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Predictors of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers
Open accessAbstract
PURPOSE: The objective of this study was to estimate the risk of contralateral breast cancer in BRCA1 and BRCA2 carriers; and measure the extent to which host, family history, and cancer treatment-related factors modify the risk. PATIENTS AND METHODS: Patients were 810 women, with stage I or II breast cancer, for whom a BRCA1 or BRCA2 mutation had been identified in the family. Patients were followed from the initial diagnosis of cancer until contralateral mastectomy, contralateral breast cancer, death, or last follow-up. RESULTS: Overall, 149 subjects (18.4%) developed a contralateral breast cancer. The 15-year actuarial risk of contralateral breast cancer was 36.1% for women with a BRCA1 mutation and was 28.5% for women with a BRCA2 mutation. Women younger than 50 years of age at the time of breast cancer diagnosis were significantly more likely to develop a contralateral breast cancer at 15 years, compared with those older than 50 years (37.6 vs 16.8%; P=0.003). Women aged <50 years with two or more first-degree relatives with early-onset breast cancer were at high risk of contralateral breast cancer, compared with women with fewer, or no first-degree relatives with breast cancer (50 vs 36%; P=0.005). The risk of contralateral breast cancer was reduced with oophorectomy (RR 0.47; 95% CI 0.30-0.76; P=0.002). CONCLUSION: The risk of contralateral breast cancer risk in BRCA mutation carriers declines with the age of diagnosis and increases with the number of first-degree relatives affected with breast cancer. Oophorectomy reduces the risk of contralateral breast cancer in young women with a BRCA mutation.
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“We observed that family history is a predictor of CBC risk in both noncarriers and mutation carriers, which is in line with previous literature.19,21”
From Impact of Age at Primary Breast Cancer on Contralateral Breast Cancer Risk in BRCA1/2 Mutation Carriers (2016) · cites this paper as [21]
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Ford, D., Easton, D., Stratton, M. R., Narod, S., Goldgar, D., Devilee, P., Bishop, D., Weber, B., Lenoir, G., Chang-Claude, J., et al. (1998) · American Journal of Human Genetics · doi:10.1086/301749 · Cited by 2,766
Self-citationRebbeck, T. R., Kauff, N. D., & Domchek, S. M. (2009) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djn442 · Cited by 939
Self-citationContralateral Breast Cancer in BRCA1 and BRCA2 Mutation Carriers
Metcalfe, K. A., Lynch, H. T., Ghadirian, P., Tung, N., Olivotto, I. A., Warner, E., Olopade, O. I., Eisen, A. F., Weber, B., McLennan, J., et al. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.04.033 · Cited by 620 · cited 1×
“…lifetime risk of breast cancer (Ford et al, 1998) and, once diagnosed with breast cancer, face a high risk of second primary cancer in the contralateral breast (Robson et al, 1998; Verhoog et al, 1998, 2000; Haffty et al, 2002; Metcalfe et al, 2004; Brekelmans et al, 2007; Graeser et al, 2009).”
BackgroundSelf-citationSurvival and tumour characteristics of breast-cancer patients with germline mutations of BRCA1
Verhoog, L., Brekelmans, C., Seynaeve, C., van den Bosch, L., Dahmen, G., van Geel, A., Tilanus-Linthorst, M., Bartels, C., Wagner, A., van den Ouweland, A., et al. (1998) · The Lancet · doi:10.1016/s0140-6736(97)07065-7 · Cited by 452 · cited 1×
“…lifetime risk of breast cancer (Ford et al, 1998) and, once diagnosed with breast cancer, face a high risk of second primary cancer in the contralateral breast (Robson et al, 1998; Verhoog et al, 1998, 2000; Haffty et al, 2002; Metcalfe et al, 2004; Brekelmans et al, 2007; Graeser et al, 2009).”
BackgroundEisen, A. F., Lubiński, J., Klijn, J. G. M., Møller, P., Lynch, H. T., Offit, K., Weber, B., Rebbeck, T., Neuhausen, S. L., Ghadirian, P., et al. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2004.00.7138 · Cited by 442
Self-citationContralateral Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
Graeser, M. K., Engel, C., Rhiem, K., Gadzicki, D., Bick, U., Kast, K., Froster, U. G., Schlehe, B., Bechtold, A., Arnold, N., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2008.19.9430 · Cited by 314 · cited 1×
“…lifetime risk of breast cancer (Ford et al, 1998) and, once diagnosed with breast cancer, face a high risk of second primary cancer in the contralateral breast (Robson et al, 1998; Verhoog et al, 1998, 2000; Haffty et al, 2002; Metcalfe et al, 2004; Brekelmans et al, 2007; Graeser et al, 2009).”
BackgroundOutcome of conservatively managed early-onset breast cancer by BRCA1/2 status
Haffty, B. G., Harrold, E., Khan, A. J., Pathare, P., Smith, T. E., Turner, B. C., Glazer, P. M., Ward, B., Carter, D., Matloff, E., et al. (2002) · The Lancet · doi:10.1016/s0140-6736(02)08434-9 · Cited by 307 · cited 1×
“…lifetime risk of breast cancer (Ford et al, 1998) and, once diagnosed with breast cancer, face a high risk of second primary cancer in the contralateral breast (Robson et al, 1998; Verhoog et al, 1998, 2000; Haffty et al, 2002; Metcalfe et al, 2004; Brekelmans et al, 2007; Graeser et al, 2009).”
BackgroundBRCA-associated breast cancer in young women.
Robson, M. E., Gilewski, T., Haas, B. R., Levin, D. R., Borgen, P. I., Rajan, P., Hirschaut, Y., Pressman, P., Rosen, P. P., LESSER, M. L., et al. (1998) · Journal of Clinical Oncology · doi:10.1200/jco.1998.16.5.1642 · Cited by 303 · cited 1×
“…lifetime risk of breast cancer (Ford et al, 1998) and, once diagnosed with breast cancer, face a high risk of second primary cancer in the contralateral breast (Robson et al, 1998; Verhoog et al, 1998, 2000; Haffty et al, 2002; Metcalfe et al, 2004; Brekelmans et al, 2007; Graeser et al, 2009).”
BackgroundTamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: An update
Gronwald, J., Tung, N., Foulkes, W. D., Offit, K., Gershoni, R., Daly, M. B., Kim‐Sing, C., Olsson, H. L., Ainsworth, P., Eisen, A. F., et al. (2005) · International Journal of Cancer · doi:10.1002/ijc.21536 · Cited by 253
Self-citationBrekelmans, C. T. M., Tilanus-Linthorst, M. M. A., Seynaeve, C., vd Ouweland, A., Menke-Pluymers, M. B. E., Bartels, C. C. M., Kriege, M., van Geel, A. N., Burger, C. W., Eggermont, A. M. M., et al. (2007) · European Journal of Cancer · doi:10.1016/j.ejca.2006.12.009 · Cited by 233 · cited 1×
“…lifetime risk of breast cancer (Ford et al, 1998) and, once diagnosed with breast cancer, face a high risk of second primary cancer in the contralateral breast (Robson et al, 1998; Verhoog et al, 1998, 2000; Haffty et al, 2002; Metcalfe et al, 2004; Brekelmans et al, 2007; Graeser et al, 2009).”
BackgroundMalone, K. E., Begg, C. B., Haile, R. W., Borg, A., Concannon, P., Tellhed, L., Xue, S., Teraoka, S., Bernstein, L., Capanu, M., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.24.2495 · Cited by 191
Contralateral breast cancer risk is influenced by the age at onset in BRCA1-