrogen pattern score had a 29% (95% CI = 1.08-1.55) increased risk of breast cancer compared to women in the lowest quartile (p(trend) = 0.006). When the association was examined by estrogen-receptor status, it was only significant for those with estrogen-receptor-positive tumors; however, in the competing risk analysis there were no significant differences in the effect estimates by receptor subtype (p(heterogeneity) = 0.65). Our findings suggest that a dietary pattern associated with higher estrogen levels may increase breast cancer risk. However, whether the influence of this dietary pattern is through a direct effect on estrogen levels deserves further study.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    Patrícia Helena Costa Mendes

    2016-07-01

    Full Text Available 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 digital Vernier calliper. Mean digit ratios of right hands, left hands, and right minus left hand 2D:4D (DR-L were compared between both groups. Data were analysed by the Student's t-test for unpaired samples, Mann-Whitney test, and Spearman`s correlation with a significance level of 5%.Results: The patients with breast cancer presented significantly higher right and left 2D:4D (both p < 0.001 and higher DR-L (p = 0.032 than controls. Among breast cancer cases, there was a significantly negative correlation between left 2D:4D and age diagnosed with breast cancer (p = 0.018.Conclusion: Digit ratio offers a valid retrospective biomarker of action of prenatal hormones and might be associated with breast cancer risk and age at onset of breast cancer. It suggests that higher exposure or sensitivity to prenatal oestrogen might be associated with a higher risk of breast cancer and with earlier onset of the disease.

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

    Science.gov (United States)

    Michailidou, Kyriaki; Hall, Per; Gonzalez-Neira, Anna; Ghoussaini, Maya; Dennis, Joe; Milne, Roger L; Schmidt, Marjanka K; Chang-Claude, Jenny; Bojesen, Stig E; Bolla, Manjeet K; Wang, Qin; Dicks, Ed; Lee, Andrew; Turnbull, Clare; Rahman, Nazneen; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; Silva, Isabel dos Santos; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel; van der Luijt, Rob B; Hein, Rebecca; Dahmen, Norbert; Beckman, Lars; Meindl, Alfons; Schmutzler, Rita K; Müller-Myhsok, Bertram; Lichtner, Peter; Hopper, John L; Southey, Melissa C; Makalic, Enes; Schmidt, Daniel F; Uitterlinden, Andre G; Hofman, Albert; Hunter, David J; Chanock, Stephen J; Vincent, Daniel; Bacot, François; Tessier, Daniel C; Canisius, Sander; Wessels, Lodewyk F A; Haiman, Christopher A; Shah, Mitul; Luben, Robert; Brown, Judith; Luccarini, Craig; Schoof, Nils; Humphreys, Keith; Li, Jingmei; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Couch, Fergus J; Wang, Xianshu; Vachon, Celine; Stevens, Kristen N; Lambrechts, Diether; Moisse, Matthieu; Paridaens, Robert; Christiaens, Marie-Rose; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Johnson, Nichola; Aitken, Zoe; Aaltonen, Kirsimari; Heikkinen, Tuomas; Broeks, Annegien; Van’t Veer, Laura J; van der Schoot, C Ellen; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Menegaux, Florence; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Zamora, M Pilar; Perez, Jose Ignacio Arias; Pita, Guillermo; Alonso, M Rosario; Cox, Angela; Brock, Ian W; Cross, Simon S; Reed, Malcolm W R; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Lindblom, Annika; Margolin, Sara; Hooning, Maartje J; Hollestelle, Antoinette; van den Ouweland, Ans M W; Jager, Agnes; Bui, Quang M; Stone, Jennifer; Dite, Gillian S; Apicella, Carmel; Tsimiklis, Helen; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; 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; Bonanni, Bernardo; Devilee, Peter; Tollenaar, Rob A E M; Seynaeve, Caroline; van Asperen, Christi J; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Bogdanova, Natalia V; Antonenkova, Natalia N; Dörk, Thilo; Kristensen, Vessela N; Anton-Culver, Hoda; Slager, Susan; Toland, Amanda E; Edge, Stephen; Fostira, Florentia; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Sueta, Aiko; Wu, Anna H; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Teo, Soo Hwang; Yip, Cheng Har; Phuah, Sze Yee; Cornes, Belinda K; Hartman, Mikael; Miao, Hui; Lim, Wei Yen; Sng, Jen-Hwei; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Ding, Shian-Ling; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Blot, William J; Signorello, Lisa B; Cai, Qiuyin; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha; Long, Jirong; Simard, Jacques; Garcia-Closas, Montse; Pharoah, Paul D P; Chenevix-Trench, Georgia; Dunning, Alison M; Benitez, Javier; Easton, Douglas F

    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 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs. We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10−8). Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility. PMID:23535729

  8. Associations of polymorphisms in microRNAs with female breast cancer risk in Chinese population.

    Science.gov (United States)

    He, Bangshun; Pan, Yuqin; Xu, Yeqiong; Deng, Qiwen; Sun, Huling; Gao, Tianyi; Wang, Shukui

    2015-06-01

    Polymorphisms in microRNA (miRNA) have been discussed to be associated with breast cancer risk; however, the conclusions were always inconsistent in different ethnicities. This case-control study enrolled 450 breast cancer cases, and 450 health controls was carried out to investigate the association between six polymorphisms in miRNAs and breast cancer risk. Sequenom MassARRAY was used to detect the polymorphisms in miRNAs, and the immunohistochemistry assay was applied to detect the expression of estrogen receptor (ER) and progesterone receptor (PR) in cancer tissue. The data showed that the 3746444 GG was associated with increased breast cancer risk (adjusted odds ratio (OR) = 1.71, 95 % confidence interval (CI) = 1.16-2.52) and that rs2292832 CC (adjusted OR = 0.54, 95 % CI = 0.34-0.85) was associated with decreased breast cancer risk. In addition, menopausal status subgroup analysis revealed that rs3746444 GG (adjusted OR = 2.34, 95 % CI = 1.31-4.15) and GA/GG (adjusted OR = 1.60, 95 % CI = 1.08-2.37) genotypes were associated with increased breast cancer risk for the subgroup of women with premenopausal status, respectively. Moreover, rs2910164 GG (adjusted OR = 1.84, 95 % CI = 1.07-3.15) and CG/GG (adjusted OR = 1.47, 95 % CI = 1.01-2.15) genotypes were associated with increased breast cancer risk in the postmenopausal status subcohort, respectively. Furthermore, rs3746444 AG (adjusted OR = 1.61, 95 % CI = 1.06-2.45) and AG/GG (adjusted OR = 1.49, 95 % CI = 1.02-2.18) genotypes were observed to be associated with increased risk of lymph node involvement and breast cancer with negative PR expression, separately. In short, rs3746444 was associated with breast cancer risk, especially for women with premenopausal status, and rs2910164 CG and CG/GG genotypes were associated with breast cancer risk for the women with premenopausal status.

  9. 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.

  10. 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.

  11. 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,...

  12. 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.

  13. 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...

  14. 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.

  15. Shoulder impairments and their association with symptomatic rotator cuff disease in breast cancer survivors.

    Science.gov (United States)

    Ebaugh, David; Spinelli, Bryan; Schmitz, Kathryn H

    2011-10-01

    Over 2.6 million breast cancer survivors currently reside in the United States. While improvements in the medical management of women diagnosed with breast cancer have resulted in a 5-year survival rate of 89%, curative treatments are associated with a high prevalence of shoulder and arm morbidity, which, in turn, can negatively impact a woman's quality of life. Breast cancer survivors frequently experience shoulder and arm pain, decreased range of motion, muscle weakness, and lymphedema. These symptoms can lead to difficulties with daily activities ranging from overhead reaching and carrying objects to caring for family and returning to work. Despite health care professionals awareness of these problems, a significant number of breast cancer survivors are confronted with long-term, restricted use of their affected shoulder and upper extremity. This problem may partially be explained by: (1) an incomplete understanding of relevant impairments and diagnoses associated with shoulder/arm pain and limited upper extremity use, and (2) the limited effectiveness of current rehabilitation interventions for managing shoulder pain and decreased upper extremity function in breast cancer survivors. Because breast cancer treatment directly involves the neuromusculoskeletal tissues of the shoulder girdle, it is understandable why breast cancer survivors are likely to develop shoulder girdle muscle weakness and fatigue, decreased shoulder motion, altered shoulder girdle alignment, and lymphedema. These impairments can be associated with diagnoses such as post-mastectomy syndrome, adhesive capsulitis, myofascial dysfunction, and brachial plexopathy, all of which have been reported among breast cancer survivors. It is our belief that these impairments also put women at risk for developing symptomatic rotator cuff disease. In this paper we set forth the rationale for our belief that breast cancer treatments and subsequent impairments of shoulder girdle neuromusculoskeletal tissues

  16. 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

  17. 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

  18. Prevalence of and factors associated with persistent pain following breast cancer surgery

    DEFF Research Database (Denmark)

    Gärtner, Rune; Jensen, Maj-Britt; Nielsen, Jeanette;

    2009-01-01

    of and factors associated with persistent pain after surgical treatment for breast cancer. DESIGN, SETTING, AND PATIENTS: A nationwide cross-sectional questionnaire study of 3754 women aged 18 to 70 years who received surgery and adjuvant therapy (if indicated) for primary breast cancer in Denmark between......CONTEXT: Persistent pain and sensory disturbances following surgical treatment for breast cancer is a significant clinical problem. The pathogenic mechanisms are complex and may be related to patient characteristics, surgical technique, and adjuvant therapy. OBJECTIVE: To examine prevalence....... CONCLUSION: Two to 3 years after breast cancer treatment, persistent pain and sensory disturbances remain clinically significant problems among Danish women who received surgery in 2005 and 2006....

  19. 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.

  20. 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 ...

  1. 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

  2. Association of cyclin D1 genotype with breast cancer risk and survival.

    Science.gov (United States)

    Shu, Xiao Ou; Moore, Derek B; Cai, Qiuyin; Cheng, Jiarong; Wen, Wanqing; Pierce, Larry; Cai, Hui; Gao, Yu-Tang; Zheng, Wei

    2005-01-01

    Cyclin D1 (CCND1) is a key cell cycle regulatory protein that governs cell cycle progression from the G(1) to S phase. A common polymorphism (A870G) in exon 4 of the CCND1 gene produces an alternate transcript (transcript-b) that preferentially encodes a protein with enhanced cell transformation activity and possible prolonged half-life. We evaluated the association of CCND1 A870G polymorphism with breast cancer risk and survival in 1,130 breast cancer cases and 1,196 controls who participated in the Shanghai Breast Cancer Study. Approximately 81% of cases and 79% of controls carried the A allele at A870G of the CCND1 gene [odds ratio, 1.1; 95% confidence interval (95% CI), 0.9-1.4]. As lightly stronger but nonsignificant association was found for the A allele among younger women (odds ratio, 1.3; 95% CI, 0.9-1.8). However, this polymorphism seems to modify the effect of hormonal exposures on postmenopausal breast cancer, as the positive associations of postmenopausal breast cancer with body mass index (Pfor interaction = 0.02) and waist-to-hip ratios (P for interaction < 0.03; all Ps are two sided) were only observed among women who carry the A allele at A870G of the CCND1 gene. Following up with this cohort of patients for an average of 4.84 years, we found that the CCND1 A870G polymorphism was inversely associated with overall and disease-free survival, particularly among women with late stage or estrogen/progesterone receptor-negative breast cancer. The adjusted hazard ratios for disease-free survival associated with GA and AA genotypes were 0.94 (95% CI, 0.49-1.82) and 0.41 (95% CI, 0.19-0.91) for tumor-node-metastasis stage III to IV breast cancer, and 0.35 (95% CI, 0.15-0.80) and 0.32 (95% CI, 0.13-0.79) for estrogen/progesterone receptor-negative breast cancer. This study suggests that CCND1 A870G polymorphism may modify the postmenopausal breast cancer risk associated with hormonal exposure and predict survival after breast cancer diagnosis. PMID:15668481

  3. 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.

  4. 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

  5. Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations

    NARCIS (Netherlands)

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

    2016-01-01

    Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 c

  6. Cross-cancer genome-wide analysis of lung, ovary, breast, prostate and colorectal cancer reveals novel pleiotropic associations

    NARCIS (Netherlands)

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

    2016-01-01

    Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-staged approach to conduct genome-wide association studies for lung, ovary, breast, prostate and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 c

  7. Associations of Breast Cancer Risk Factors with Premenopausal Sex Hormones in Women with Very Low Breast Cancer Risk

    Directory of Open Access Journals (Sweden)

    Lauren C. Houghton

    2016-10-01

    Full Text Available Breast cancer incidence rates are low but rising in urban Mongolia. We collected reproductive and lifestyle factor information and measured anthropometrics and serum sex steroid concentrations among 314 premenopausal women living in Ulaanbaatar, Mongolia. Mean differences in hormone concentrations by these factors were calculated using age-adjusted quadratic regression splines. Estrone and estradiol in college-educated women were, respectively, 18.2% (p = 0.03 and 23.6% (p = 0.03 lower than in high-school-educated women. Progesterone concentrations appeared 55.8% lower (p = 0.10 in women residing in modern housing compared with women living in traditional housing (gers, although this finding was not statistically significant. Testosterone concentrations were positively associated with adiposity and central fat distribution % difference for highest vs. lowest quarter for body mass index (17.1% (p = 0.001 and waist-to-height ratio (15.1% (p = 0.005. Estrogens were higher in the follicular phase of women who breastfed each child for shorter durations. A distinct hormonal profile was associated with an urban lifestyle in premenopausal, Mongol women. In particular, heavier, more-educated women living in urban dwellings had higher testosterone and lower estrogen and progesterone levels. Higher breast cancer incidence in urban compared with rural women suggest that the hormonal profile associated with a more traditional lifestyle may be protective among Mongol women.

  8. 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

  9. Recurrent HOXB13 mutations in the Dutch population do not associate with increased breast cancer risk.

    Science.gov (United States)

    Liu, Jingjing; Prager-van der Smissen, Wendy J C; Schmidt, Marjanka K; Collée, J Margriet; Cornelissen, Sten; Lamping, Roy; Nieuwlaat, Anja; Foekens, John A; Hooning, Maartje J; Verhoef, Senno; van den Ouweland, Ans M W; Hogervorst, Frans B L; Martens, John W M; Hollestelle, Antoinette

    2016-01-01

    The HOXB13 p.G84E mutation has been firmly established as a prostate cancer susceptibility allele. Although HOXB13 also plays a role in breast tumor progression, the association of HOXB13 p.G84E with breast cancer risk is less evident. Therefore, we comprehensively interrogated the entire HOXB13 coding sequence for mutations in 1,250 non-BRCA1/2 familial breast cancer cases and 800 controls. We identified two predicted deleterious missense mutations, p.G84E and p.R217C, that were recurrent among breast cancer cases and further evaluated their association with breast cancer risk in a larger study. Taken together, 4,520 familial non-BRCA1/2 breast cancer cases and 3,127 controls were genotyped including the cases and controls of the whole gene screen. The concordance rate for the genotyping assays compared with Sanger sequencing was 100%. The prostate cancer risk allele p.G84E was identified in 18 (0.56%) of 3,187 cases and 16 (0.70%) of 2,300 controls (OR = 0.81, 95% CI = 0.41-1.59, P = 0.54). Additionally, p.R217C was identified in 10 (0.31%) of 3,208 cases and 2 (0.087%) of 2,288 controls (OR = 3.57, 95% CI = 0.76-33.57, P = 0.14). These results imply that none of the recurrent HOXB13 mutations in the Dutch population are associated with breast cancer risk, although it may be worthwhile to evaluate p.R217C in a larger study.

  10. Breast cancer associated a2 isoform vacuolar ATPase immunomodulates neutrophils: potential role in tumor progression.

    Science.gov (United States)

    Ibrahim, Safaa A; Katara, Gajendra K; Kulshrestha, Arpita; Jaiswal, Mukesh K; Amin, Magdy A; Beaman, Kenneth D

    2015-10-20

    In invasive breast cancer, tumor associated neutrophils (TAN) represent a significant portion of the tumor mass and are associated with increased angiogenesis and metastasis. Identifying the regulatory factors that control TAN behavior will help in developing ideal immunotherapies. Vacuolar ATPases (V-ATPases), multi-subunit proton pumps, are highly expressed in metastatic breast cancer cells. A cleaved peptide from a2 isoform V-ATPase (a2NTD) has immunomodulatory role in tumor microenvironment. Here, we report for the first time the role of V-ATPase in neutrophils modulation. In invasive breast cancer cells, a2NTD was detected and a2V was highly expressed on the surface. Immunohistochemical analysis of invasive breast cancer tissues revealed that increased neutrophil recruitment and blood vessel density correlated with increased a2NTD levels. In order to determine the direct regulatory role of a2NTD on neutrophils, recombinant a2NTD was used for the treatment of neutrophils isolated from the peripheral blood of healthy volunteers. Neutrophils treated with a2NTD (a2Neuɸ) showed increased secretion of IL-1RA, IL-10, CCL-2 and IL-6 that are important mediators in cancer related inflammation. Moreover, a2Neuɸ exhibited an increased production of protumorigenic factors including IL-8, matrix metaloprotinase-9 and vascular endothelial growth factor. Further, functional characterization of a2Neuɸ revealed that a2Neuɸ derived products induce in vitro angiogenesis as well as increase the invasiveness of breast cancer cells. This study establishes the modulatory effect of breast cancer associated a2V on neutrophils, by the action of a2NTD, which has a positive impact on tumor progression, supporting that a2V can be a potential selective target for breast cancer therapy.

  11. 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)

  12. Intake of freshwater fish and associated fatty acids and risk of breast cancer.

    Science.gov (United States)

    Gao, Chang-Ming; Ding, Jian-Hua; Li, Su-Ping; Liu, Yan-Ting; Tang, Jin-Hai; Tajima, Kazuo

    2014-01-01

    To investigate the association between intake of freshwater fish and their fatty acids and the risk of breast cancer in Chinese women, we conducted a case-control study with 669 cases and 682 population-based controls in Jiangsu Province of China. A structured questionnaire was used to elicit detailed information. Unconditional logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Total freshwater fish intake was linked to decrease in the adjusted OR for breast cancer, but without dose-dependence. Analyses by freshwater fish species showed that consumption of black carp and silver carp was inversely related to breast cancer risk, with adjusted-ORs for the highest intake category of black carp (≥500g/month) of 0.54 (95%CI=0.33-0.92; P trendcarp (≥1000g/month) of 0.19 (95%CI=0.11-0.33; P trendcarp was positively related to breast cancer risk, with an adjusted OR for the highest intake category (≥1000g/month) of 6.09 (95%CI=3.04-12.2; P trend<0.001). Moderate intakes of SFA, PUFA, n3-PUFA and n6-PUFA from freshwater fish may decrease the risk of breast cancer among premenopausal women. The findings of this study suggest that intake of freshwater fish and their fatty acids may modify risk of breast cancer, and that different species of freshwater fish could have a different actions on breast cancer risk. Future epidemiologic studies are needed to know the effects of freshwater fish intake on breast cancer risk and the cause of these effects.

  13. 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)

  14. 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 ...

  15. 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 ...

  16. 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. ...

  17. Hereditary epidermolytic palmoplantar keratoderma associated with breast and ovarian cancer in a large kindred.

    Science.gov (United States)

    Blanchet-Bardon, C; Nazzaro, V; Chevrant-Breton, J; Espie, M; Kerbrat, P; Le Marec, B

    1987-09-01

    We report a large kindred in which palmoplantar keratoderma occurred in association with breast or ovarian cancer or both. This kindred consisted of 61 members of four generations. Thirty-five individuals had palmoplantar keratoderma, including eight women who also had breast or ovarian cancer or both. Five of the six women with breast cancer and both the women with ovarian cancer have died. The proband presented with a yellowish, uniform hyperkeratosis surrounded by a red border covering the entire surface of the palms and soles. Light microscopic examination showed features of epidermolytic hyperkeratosis, and ultrastructural examination revealed the typical markers for this entity, cytolysis and clumps of keratin filaments. This kindred is the first, to our knowledge, to have an association of epidermolytic hyperkeratosis and internal malignancy.

  18. 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

  19. 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 ...

  20. 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

  1. 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

  2. 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...

  3. The association between polycystic ovary syndrome and breast cancer: a meta-analysis

    Science.gov (United States)

    Shobeiri, Fatemeh

    2016-01-01

    Objective The results of epidemiological studies investigated the association between polycystic ovary syndrome (PCOS) and the breast cancer are inconsistent. This meta-analysis was conducted to estimate the association between PCOS and the breast cancer risk. We searched PubMed, Web of Science, and Scopus for observational studies until June 2015. Data were independently extracted and analyzed using 95% odds ratio, and confidence intervals (CIs) based on the random-effects models. Methods We identified 970 references and conducted eight studies with 45,470 participants and 243,064 person- year. Results The association between PCOS and the breast cancer risk in case-control studies 0.87 (95% CI, 0.44 to 1.31) and that of cohort studies was estimated 1.18 (95% CI, 0.93 to 1.43). Conclusion This meta-analysis demonstrated that PCOS no does increase the risk of breast cancer. Further prospective cohort studies are needed to provide convincing evidence in order to PCOS can increase or not effect on the risk of the breast cancer. PMID:27668199

  4. The association between polycystic ovary syndrome and breast cancer: a meta-analysis

    Science.gov (United States)

    Shobeiri, Fatemeh

    2016-01-01

    Objective The results of epidemiological studies investigated the association between polycystic ovary syndrome (PCOS) and the breast cancer are inconsistent. This meta-analysis was conducted to estimate the association between PCOS and the breast cancer risk. We searched PubMed, Web of Science, and Scopus for observational studies until June 2015. Data were independently extracted and analyzed using 95% odds ratio, and confidence intervals (CIs) based on the random-effects models. Methods We identified 970 references and conducted eight studies with 45,470 participants and 243,064 person- year. Results The association between PCOS and the breast cancer risk in case-control studies 0.87 (95% CI, 0.44 to 1.31) and that of cohort studies was estimated 1.18 (95% CI, 0.93 to 1.43). Conclusion This meta-analysis demonstrated that PCOS no does increase the risk of breast cancer. Further prospective cohort studies are needed to provide convincing evidence in order to PCOS can increase or not effect on the risk of the breast cancer.

  5. 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...

  6. 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

  7. 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...

  8. 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

  9. 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...

  10. Genetic association of deleted in colorectal carcinoma variants with breast cancer risk: A case-control study.

    Science.gov (United States)

    Liu, Xinghan; Wang, Xijing; Fu, Sidney W; Wang, Meng; Kang, Huafeng; Guan, Haitao; Zhang, Shuqun; Ma, Xiaobin; Lin, Shuai; Liu, Kang; Feng, Yanjing; Dai, Cong; Dai, Zhijun

    2016-05-31

    Deleted in colorectal carcinoma (DCC), a netrin-1 dependence receptor, is correlated with cell progression, migration, and adhesion. Evidence indicated that DCC was frequently down-regulated in many cancers. However, the association of DCC with breast cancer remains uncertain. We conducted a case-control study to investigate the impact of three DCC gene variants (rs2229080, rs7504990, and rs4078288) on breast cancer susceptibility in Chinese women. This study included 560 breast cancer patients and 583 age-matched healthy controls from Northwest China. The three gene variants were genotyped via Sequenom MassARRAY. Odds ratios (ORs) and 95% confidence intervals (CIs) were utilized to evaluate the associations. We found that individuals with the rs2229080 C/G, C/C, and C/G-CC genotypes had a higher breast cancer risk, and the minor allele C was associated with increased breast cancer risk in an allele model. We observed a significantly decreased breast cancer risk with the rs7504990 C/T, T/T, and C/T-T/T genotypes, and the minor allele T was protective against breast cancer in an allele model. In addition, rs2229080 was associated with the axillary lymph node (LN) metastasis status. An age-stratified analysis revealed an association between rs2229080 and reduced breast cancer risk among older patients (≥ 49 years). Furthermore, the haplotype analysis showed that the Crs2229080Crs7504990Ars4078288 haplotype was associated with a decreased breast cancer risk. However, the results indicated a lack of association between rs4078288 and breast cancer risk. These findings affirmed that rs2229080 and rs7504990 polymorphisms in DCC might be related with breast cancer susceptibility in Chinese women.

  11. Association of Epstein-Barr virus and passive smoking with the risk of breast cancer among Chinese women.

    Science.gov (United States)

    Qi, Mei-Ling; Xi, Jing; Chen, Li-Juan; Su, Yi; Cen, Yu-Ling; Su, Feng-Xi; Lin, Ying; Zhuang, Zhi-Xiong; Tang, Lu-Ying; Ren, Ze-Fang

    2014-09-01

    Reactivation of Epstein-Barr virus (EBV), as indexed by the higher immunoglobulin A (IgA) antibody titers, was reported to be associated with an increased risk of breast cancer. Passive smoking plays a role in host immune responses and may modify the association of EBV with breast cancer. We carried out a case-control study using data from 349 incident breast cancer cases and 500 age-matched controls in the Guangzhou Breast Cancer Study to investigate the interactions of EBV antibodies and passive smoking on breast cancer risk. A higher risk of breast cancer was observed in passive smokers who were seropositive for EBV viral capsid antigen IgA or nuclear antigen-1 IgA in serum compared with those with the seronegativity and no passive smoking [odds ratio 3.13 (95% confidence interval, 1.76-5.56)]. There was a significant linear trend for the risk of breast cancer from IgA seropositivity with passive smoking, only IgA seropositivity, only passive smoking, to seronegativity without passive smoking (P<0.001), but the interaction in either multiplicative or additive models was not significant. No significant association was found between passive smoking and EBV IgA seropositivity. The present study confirmed the associations of EBV IgA antibodies and passive smoking with the risk of breast cancer and suggested that there was no synergic action between passive smoking and EBV IgA seropositivity on the risk of breast cancer. PMID:25010836

  12. 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.

  13. 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.

  14. 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

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

    Directory of Open Access Journals (Sweden)

    Bauer M

    2012-06-01

    Full Text Available 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 the associated increase in risk of fractures. This paper reviews the recent literature pertaining to aromatase inhibitor (AI-associated bone loss, and discusses suggested management and preventative approaches that may help patients remain on therapy to derive maximum clinical benefit. A case study is presented to illustrate the discussion. We observed that AIs are in widespread use for women with hormone receptor-positive breast cancer and are now recommended as adjuvant therapy, either as primary therapy or sequential to tamoxifen, for postmenopausal women. AIs target the estrogen biosynthetic pathway and deprive tumor cells of the growth-promoting effects of estrogen, and AI therapies provide benefits to patients in terms of improved disease-free survival. However, there is a concern regarding the increased risk of bone loss with prolonged AI therapy, which can be managed in many cases with the use of bisphosphonates and other interventions (eg, calcium, vitamin D supplementation, exercise.Keywords: aromatase inhibitors, bisphosphonates, bone loss, breast cancer, estrogen

  16. 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

  17. 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

  18. 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 ...

  19. A Comprehensive Multistate Model Analyzing Associations of Various Risk Factors With the Course of Breast Cancer in a Population-Based Cohort of Breast Cancer Cases.

    Science.gov (United States)

    Eulenburg, Christine; Schroeder, Jennifer; Obi, Nadia; Heinz, Judith; Seibold, Petra; Rudolph, Anja; Chang-Claude, Jenny; Flesch-Janys, Dieter

    2016-02-15

    We employed a semi-Markov multistate model for the simultaneous analysis of various endpoints describing the course of breast cancer. Results were compared with those from standard analyses using a Cox proportional hazards model. We included 3,012 patients with invasive breast cancer newly diagnosed between 2001 and 2005 who were recruited in Germany for a population-based study, the Mamma Carcinoma Risk Factor Investigation (MARIE Study), and prospectively followed up until the end of 2009. Locoregional recurrence and distant metastasis were included as intermediate states, and deaths from breast cancer, secondary cancer, and other causes were included as competing absorbing states. Tumor characteristics were significantly associated with all breast cancer-related endpoints. Nodal involvement was significantly related to local recurrence but more strongly related to distant metastases. Smoking was significantly associated with mortality from second cancers and other causes, whereas menopausal hormone use was significantly associated with reduced distant metastasis and death from causes other than cancer. The presence of cardiovascular disease at diagnosis was solely associated with mortality from other causes. Compared with separate Cox models, multistate models allow for dissection of prognostic factors and intermediate events in the analysis of cause-specific mortality and can yield new insights into disease progression and associated pathways.

  20. Alu and LINE-1 hypomethylation is associated with HER2 enriched subtype of breast cancer.

    Science.gov (United States)

    Park, So Yeon; Seo, An Na; Jung, Hae Yoen; Gwak, Jae Moon; Jung, Namhee; Cho, Nam-Yun; Kang, Gyeong Hoon

    2014-01-01

    The changes in DNA methylation status in cancer cells are characterized by hypermethylation of promoter CpG islands and diffuse genomic hypomethylation. Alu and long interspersed nucleotide element-1 (LINE-1) are non-coding genomic repetitive sequences and methylation of these elements can be used as a surrogate marker for genome-wide methylation status. This study was designed to evaluate the changes of Alu and LINE-1 hypomethylation during breast cancer progression from normal to pre-invasive lesions and invasive breast cancer (IBC), and their relationship with characteristics of IBC. We analyzed the methylation status of Alu and LINE-1 in 145 cases of breast samples including normal breast tissue, atypical ductal hyperplasia/flat epithelial atypia (ADH/FEA), ductal carcinoma in situ (DCIS) and IBC, and another set of 129 cases of IBC by pyrosequencing. Alu methylation showed no significant changes during multistep progression of breast cancer, although it tended to decrease during the transition from DCIS to IBC. In contrast, LINE-1 methylation significantly decreased from normal to ADH/FEA, while it was similar in ADH/FEA, DCIS and IBC. In IBC, Alu hypomethylation correlated with negative estrogen receptor (ER) status, and LINE-1 hypomethylation was associated with negative ER status, ERBB2 (HER2) amplification and p53 overexpression. Alu and LINE-1 methylation status was significantly different between breast cancer subtypes, and the HER2 enriched subtype had lowest methylation levels. In survival analyses, low Alu methylation status tended to be associated with poor disease-free survival of the patients. Our findings suggest that LINE-1 hypomethylation is an early event and Alu hypomethylation is probably a late event during breast cancer progression, and prominent hypomethylation of Alu and LINE-1 in HER2 enriched subtype may be related to chromosomal instability of this specific subtype.

  1. Association of OX40L polymorphisms with sporadic breast cancer in northeast Chinese Han population.

    Directory of Open Access Journals (Sweden)

    Yuan Weiguang

    Full Text Available OX40L is an important costimulatory molecule that plays a crucial role in the regulation of T-cell-mediated immunity. The interaction of OX40-OX40L is involved in the pathogenesis of multiple autoimmune and inflammatory diseases such as systemic lupus erythematosus (SLE, carotid artery disease and cancer. The genetic variants of OX40L can increase the risk of SLE, atherosclerosis, systemic sclerosis and show gender-specific effects in some studies. Accordingly, we performed a case-control study including 557 breast cancer patients and 580 age- and sex-matched healthy controls to investigate whether single nucleotide polymorphisms (SNPs in the OX40L gene are associated with sporadic breast cancer susceptibility and progression in Chinese Han women. Seven SNPs of OX40L (rs6661173, rs1234313, rs3850641, rs1234315, rs12039904, rs844648 and rs10912580 were genotyped with the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP. The results indicated that rs3850641G allele could increase the susceptibility to breast cancer (P = 0.009662, even in the validation study (P = 0.0001515. A significant association between rs3850641 and breast cancer risk was observed under the additive model and dominant model (P = 0.01042 and 0.01942, respectively. The haplotype analysis showed that haplotype A(rs844648A(rs10912580 was significantly associated with breast cancer, even after 10,000 permutations for haplotypes in block only (P = 0.0003. In clinicopathologic features analysis, the association between rs1234315 and C-erbB2 status was significant (P = 0.02541. Our data primarily indicates that rs3850641 of OX40L gene contributes to sporadic breast carcinogenesis in a northeast Chinese Han population.

  2. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Mahfouz, A.E.; Sherif, H. [Dept. of Radiology, Charite Medical Center, Humboldt-Univ. zu Berlin (Germany); Dept. of Radiology, Cairo University Hospital, Cairo (Egypt); Saad, A. [Dept. of Radiology, Charite Medical Center, Humboldt-Univ. zu Berlin (Germany); Dept. of Public Health and Environmental Medicine, National Research Center, Cairo (Egypt); Taupitz, M.; Filimonow, S.; Kivelitz, D.; Hamm, B. [Dept. of Radiology, Charite Medical Center, Humboldt-Univ. zu Berlin (Germany)

    2001-06-01

    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.)

  4. 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…

  5. 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.

  6. 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 ...

  7. Does Pregnancy-Associated Breast Cancer Imply a Worse Prognosis? A Matched Case-Case Study

    Science.gov (United States)

    Dimitrakakis, Constantine; Zagouri, Flora; Tsigginou, Alexandra; Marinopoulos, Spyros; Sergentanis, Theodoros N.; Keramopoulos, Antonis; Zografos, George C.; Ampela, Konstantina; Mpaltas, Dimosthenis; Papadimitriou, Christos; Dimopoulos, Meletios-Athanassios; Antsaklis, Aris

    2013-01-01

    Summary Background Significant controversy exists in the literature regarding the role of pregnancy in the prognosis of breast cancer. We designed a matched case-case study, matching pregnancy-associated breast cancer (PABC) cases with breast cancer cases for stage, age, and year of diagnosis. Patients and Methods 39 consecutive cases of PABC were matched with 39 premenopausal cases of breast cancer. Univariate and multivariate survival analyses followed by adjustment for stage, grade, estrogen receptor status, and age at diagnosis, were performed. Results Regarding overall survival (OS), univariate analysis pointed to longer OS in non-PABC cases vs. PABC cases. Accordingly, a more advanced stage predicted shorter survival. In the multivariate analysis, the independent aggravating effect mediated by pregnancy persisted. Interestingly, a post hoc nested analysis within PABC cases indicated that the 3rd trimester pointed to shorter OS. The aforementioned results on OS were also replicated during the examination of relapse-free survival. Conclusion Implementing a matched case-case design, the present study points to pregnancy as a poor prognostic factor for breast cancer. PMID:24415971

  8. BRCA2 promoter polymorphism is associated with breast cancer prognosis in Chinese women

    Institute of Scientific and Technical Information of China (English)

    Liu Lu; Fang Yi; Fan Jianlin; Hu Jianming; Xu Xiaoting; Jin Xiaohong; Wang Xiuzhen

    2014-01-01

    Background Breast cancer 2 (BRCA2) is an important breast cancer-susceptibility gene.Promoter polymorphisms in BRCA2 may affect its transcription and be associated with cancer prognosis.Methods We identified five polymorphisms of the BRCA2 promoter region by in silico searching and direct sequencing:-254A/G (rs3092989),-908A/G (rs206117),-1134A/G (rs206115),-1144C/T (rs206116),and-1260CTTAGA/-(rs3072036).The-908A/G,-1134A/G,-1144C/T,and-1260CTTAGA/-polymorphisms were genotyped by direct sequencing in 491 breast cancer patients,and the-254A/G polymorphism was genotyped by Sequenom.Results The-1144C/T polymorphism was associated with clinical outcome.Carriers of the TT genotype had longer disease-free intervals (DFIs,P=0.029),especially among patients with sporadic unilateral breast cancer (P=0.010).Linkage disequilibrium (LD) analysis showed that all the five single nucleotide polymorphisms (SNPs) were in LD (D'>0.8).Carriers of haplotypes containing the-1144T allele showed longer DFIs (P=0.049),and the result was more significant in patients with sporadic unilateral cancer (P=0.018).There were no significant associations between the other polymorphisms and DFI.Conclusions The results of this study suggest that homozygosity for the BRCA2 T(-1144) allele is associated with a longer DFI in Chinese women with breast cancer.Further functional studies are warranted to clarify this relationship.

  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. A single nucleotide polymorphism of the TNRC9 gene associated with breast cancer risk in Chinese Han women.

    Science.gov (United States)

    Chen, F; Zhou, J; Xue, Y; Yang, S; Xiong, M; Li, Y; Liu, Q

    2014-01-01

    A single nucleotide polymorphism (SNP) in the TNRC9 gene was identified as a breast cancer susceptibility genetic variant in recent genome-wide association studies of women of European ancestry. We investigated whether TNRC9 polymorphisms are associated with risk of breast cancer in Chinese women of the Han nationality. We genotyped the SNPs rs3803662, rs1362548, rs1123428 in 870 women, including 388 breast cancer patients and 482 healthy controls, via the PCR-single strand conformation polymorphism procedure and by sequence detection. We found that the T allele and the TT genotype of the SNP rs38033662 is significantly associated with risk for breast cancer in Chinese Han women; however, no significant association was found for rs1362548 or rs1123428. We conclude that SNP rs3803662 is a putative risk factor for breast cancer in Chinese Han women.

  11. 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...

  12. Annexin A1 expression in a pooled breast cancer series : Association with tumor subtypes and prognosis

    NARCIS (Netherlands)

    Sobral-Leite, Marcelo; Wesseling, Jelle; Smit, Vincent T H B M; Nevanlinna, Heli; van Miltenburg, Martine H.; Sanders, Joyce; Hofland, Ingrid; Blows, Fiona M.; Coulson, Penny; Patrycja, Gazinska; Schellens, Jan H M; Fagerholm, Rainer; Heikkilä, Päivi; Aittomäki, Kristiina; Blomqvist, Carl; Provenzano, Elena; Ali, Hamid Raza; Figueroa, Jonine; Sherman, Mark; Lissowska, Jolanta; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli Matti; Hartikainen, Jaana M.; Phillips, Kelly Anne; Couch, Fergus J.; Olson, Janet E.; Vachon, Celine; Visscher, Daniel; Brenner, Hermann; Butterbach, Katja; Arndt, Volker; Holleczek, Bernd; Hooning, Maartje J.; Hollestelle, Antoinette; Martens, John W M; van Deurzen, Carolien H M; van de Water, Bob; Broeks, Annegien; Chang-Claude, Jenny; Chenevix-Trench, Georgia; Easton, Douglas F.; Pharoah, Paul D P; García-Closas, Montserrat; de Graauw, Marjo; Schmidt, Marjanka K.; Aghmesheh, Morteza; Amor, David; Andrews, Lesley; Antill, Yoland; Armitage, Shane; Arnold, Leanne; Balleine, Rosemary; Bankier, Agnes; Bastick, Patti; Beesley, Jonathan; Beilby, John; Bennett, Barbara; Bennett, Ian; Berry, Geoffrey; Blackburn, Anneke; Bogwitz, Michael; Brennan, Meagan; Brown, Melissa; Buckley, Michael; Burgess, Matthew; Burke, Jo; Butow, Phyllis; Byron, Keith; Callen, David; Campbell, Ian; Chauhan, Deepa; Chauhan, Manisha; Christian, Alice; Clarke, Christine; Colley, Alison; Cotton, Dick; Crook, Ashley; Cui, James; Culling, Bronwyn; Cummings, Margaret; Dawson, Sarah Jane; deFazio, Anna; Delatycki, Martin; Dickson, Rebecca; Dixon, Joanne; Dobrovic, Alexander; Dudding, Tracy; Edkins, Ted; Edwards, Stacey; Eisenbruch, Maurice; Farshid, Gelareh; Fawcett, Susan; Fellows, Andrew; Fenton, Georgina; Field, Michael; Firgaira, Frank; Flanagan, James; Fleming, Jean; Fong, Peter; Forbes, John; Fox, Stephen; French, Juliet; Friedlander, Michael; Gaff, Clara; Gardner, Mac; Gattas, Mike; George, Peter; Giles, Graham; Gill, Grantley; Goldblatt, Jack; Greening, Sian; Grist, Scott; Haan, Eric; Hardie, Kate; Harris, Marion; Hart, Stewart; Hayward, Nick; Healey, Sue; Heiniger, Louise; Hopper, John; Humphrey, Evelyn; Hunt, Clare; James, Paul; Jenkins, Mark; Jones, Alison; Kefford, Rick; Kidd, Alexa; Kiely, Belinda; Kirk, Judy; Koehler, Jessica; Kollias, James; Kovalenko, Serguei; Lakhani, Sunil; Leaming, Amanda; Leary, Jennifer; Lim, Jacqueline; Lindeman, Geoff; Lipton, Lara; Lobb, Liz; Mann, Graham; Marsh, Deborah; McLachlan, Sue Anne; Meiser, Bettina; Meldrum, Cliff; Milne, Roger; Mitchell, Gillian; Newman, Beth; Niedermayr, Eveline; Nightingale, Sophie; O'Connell, Shona; O'Loughlin, Imelda; Osborne, Richard; Pachter, Nick; Patterson, Briony; Peters, Lester; Phillips, Kelly; Price, Melanie; Purser, Lynne; Reeve, Tony; Reeve, Jeanne; Richards, Robert; Rickard, Edwina; Robinson, Bridget; Rudzki, Barney; Saleh, Mona; Salisbury, Elizabeth; Sambrook, Joe; Saunders, Christobel; Saunus, Jodi; Sayer, Robyn; Scott, Elizabeth; Scott, Rodney; Scott, Clare; Seshadri, Ram; Sexton, Adrienne; Sharma, Raghwa; Shelling, Andrew; Simpson, Peter; Southey, Melissa; Spurdle, Amanda; Suthers, Graeme; Sykes, Pamela; Tassell, Margaret; Taylor, Donna; Taylor, Jessica; Thierry, Benjamin; Thomas, Susan; Thompson, Ella; Thorne, Heather; Townshend, Sharron; Trainer, Alison; Tran, Lan; Tucker, Kathy; Tyler, Janet; Visvader, Jane; Walker, Logan; Walpole, Ian; Ward, Robin; Waring, Paul; Warner, Bev; Warren, Graham; Williams, Rachael; Wilson, Judy; Winship, Ingrid; Wu, Kathy; Young, Mary Ann; Bowtell, D.; Green, A.; Webb, P.; de Fazio, A.; Gertig, D.

    2015-01-01

    Background: Annexin A1 (ANXA1) is a protein related with the carcinogenesis process and metastasis formation in many tumors. However, little is known about the prognostic value of ANXA1 in breast cancer. The purpose of this study is to evaluate the association between ANXA1 expression, BRCA1/2 germl

  13. 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

  14. 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...

  15. 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

    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/progesterone ...

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

    NARCIS (Netherlands)

    K.B. Kuchenbaecker (Karoline); S.L. Neuhausen (Susan); M. Robson (Mark); D. Barrowdale (Daniel); L. McGuffog (Lesley); A.M. Mulligan (Anna Marie); I.L. Andrulis (Irene); A.B. Spurdle (Amanda); M.K. Schmidt (Marjanka); R.K. Schmutzler (Rita); C. Engel (Christoph); B. Wapenschmidt (Barbara); H. Nevanlinna (Heli); M. Thomassen (Mads); M.C. Southey (Melissa); P. Radice (Paolo); S.J. Ramus (Susan); S.M. Domchek (Susan); K.L. Nathanson (Katherine); A. Lee (Andrew); S. Healey (Sue); R. Nussbaum (Robert); R. Rebbeck (Timothy); B.K. Arun (Banu); M. James (Margaret); B. Karlan; K.J. Lester (Kathryn); I. Cass (Ilana); M.B. Terry (Mary Beth); M.J. Daly (Mark); D. Goldgar (David); S.S. Buys (Saundra); R. Janavicius (Ramunas); L. Tihomirova (Laima); N. Tung (Nadine); C.M. Dorfling (Cecilia); E.J. van Rensburg (Elizabeth); L. Steele (Linda); T. v O Hansen (Thomas); B. Ejlertsen (Bent); A-M. Gerdes (Anne-Marie); F. Nielsen (Finn); J. Dennis (Joe); J.M. Cunningham (Julie); S. Hart (Stewart); S. Slager (Susan); A. Osorio (Ana); J. Benítez (Javier); M. Duran (Mercedes); J.N. Weitzel (Jeffrey); I. Tafur (Isaac); M. Hander (Mary); P. Peterlongo (Paolo); S. Manoukian (Siranoush); B. Peissel (Bernard); G. Roversi (Gaia); G. Scuvera (Giulietta); B. Bonnani (Bernardo); P. Mariani (Paolo); S. Volorio (Sara); R. Dolcetti (Riccardo); L. Varesco (Liliana); L. Papi (Laura); M.G. Tibiletti (Maria Grazia); G. Giannini (Giuseppe); F. Fostira (Florentia); I. Konstantopoulou (I.); J. Garber (Judy); U. Hamann (Ute); A. Donaldson (Alan); C. Brewer (Carole); C. Foo (Claire); D.G. Evans (Gareth); D. Frost (Debra); D. Eccles (Diana); F. Douglas (Fiona); A. Brady (A.); J. Cook (Jackie); M. Tischkowitz (Marc); L. Adlard; J. Barwell (Julian); K. Ong; L.J. Walker (Lisa); L. Izatt (Louise); L. Side (Lucy); M.J. Kennedy (John); M.T. Rogers (Mark); M.E. Porteous (Mary); P.J. Morrison (Patrick); R. Platte (Radka); R. Eeles (Ros); R. Davidson (Rosemarie); S. Hodgson (Shirley); S.D. Ellis (Steve); A.K. Godwin (Andrew); K. Rhiem (Kerstin); A. Meindl (Alfons); N. Ditsch (Nina); N. Arnold (Norbert); H. Plendl (Hansjoerg); D. Niederacher (Dieter); C. Sutter (Christian); D. Steinemann (Doris); N. Bogdanova-Markov (Nadja); K. Kast (Karin); R. Varon-Mateeva (Raymonda); S. Wang-Gohrke (Shan); P.A. Gehrig (Paola A.); B. Markiefka (Birgid); B. Buecher (Bruno); C. Lefol (Cédrick); D. Stoppa-Lyonnet (Dominique); E. Rouleau (Etienne); F. Prieur (Fabienne); F. Damiola (Francesca); L. Barjhoux (Laure); L. Faivre (Laurence); M. Longy (Michel); N. Sevenet (Nicolas); O. Sinilnikova (Olga); S. Mazoyer (Sylvie); V. Bonadona (Valérie); V. Caux-Moncoutier (Virginie); C. Isaacs (Claudine); T. Van Maerken (Tom); K.B.M. Claes (Kathleen B.M.); M. Piedmonte (Marion); L. Andrews (Lesley); J. Hays (John); G.C. Rodriguez (Gustavo); T. Caldes (Trinidad); M. de La Hoya (Miguel); S. Khan (Sofia); F.B.L. Hogervorst (Frans); C.M. Aalfs (Cora); J.L. de Lange (J.); E.J. Meijers-Heijboer (Hanne); A.H. van der Hout (Annemarie); J.T. Wijnen (Juul); K.E. van Roozendaal (Kees); A.R. Mensenkamp (Arjen); A.M.W. van den Ouweland (Ans); C.H.M. van Deurzen (Carolien); R.B. van der Luijt (Rob); E. Olah; O. Díez (Orland); C. Lazaro (Conxi); I. Blanco (Ignacio); A. Teulé (A.); M. Menéndez (Mireia); A. Jakubowska (Anna); J. Lubinski (Jan); C. Cybulski (Cezary); J. Gronwald (Jacek); K. Jaworska-Bieniek (Katarzyna); K. Durda (Katarzyna); A. Arason (Adalgeir); C. Maugard; P. Soucy (Penny); M. Montagna (Marco); S. Agata (Simona); P.J. Teixeira; C. Olswold (Curtis); N.M. Lindor (Noralane); V.S. Pankratz (Shane); B. Hallberg (Boubou); X. Wang (Xianshu); C. Szabo (Csilla); J. Vijai (Joseph); L. Jacobs (Lauren); M. Corines (Marina); A. Lincoln (Anne); A. Berger (Andreas); A. Fink-Retter (Anneliese); C.F. Singer (Christian); C. Rappaport (Christine); D.G. Kaulich (Daphne Gschwantler); G. Pfeiler (Georg); M.-K. Tea; C. Phelan (Catherine); P.L. Mai (Phuong); M.H. Greene (Mark); G. Rennert (Gad); E.N. Imyanitov (Evgeny); G. Glendon (Gord); A.E. Toland (Amanda); A. Bojesen (Anders); I.S. Pedersen (Inge Sokilde); U.B. Jensen; M.A. Caligo (Maria); E. Friedman (Eitan); R. Berger (Raanan); Y. Laitman (Yael); J. Rantala (Johanna); B. Arver (Brita Wasteson); N. Loman (Niklas); Å. Borg (Åke); H. Ehrencrona (Hans); O.I. Olopade (Olofunmilayo); J. Simard (Jacques); D.F. Easton (Douglas); G. Chenevix-Trench (Georgia); K. Offit (Kenneth); F.J. Couch (Fergus); A.C. Antoniou (Antonis C.); CIMBA; EMBRACE Study; Breast Cancer Family; GEMO Study Collaborators; HEBON; KConFab Investigators

    2014-01-01

    textabstractIntroduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 muta

  1. Breast cancer risk and 6q22.33: Combined results from breast cancer association consortium and consortium of investigators on modifiers of brca1/2

    NARCIS (Netherlands)

    T. Kircchoff (Tomas); K. Offit (Kenneth); M.M. Gaudet (Mia); P.D.P. Pharoah (Paul); D.F. Easton (Douglas); A.C. Antoniou (Antonis); L. McGuffog (Lesley); M.K. Humphreys (Manjeet); A.M. Dunning (Alison); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); H. Flyger (Henrik); D. Kang (Daehee); K-Y. Yoo (Keun-Young); D-Y. Noh (Dong-Young); S.-H. Ahn (Sei-Hyun); T. Dörk (Thilo); P. Schürmann (Peter); J.H. Karstens (Johann); P. Hillemanns (Peter); F.J. Couch (Fergus); J.E. Olson (Janet); C. Vachon (Celine); A. Cox (Angela); I.W. Brock (Ian); G. Elliott (Graeme); M.W.R. Reed (Malcolm); B. Burwinkel (Barbara); A. Meindl (Alfons); H. Brauch (Hiltrud); C. Justenhoven (Christina); U. Hamann (Ute); Y-D. Ko (Yon-Dschun); H.-P. Fischer; T. Brüning (Thomas); B. Pesch (Beate); V. Harth (Volker); S. Rabstein (Sylvia); A. Broeks (Annegien); M.K. Schmidt (Marjanka); L.J. Van 't Veer (Laura); L.M. Braaf (Linde); N. Johnson (Nichola); O. Fletcher (Olivia); L.J. Gibson (Lorna); J. Peto (Julian); C. Turnbull (Clare); S. Seal (Sheila); A. Renwick (Anthony); N. Rahman (Nazneen); P.-E. Wu (Pei-Ei); J-C. Yu (Jyh-Cherng); C.-N. Hsiung (Chia-Ni); C-Y. Shen (Chen-Yang); M.C. Southey (Melissa); J.L. Hopper (John); F. Hammet (Fleur); T. van Dorpe (Thijs); A.-S. Dieudonné (Anne-Sophie); S. Hatse (Sigrid); D. Lambrechts (Diether); I.L. Andrulis (Irene); N.V. Bogdanova (Natalia); N.N. Antonenkova (Natalia); J.I. Rogov (Juri); D. Prokofieva (Daria); M. Bermisheva (Marina); E.K. Khusnutdinova (Elza); C.J. van Asperen (Christi); R.A.E.M. Tollenaar (Robert); M.J. Hooning (Maartje); P. Devilee (Peter); S. Margolin (Sara); A. Lindblom (Annika); R.L. Milne (Roger); J.I. Arias Pérez (José Ignacio); M.P. Zamora (Pilar); J. Benítez (Javier); G. Severi (Gianluca); L. Baglietto (Laura); G.G. Giles (Graham); G. Chenevix-Trench (Georgia); A.B. Spurdle (Amanda); J. Beesley (Jonathan); X. Chen (Xiaoqing); H. Holland (Helene); S. Healey (Sue); S. Wang-Gohrke (Shan); J. Chang-Claude (Jenny); A. Mannermaa (Arto); V-M. Kosma (Veli-Matti); J. Kauppinen (Jaana); V. Kataja (Vesa); B.A. Agnarsson (Bjarni); M.A. Caligo (Maria); A.K. Godwin (Andrew); H. Nevanlinna (Heli); T. Heikinen (Tuomas); Z. Fredericksen (Zachary); N.M. Lindor (Noralane); K.L. Nathanson (Katherine); S.M. Domchek (Susan); N. Loman (Niklas); P. Karlsson (Per); M.S. Askmalm (Marie); B. Melin (Beatrice); A. von Wachenfeldt (Anna); F.B.L. Hogervorst (Frans); M. Verheus (Martijn); M.A. Rookus (Matti); C.M. Seynaeve (Caroline); R.A. Oldenburg (Rogier); M.J. Ligtenberg (Marjolijn); M.G.E.M. Ausems (Margreet); C.M. Aalfs (Cora); H.J.P. Gille (Hans); J.T. Wijnen (Juul); E.B. Gómez García (Encarna); S. Peock (Susan); M. Cook (Margaret); C.T. Oliver (Clare); D. Frost (Debra); C. Luccarini (Craig); G. Pichert (Gabriella); R. Davidson (Rosemarie); D. Eccles (Diana); K.-R. Ong (Kai-Ren); J. Cook (Jackie); F. Douglas (Fiona); S.V. Hodgson (Shirley); D.G. Evans (Gareth); R. Eeles (Rosalind); B. Gold (Bert); X. Wang (Xianshu); C. Chu (Carol)

    2012-01-01

    textabstractRecently, 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 repli

  2. 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.

  3. 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 ...

  4. 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.

  5. Factors associated with breast and cervical cancer screening behavior among African immigrant women in Minnesota.

    Science.gov (United States)

    Harcourt, Nonyelum; Ghebre, Rahel G; Whembolua, Guy-Lucien; Zhang, Yan; Warfa Osman, S; Okuyemi, Kolawole S

    2014-06-01

    Immigrant populations in the United States (US) have lower cancer screening rates compared to none immigrant populations. The purpose of this study was to assess the rates of cancer screening and examine factors associated with cancer screening behavior among African immigrant women in Minnesota. A cross sectional survey of a community based sample was conducted among African immigrants in the Twin Cities. Cancer screening outcome measures were mammography and Papanicolau smear test. The revised theoretical model of health care access and utilization and the behavioral model for vulnerable populations were utilized to assess factors associated with cancer screening. Only 61 and 52% of the age eligible women in the sample had ever been screened for breast and cervical cancer respectively. Among these women, duration of residence in the US and ethnicity were significant determinants associated with non-screening. Programs to enhance screening rates among this population must begin to address barriers identified by the community.

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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.

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

    Science.gov (United States)

    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; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K; Nevanlinna, Heli; Giles, Graham G; Cox, Angela; Hopper, John L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J; Schoof, Nils; Bojesen, Stig E; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C; Park, Daniel J; Hammet, Fleur; Stone, Jennifer; Veer, Laura J Van’t; Rutgers, Emiel J; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Silva, Isabel dos Santos; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Balleine, Rosemary; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; Mclean, Catriona; Coetzee, Gerhard A; Feng, Ye; Henderson, Brian E; Schumacher, Fredrick; Bogdanova, Natalia V; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Kriege, Mieke; Hooning, Maartje J; Van den Ouweland, Ans M W; Van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P; Cross, Simon S; Reed, Malcolm W R; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B; Bandera, Elisa V; John, Esther M; Chen, Gary K; Hu, Jennifer J; Rodriguez-gil, Jorge L; Bernstein, Leslie; Press, Michael F; Ziegler, Regina G; Millikan, Robert M; Deming-Halverson, Sandra L; Nyante, Sarah; Ingles, Sue A; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G; Montgomery, Grant W; Slamon, Dennis J; Rauh, Claudia; Lux, Michael P; Jud, Sebastian M; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N; Chen, Constance; Beck, Andy; Hankinson, Susan E; Berg, Christine D; Hoover, Robert N; Lissowska, Jolanta; Figueroa, Jonine D; Chasman, Daniel I; Gaudet, Mia M; Diver, W Ryan

    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 cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10−12 and LGR6, P = 1.4 × 10−8), 2p24.1 (P = 4.6 × 10−8) and 16q12.2 (FTO, P = 4.0 × 10−8), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers. PMID:23535733

  12. 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

  13. Viruses and Breast Cancer

    Directory of Open Access Journals (Sweden)

    James S. Lawson

    2010-04-01

    Full Text Available 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.

  14. 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.

  15. 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

  16. 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.

  17. Association of three SNPs in TOX3 and breast cancer risk: Evidence from 97275 cases and 128686 controls.

    Science.gov (United States)

    Zhang, Li; Long, Xinghua

    2015-01-01

    The associations of SNPs in TOX3 gene with breast cancer risk were investigated by some Genome-wide association studies and epidemiological studies, but the study results were contradictory. To derive a more precise estimate of the associations, we conducted a meta-analysis. ORs with 95% CI were used to assess the strength of association between TOX3 polymorphisms and breast cancer risk in fixed or random effect model. A total of 37 publications with 97275 cases and 128686 controls were identified. We observed that the rs3803662 C > T, rs12443621 A > G and rs8051542 C > T were all correlated with increased risk of breast cancer. In the stratified analyses by ethnicity, significantly elevated risk was detected for all genetic models of the three SNPs in Caucasians. In Asian populations, there were significant associations of rs3803662 and rs8051542 with breast cancer risk. Whereas there was no evidence for statistical significant association between the three SNPs and breast cancer risk in Africans. Additionally, we observed different associations of rs3803662 with breast cancer risk based on different ER subtype and BRCA1/BRCA2 mutation carriers. In conclusion, the meta-analysis suggested that three SNPs in TOX3 were significantly associated with breast cancer risk in different populations.

  18. 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 ...

  19. 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.

  20. 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 c...

  1. 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.

  2. A functional and regulatory network associated with PIP expression in human breast cancer.

    Directory of Open Access Journals (Sweden)

    Marie-Anne Debily

    Full Text Available BACKGROUND: The PIP (prolactin-inducible protein gene has been shown to be expressed in breast cancers, with contradictory results concerning its implication. As both the physiological role and the molecular pathways in which PIP is involved are poorly understood, we conducted combined gene expression profiling and network analysis studies on selected breast cancer cell lines presenting distinct PIP expression levels and hormonal receptor status, to explore the functional and regulatory network of PIP co-modulated genes. PRINCIPAL FINDINGS: Microarray analysis allowed identification of genes co-modulated with PIP independently of modulations resulting from hormonal treatment or cell line heterogeneity. Relevant clusters of genes that can discriminate between [PIP+] and [PIP-] cells were identified. Functional and regulatory network analyses based on a knowledge database revealed a master network of PIP co-modulated genes, including many interconnecting oncogenes and tumor suppressor genes, half of which were detected as differentially expressed through high-precision measurements. The network identified appears associated with an inhibition of proliferation coupled with an increase of apoptosis and an enhancement of cell adhesion in breast cancer cell lines, and contains many genes with a STAT5 regulatory motif in their promoters. CONCLUSIONS: Our global exploratory approach identified biological pathways modulated along with PIP expression, providing further support for its good prognostic value of disease-free survival in breast cancer. Moreover, our data pointed to the importance of a regulatory subnetwork associated with PIP expression in which STAT5 appears as a potential transcriptional regulator.

  3. 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.

  4. 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...

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

    NARCIS (Netherlands)

    Wei-Yu Lin; N.J. Camp (Nicola); M. Ghoussaini (Maya); J. Beesley (Jonathan); K. Michailidou (Kyriaki); J. Hopper (John); C. Apicella (Carmel); M.C. Southey (Melissa); J. Stone (Jennifer); M.K. Schmidt (Marjanka); A. Broeks (Annegien); L.J. van 't Veer (Laura); E.J. Th Rutgers (Emiel J.); K.R. Muir (K.); A. Lophatananon (Artitaya); S. Stewart-Brown (Sarah); P. Siriwanarangsan (Pornthep); P.A. Fasching (Peter); L. Haeberle (Lothar); A.B. Ekici (Arif); M.W. Beckmann (Matthias W.); J. Peto (Julian); I. dos Santos Silva (Isabel); O. Fletcher (Olivia); N. Johnson (Nichola); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); E.J. Sawyer (Elinor); T. Cheng (Timothy); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); Frederik Marmé; H. Surowy (Harald); B. Burwinkel (Barbara); P. Guénel (Pascal); T. Truong (Thérèse); F. Menegaux (Florence); C. Mulot (Claire); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune); H. Flyger (Henrik); J. Benítez (Javier); M.P. Zamora (Pilar); J.I.A. Perez (Jose Ignacio Arias); P. Menéndez (Primitiva); A. González-Neira (Anna); G. Pita (G.); M. Rosario Alonso; N. Álvarez (Nuria); D. Herrero (Daniel); H. Anton-Culver (Hoda); H. Brenner (Hermann); A.K. Dieffenbach (Aida Karina); V. Arndt (Volker); C. Stegmaier (Christa); A. Meindl (Alfons); P. Lichtner (Peter); R.K. Schmutzler (Rita); B. Müller-Myhsok (B.); H. Brauch (Hiltrud); T. Brüning (Thomas); Y.-D. Ko (Yon-Dschun); D.C. Tessier (Daniel C.); D. Vincent (Daniel); F. Bacot (Francois); H. Nevanlinna (Heli); K. Aittomäki (Kristiina); C. Blomqvist (Carl); S. Khan (Sofia); K. Matsuo (Keitaro); H. Ito (Hidemi); H. Iwata (Hisato); A. Horio (Akiyo); N.V. Bogdanova (Natalia); N.N. Antonenkova (Natalia); T. Dörk (Thilo); A. Lindblom (Annika); S. Margolin (Sara); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); A.H. Wu (Anna H.); C.-C. Tseng (Chiu-chen); D. Van Den Berg (David); D.O. Stram (Daniel O.); P. Neven (Patrick); E. Wauters (Erwin); H. Wildiers (Hans); D. Lambrechts (Diether); J. Chang-Claude (Jenny); A. Rudolph (Anja); P. Seibold (Petra); D. Flesch-Janys (Dieter); P. Radice (Paolo); P. Peterlongo (Paolo); S. Manoukian (Siranoush); B. Bonnani (Bernardo); F.J. Couch (Fergus); X. Wang (Xianshu); C. Vachon (Celine); K. Purrington (Kristen); G.G. Giles (Graham G.); R.L. Milne (Roger L.); C.A. McLean (Catriona Ann); C.A. Haiman (Christopher); B.E. Henderson (Brian); F.R. Schumacher (Fredrick); L. Le Marchand (Loic); J. Simard (Jacques); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); S.-H. Teo; C.H. Yip (Cheng Har); N. Hassan (Norhashimah); E.N. Vithana (Eranga); V. Kristensen (Vessela); W. Zheng (Wei); S.L. Deming-Halverson (Sandra); M. Shrubsole (Martha); J. Long (Jirong); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); S. Kauppila (Saila); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); S. Tchatchou (Sandrine); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); C.J. van Asperen (Christi); M. García-Closas (Montserrat); J.D. Figueroa (Jonine); J. Lissowska (Jolanta); L.A. Brinton (Louise); K. Czene (Kamila); H. Darabi (Hatef); M. Eriksson (Mikael); J.S. Brand (Judith S.); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); A.M.W. Van DenOuweland (Ans M.W.); A. Jager (Agnes); J. Li (Jingmei); J. Liu (Jianjun); M.K. Humphreys (Manjeet); X.-O. Shu (Xiao-Ou); W. Lu (Wei); Y. Gao; H. Cai (Hui); S.S. Cross (Simon); M.W.R. Reed (Malcolm); W.J. Blot (William); L.B. Signorello (Lisa B.); Q. Cai (Qiuyin); P.D.P. Pharoah (Paul); B. Perkins (Barbara); M. Shah (Mitul); F. Blows (Fiona); D. Kang (Daehee); K.Y. Yoo; D-Y. Noh (Dong-Young); J.M. Hartman (Joost); X. Miao; K.S. Chia (Kee Seng); T.C. Putti (Thomas Choudary); U. Hamann (Ute); C. Luccarini (Craig); C. Baynes (Caroline); S. Ahmed (Shahana); M. Maranian (Melanie); S. Healey (Sue); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska-Bieniek (Katarzyna); K. Durda (Katarzyna); S. Sangrajrang (Suleeporn); V. Gaborieau (Valerie); P. Brennan (Paul); J.D. McKay (James); S. Slager (Susan); A.E. Toland (Amanda); D. Yannoukakos (Drakoulis); C-Y. Shen (Chen-Yang); C.-N. Hsiung (Chia-Ni); P.-E. Wu (Pei-Ei); S.-L. Ding (Shian-Ling); A. Ashworth (Alan); M. Jones (Michael); N. Orr (Nick); A.J. Swerdlow (Anthony ); H. Tsimiklis (Helen); E. Makalic (Enes); D.F. Schmidt (Daniel); Q.M. Bui (Quang); S.J. Chanock (Stephen); D. Hunter (David); R. Hein (Rebecca)

    2015-01-01

    textabstractPrevious 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-nucl

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

    NARCIS (Netherlands)

    Wei-Yu Lin, Lin; Camp, Nicola J.; Ghoussaini, Maya; Beesley, Jonathan; Michailidou, Kyriaki; Hopper, John L.; Apicella, Carmel; Southey, Melissa C.; Stone, Jennifer; Schmidt, Marjanka K.; Broeks, Annegien; Van't Veer, Laura J.; Th Rutgers, Emiel J.; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Fasching, Peter A.; Haeberle, Lothar; Ekici, Arif B.; Beckmann, Matthias W.; Peto, Julian; Dos-Santos-Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Sawyer, Elinor J.; Cheng, Timothy; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Frederik Marmé, Marmé; Surowy, Harald M.; Burwinkel, Barbara; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Mulot, Claire; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Benitez, Javier; Pilar Zamora, M.; Perez, Jose Ignacio Arias; Menéndez, Primitiva; González-Neira, Anna; Pita, Guillermo; Rosario Alonso, M.; Álvarez, Nuria; Herrero, Daniel; Anton-Culver, Hoda; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Lichtner, Peter; Schmutzler, Rita K.; Müller-Myhsok, Bertram; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon Dschun; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Nevanlinna, Heli; Aittomäki, Kristiina; Blomqvist, Carl; Khan, Sofia; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Horio, Akiyo; Bogdanova, Natalia V.; Antonenkova, Natalia N.; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli Matti; Hartikainen, Jaana M.; Wu, Anna H.; Tseng, Chiu Chen; Van Den Berg, David; Stram, Daniel O.; Neven, Patrick; Wauters, Els; Wildiers, Hans; Lambrechts, Diether; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bonanni, Bernardo; Couch, Fergus J.; Wang, Xianshu; Vachon, Celine; Purrington, Kristen; Giles, Graham G.; Milne, Roger L.; Mclean, Catriona; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Marchand, Loic Le; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Teo, Soo Hwang; Yip, Cheng Har; Hassan, Norhashimah; Vithana, Eranga Nishanthie; Kristensen, Vessela; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha J.; Long, Jirong; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; Van Asperen, Christi J.; García-Closas, Montserrat; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Brand, Judith S.; Hooning, Maartje J.; Hollestelle, Antoinette; Van DenOuweland, Ans M W; Jager, Agnes; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Shu, Xiao Ou; Lu, Wei; Gao, Yu Tang; Cai, Hui; Cross, Simon S.; Reed, Malcolm W R; Blot, William; Signorello, Lisa B.; Cai, Qiuyin; Pharoah, Paul D P; Perkins, Barbara; Shah, Mitul; Blows, Fiona M.; Kang, Daehee; Yoo, Keun Young; Noh, Dong Young; Hartman, Mikael; Miao, Hui; Chia, Kee Seng; Putti, Thomas Choudary; Hamann, Ute; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Maranian, Mel; Healey, Catherine S.; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; Mckay, James; Slager, Susan; Toland, Amanda E.; Yannoukakos, Drakoulis; Shen, Chen Yang; Hsiung, Chia Ni; Wu, Pei Ei; Ding, Shian Ling; Ashworth, Alan; Jones, Michael; Orr, Nick; Swerdlow, Anthony J.; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel F.; Bui, Quang M.; Chanock, Stephen J.; Hunter, David J.; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Muranen, Taru A.; Heikkinen, Tuomas; Irwanto, Astrid; Rahman, Nazneen; Turnbull, Clare A.; Waisfisz, Quinten; Meijers-Heijboer, Hanne E J; Adank, Muriel A.; Van Der Luijt, Rob B.; Hall, Per; Chenevix-Trench, Georgia; Dunning, Alison; Easton, Douglas F.; Cox, Angela

    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 polym

  7. 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

  8. 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.

  9. 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

  10. Fiber intake modulates the association of alcohol intake with breast cancer

    DEFF Research Database (Denmark)

    Romieu, Isabelle; Ferrari, Pietro; Chajès, Veronique;

    2016-01-01

    fiber as a modifying factor of the association of alcohol and breast cancer using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). This study included 334,850 women aged 35-70 years at baseline enrolled in the ten countries of the EPIC study and followed up for 11...... computed. During 3,670,439 person-years, 11,576 incident breast cancer cases were diagnosed. For subjects with low intake of fiber (24.2 g/day) the risk of BC was 1.02 (0.......99-1.05) (test for interaction p=0.011). This modulating effect was stronger for fiber from vegetables. Our results suggest that fiber intake may modulate the positive association of alcohol intake and BC. This article is protected by copyright. All rights reserved. © 2014 Wiley Periodicals, Inc....

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. Prostate-specific membrane antigen expression in tumor-associated vasculature of breast cancers.

    Science.gov (United States)

    Wernicke, Alla Gabriella; Varma, Sonal; Greenwood, Eleni A; Christos, Paul J; Chao, K S Clifford; Liu, He; Bander, Neil H; Shin, Sandra J

    2014-06-01

    Prostate-specific membrane antigen (PSMA) has been found to be expressed in the tumor-associated neovasculature of multiple solid tumor types including breast cancers. However, thus far, the number of cases studied from some tumor types has been limited. In this study, we set out to assess PSMA expression in the tumor-associated vasculature associated with invasive breast carcinomas in a sizable cohort of patients. One hundred and six patients with AJCC stage 0-IV breast cancer were identified. Ninety-two of these patients had primary breast cancer [invasive breast carcinoma with or without co-existing ductal carcinoma in situ (DCIS) (74) or DCIS alone (18)]. In addition, 14 patients with breast cancer metastases to the brain were identified. Immunohistochemical staining for PSMA and CD31 was performed on parallel representative tumor sections in each case. Tumor-associated vascular endothelial cell PSMA immunoreactivity was semi-quantitatively assessed based on two parameters: overall percent of endothelial positivity and staining intensity. PSMA expression for tumor-associated vascular endothelial cells was scored 0 if there was no detectable PSMA expression, 1 if PSMA staining was detectable in 5-50%, and 2 if PSMA expression was positive in >50% of microvessels. CD 31 staining was concurrently reviewed to confirm the presence of vasculature in each case. Tumor-associated vasculature was PSMA-positive in 68/92 (74%) of primary breast cancers and in 14/14 (100%) of breast cancers metastatic to brain. PSMA was not detected in normal breast tissue or carcinoma cells. All but 2 cases (98%) showed absence of PSMA expression in normal breast tissue-associated vasculature. The 10-year overall survival was 88.7% (95% CI = 80.0%, 93.8%) in patients without brain metastases. When overall survival (OS) was stratified based on PSMA score group, patients with PSMA scores of 0, 1, and 2 had 10-year OS of 95.8%, 96.0%, and 79.7%, respectively (p = 0.12). When PSMA scores

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

    Directory of Open Access Journals (Sweden)

    Hartmann Arndt

    2009-08-01

    previously analysed on the same tissue microarray. Conclusion 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.

  20. 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

    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

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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...

  8. 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...

  9. TIMP-1 increases expression and phosphorylation of proteins associated with drug resistance in breast cancer cells

    DEFF Research Database (Denmark)

    Hekmat, Omid; Munk, Stephanie; Fogh, Louise;

    2013-01-01

    spectrometry to analyze global proteome and phosphoproteome differences of MCF-7 breast cancer cells expressing high or low levels of TIMP-1. In TIMP-1 high expressing cells, 312 proteins and 452 phosphorylation sites were up-regulated. Among these were the cancer drug targets topoisomerase 1, 2A and 2B, which...... high expressing cells may be part of the mechanisms by which TIMP-1 confers resistance to treatment with the widely-used topoisomerase inhibitors in breast- and colorectal cancer.......Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a protein with a potential biological role in drug resistance. To elucidate the unknown molecular mechanisms underlying the association between high TIMP-1 levels and increased chemotherapy resistance, we employed SILAC-based quantitative mass...

  10. Differential expression of matrix metalloproteinase-13 in association with invasion of breast cancer.

    Science.gov (United States)

    Kotepui, Manas; Punsawad, Chuchard; Chupeerach, Chaowanee; Songsri, Apiram; Charoenkijkajorn, Lek; Petmitr, Songsak

    2016-01-01

    Matrix metalloproteinase-13 (MMP-13) has a potential role in tumour invasion and metastasis. However, its relevance to the prognosis of human breast cancer is poorly understood. The aim of this study is to investigate the expression patterns of MMP-13 protein and to determine its prognostic value in breast cancer, and to define its relation to the clinicopathological features. Immunohistochemistry analysis of MMP-13 was performed on formalin-fixed, paraffin-embedded sections of cancerous breast tissue (n = 76) and normal breast tissue (n = 20), all of which had clinicopathological information available. Based on the principle of immunoreactivity, the detection of MMP-13 on breast tissue was conducted using monoclonal antibodies against MMP-13. A semi-quantitative scoring system was used to assess the presence of, as well as the cellular localisation of MMP-13. MMP-13 expression was significantly greater in the cancerous breast tissues in comparison to those of normal breast tissues. In addition, high levels of MMP-13 expression were also found to be related to the positive detection of breast cancer cells in lymph nodes-amongst breast cancer patients. The results of this study showed that MMP-13 was frequently present in breast tumours, especially when tumours were accompanied by positive breast cancer cell detection in lymph nodes. This suggests that MMP-13 plays a potentially significant role in breast cancer invasion and metastasis. PMID:27647987

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. Association of ESR1 gene tagging SNPs with breast cancer risk

    Science.gov (United States)

    Dunning, Alison M.; Healey, Catherine S.; Baynes, Caroline; Maia, Ana-Teresa; Scollen, Serena; Vega, Ana; Rodríguez, Raquel; Barbosa-Morais, Nuno L.; Ponder, Bruce A.J.; Low, Yen-Ling; Bingham, Sheila; Haiman, Christopher A.; Le Marchand, Loic; Broeks, Annegien; Schmidt, Marjanka K.; Hopper, John; Southey, Melissa; Beckmann, Matthias W.; Fasching, Peter A.; Peto, Julian; Johnson, Nichola; Bojesen, Stig E.; Nordestgaard, Børge; Milne, Roger L.; Benitez, Javier; Hamann, Ute; Ko, Yon; Schmutzler, Rita K.; Burwinkel, Barbara; Schürmann, Peter; Dörk, Thilo; Heikkinen, Tuomas; Nevanlinna, Heli; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Chen, Xiaoqing; Spurdle, Amanda; Change-Claude, Jenny; Flesch-Janys, Dieter; Couch, Fergus J.; Olson, Janet E.; Severi, Gianluca; Baglietto, Laura; Børresen-Dale, Anne-Lise; Kristensen, Vessela; Hunter, David J.; Hankinson, Susan E.; Devilee, Peter; Vreeswijk, Maaike; Lissowska, Jolanta; Brinton, Louise; Liu, Jianjun; Hall, Per; Kang, Daehee; Yoo, Keun-Young; Shen, Chen-Yang; Yu, Jyh-Cherng; Anton-Culver, Hoda; Ziogoas, Argyrios; Sigurdson, Alice; Struewing, Jeff; Easton, Douglas F.; Garcia-Closas, Montserrat; Humphreys, Manjeet K.; Morrison, Jonathan; Pharoah, Paul D.P.; Pooley, Karen A.; Chenevix-Trench, Georgia

    2009-01-01

    We have conducted a three-stage, comprehensive single nucleotide polymorphism (SNP)-tagging association study of ESR1 gene variants (SNPs) in more than 55 000 breast cancer cases and controls from studies within the Breast Cancer Association Consortium (BCAC). No large risks or highly significant associations were revealed. SNP rs3020314, tagging a region of ESR1 intron 4, is associated with an increase in breast cancer susceptibility with a dominant mode of action in European populations. Carriers of the c-allele have an odds ratio (OR) of 1.05 [95% Confidence Intervals (CI) 1.02–1.09] relative to t-allele homozygotes, P = 0.004. There is significant heterogeneity between studies, P = 0.002. The increased risk appears largely confined to oestrogen receptor-positive tumour risk. The region tagged by SNP rs3020314 contains sequence that is more highly conserved across mammalian species than the rest of intron 4, and it may subtly alter the ratio of two mRNA splice forms. PMID:19126777

  17. 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.

  18. 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.

  19. Breast cancer survival is associated with telomere length in peripheral blood cells.

    Science.gov (United States)

    Svenson, Ulrika; Nordfjäll, Katarina; Stegmayr, Birgitta; Manjer, Jonas; Nilsson, Peter; Tavelin, Björn; Henriksson, Roger; Lenner, Per; Roos, Göran

    2008-05-15

    Telomeres are essential for maintaining chromosomal stability. Previous studies have indicated that individuals with shorter blood telomeres may be at higher risk of developing various types of cancer, such as in lung, bladder, and kidney. We have analyzed relative telomere length (RTL) of peripheral blood cells in relation to breast cancer incidence and prognosis. The study included 265 newly diagnosed breast cancer patients and 446 female controls. RTL was measured by real-time PCR, and our results show that the patient group displayed significantly longer telomeres compared with controls (P cancer risk increased with increasing telomere length, with a maximal OR of 5.17 [95% confidence interval (95% CI), 3.09-8.64] for the quartile with the longest telomeres. Furthermore, RTL carried prognostic information for patients with advanced disease. Node positive (N+) patients with short telomeres (telomeres (P = 0.001). For patients with ages 16 mm (median tumor diameter), short telomeres were associated with a significantly better outcome than longer telomeres (P = 0.006). Cox regression analysis showed that long RTL was a significant independent negative prognostic factor (hazards ratio, 2.92; 95% CI, 1.33-6.39; P = 0.007). Our results indicate that blood RTL may serve as a prognostic indicator in breast cancer patients with advanced disease.

  20. 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;

    2014-01-01

    , 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 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 assessing CIN status...... in parallel with the expression of the mitotic regulators AURKA and SURVIVIN. These data suggest that elevated expression of AURKA and SURVIVIN, together with AURKA gene amplification, are associated with increased CIN in breast cancer, and may be used as a proxy for CIN in breast cancer samples...

  1. 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.

  2. 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.

  3. 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 ...

  4. 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. ...

  5. 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.

  6. The associations between immunity-related genes and breast cancer prognosis in Korean women.

    Directory of Open Access Journals (Sweden)

    Jaesung Choi

    Full Text Available We investigated the role of common genetic variation in immune-related genes on breast cancer disease-free survival (DFS in Korean women. 107 breast cancer patients of the Seoul Breast Cancer Study (SEBCS were selected for this study. A total of 2,432 tag single nucleotide polymorphisms (SNPs in 283 immune-related genes were genotyped with the GoldenGate Oligonucleotide pool assay (OPA. A multivariate Cox-proportional hazard model and polygenic risk score model were used to estimate the effects of SNPs on breast cancer prognosis. Harrell's C index was calculated to estimate the predictive accuracy of polygenic risk score model. Subsequently, an extended gene set enrichment analysis (GSEA-SNP was conducted to approximate the biological pathway. In addition, to confirm our results with current evidence, previous studies were systematically reviewed. Sixty-two SNPs were statistically significant at p-value less than 0.05. The most significant SNPs were rs1952438 in SOCS4 gene (hazard ratio (HR = 11.99, 95% CI = 3.62-39.72, P = 4.84E-05, rs2289278 in TSLP gene (HR = 4.25, 95% CI = 2.10-8.62, P = 5.99E-05 and rs2074724 in HGF gene (HR = 4.63, 95% CI = 2.18-9.87, P = 7.04E-05. In the polygenic risk score model, the HR of women in the 3rd tertile was 6.78 (95% CI = 1.48-31.06 compared to patients in the 1st tertile of polygenic risk score. Harrell's C index was 0.813 with total patients and 0.924 in 4-fold cross validation. In the pathway analysis, 18 pathways were significantly associated with breast cancer prognosis (P<0.1. The IL-6R, IL-8, IL-10RB, IL-12A, and IL-12B was associated with the prognosis of cancer in data of both our study and a previous study. Therefore, our results suggest that genetic polymorphisms in immune-related genes have relevance to breast cancer prognosis among Korean women.

  7. Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics

    DEFF Research Database (Denmark)

    Garcia-Closas, M.; Hall, P.; Nevanlinna, H.;

    2008-01-01

    )) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival......A three-stage genome-wide association study recently identified single nucleotide polymorphisms ( SNPs) in five loci ( fibroblast growth receptor 2 ( FGFR2), trinucleotide repeat containing 9 ( TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte- specific protein 1 ( LSP1...... in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER- positive ( per- allele OR ( 95%CI) = 1.31 (1.27-1.36)) than ER- negative (1.08 (1.03- 1.14)) disease ( P for heterogeneity = 10-(13)). This SNP was also more strongly...

  8. Shigella mediated depletion of macrophages in a murine breast cancer model is associated with tumor regression.

    Directory of Open Access Journals (Sweden)

    Katharina Galmbacher

    Full Text Available A tumor promoting role of macrophages has been described for a transgenic murine breast cancer model. In this model tumor-associated macrophages (TAMs represent a major component of the leukocytic infiltrate and are associated with tumor progression. Shigella flexneri is a bacterial pathogen known to specificly induce apotosis in macrophages. To evaluate whether Shigella-induced removal of macrophages may be sufficient for achieving tumor regression we have developed an attenuated strain of S. flexneri (M90TDeltaaroA and infected tumor bearing mice. Two mouse models were employed, xenotransplantation of a murine breast cancer cell line and spontanous breast cancer development in MMTV-HER2 transgenic mice. Quantitative analysis of bacterial tumor targeting demonstrated that attenuated, invasive Shigella flexneri primarily infected TAMs after systemic administration. A single i.v. injection of invasive M90TDeltaaroA resulted in caspase-1 dependent apoptosis of TAMs followed by a 74% reduction in tumors of transgenic MMTV-HER-2 mice 7 days post infection. TAM depletion was sustained and associated with complete tumor regression.These data support TAMs as useful targets for antitumor therapy and highlight attenuated bacterial pathogens as potential tools.

  9. 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 ...

  10. Association of MTHFR (C677T) Gene Polymorphism With Breast Cancer in North India

    Science.gov (United States)

    Waseem, Mohammad; Hussain, Syed Rizwan; Kumar, Shashank; Serajuddin, Mohammad; Mahdi, Farzana; Sonkar, Satyendra Kumar; Bansal, Cherry; Ahmad, Mohammad Kaleem

    2016-01-01

    BACKGROUND Breast cancer is one of the most common malignancies in women and is associated with a variety of risk factors. The functional single-nucleotide polymorphism (SNP) C677T in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR) may lead to decreased enzyme activity and affect the chemosensitivity of tumor cells. This study was designed to investigate the association of MTHFR gene polymorphism (SNP) in the pathogenesis of breast cancer among the North Indian women population. MATERIALS AND METHODS Genotyping was performed by polymerase chain reaction (PCR) using genomic DNA, extracted from the peripheral blood of subjects with (275 cases) or without (275 controls) breast cancer. Restriction fragment length polymorphism was used to study C677T polymorphism in the study groups. RESULTS The distribution of MTHFR (C677T) genotype frequencies, ie, CC, TT, and CT, among the patients was 64.7%, 2.18%, and 33.09%, respectively. In the healthy control group, the CC, TT, and CT frequencies were 78.91%, 1.09%, and 20.1%, respectively. The frequencies of C and T alleles were 81.2% and 18.7%, respectively, in the patient subjects, while they were 88.9% and 11.09%, respectively, among the healthy control group. Frequencies of the CT genotype and the T allele were significantly different (P = 0.007 and P = 0.005, respectively) between the control and the case subjects. CONCLUSION This study shows an association of the CT genotype and the T allele of the MTHFR (C667T) gene with increased genetic risk for breast cancer among Indian women. PMID:27721657

  11. 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...

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

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    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.

  13. 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

  14. Molecular subtype analysis determines the association of advanced breast cancer in Egypt with favorable biology

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    DuQuette Rachelle A

    2011-09-01

    Full Text Available Abstract Background Prognostic markers and molecular breast cancer subtypes reflect underlying biological tumor behavior and are important for patient management. Compared to Western countries, women in North Africa are less likely to be prognosticated and treated based on well-characterized markers such as the estrogen receptor (ER, progesterone receptor (PR and Her2. We conducted this study to determine the prevalence of breast cancer molecular subtypes in the North African country of Egypt as a measure of underlying biological characteristics driving tumor manifestations. Methods To determine molecular subtypes we characterized over 200 tumor specimens obtained from Egypt by performing ER, PR, Her2, CK5/6, EGFR and Ki67 immunohistochemistry. Results Our study demonstrated that the Luminal A subtype, associated with favorable prognosis, was found in nearly 45% of cases examined. However, the basal-like subtype, associated with poor prognosis, was found in 11% of cases. These findings are in sharp contrast to other parts of Africa in which the basal-like subtype is over-represented. Conclusions Egyptians appear to have favorable underlying biology, albeit having advanced disease at diagnosis. These data suggest that Egyptians would largely profit from early detection of their disease. Intervention at the public health level, including education on the benefits of early detection is necessary and would likely have tremendous impact on breast cancer outcome in Egypt.

  15. Association of XRCC1 Trp194 allele with risk of breast cancer, and Ki67 protein status in breast tumor tissues

    Science.gov (United States)

    Jalali, Chiya; Ghaderi, Bayazid; Amini, Sabrieh; Abdi, Mohammad; Roshani, Daem

    2016-01-01

    Objectives: To evaluate the role of this polymorphism as a risk factor for breast cancer in Kurdish patients and to investigate the possible association between Arg194Trp x-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms with clinical and histopathological outcomes of patients with breast cancer. Methods: A total of 100 breast cancer patients and 200 cancer-free controls in Kurdish population of Kurdistan state admitted to Tohid Hospital, Sanandaj, Kurdistan, Iran between January 2012 and May 2015 were enrolled in this cross-sectional study. Tissue expression of estrogen receptor (ER), progesteron receptor (PR), human epidermal growth factor receptor 2 (Her2/neu), and Ki67 were evaluated by immunohistochemistry (IHC). The Arg194Trp genotypes were determined by polymerase chain reaction- restriction fragment length polymorphism method. Results: Our data showed that the risk for breast cancer increased significantly among the Trp variant of XRCC1. Statistically significant association was found between codon 194 polymorphisms and tissue expression of Ki67. Conclusion: The Trp allele of codon 194 XRCC1 is a potential risk factor for breast cancer in Kurdish ethnicity. Furthermore, effect of this polymorphism on clinical and histological features of breast cancer was significant. PMID:27279507

  16. 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......R cells had no effect on anti‐estrogen sensitivity, but significantly decreased cell motility. MARCKS expression was significantly higher in breast cancer cell lines than normal mammary epithelial cells and in ER‐negative versus ER‐positive breast cancer cell lines. In primary breast cancers, cytoplasmic...... MARCKS staining was significantly higher in basal‐like and HER2 cancers than in luminal cancers, and was independently predictive of poor survival in multivariate analyses of the whole cohort (P

  17. 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.

  18. Association between chronic viral hepatitis infection and breast cancer risk: a nationwide population-based case-control study

    Directory of Open Access Journals (Sweden)

    Su Fu-Hsiung

    2011-11-01

    Full Text Available Abstract Background In Taiwan, there is a high incidence of breast cancer and a high prevalence of viral hepatitis. In this case-control study, we used a population-based insurance dataset to evaluate whether breast cancer in women is associated with chronic viral hepatitis infection. Methods From the claims data, we identified 1,958 patients with newly diagnosed breast cancer during the period 2000-2008. A randomly selected, age-matched cohort of 7,832 subjects without cancer was selected for comparison. Multivariable logistic regression models were constructed to calculate odds ratios of breast cancer associated with viral hepatitis after adjustment for age, residential area, occupation, urbanization, and income. The age-specific ( Results There were no significant differences in the prevalence of hepatitis C virus (HCV infection, hepatitis B virus (HBV, or the prevalence of combined HBC/HBV infection between breast cancer patients and control subjects (p = 0.48. Multivariable logistic regression analysis, however, revealed that age Conclusions HCV infection, but not HBV infection, appears to be associated with early onset risk of breast cancer in areas endemic for HCV and HBV. This finding needs to be replicated in further studies.

  19. 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

  20. 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.

  1. 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......-allele but not for the T-allele. Results from this prospective study suggest that the GPX1 Pro198Leu-associated lowered GPX activity is associated with higher breast cancer risk among Danish women....

  2. 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.

  3. 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 involved...

  4. Height and Breast Cancer Risk

    DEFF Research Database (Denmark)

    Zhang, Ben; Shu, Xiao-Ou; Delahanty, Ryan J;

    2015-01-01

    BACKGROUND: Epidemiological studies have linked adult height with breast cancer risk in women. However, the magnitude of the association, particularly by subtypes of breast cancer, has not been established. Furthermore, the mechanisms of the association remain unclear. METHODS: We performed a meta......-analysis to investigate associations between height and breast cancer risk using data from 159 prospective cohorts totaling 5216302 women, including 113178 events. In a consortium with individual-level data from 46325 case patients and 42482 control patients, we conducted a Mendelian randomization analysis using...... a genetic score that comprised 168 height-associated variants as an instrument. This association was further evaluated in a second consortium using summary statistics data from 16003 case patients and 41335 control patients. RESULTS: The pooled relative risk of breast cancer was 1.17 (95% confidence...

  5. 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.

  6. 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.

  7. BRCA1-Associated Triple-Negative Breast Cancer and Potential Treatment for Ruthenium-Based Compounds.

    Science.gov (United States)

    Hongthong, Khwanjira; Ratanaphan, Adisorn

    2016-01-01

    Triple-negative breast cancer (TNBC) is defined by the absence of expression of estrogen receptor (ER), progesterone receptor (PR), and a lack of overexpression or amplification of human epidermal growth factor receptor 2 (HER2). The clinicopathological characteristics of TNBC include a high grading, a high rate of cell proliferation and a greater degree of chromosomal rearrangement. Patients with triple-negative breast cancer are more likely to be drug resistant and more difficult to treat, and are also frequently BRCA1 mutants. Methylation of the BRCA1 promoter region is associated with a reduction of the BRCA1 mRNA level. TNBC patients with a methylated BRCA1 had a better disease-free survival compared with those with non-methylated BRCA1. From a therapeutic perspective, the expression level of BRCA1 has been a major determinant of the responses to different classes of chemotherapy. BRCA1-dysfunctional tumors are hypersensitive to DNA damaging chemotherapeutic agents like platinum drugs. Although platinum based drugs are currently widely used as conventional chemotherapeutic drugs in breast cancer chemotherapy, their use has several disadvantages. It is therefore of interest to seek out alternative therapeutic metal-based compounds that could overcome the limitations of these platinum based drugs. Ruthenium-based compounds could be the most promising alternative to the platinum drugs. This review highlights the use of BRCA1 as a predictive marker as well as for a potential drug target for anticancer ruthenium compounds.

  8. Variants of FGFR2 and their associations with breast cancer risk: a HUGE systematic review and meta-analysis.

    Science.gov (United States)

    Cui, Fei; Wu, Duoguang; Wang, Wenjian; He, Xiaotian; Wang, Minghui

    2016-01-01

    Extensive epidemiological studies have demonstrated that there are associations between variants in intron 2 of FGFR2 and the breast cancer risk in various populations; however, the relationships are not yet conclusively established. To comprehensively review the epidemiological studies showing associations between the variants of FGFR2 and the breast cancer risk, and to establish correlations via a meta-analysis. The PubMed and MEDLINE databases were searched for eligible studies. The associations between the variants and breast cancer risk were evaluated using a random-effects model. The heterogeneity among the studies and the potential publication bias were also evaluated. Fifty-three studies with a total of 121,740 cases and 198,549 controls have examined the associations between 23 variants in intron 2 of FGFR2 and the breast cancer risk. The relationships for the 10 most frequently evaluated variants-rs1078806, rs11200014, rs1219648, rs2420946, rs2981578, rs2981579, rs2981582, rs3135718, rs10736303, and rs3750817-were synthesized based on a meta-analysis. Interestingly, we found that all 10 variants were significantly associated with the risk of breast cancer. In studies stratified by ethnicity, we found that the associations were more notable in Caucasians and Asians compared to Africans. Similar pooled results were found in population-based and hospital-based case-control studies and in studies with small and large sample sizes. FGFR2 is a breast cancer susceptibility gene, and various variants of FGFR2 are significantly associated with the breast cancer risk. However, the biological mechanisms underlying the associations need to be elucidated in future studies.

  9. 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

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

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    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.

  11. 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

  12. A genome-wide association scan on estrogen receptor-negative breast cancer

    NARCIS (Netherlands)

    J. Li (Jingmei); M.K. Humphreys (Manjeet); H. Darabi (Hatef); G. Rosin (Gustaf); U. Hannelius (Ulf); T. Heikinen (Tuomas); K. Aittomäki (Kristiina); C. Blomqvist (Carl); P.D.P. Pharoah (Paul); A.M. Dunning (Alison); S. Ahmed (Shahana); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); R.A. Oldenburg (Rogier); L. Alfredsson (Lars); A. Palotie (Aarno); L. Peltonen-Palotie (Leena); A. Irwanto (Astrid); H.Q. Low (Hui); G.H.K. Teoh (Garrett); A. Thalamuthu (Anbupalam); J. Kere (Juha); M. D'Amato (Mauro); D.F. Easton (Douglas); H. Nevanlinna (Heli); J. Liu (Jianjun); K. Czene (Kamila); A.S. Hall (Alistair)

    2010-01-01

    textabstractIntroduction: Breast cancer is a heterogeneous disease and may be characterized on the basis of whether estrogen receptors (ER) are expressed in the tumour cells. ER status of breast cancer is important clinically, and is used both as a prognostic indicator and treatment predictor. In th

  13. 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

  14. High resolution MRI of the breast at 3 T: which BI-RADS {sup registered} descriptors are most strongly associated with the diagnosis of breast cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Pinker-Domenig, K.; Helbich, T.H. [Medical University Vienna, Dept. of Radiology, Division of Molecular and Gender Imaging, Vienna (Austria); Bogner, W.; Gruber, S. [Medical University Vienna, Dept. of Radiology, MR Centre of Excellence, Vienna (Austria); Medical University Vienna, Dept. of Radiology, Vienna (Austria); Bickel, H. [Medical University Vienna, Dept. of Radiology, Division of Molecular and Gender Imaging, Vienna (Austria); Medical University Vienna, Dept. of Radiology, Vienna (Austria); Duffy, S. [Queen Mary University of London, Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry, London (United Kingdom); Schernthaner, M. [Medical University Vienna, Dept. of Radiology, Vienna (Austria); Dubsky, P. [Medical University Vienna, Dept. of Surgery, Vienna (Austria); Pluschnig, U. [Medical University Vienna, Dept. of Internal Medicine, Division of Oncology, Vienna (Austria); Rudas, M. [Medical University Vienna, Clinical Institute of Pathology, Vienna (Austria); Trattnig, S. [Medical University Vienna, Dept. of Radiology, MR Centre of Excellence, Vienna (Austria)

    2012-02-15

    To identify which breast lesion descriptors in the ACR BI-RADS registered MRI lexicon are most strongly associated with the diagnosis of breast cancer when performing breast MR imaging at 3 T. 150 patients underwent breast MR imaging at 3 T. Lesion size, morphology and enhancement kinetics were assessed according to the BI-RADS {sup registered} classification. Sensitivity, specificity and diagnostic accuracy were assessed. The effects of the BI-RADS {sup registered} descriptors on sensitivity and specificity were evaluated. Data were analysed using logistic regression. Histopathological diagnoses were used as the standard of reference. The sensitivity, specificity and diagnostic accuracy of breast MRI at 3 T was 99%, 81% and 93%, respectively. In univariate analysis, the final diagnosis of malignancy was positively associated with irregular shape (p < 0.001), irregular margin (p < 0.001), heterogeneous enhancement (p < 0.001), Type 3 enhancement kinetics (p = 0.02), increasing patient age (p = 0.02) and larger lesion size (p < 0.001). In multivariate analysis, significant associations with malignancy remained for mass shape (p = 0.06), mass margin (p < 0.001), internal enhancement pattern (p = 0.03) and Type 3 enhancement kinetics (p = 0.06). The ACR BI-RADS {sup registered} breast lesion descriptors that are mostly strongly associated with breast cancer in breast MR imaging at 3 T are lesion shape, lesion margin, internal enhancement pattern and Type 3 enhancement kinetics. (orig.)

  15. PD-1 rs2227982 Polymorphism Is Associated With the Decreased Risk of Breast Cancer in Northwest Chinese Women

    Science.gov (United States)

    Ren, Hong-Tao; Li, Yi-Ming; Wang, Xi-Jing; Kang, Hua-Feng; Jin, Tian-Bo; Ma, Xiao-Bin; Liu, Xing-Han; Wang, Meng; Liu, Kang; Xu, Peng; Yao, Qing-Ling; Dai, Zhi-Jun

    2016-01-01

    Abstract Programmed death-1 (PD-1) is crucial in cancer and is well characterized as a negative T-cell regulator that functions by delivering inhibitory signals. We aimed to evaluate the relationship between PD-1 polymorphisms (rs10204525, rs2227982, and rs7421861) and breast cancer risk. We selected 560 breast cancer patients and 583 age-, sex-, and ethnicity-matched healthy controls from Northwest China. The PD-1 polymorphisms were genotyped by using Sequenom MassARRAY. Associations were estimated with odds ratios (ORs) and 95% confidence intervals (95% CIs). For the rs10204525 and rs7421861 polymorphisms, no differences in breast cancer risk were found in any of the genetic models. For the rs2227982 polymorphism, the variant genotypes were significantly associated with decreased breast cancer risk (CT vs CC: OR = 0.68, 95% CI = 0.52–0.91; CT + TT vs CC: OR = 0.69, 95% CI = 0.53–0.90). In analyses stratified by age, the decreased risk was observed among the younger subjects (OR = 0.68, 95% CI = 0.47–0.97). We found that the decreased risk observed for the variant genotypes of rs2227982 was associated with the Her-2 status (CT vs CC: OR = 0.55, 95% CI = 0.37–0.84; CT + TT vs CC: OR = 0.56, 95% CI = 0.38–0.82). The haplotype analysis showed that the Ars10204525 Trs2227982 Crs7421861 haplotype was associated with a significantly decreased risk of breast cancer (OR = 0.50, 95% CI = 0.34–0.75). Our findings support an association between the PD-1 rs2227982 polymorphism and decreased breast cancer risk, especially in Her-2 positive breast cancer patients in the Chinese population. PMID:27227944

  16. 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...

  17. 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.;

    2015-01-01

    Introduction: Radiotherapy is an important treatment in early stage breast cancer but it is claimed that radiotherapy causes damage to the cardiac conduction system and increases the risk implantation of CIED (pacemaker or ICD). However, this paradigm is based on smaller series of case reports. Due...... to the anatomy, radiotherapy will potential mainly affect the conduction system in left sided breast cancer. The aim of this study was to evaluate risk of implantation of a CIED subsequent to radiotherapy for breast cancer by comparing left- versus right sided radiotherapy in a nationwide cohort. 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...

  18. 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 ...

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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...

  7. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

    NARCIS (Netherlands)

    Bojesen, Stig E.; Pooley, Karen A.; Johnatty, Sharon E.; Beesley, Jonathan; Michailidou, Kyriaki; Tyrer, Jonathan P.; Edwards, Stacey L.; Pickett, Hilda A.; Shen, Howard C.; Smart, Chanel E.; Hillman, Kristine M.; Mai, Phuong L.; Lawrenson, Kate; Stutz, Michael D.; Lu, Yi; Karevan, Rod; Woods, Nicholas; Johnstonw, Rebecca L.; French, Juliet D.; Chen, Xiaoqing; Weischer, Maren; Nielsen, Sune F.; Maranian, Melanie J.; Ghoussaini, Maya; Ahmed, Shahana; Baynes, Caroline; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Healey, Sue; Lush, Michael; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francis; Vergote, Ignace; Lambrechts, Sandrina; Despierre, Evelyn; Risch, Harvey A.; Gonzalez-Neira, Anna; Rossing, Mary Anne; Pita, Guillermo; Doherty, Jennifer A.; Alvarez, Nuria; Larson, Melissa C.; Fridley, Brooke L.; Schoof, Nils; Chang-Claude, Jenny; Cicek, Mine S.; Peto, Julian; Kalli, Kimberly R.; Broeks, Annegien; Armasu, Sebastian M.; Schmidt, Marjanka K.; Braaf, Linde M.; Winterhoff, Boris; Nevanlinna, Heli; Konecny, Gottfried E.; Lambrechts, Diether; Rogmann, Lisa; Guenel, Pascal; Teoman, Attila; Milne, Roger L.; Garcia, Joaquin J.; Cox, Angela; Shridhar, Vijayalakshmi; Burwinkel, Barbara; Marme, Frederik; Hein, Rebecca; Sawyer, Elinor J.; Haiman, Christopher A.; Wang-Gohrke, Shan; Andrulis, Irene L.; Moysich, Kirsten B.; Hopper, John L.; Odunsi, Kunle; Lindblom, Annika; Giles, Graham G.; Brenner, Hermann; Simard, Jacques; Lurie, Galina; Fasching, Peter A.; Carney, Michael E.; Radice, Paolo; Wilkens, Lynne R.; Swerdlow, Anthony; Goodman, Marc T.; Brauch, Hiltrud; Garcia-Closas, Montserrat; Hillemanns, Peter; Winqvist, Robert; Durst, Matthias; Devilee, Peter; Runnebaum, Ingo; Jakubowska, Anna; Lubinski, Jan; Mannermaa, Arto; Butzow, Ralf; Bogdanova, Natalia V.; Doerk, Thilo; Pelttari, Liisa M.; Zheng, Wei; Leminen, Arto; Anton-Culver, Hoda; Bunker, Clareann H.; Kristensen, Vessela; Ness, Roberta B.; Muir, Kenneth; Edwards, Robert; Meindl, Alfons; Heitz, Florian; Matsuo, Keitaro; du Bois, Andreas; Wu, Anna H.; Harter, Philipp; Teo, Soo-Hwang; Schwaab, Ira; Shu, Xiao-Ou; Blot, William; Hosono, Satoyo; Kang, Daehee; Nakanishi, Toru; Hartman, Mikael; Yatabe, Yasushi; Hamann, Ute; Karlan, Beth Y.; Sangrajrang, Suleeporn; Kjaer, Susanne Kruger; Gaborieau, Valerie; Jensen, Allan; Eccles, Diana; Hogdall, Estrid; Shen, Chen-Yang; Brown, Judith; Woo, Yin Ling; Shah, Mitul; Azmi, Mat Adenan Noor; Luben, Robert; Omar, Siti Zawiah; Czene, Kamila; Vierkant, Robert A.; Nordestgaard, Borge G.; Flyger, Henrik; Vachon, Celine; Olson, Janet E.; Wang, Xianshu; Levine, Douglas A.; Rudolph, Anja; Weber, Rachel Palmieri; Flesch-Janys, Dieter; Iversen, Edwin; Nickels, Stefan; Schildkraut, Joellen M.; Silva, Isabel Dos Santos; Cramer, Daniel W.; Gibson, Lorna; Terry, Kathryn L.; Fletcher, Olivia; Vitonis, Allison F.; van der Schoot, C. Ellen; Poole, Elizabeth M.; Hogervorst, Frans B. L.; Tworoger, Shelley S.; Liu, Jianjun; Bandera, Elisa V.; Li, Jingmei; Olson, Sara H.; Humphreys, Keith; Row, Irene; Blomqvist, Carl; Rodriguez-Rodriguez, Lorna; Aittomaki, Kristiina; Salvesen, Helga B.; Muranen, Taru A.; Wik, Elisabeth; Brouwers, Barbara; Krakstad, Camilla; Wauters, Els; Halle, Mari K.; Wildiers, Hans; Kiemeney, Lambertus A.; Mulot, Claire; Aben, Katja K.; Laurent-Puig, Pierre; Altena, Anne Mvan; Therese Truong, [No Value; Massuger, Leon F. A. G.; Benitez, Javier; Pejovic, Tanja; Arias Perez, Jose Ignacio; Hoatlin, Maureen; Zamora, M. Pilar; Cook, Linda S.; Balasubramanian, Sabapathy P.; Kelemen, Linda E.; Schneeweiss, Andreas; Le, Nhu D.; Sohn, Christof; Brooks-Wilson, Angela; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Cybulski, Cezary; Henderson, Brian E.; Menkiszak, Janusz; Schumacher, Fredrick; Wentzensen, Nicolas; Marchand, Loic Le; Yang, Hannah P.; Mulligan, Anna Marie; Glendon, Gord; Engelholm, Svend Aage; Knight, Julia A.; Hogdall, Claus K.; Apicella, Carmel; Gore, Martin; Tsimiklis, Helen; Song, Honglin; Southey, Melissa C.; Jager, Agnes; den Ouweland, Ans M. Wvan; Brown, Robert; Martens, John W. M.; Flanagan, James M.; Kriege, Mieke; Paul, James; Margolin, Sara; Siddiqui, Nadeem; Severi, Gianluca; Whittemore, Alice S.; Baglietto, Laura; McGuire, Valerie; Stegmaier, Christa; Sieh, Weiva; Mueller, Heiko; Arndt, Volker; Labreche, France; Gao, Yu-Tang; Goldberg, Mark S.; Yang, Gong; Dumont, Martine; McLaughlin, John R.; Hartmann, Arndt; Ekici, Arif B.; Beckmann, Matthias W.; Phelan, Catherine M.; Lux, Michael P.; Permuth-Wey, Jenny; Peissel, Bernard; Sellers, Thomas A.; Ficarazzi, Filomena; Barile, Monica; Ziogas, Argyrios; Ashworth, Alan; Gentry-Maharaj, Aleksandra; Jones, Michael; Ramus, Susan J.; Orr, Nick; Menon, Usha; Pearce, Celeste L.; Bruening, Thomas; Pike, Malcolm C.; Ko, Yon-Dschun; Lissowska, Jolanta; Figueroa, Jonine; Kupryjanczyk, Jolanta; Chanock, Stephen J.; Dansonka-Mieszkowska, Agnieszka; Jukkola-Vuorinen, Arja; Rzepecka, Iwona K.; Pylkas, Katri; Bidzinski, Mariusz; Kauppila, Saila; Hollestelle, Antoinette; Seynaeve, Caroline; Tollenaar, Rob A. E. M.; Durda, Katarzyna; Jaworska, Katarzyna; Hartikainen, Jaana M.; Kosma, Veli-Matti; Kataja, Vesa; Antonenkova, Natalia N.; Long, Jirong; Shrubsole, Martha; Deming-Halverson, Sandra; Lophatananon, Artitaya; Siriwanarangsan, Pornthep; Stewart-Brown, Sarah; Ditsch, Nina; Lichtner, Peter; Schmutzler, Rita K.; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Tseng, Chiu-Chen; Stram, Daniel O.; van den Berg, David; Yip, Cheng Har; Ikrarn, M. Kamran; Teh, Yew-Ching; Cai, Hui; Lu, Wei; Signorello, Lisa B.; Cai, Qiuyin; Noh, Dong-Young; Yoo, Keun-Young; Miao, Hui; Iau, Philip Tsau-Choong; Teo, Yik Ying; McKay, James; Shapiro, Charles; Ademuyiwa, Foluso; Fountzilas, George; Hsiung, Chia-Ni; Yu, Jyh-Cherng; Hou, Ming-Feng; Healey, Catherine S.; Luccarini, Craig; Peock, Susan; Stoppa-Lyonnet, Dominique; Peterlongo, Paolo; Rebbeck, Timothy R.; Piedmonte, Marion; Singer, Christian F.; Friedman, Eitan; Thomassen, Mads; Offit, Kenneth; Hansen, Thomas V. O.; Neuhausen, Susan L.; Szabo, Csilla I.; Blanco, Ignacio; Garber, Judy; Narod, Steven A.; Weitzel, Jeffrey N.; Montagna, Marco; Olah, Edith; Godwin, Andrew K.; Yannoukakos, Drakoulis; Goldgar, David E.; Caldes, Trinidad; Imyanitov, Evgeny N.; Tihomirova, Laima; Arun, Banu K.; Campbell, Ian; Mensenkamp, Arjen R.; van Asperen, Christi J.; van Roozendaa, Kees E. P.; Meijers-Heijboer, Hanne; Collee, J. Margriet; Oosterwijk, Jan C.; Hooning, Maartje J.; Rookus, Matti A.; van der Luijt, Rob B.; Os, Theo A. Mvan; Evans, D. Gareth; Frost, Debra; Fineberg, Elena; Barwell, Julian; Walker, Lisa; Kennedy, M. John; Platte, Radka; Davidson, Rosemarie; Ellis, Steve D.; Cole, Trevor; Bressac-de Paillerets, Brigitte; Buecher, Bruno; Damiola, Francesca; Faivre, Laurence; Frenay, Marc; Sinilnikova, Olga M.; Caron, Olivier; Giraud, Sophie; Mazoyer, Sylvie; Bonadona, Valerie; Caux-Moncoutier, Virginie; Toloczko-Grabarek, Aleksandra; Gronwald, Jacek; Byrski, Tomasz; Spurdle, Amanda B.; Bonanni, Bernardo; Zaffaroni, Daniela; Giannini, Giuseppe; Bernard, Loris; Dolcetti, Riccardo; Manoukian, Siranoush; Arnold, Norbert; Engel, Christoph; Deissler, Helmut; Rhiem, Kerstin; Niederacher, Dieter; Pendl, Hansjoerg; Sutter, Christian; Wappenschmidt, Barbara; Borg, Ake; Mein, Beatrice; Rantala, Johanna; Soller, Maria; Nathanson, Katherine L.; Domchek, Susan M.; Rodriguez, Gustavo C.; Salani, Ritu; Kaulich, Daphne Gschwantler; Tea, Muy-Kheng; Paluch, Shani Shimon; Laitman, Yael; Skytte, Anne-Bine; Kruse, Torben A.; Jensen, Uffe Birk; Robson, Mark; Gerdes, Anne-Marie; Ejlertsen, Bent; Foretova, Lenka; Savage, Sharon A.; Lesterm, Jenny; Soucy, Penny; Kuchenbaecker, Karoline B.; Olswold, Curtis; Cunningham, Julie M.; Slager, Susan; Pankratz, Vernon S.; Dicks, Ed; Lakhani, Sunil R.; Couch, Fergus J.; Hall, Per; Monteiro, Alvaro N. A.; Gayther, Simon A.; Pharoah, Paul D. P.; Reddel, Roger R.; Goode, Ellen L.; Greene, Mark H.; Easton, Douglas F.; Berchuck, Andrew; Antoniou, Antonis C.; Chenevix-Trench, Georgia; Dunning, Alison M.

    2013-01-01

    TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOG, we analyzed similar to 480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer ca

  8. 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...

  9. 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....

  10. 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

  11. 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 ...

  12. 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 ...

  13. 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

  14. 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.

  15. 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

  16. 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...

  17. Association of active and passive smoking with risk of breast cancer among postmenopausal women: a prospective cohort study

    Science.gov (United States)

    Luo, Juhua; Wactawski-Wende, Jean; Horn, Kimberly; Messina, Catherine; Stefanick, Marcia L; Tindle, Hilary A; Tong, Elisa; Rohan, Thomas E

    2011-01-01

    Objective To examine the association between smoking and risk of invasive breast cancer using quantitative measures of lifetime passive and active smoking exposure among postmenopausal women. Design Prospective cohort study. Setting 40 clinical centres in the United States. Participants 79 990 women aged 50–79 enrolled in the Women’s Health Initiative Observational Study during 1993–8. Main outcome measures Self reported active and passive smoking, pathologically confirmed invasive breast cancer. Results In total, 3520 incident cases of invasive breast cancer were identified during an average of 10.3 years of follow-up. Compared with women who had never smoked, breast cancer risk was elevated by 9% among former smokers (hazard ratio 1.09 (95% CI 1.02 to 1.17)) and by 16% among current smokers (hazard ratio 1.16 (1.00 to 1.34)). Significantly higher breast cancer risk was observed in active smokers with high intensity and duration of smoking, as well as with initiation of smoking in the teenage years. The highest breast cancer risk was found among women who had smoked for ≥50 years or more (hazard ratio 1.35 (1.03 to1.77) compared with all lifetime non-smokers, hazard ratio 1.45 (1.06 to 1.98) compared with lifetime non-smokers with no exposure to passive smoking). An increased risk of breast cancer persisted for up to 20 years after smoking cessation. Among women who had never smoked, after adjustment for potential confounders, those with the most extensive exposure to passive smoking (≥10 years’ exposure in childhood, ≥20 years’ exposure as an adult at home, and ≥10 years’ exposure as an adult at work) had a 32% excess risk of breast cancer compared with those who had never been exposed to passive smoking (hazard ratio 1.32 (1.04 to 1.67)). However, there was no significant association in the other groups with lower exposure and no clear dose response to cumulative passive smoking exposure. Conclusions Active smoking was associated with an

  18. 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...

  19. 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 ...

  20. 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.

  1. The association between phosphatase and tensin homolog hypermethylation and patients with breast cancer, a meta-analysis and literature review

    Science.gov (United States)

    Lu, Yi-Min; Cheng, Feng; Teng, Li-Song

    2016-01-01

    The Phosphatase and tensin homolog (PTEN) protein is a negative regulator of the Akt pathway, leading to suppression of apoptois and increased cell survival. Its role as a tumor-suppressor gene has been adequately substantiated, and PTEN hypermethylation has been demonstrated in familial and sporadic cancers. However, the association and clinical significance between PTEN hypermethylation and breast cancer remains unclear. In this study, we systematically reviewed studies of PTEN hypermethylation and breast cancer and quantify the association between PTEN hypermethylation and breast cancer using meta-analysis methods. The pooled OR, 22.30, 95% confidential intervals, CI = 1.98–251.51, P = 0.01, which demonstrates that loss of PTEN expression by hypermethylation plays a critical role in the early tumorigenesis of ductal carcinoma in situ (DCIS). In addition, PTEN hypermethylation also is detected in invasive ductal carcinomas (IDCs) and is significantly higher than in normal controls, OR = 23.32, 95% CI = 10.43–52.13, P < 0.00001. Further analysis did not show significant correlation between PTEN hypermethylation and the progression of breast cancer, estrogen receptor (ER), progesterone receptor (PgR), as well as HER2 status. These results indicate the PTEN hypermethylation is significantly associated with both DCIS and IDCs. The detection of PTEN hypermethylation could be an early tumorigenesis marker for breast cancer patients. PMID:27620353

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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...

  7. 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.

  8. 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

  9. 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...

  10. 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 (pbreast 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.

  11. 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.

  12. 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...

  13. 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...

  14. TFF3 is a normal breast epithelial protein and is associated with differentiated phenotype in early breast cancer but predisposes to invasion and metastasis in advanced disease.

    Science.gov (United States)

    Ahmed, Ahmed R H; Griffiths, Andrew B; Tilby, Michael T; Westley, Bruce R; May, Felicity E B

    2012-03-01

    The trefoil protein TFF3 stimulates invasion and angiogenesis in vitro. To determine whether it has a role in breast tumor metastasis and angiogenesis, its levels were measured by immunohistochemistry in breast tissue with a specific monoclonal antibody raised against human TFF3. TFF3 is expressed in normal breast lobules and ducts, at higher levels in areas of fibrocystic change and papillomas, in all benign breast disease lesions, and in 89% of in situ and in 83% of invasive carcinomas. In well-differentiated tumor cells, TFF3 is concentrated at the luminal edge, whereas in poorly differentiated cells polarity is inverted and expression is directed toward the stroma. Expression was high in well-differentiated tumors and was associated significantly with low histological grade and with estrogen and progesterone receptor expression, accordant with induction of TFF3 mRNA by estrogen in breast cancer cells. Paradoxically, TFF3 expression was associated with muscle, neural, and lymphovascular invasion and the presence and number of involved lymph nodes, and it was an independent predictive marker of lymphovascular invasion and lymph node involvement. Consistent with an angiogenic function, TFF3 expression correlated strongly with microvessel density evaluated with CD31 and CD34. In conclusion, TFF3 is expressed in both the normal and diseased breast. Although associated with features of good prognosis, its profile of expression in invasive cancer is consistent with a role in breast tumor progression and tumor cell dissemination.

  15. 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...

  16. 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.

  17. A case-control study on association of SULT1A1 polymorphism and smoked meat intake with breast cancer risk

    Institute of Scientific and Technical Information of China (English)

    陶蘋

    2012-01-01

    Objective To assess the association of smoked meat intake,SULT1A1 polymorphism as well as their combined effects with breast cancer risk. Methods A total of 400 newly diagnosed breast cancer cases from a cancer hospital in Sichuan province and 400 healthy controls from participants

  18. A Comprehensive Multistate Model Analyzing Associations of Various Risk Factors With the Course of Breast Cancer in a Population-Based Cohort of Breast Cancer Cases

    NARCIS (Netherlands)

    Eulenburg, Christine; Schroeder, Jennifer; Obi, Nadia; Heinz, Judith; Seibold, Petra; Rudolph, Anja; Chang-Claude, Jenny; Flesch-Janys, Dieter

    2016-01-01

    We employed a semi-Markov multistate model for the simultaneous analysis of various endpoints describing the course of breast cancer. Results were compared with those from standard analyses using a Cox proportional hazards model. We included 3,012 patients with invasive breast cancer newly diagnosed

  19. 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: 0.97-2.62, P = 0...

  20. PIK3CA rs7640662 (C/G) single nucleotide polymorphism lacks association with breast cancer cases in Persians.

    Science.gov (United States)

    Mir, Atefeh; Sadegh, Mahdiyeh Harati; Ahmadinia, Zahra; Kaboli, Parham Jabbarzadeh

    2015-03-01

    Phosphatidylinositol-3-kinase (PI3K) is a group of enzymes involved in cellular growth, proliferation, differentiation, cell motility, intracellular trafficking, and survival that play very important roles in developing breast cancer. PIK3CA is a gene that encodes α catalytic subunit of this enzyme. A common polymorphism of PIK3CA, rs7640662 (C/G), was analyzed, and its association to breast cancer cases was determined. In this study, DNA was extracted from peripheral blood samples of 278 women suffering from breast cancer and 128 healthy women. Tetra-primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) method was performed to genotype rs7640662. P values and ODD ratios were measured using SPSS. P value less than 0.05 and ODD ratios more than 1 were considered as significant. All ODD ratios were less than 1, and P values were more than 0.05 showing that rs7640662 (C/G) and breast cancer are not significantly associated. However, the genotypes observed in the Persian population, as an ancient population living in the Middle East, was significantly different from the genotypes reported by HapMap for Asian populations. As a conclusion, rs7640662 was not associated with the risk of breast cancer in a Persian population; however, it was observed that heterozygote (GC) is the most common genotypes in both case and control samples. PMID:25838920

  1. 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.

  2. 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.

  3. Riposte to Guest Commentaries on 'Problems associated with randomized controlled clinical trials in breast cancer.

    Science.gov (United States)

    Johnson, A E

    1998-08-01

    This paper addresses the objections of Professor M. Baum and Mr W. J. Cunliffe to my thesis that the randomized controlled clinical trial is a poor tool for the investigation of the treatment of breast cancer, argued in a discussion paper entitled 'Problems associated with randomized controlled clinical trials in breast cancer' (A.E. Johnson, 1998, Journal of Evaluation in Clinical Practice 4, 119-126). The objections range from those that have a philosophical basis, through those founded on differing concepts of the classification of primary tumours and the nature of the metastatic tumour, to those that question the reliability and usefulness of the clinical evaluation of response to treatment in terms of histological grade and rate of tumour shrinkage. An alternative approach to research through primary systemic therapy with selection of treatment according to predicted tumour behaviour was severely criticized, both on the preceding grounds and because it was assumed that the alternative to randomization is management by anecdote. These objections are examined and evidence in support of reliable and useful clinical measurement of response is presented in some detail. The problems associated with randomization as a technique for the evaluation of treatments, when the intrinsic variability of tumours is very large without the intervention of treatment, remain unsolved.

  4. 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.

  5. Molecular phenotype is associated with survival in breast cancer patients with spinal bone metastases.

    Science.gov (United States)

    Bollen, L; Wibmer, C; Wang, M; van der Linden, Y M; Leithner, A; Bünger, C E; Jensen, A B; Fiocco, M; Bratschitsch, G; Pondaag, W; Bovée, J V M G; Dijkstra, P D S

    2015-01-01

    To aid in therapy selection for patients with spinal bone metastases (SBM), predictive models have been developed. These models consider SBM from breast cancer a positive predictive factor, but do not take phenotypes based on estrogen (ER), progesterone (PR) and human epidermal growth factor 2 (HER2) receptors into account. The aim of this study was to ascertain whether receptors are associated with survival, when the disease has progressed up to SBM. All patients who were treated for SBM from breast cancer between 2005 and 2012 were included in this international multi-center retrospective study (n = 111). Reports were reviewed for ER, PR and HER2 status and subsequently subdivided into one of four categories; luminal A, luminal B, HER2 and triple negative. Survival time was calculated as the difference between start of treatment for SBM and date of death. Analysis was performed using the Kaplan-Meier method and log-rank tests. Median follow-up was 3.7 years. Survival times in the luminal B and HER2 categories were not significantly different to the luminal A category and were joined into a single receptor positive category. Eighty-five patients (77 %) had a receptor positive phenotype and 25 (23 %) had a triple negative phenotype. Median survival time was 22.5 months (95 %CI 18.0-26.9) for the receptor positive category and 6.7 months (95 %CI 2.4-10.9) for the triple negative category (p < 0.001). Patients with SBM from breast cancer with a triple negative phenotype have a shorter survival time than patients with a receptor positive phenotype. Models estimating survival should be adjusted accordingly. PMID:25359620

  6. 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

  7. 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, A S M; Varma, Nadimpalli Ravi S; Shankar, Adarsh; Coimbra, Verena Benedick; Fabri, Vanessa Alves; de Oliveira, Juliana Garcia; Zuccari, Debora Aparecida Pires de Campos

    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

  8. Compliance after 17 years of breast cancer screening - Factors associated with reattendance for periodic breast screening

    NARCIS (Netherlands)

    ScafKlomp, W; VanSonderen, E; VandenHeuvel, W

    1997-01-01

    The motives and reasons for regular attendance, irregular attendance and drop-out were studied in women who were enrolled in a biennial breast screening programme in 1975 and who were invited to each subsequent screening round until 1992. Three compliance groups were compared: 'attended all rounds'

  9. 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

  10. 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.

  11. 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...

  12. Association of genetic susceptibility variants for type 2 diabetes with breast cancer risk in women of European ancestry

    NARCIS (Netherlands)

    Zhao, Zhiguo; Wen, Wanqing; Michailidou, Kyriaki; Bolla, Manjeet K; Wang, Qin; Zhang, Ben; Long, Jirong; Shu, Xiao-Ou; Schmidt, Marjanka K; Milne, Roger L; García-Closas, Montserrat; Chang-Claude, Jenny; Lindstrom, Sara; Bojesen, Stig E; Ahsan, Habibul; Aittomäki, Kristiina; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Beckmann, Matthias W; Beeghly-Fadiel, Alicia; Benitez, Javier; Blomqvist, Carl; Bogdanova, Natalia V; Børresen-Dale, Anne-Lise; Brand, Judith; Brauch, Hiltrud; Brenner, Hermann; Burwinkel, Barbara; Cai, Qiuyin; Casey, Graham; Chenevix-Trench, Georgia; Couch, Fergus J; Cox, Angela; Cross, Simon S; Czene, Kamila; Dörk, Thilo; Dumont, Martine; Fasching, Peter A; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Fostira, Florentia; Gammon, Marilie; Giles, Graham G; Guénel, Pascal; Haiman, Christopher A; Hamann, Ute; Harrington, Patricia; Hartman, Mikael; Hooning, Maartje J; Hopper, John L; Jakubowska, Anna; Jasmine, Farzana; John, Esther M; Johnson, Nichola; Kabisch, Maria; Khan, Sofia; Kibriya, Muhammad; Knight, Julia A; Kosma, Veli-Matti; Kriege, Mieke; Kristensen, Vessela; Le Marchand, Loic; Lee, Eunjung; Li, Jingmei; Lindblom, Annika; Lophatananon, Artitaya; Luben, Robert; Lubinski, Jan; Malone, Kathleen E; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Marme, Frederik; McLean, Catriona; Meijers-Heijboer, Hanne; Meindl, Alfons; Miao, Hui; Muir, Kenneth; Neuhausen, Susan L; Nevanlinna, Heli; Neven, Patrick; Olson, Janet E; Perkins, Barbara; Peterlongo, Paolo; Phillips, Kelly-Anne; Pylkäs, Katri; Rudolph, Anja; Santella, Regina; Sawyer, Elinor J; Schmutzler, Rita K; Schoemaker, Minouk; Shah, Mitul; Shrubsole, Martha; Southey, Melissa C; Swerdlow, Anthony J; Toland, Amanda E; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Ursin, Giske; Van Der Luijt, Rob B; Verhoef, Senno; Wang-Gohrke, Shan; Whittemore, Alice S; Winqvist, Robert; Pilar Zamora, M; Zhao, Hui; Dunning, Alison M; Simard, Jacques; Hall, Per; Kraft, Peter; Pharoah, Paul; Hunter, David; Easton, Douglas F; Zheng, Wei

    2016-01-01

    PURPOSE: Type 2 diabetes (T2D) has been reported to be associated with an elevated risk of breast cancer. It is unclear, however, whether this association is due to shared genetic factors. METHODS: We constructed a genetic risk score (GRS) using risk variants from 33 known independent T2D susceptibi

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

    NARCIS (Netherlands)

    K. Michailidou (Kyriaki); J. Beesley (Jonathan); S. Lindstrom (Stephen); S. Canisius (Sander); J. Dennis (Joe); M. Lush (Michael); M. Maranian (Melanie); M.K. Bolla (Manjeet); Q. Wang (Qing); M. Shah (Mitul); B. Perkins (Barbara); K. Czene (Kamila); M. Eriksson (Mikael); H. Darabi (Hatef); J.S. Brand (Judith S.); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); H. Flyger (Henrik); S.F. Nielsen (Sune); N. Rahman (Nazneen); C. Turnbull (Clare); O. Fletcher (Olivia); J. Peto (Julian); L.J. Gibson (Lorna); I. dos Santos Silva (Isabel); J. Chang-Claude (Jenny); D. Flesch-Janys (Dieter); A. Rudolph (Anja); U. Eilber (Ursula); T.W. Behrens (Timothy); H. Nevanlinna (Heli); T.A. Muranen (Taru); K. Aittomäki (Kristiina); C. Blomqvist (Carl); S. Khan (Sofia); K. Aaltonen (Kirsimari); H. Ahsan (Habibul); M.G. Kibriya (Muhammad); A.S. Whittemore (Alice S.); E.M. John (Esther M.); K.E. Malone (Kathleen E.); M.D. Gammon (Marilie); R.M. Santella (Regina M.); G. Ursin (Giske); E. Makalic (Enes); D.F. Schmidt (Daniel); G. Casey (Graham); D.J. Hunter (David J.); S.M. Gapstur (Susan M.); M.M. Gaudet (Mia); W.R. Diver (Ryan); C.A. Haiman (Christopher A.); F.R. Schumacher (Fredrick); B.E. Henderson (Brian); L. Le Marchand (Loic); C.D. Berg (Christine); S.J. Chanock (Stephen); J.D. Figueroa (Jonine); R.N. Hoover (Robert N.); D. Lambrechts (Diether); P. Neven (Patrick); H. Wildiers (Hans); E. van Limbergen (Erik); M.K. Schmidt (Marjanka); A. Broeks (Annegien); S. Verhoef; S. Cornelissen (Sten); F.J. Couch (Fergus); J.E. Olson (Janet); B. Hallberg (Boubou); C. Vachon (Celine); Q. Waisfisz (Quinten); E.J. Meijers-Heijboer (Hanne); M.A. Adank (Muriel); R.B. van der Luijt (Rob); J. Li (Jingmei); J. Liu (Jianjun); M.K. Humphreys (Manjeet); D. Kang (Daehee); J.-Y. Choi (Ji-Yeob); S.K. Park (Sue K.); K.Y. Yoo; K. Matsuo (Keitaro); H. Ito (Hidemi); H. Iwata (Hiroji); K. Tajima (Kazuo); P. Guénel (Pascal); T. Truong (Thérèse); C. Mulot (Claire); M. Sanchez (Marie); B. Burwinkel (Barbara); F. Marme (Federick); H. Surowy (Harald); C. Sohn (Christof); A.H. Wu (Anna H); C.-C. Tseng (Chiu-chen); D. Van Den Berg (David); D.O. Stram (Daniel O.); A. González-Neira (Anna); J. Benítez (Javier); M.P. Zamora (Pilar); J.I.A. Perez (Jose Ignacio Arias); X.-O. Shu (Xiao-Ou); W. Lu (Wei); Y. Gao; H. Cai (Hui); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); A.-M. Mulligan (Anna-Marie); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); A. Lindblom (Annika); S. Margolin (Sara); S.H. Teo (Soo Hwang); C.H. Yip (Cheng Har); N.A.M. Taib (Nur Aishah Mohd); G.-H. Tan (Gie-Hooi); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); J.W.M. Martens (John); J. Margriet Collée; W.J. Blot (William); L.B. Signorello (Lisa B.); Q. Cai (Qiuyin); J. Hopper (John); M.C. Southey (Melissa); H. Tsimiklis (Helen); C. Apicella (Carmel); C-Y. Shen (Chen-Yang); C.-N. Hsiung (Chia-Ni); P.-E. Wu (Pei-Ei); M.-F. Hou (Ming-Feng); V. Kristensen (Vessela); S. Nord (Silje); G.G. Alnæs (Grethe Grenaker); G.G. Giles (Graham G.); R.L. Milne (Roger); C.A. McLean (Catriona Ann); F. Canzian (Federico); D. Trichopoulos (Dimitrios); P.H.M. Peeters; E. Lund (Eiliv); R. Sund (Reijo); K.T. Khaw; M.J. Gunter (Marc J.); D. Palli (Domenico); L.M. Mortensen (Lotte Maxild); L. Dossus (Laure); J.-M. Huerta (Jose-Maria); A. Meindl (Alfons); R.K. Schmutzler (Rita); C. Sutter (Christian); R. Yang (Rongxi); K. Muir (Kenneth); A. Lophatananon (Artitaya); S. Stewart-Brown (Sarah); P. Siriwanarangsan (Pornthep); J.M. Hartman (Joost); X. Miao; K.S. Chia (Kee Seng); C.W. Chan (Ching Wan); P.A. Fasching (Peter); R. Hein (Rebecca); M.W. Beckmann (Matthias W.); L. Haeberle (Lothar); H. Brenner (Hermann); A.K. Dieffenbach (Aida Karina); V. Arndt (Volker); C. Stegmaier (Christa); A. Ashworth (Alan); N. Orr (Nick); M. Schoemaker (Minouk); A.J. Swerdlow (Anthony ); L.A. Brinton (Louise); M. García-Closas (Montserrat); W. Zheng (Wei); S.L. Halverson (Sandra L.); M. Shrubsole (Martha); J. Long (Jirong); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); M. Grip (Mervi); H. Brauch (Hiltrud); U. Hamann (Ute); T. Brüning (Thomas); P. Radice (Paolo); P. Peterlongo (Paolo); S. Manoukian (Siranoush); L. Bernard (Loris); N.V. Bogdanova (Natalia); T. Dörk (Thilo); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti)

    2015-01-01

    textabstractGenome-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, comprisi

  14. Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression

    DEFF Research Database (Denmark)

    Hamdi, Yosr; Soucy, Penny; Kuchenbaeker, Karoline B;

    2016-01-01

    PURPOSE: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BR...

  15. 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.

  16. 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...

  17. 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

  18. 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.

  19. 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 ...

  20. 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....

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

    Directory of Open Access Journals (Sweden)

    Tuenchit Khammapirad

    2011-04-01

    Full Text Available 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 Array HPV 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 types 16, 33, 58 and 71 were detected after use of Linear Array HPV genotyping test.

  2. 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.

  3. 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.

  4. 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 ...

  5. Melatonin: an Inhibitor of Breast Cancer

    OpenAIRE

    Steven M. Hill; Belancio, Victoria P; Dauchy, Robert T; Xiang, Shulin; Brimer, Samantha; Mao, Lulu; Hauch, Adam; Lundberg, Peter W.; Summers, Whitney; YUAN, LIN; Frasch, Tripp; Blask, David E.

    2015-01-01

    This review discusses recent work on melatonin-mediated circadian regulation and metabolic and molecular signaling mechanisms involved in human breast cancer growth and associated consequences of circadian disruption by exposure to light at night (LEN). The anti-cancer actions of the circadian melatonin signal in human breast cancer cell lines and xenografts heavily involve MT1 receptor-mediated mechanisms. In estrogen receptor alpha (ERα)-positive human breast cancer, melatonin, via the MT1 ...

  6. Association of Single Nucleotide Polymorphisms in CYP1B1 and COMT Genes with Breast Cancer Susceptibility in Indian Women

    Directory of Open Access Journals (Sweden)

    Sharawan Yadav

    2009-01-01

    Full Text Available Cytochrome P450 1B1 (CYP1B1 and catechol-$O$-methyltransferase (COMT enzymes play critical roles in estrogen metabolism. Alterations in the catalytic activity of CYP1B1 and COMT enzymes have been found associated with altered breast cancer risk in postmenopausal women in many populations. The substitution of leucine (Leu to valine (Val at codon 432 increases the catalytic activity of CYP1B1, however, substitution of Val to methionine (Met at codon 158 decreases the catalytic activity of COMT. The present study was performed to evaluate the associations of CYP1B1 Leu432Val and/or COMT Val158Met polymorphisms with total, premenopausal and postmenopausal breast cancer risks in Indian women. COMT and CYP1B1 polymorphisms in controls and breast cancer patients were analyzed employing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP followed by gel electrophoresis. Although CYP1B1 and COMT genotypes did not exhibit statistically significant association with breast cancer risks when analyzed individually, COMT wild type (Val158Val in combination with CYP1B1 heterozygous variant (Leu432Val [OR: 0.21; 95% CI (0.05–0.82, p value; 0.021] and COMT heterozygous variant (Val158Met in combination with CYP1B1 wild type (Leu432Leu [OR: 0.29; 95% CI (0.08–0.96, p value; 0.042] showed significant protective association with premenopausal breast cancer risk. The results demonstrate that CYP1B1 wild type in combination with COMT heterozygous or their inverse combination offer protection against breast cancer in premenopausal Indian women.

  7. CLINICOPATHOLOGICAL FACTORS ASSOCIATED WITH POSITIVE PREOPERATIVE AXILLARY ULTRASOUND SCANNING IN BREAST CANCER PATIENTS

    Directory of Open Access Journals (Sweden)

    Lona Jalini

    2016-01-01

    Full Text Available Background: Axillary lymph node status is the most important breast cancer prognostic factor. Preoperative axillary ultrasound examination (PAUS is used to triage patients for sentinel lymph node biopsy (SLNB or axillary lymph node dissection (ALND. We assessed the detection rate of lymph node metastases by PAUS in a screening unit and evaluated associations between clinicopathological factors and PAUS positivity. Patients and Methods: This was a single-centre retrospective analysis of data extracted from a hospital breast cancer database and clinical records. Clinical, radiological, and pathological and prognostic indices were compared between PAUS-positive and PAUS-negative patients subsequently found to have lymph node metastases on histopathological analysis. Results: Two hundred and two patients were eligible for analysis. 50.5% of lymph node-positive patients were correctly identified as PAUS positive. Patients with PAUS-positive lymph nodes had less favorable disease characteristics, namely clinically palpable lymph nodes, higher Nottingham prognostic (NPI index, high lymph node burden according to the European Society of Medical Oncology (ESMO group classification, and larger, grade 3 tumors with lymphovascular invasion and extranodal spread. Moreover, PAUS-positive patients had more macrometastases and lymph node involvement than PAUS-negative patients. Conclusion: PAUS-positive patients and PAUS-negative (SLNB-positive patients have different clinicopathological characteristics. The presence of LVI, extranodal spread, grade 3 histology, or large tumors with poor prognostic indices in PAUS-negative patients should be regarded with caution and perhaps prompt second-look ultrasound examination.

  8. 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.

  9. 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

  10. 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.

  11. 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 ...

  12. 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

  13. 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

  14. 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 ...

  15. 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

  16. Dephosphorylated cofilin expression is associated with poor prognosis in cases of human breast cancer: a tissue microarray analysis

    Directory of Open Access Journals (Sweden)

    Maimaiti Y

    2016-10-01

    Full Text Available Yusufu Maimaiti,1,2,* Zeming Liu,1,* Jie Tan,1 Kelimu Abudureyimu,2 Bangxing Huang,3 Chunping Liu,1 Yawen Guo,1 Changwen Wang,1 Xiu Nie,3 Jing Zhou,1 Tao Huang1 1Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 2Department of General Surgery, Research Institute of Minimally Invasive, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 3Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China *These authors contributed equally to this work Background: Proteins in the cofilin pathway regulate actin dynamics and may be involved in cancer cell migration and invasion. However, there are no direct data that suggest that dephosphorylated cofilin can affect breast cancer prognosis.Methods: We assessed the expressions of cofilin and phosphorylated cofilin (P-cofilin in breast cancer tissue microarrays (290 patients, mean follow-up: 95.7±2.49 months to evaluate dephosphorylated cofilin and its relationship with breast cancer prognosis. The associations of pathological characteristics with cumulative survival were evaluated using Kaplan–Meier analysis.Results: Univariate analyses revealed that overall survival was associated with cofilin levels, N category, TNM stage, estrogen receptor status, progesterone receptor status, and molecular subtypes. Cofilin status and TNM stage independently affected overall survival, although P-cofilin expression was not associated with patient survival. In the P-cofilin-negative subgroup, cofilin expression was significantly associated with patient survival, although cofilin expression was not significantly associated with patient survival in the P-cofilin-positive subgroup. We further analyzed the P-cofilin-negative cases and found that Ki-67 expression was significantly elevated in the subgroup that was strongly positive for

  17. Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

    DEFF Research Database (Denmark)

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

    2016-01-01

    UNLABELLED: Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349...

  18. 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

  19. 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.

  20. Breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    Thomas W Owens

    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.

  1. 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

  2. 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...

  3. Functional polymorphisms in the TERT promoter are associated with risk of serous epithelial ovarian and breast cancers.

    Directory of Open Access Journals (Sweden)

    Jonathan Beesley

    Full Text Available Genetic variation at the TERT-CLPTM1L locus at 5p15.33 is associated with susceptibility to several cancers, including epithelial ovarian cancer (EOC. We have carried out fine-mapping of this region in EOC which implicates an association with a single nucleotide polymorphism (SNP within the TERT promoter. We demonstrate that the minor alleles at rs2736109, and at an additional TERT promoter SNP, rs2736108, are associated with decreased breast cancer risk, and that the combination of both SNPs substantially reduces TERT promoter activity.

  4. 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

  5. Common variants at the 19p13.1 and ZNF365 loci are associated with ER subtypes of breast cancer and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers

    NARCIS (Netherlands)

    Couch, F.J.; Gaudet, M.M.; Antoniou, A.C.; Ramus, S.J.; Kuchenbaecker, K.B.; Soucy, P.; Beesley, J.; Chen, X.; Wang, X.; Kirchhoff, T.; McGuffog, L.; Barrowdale, D.; Lee, A.; Healey, S.; Sinilnikova, O.M.; Andrulis, I.L.; Ocgn, .; Ozcelik, H.; Mulligan, A.M.; Thomassen, M.; Gerdes, A.M.; Jensen, U.B.; Skytte, A.B.; Kruse, T.A.; Caligo, M.A.; Wachenfeldt, A. von; Barbany-Bustinza, G.; Loman, N.; Soller, M.; Ehrencrona, H.; Karlsson, P.; Swe, B.; Nathanson, K.L.; Rebbeck, T.R.; Domchek, S.M.; Jakubowska, A.; Lubinski, J.; Jaworska, K.; Durda, K.; Zlowocka, E.; Huzarski, T.; Byrski, T.; Gronwald, J.; Cybulski, C.; Gorski, B.; Osorio, A.; Duran, M.; Tejada, M.I.; Benitez, J.; Hamann, U.; Hogervorst, F.B.; Hebon, .; Os, T.A. van; Leeuwen, F.E. van; Meijers-Heijboer, H.E.; Wijnen, J.; Blok, M.J.; Kets, M.; Hooning, M.J.; Oldenburg, R.A.; Ausems, M.G.; Peock, S.; Frost, D.; Ellis, S.D.; Platte, R.; Fineberg, E.; Evans, D.G.; Jacobs, C.; Eeles, R.A.; Adlard, J.; Davidson, R.; Eccles, D.M.; Cole, T.; Cook, J.; Paterson, J.; Brewer, C.; Douglas, F.; Hodgson, S.V.; Morrison, P.J.; Walker, L.; Porteous, M.E.; Kennedy, M.J.; Side, L.E.; Embrace, .; Bove, B.; Godwin, A.K.; Stoppa-Lyonnet, D.; Collaborators, G.S.; Fassy-Colcombet, M.; Castera, L.; Cornelis, F.; Mazoyer, S.; Leone, M.; Boutry-Kryza, N.; Bressac-de Paillerets, B.; Caron, O.; Pujol, P.; Coupier, I.; Delnatte, C.; Akloul, L.; Ligtenberg, M.J.; Hoogerbrugge, N.

    2012-01-01

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

  6. 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...

  7. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

    Science.gov (United States)

    Bojesen, Stig E; Pooley, Karen A; Johnatty, Sharon E; Beesley, Jonathan; Michailidou, Kyriaki; Tyrer, Jonathan P; Edwards, Stacey L; Pickett, Hilda A; Shen, Howard C; Smart, Chanel E; Hillman, Kristine M; Mai, Phuong L; Lawrenson, Kate; Stutz, Michael D; Lu, Yi; Karevan, Rod; Woods, Nicholas; Johnston, Rebecca L; French, Juliet D; Chen, Xiaoqing; Weischer, Maren; Nielsen, Sune F; Maranian, Melanie J; Ghoussaini, Maya; Ahmed, Shahana; Baynes, Caroline; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Healey, Sue; Lush, Michael; Tessier, Daniel C; Vincent, Daniel; Bacot, Françis; Vergote, Ignace; Lambrechts, Sandrina; Despierre, Evelyn; Risch, Harvey A; González-Neira, Anna; Rossing, Mary Anne; Pita, Guillermo; Doherty, Jennifer A; Álvarez, Nuria; Larson, Melissa C; Fridley, Brooke L; Schoof, Nils; Chang-Claude, Jenny; Cicek, Mine S; Peto, Julian; Kalli, Kimberly R; Broeks, Annegien; Armasu, Sebastian M; Schmidt, Marjanka K; Braaf, Linde M; Winterhoff, Boris; Nevanlinna, Heli; Konecny, Gottfried E; Lambrechts, Diether; Rogmann, Lisa; Guénel, Pascal; Teoman, Attila; Milne, Roger L; Garcia, Joaquin J; Cox, Angela; Shridhar, Vijayalakshmi; Burwinkel, Barbara; Marme, Frederik; Hein, Rebecca; Sawyer, Elinor J; Haiman, Christopher A; Wang-Gohrke, Shan; Andrulis, Irene L; Moysich, Kirsten B; Hopper, John L; Odunsi, Kunle; Lindblom, Annika; Giles, Graham G; Brenner, Hermann; Simard, Jacques; Lurie, Galina; Fasching, Peter A; Carney, Michael E; Radice, Paolo; Wilkens, Lynne R; Swerdlow, Anthony; Goodman, Marc T; Brauch, Hiltrud; García-Closas, Montserrat; Hillemanns, Peter; Winqvist, Robert; Dürst, Matthias; Devilee, Peter; Runnebaum, Ingo; Jakubowska, Anna; Lubinski, Jan; Mannermaa, Arto; Butzow, Ralf; Bogdanova, Natalia V; Dörk, Thilo; Pelttari, Liisa M; Zheng, Wei; Leminen, Arto; Anton-Culver, Hoda; Bunker, Clareann H; Kristensen, Vessela; Ness, Roberta B; Muir, Kenneth; Edwards, Robert; Meindl, Alfons; Heitz, Florian; Matsuo, Keitaro; du Bois, Andreas; Wu, Anna H; Harter, Philipp; Teo, Soo-Hwang; Schwaab, Ira; Shu, Xiao-Ou; Blot, William; Hosono, Satoyo; Kang, Daehee; Nakanishi, Toru; Hartman, Mikael; Yatabe, Yasushi; Hamann, Ute; Karlan, Beth Y; Sangrajrang, Suleeporn; Kjaer, Susanne Krüger; Gaborieau, Valerie; Jensen, Allan; Eccles, Diana; Høgdall, Estrid; Shen, Chen-Yang; Brown, Judith; Woo, Yin Ling; Shah, Mitul; Azmi, Mat Adenan Noor; Luben, Robert; Omar, Siti Zawiah; Czene, Kamila; Vierkant, Robert A; Nordestgaard, Børge G; Flyger, Henrik; Vachon, Celine; Olson, Janet E; Wang, Xianshu; Levine, Douglas A; Rudolph, Anja; Weber, Rachel Palmieri; Flesch-Janys, Dieter; Iversen, Edwin; Nickels, Stefan; Schildkraut, Joellen M; Silva, Isabel Dos Santos; Cramer, Daniel W; Gibson, Lorna; Terry, Kathryn L; Fletcher, Olivia; Vitonis, Allison F; van der Schoot, C Ellen; Poole, Elizabeth M; Hogervorst, Frans B L; Tworoger, Shelley S; Liu, Jianjun; Bandera, Elisa V; Li, Jingmei; Olson, Sara H; Humphreys, Keith; Orlow, Irene; Blomqvist, Carl; Rodriguez-Rodriguez, Lorna; Aittomäki, Kristiina; Salvesen, Helga B; Muranen, Taru A; Wik, Elisabeth; Brouwers, Barbara; Krakstad, Camilla; Wauters, Els; Halle, Mari K; Wildiers, Hans; Kiemeney, Lambertus A; Mulot, Claire; Aben, Katja K; Laurent-Puig, Pierre; van Altena, Anne M; Truong, Thérèse; Massuger, Leon F A G; Benitez, Javier; Pejovic, Tanja; Perez, Jose Ignacio Arias; Hoatlin, Maureen; Zamora, M Pilar; Cook, Linda S; Balasubramanian, Sabapathy P; Kelemen, Linda E; Schneeweiss, Andreas; Le, Nhu D; Sohn, Christof; Brooks-Wilson, Angela; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Cybulski, Cezary; Henderson, Brian E; Menkiszak, Janusz; Schumacher, Fredrick; Wentzensen, Nicolas; Marchand, Loic Le; Yang, Hannah P; Mulligan, Anna Marie; Glendon, Gord; Engelholm, Svend Aage; Knight, Julia A; Høgdall, Claus K; Apicella, Carmel; Gore, Martin; Tsimiklis, Helen; Song, Honglin; Southey, Melissa C; Jager, Agnes; van den Ouweland, Ans M W; Brown, Robert; Martens, John W M; Flanagan, James M; Kriege, Mieke; Paul, James; Margolin, Sara; Siddiqui, Nadeem; Severi, Gianluca; Whittemore, Alice S; Baglietto, Laura; McGuire, Valerie; Stegmaier, Christa; Sieh, Weiva; Müller, Heiko; Arndt, Volker; Labrèche, France; Gao, Yu-Tang; Goldberg, Mark S; Yang, Gong; Dumont, Martine; McLaughlin, John R; Hartmann, Arndt; Ekici, Arif B; Beckmann, Matthias W; Phelan, Catherine M; Lux, Michael P; Permuth-Wey, Jenny; Peissel, Bernard; Sellers, Thomas A; Ficarazzi, Filomena; Barile, Monica; Ziogas, Argyrios; Ashworth, Alan; Gentry-Maharaj, Aleksandra; Jones, Michael

    2013-01-01

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

  8. The prognostic effect of the number of histologically examined axillary lymph nodes in breast cancer : Stage migration or age association?

    NARCIS (Netherlands)

    Schaapveld, M; de Vries, EGE; van der Graaf, WTA; Otter, R; de Vries, J; Willemse, PHB

    2006-01-01

    Background: The number of pathologically examined axillary nodes has been associated with breast cancer survival, and examination of >= 10 nodes has been advocated for reliable axillary staging. The considerable variation observed in axillary staging prompted this population-based study, which evalu

  9. 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

  10. 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

  11. 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

  12. The association between phosphatase and tensin homolog hypermethylation and patients with breast cancer, a meta-analysis and literature review.

    Science.gov (United States)

    Lu, Yi-Min; Cheng, Feng; Teng, Li-Song

    2016-01-01

    The Phosphatase and tensin homolog (PTEN) protein is a negative regulator of the Akt pathway, leading to suppression of apoptois and increased cell survival. Its role as a tumor-suppressor gene has been adequately substantiated, and PTEN hypermethylation has been demonstrated in familial and sporadic cancers. However, the association and clinical significance between PTEN hypermethylation and breast cancer remains unclear. In this study, we systematically reviewed studies of PTEN hypermethylation and breast cancer and quantify the association between PTEN hypermethylation and breast cancer using meta-analysis methods. The pooled OR, 22.30, 95% confidential intervals, CI = 1.98-251.51, P = 0.01, which demonstrates that loss of PTEN expression by hypermethylation plays a critical role in the early tumorigenesis of ductal carcinoma in situ (DCIS). In addition, PTEN hypermethylation also is detected in invasive ductal carcinomas (IDCs) and is significantly higher than in normal controls, OR = 23.32, 95% CI = 10.43-52.13, P detection of PTEN hypermethylation could be an early tumorigenesis marker for breast cancer patients. PMID:27620353

  13. Lung cancer after treatment for breast cancer.

    Science.gov (United States)

    Lorigan, Paul; Califano, Raffaele; Faivre-Finn, Corinne; Howell, Anthony; Thatcher, Nick

    2010-12-01

    Breast cancer is the most common cancer in women, and the second most common cause of cancer death after lung cancer. Improvements in the outcome of breast cancer mean that more patients are living longer and are, therefore, at risk of developing a second malignancy. The aim of this review is to present the current understanding of the risk of lung cancer arising in patients previously treated for early stage breast cancer. We review data on the effect of treatment factors (ie, surgery type, radiotherapy technique, and adjuvant chemotherapy) and patient factors (ie, age and smoking) on the risk of developing a subsequent lung cancer. The evidence suggests that older radiotherapy techniques were associated with a substantially increased risk of developing lung cancer in the ipsilateral lung, but there is no clear evidence of an increased risk with modern techniques. Smoking is an important risk factor, and increases the risk of lung cancer in those receiving radiotherapy. Adjuvant chemotherapy is not significantly associated with an increased risk. The risk of developing lung cancer increases with time elapsed since treatment, but any effect of age at treatment is unclear.

  14. 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.

  15. 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.

  16. Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

    Science.gov (United States)

    Pistelli, Mirco; Caramanti, Miriam; Biscotti, Tommasina; Santinelli, Alfredo; Pagliacci, Alessandra; De Lisa, Mariagrazia; Ballatore, Zelmira; Ridolfi, Francesca; Maccaroni, Elena; Bracci, Raffaella; Berardi, Rossana; Battelli, Nicola; Cascinu, Stefano

    2014-01-01

    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. PMID:24978437

  17. 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

  18. 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

  19. 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...

  20. 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...

  1. A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11

    NARCIS (Netherlands)

    Siddiq, Afshan; Couch, Fergus J.; Chen, Gary K.; Lindstrom, Sara; Eccles, Diana; Millikan, Robert C.; Michailidou, Kyriaki; Stram, Daniel O.; Beckmann, Lars; Rhie, Suhn Kyong; Ambrosone, Christine B.; Aittomaki, Kristiina; Amiano, Pilar; Apicella, Carmel; Baglietto, Laura; Bandera, Elisa V.; Beckmann, Matthias W.; Berg, Christine D.; Bernstein, Leslie; Blomqvist, Carl; Brauch, Hiltrud; Brinton, Louise; Bui, Quang M.; Buring, Julie E.; Buys, Saundra S.; Campa, Daniele; Carpenter, Jane E.; Chasman, Daniel I.; Chang-Claude, Jenny; Chen, Constance; Clavel-Chapelon, Francoise; Cox, Angela; Cross, Simon S.; Czene, Kamila; Deming, Sandra L.; Diasio, Robert B.; Diver, W. Ryan; Dunning, Alison M.; Durcan, Lorraine; Ekici, Arif B.; Fasching, Peter A.; Feigelson, Heather Spencer; Fejerman, Laura; Figueroa, Jonine D.; Fletcher, Olivia; Flesch-Janys, Dieter; Gaudet, Mia M.; Gerty, Susan M.; Rodriguez-Gil, Jorge L.; Giles, Graham G.; van Gils, Carla H.; Godwin, Andrew K.; Graham, Nikki; Greco, Dario; Hall, Per; Hankinson, Susan E.; Hartmann, Arndt; Hein, Rebecca; Heinz, Judith; Hoover, Robert N.; Hopper, John L.; Hu, Jennifer J.; Huntsman, Scott; Ingles, Sue A.; Irwanto, Astrid; Isaacs, Claudine; Jacobs, Kevin B.; John, Esther M.; Justenhoven, Christina; Kaaks, Rudolf; Kolonel, Laurence N.; Coetzee, Gerhard A.; Lathrop, Mark; Le Marchand, Loic; Lee, Adam M.; Lee, I-Min; Lesnick, Timothy; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Martin, Nicholas G.; McLean, Catriona A.; Meijers-Heijboer, Hanne; Meindl, Alfons; Miron, Penelope; Monroe, Kristine R.; Montgomery, Grant W.; Mueller-Myhsok, Bertram; Nickels, Stefan; Nyante, Sarah J.; Olswold, Curtis; Overvad, Kim; Palli, Domenico; Park, Daniel J.; Palmer, Julie R.; Pathak, Harsh; Peto, Julian; Pharoah, Paul; Rahman, Nazneen; Rivadeneira, Fernando; Schmidt, Daniel F.; Schmutzler, Rita K.; Slager, Susan; Southey, Melissa C.; Stevens, Kristen N.; Sinn, Hans-Peter; Press, Michael F.; Ross, Eric; Riboli, Elio; Ridker, Paul M.; Schumacher, Fredrick R.; Severi, Gianluca; Silva, Isabel dos Santos; Stone, Jennifer; Sund, Malin; Tapper, William J.; Thun, Michael J.; Travis, Ruth C.; Turnbull, Clare; Uitterlinden, Andre G.; Waisfisz, Quinten; Wang, Xianshu; Wang, Zhaoming; Weaver, JoEllen; Schulz-Wendtland, Ruediger; Wilkens, Lynne R.; Van Den Berg, David; Zheng, Wei; Ziegler, Regina G.; Ziv, Elad; Nevanlinna, Heli; Easton, Douglas F.; Hunter, David J.; Henderson, Brian E.; Chanock, Stephen J.; Garcia-Closas, Montserrat; Kraft, Peter; Haiman, Christopher A.; Vachon, Celine M.

    2012-01-01

    Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of E

  2. 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.

  3. 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...

  4. 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

  5. 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

  6. 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.

  7. Lifetime grain consumption and breast cancer risk.

    Science.gov (United States)

    Farvid, Maryam S; Cho, Eunyoung; Eliassen, A Heather; Chen, Wendy Y; Willett, Walter C

    2016-09-01

    We evaluated individual grain-containing foods and whole and refined grain intake during adolescence, early adulthood, and premenopausal years in relation to breast cancer risk in the Nurses' Health Study II. Grain-containing food intakes were reported on a baseline dietary questionnaire (1991) and every 4 years thereafter. Among 90,516 premenopausal women aged 27-44 years, we prospectively identified 3235 invasive breast cancer cases during follow-up to 2013. 44,263 women reported their diet during high school, and from 1998 to 2013, 1347 breast cancer cases were identified among these women. Cox proportional hazards regression was used to estimate relative risks (RR) and 95 % confidence intervals (95 % CI) of breast cancer for individual, whole and refined grain foods. After adjusting for known breast cancer risk factors, adult intake of whole grain foods was associated with lower premenopausal breast cancer risk (highest vs. lowest quintile: RR 0.82; 95 % CI 0.70-0.97; P trend = 0.03), but not postmenopausal breast cancer. This association was no longer significant after further adjustment for fiber intake. The average of adolescent and early adulthood whole grain food intake was suggestively associated with lower premenopausal breast cancer risk (highest vs lowest quintile: RR 0.74; 95 % CI 0.56-0.99; P trend = 0.09). Total refined grain food intake was not associated with risk of breast cancer. Most individual grain-containing foods were not associated with breast cancer risk. The exceptions were adult brown rice which was associated with lower risk of overall and premenopausal breast cancer (for each 2 servings/week: RR 0.94; 95 % CI 0.89-0.99 and RR 0.91; 95 % CI 0.85-0.99, respectively) and adult white bread intake which was associated with increased overall breast cancer risk (for each 2 servings/week: RR 1.02; 95 % CI 1.01-1.04), as well as breast cancer before and after menopause. Further, pasta intake was inversely associated with

  8. 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.)

  9. Breast fibromatosis associated with breast implants.

    Science.gov (United States)

    Seo, Yoon Nae; Park, Young Mi; Yoon, Hye Kyoung; Lee, Sun Joo; Choo, Hye Jung; Ryu, Ji Hwa

    2015-09-01

    Fibromatosis refers to an extra-abdominal desmoid tumor or aggressive fibromatosis. Breast fibromatosis can develop in association with the capsule around a breast implant, although reports of cases of fibromatosis associated with breast implants are rare. As the demand for breast augmentation has increased, it is important to understand the diseases associated with breast implants. In the present report, we describe a case of breast fibromatosis that developed adjacent to a breast implant and demonstrated a relatively well-defined border even though it invaded the surrounding structures. We also explore the specific imaging features for diagnosing breast fibromatosis in association with implants by reviewing previous literature.

  10. 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

  11. 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 ...

  12. 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 Imagery Hypnosis Massage Therapy Mindfulness-Based Stress Reduction Yoga and Breast Cancer Getting ...

  13. The breast cancer conundrum

    OpenAIRE

    2013-01-01

    For decades, rates of breast cancer have been going up faster in rich countries than in poor ones. Scientists are beginning to understand more about its causes but unanswered questions remain. Patrick Adams reports.

  14. 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.

  15. 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

  16. B7-H4 gene polymorphisms are associated with sporadic breast cancer in a Chinese Han population

    Directory of Open Access Journals (Sweden)

    Fu Zhenkun

    2009-11-01

    Full Text Available Abstract Background 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. Methods 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. Results 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

  17. 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

  18. 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

  19. 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)

    A.M. Mulligan (Anna Marie); F.J. Couch (Fergus); D. Barrowdale (Daniel); S.M. Domchek (Susan); D. Eccles (Diana); H. Nevanlinna (Heli); S.J. Ramus (Susan); M. Robson (Mark); M.E. Sherman (Mark); A.B. Spurdle (Amanda); B. Wapenschmidt (Barbara); A. Lee (Andrew); L. McGuffog (Lesley); S. Healey (Sue); O. Sinilnikova (Olga); R. Janavicius (Ramunas); T.V.O. Hansen (Thomas); F.C. Nielsen (Finn); B. Ejlertsen (Bent); A. Osorio (Ana); I. Muñoz-Repeto (Iván); M. Durán (Mercedes); J. Godino (Javier); M. Pertesi (Maroulio); J. Benítez (Javier); P. Peterlongo (Paolo); S. Manoukian (Siranoush); B. Peissel (Bernard); D. Zaffaroni (D.); E. Cattaneo (Elisa); B. Bonnani (Bernardo); A. Viel (Alessandra); B. Pasini (Barbara); L. Papi (Laura); L. Ottini (Laura); A. Savarese (Antonella); L. Bernard (Loris); P. Radice (Paolo); U. Hamann (Ute); M. Verheus (Martijn); E.J. Meijers-Heijboer (Hanne); J.T. Wijnen (Juul); E.B. Gómez García (Encarna); M.R. Nelen (Marcel); C.M. Kets; C.M. Seynaeve (Caroline); M.M.A. Tilanus-Linthorst (Madeleine); R.B. van der Luijt (Rob); T.V. Os (Theo); M.A. Rookus (Matti); D. Frost (Debra); J.L. Jones (J Louise); D.G. Evans (Gareth); F. Lalloo (Fiona); R. Eeles (Rosalind); L. Izatt (Louise); J.W. Adlard (Julian); R. Davidson (Rosemarie); J. Cook (Jackie); A. Donaldson (Alan); H. Dorkins (Huw); H. Gregory (Helen); J. Eason (Jacqueline); C. Houghton (Catherine); J. Barwell (Julian); L. Side (Lucy); E. McCann (Emma); A. Murray (Alexandra); S. Peock (Susan); A.K. Godwin (Andrew); R.K. Schmutzler (Rita); K. Rhiem (Kerstin); C. Engel (Christoph); A. Meindl (Alfons); I. Ruehl (Ina); N. Arnold (Norbert); D. Niederacher (Dieter); C. Sutter (Christian); H. Deissler (Helmut); D. Gadzicki (Dorothea); K. Kast (Karin); S. Preisler-Adams (Sabine); R. Varon-Mateeva (Raymonda); I. Schoenbuchner (Ines); B. Fiebig (Britta); W. Heinritz (Wolfram); D. Schäfer; H. Gevensleben (Heidrun); V. Caux-Moncoutier (Virginie); M. Fassy-Colcombet (Marion); F. Cornelis (Franco̧is); S. Mazoyer (Sylvie); M. Léone (Mélanie); N. Boutry-Kryza (N.); A. Hardouin (Agnès); P. Berthet (Pascaline); D.W. Muller (Danièle); J.P. Fricker (Jean Pierre); I. Mortemousque (Isabelle); P. Pujol (Pascal); I. Coupier (Isabelle); M. Lebrun (Marine); C. Kientz (Caroline); M. Longy (Michel); N. Sevenet (Nicolas); D. Stoppa-Lyonnet (Dominique); C. Isaacs (Claudine); T. Caldes (Trinidad); M. de La Hoya (Miguel); T. Heikinen (Tuomas); K. Aittomäki (Kristiina); I. Blanco (Ignacio); C. Lazaro (Conxi); R.B. Barkardottir (Rosa); P. Soucy (Penny); M. Dumont (Martine); J. Simard (Jacques); M. Montagna (Marco); S. Tognazzo (Silvia); E. D'Andrea (Emma); S.B. Fox (Stephen); M. Yan (Max); R. Rebbeck (Timothy); O.I. Olopade (Olofunmilayo); J.N. Weitzel (Jeffrey); H. Lynch (Henry); P.A. Ganz (Patricia); G. Tomlinson (Gail); X. Wang (Xing); Z. Fredericksen (Zachary); V.S. Pankratz (Shane); N.M. Lindor (Noralane); C. Szabo (Csilla); K. Offit (Kenneth); R. Sakr (Rita); M.M. Gaudet (Mia); K.P. Bhatia (Kailash); N. Kauff (Noah); C.F. Singer (Christian); M.-K. Tea; D. Gschwantler-Kaulich (Daphne); A. Fink-Retter (Anneliese); P.L. Mai (Phuong); M.H. Greene (Mark); E.N. Imyanitov (Evgeny); F.P. O'Malley (Frances); H. Ozcelik (Hilmi); G. Glendon (Gord); A.E. Toland (Amanda); A-M. Gerdes (Anne-Marie); M. Thomassen (Mads); T.A. Kruse (Torben); U.B. Jensen; A.-B. Skytte (Anne-Bine); M.A. Caligo (Maria); M. Soller (Maria); K. Henriksson (Karin); A. von Wachenfeldt (Anna); B. Arver (Brita Wasteson); M. Stenmark-Askmalm (M.); P. Karlsson (Per); Y.C. Ding (Yuan); S.L. Neuhausen (Susan); M.S. Beattie (Mary); P.D.P. Pharoah (Paul); K.B. Moysich (Kirsten); K.L. Nathanson (Katherine); B. Karlan; J. Gross (Jenny); E.M. John (Esther); M.B. Daly (Mary); S.S. Buys (Saundra); M.C. Southey (Melissa); J.L. Hopper (John); M.-B. Terry (Mary-Beth); W. Chung (Wendy); A. Miron (Alexander); D. Goldgar (David); G. Chenevix-Trench (Georgia); D.F. Easton (Douglas); I.L. Andrulis (Irene); A.C. Antoniou (Antonis)

    2011-01-01

    textabstractIntroduction: 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

  20. 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

  1. 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...

  2. 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

  3. 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),

  4. 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 ...

  5. 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),

  6. 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.

  7. 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

  8. Breast cancer risk-associated SNPs modulate the affinity of chromatin for FOXA1 and alter gene expression

    Science.gov (United States)

    Cowper-Sal·lari, Richard; Zhang, Xiaoyang; Wright, Jason B.; Bailey, Swneke D.; Cole, Michael D.; Eeckhoute, Jerome; Moore, Jason H.; Lupien, Mathieu

    2012-01-01

    Genome-wide association studies (GWASs) have identified thousands of single nucleotide polymorphisms (SNPs) associated with human traits and diseases. But because the vast majority of these SNPs are located in the noncoding regions of the genome their risk promoting mechanisms are elusive. Employing a new methodology combining cistromics, epigenomics and genotype imputation we annotate the noncoding regions of the genome in breast cancer cells and systematically identify the functional nature of SNPs associated with breast cancer risk. Our results demonstrate that breast cancer risk-associated SNPs are enriched in the cistromes of FOXA1 and ESR1 and the epigenome of H3K4me1 in a cancer and cell-type-specific manner. Furthermore, the majority of these risk-associated SNPs modulate the affinity of chromatin for FOXA1 at distal regulatory elements, which results in allele-specific gene expression, exemplified by the effect of the rs4784227 SNP on the TOX3 gene found within the 16q12.1 risk locus. PMID:23001124

  9. Volumetric breast density from full-field digital mammograms and its association with breast cancer risk factors: a comparison with a threshold method.

    NARCIS (Netherlands)

    Lokate, M.; Kallenberg, M.G.J.; Karssemeijer, N.; Bosch, M.H.J. van den; Peeters, P.H.M.; Gils, C.H. van

    2010-01-01

    INTRODUCTION: Breast density, a strong breast cancer risk factor, is usually measured on the projected breast area from film screen mammograms. This is far from ideal, as breast thickness and technical characteristics are not taken into account. We investigated whether volumetric density measurement

  10. 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.

  11. 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...

  12. 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...

  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. 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

    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 (P(trend) = 2.3 × 10¿¿ to P(trend) = 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, P(trend) = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P(trend) = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases...

  15. 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.

  16. 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...

  17. 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

    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...... 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......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...

  18. 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

  19. 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.

  20. 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...... genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium.Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry......, 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...

  1. 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 fibrocys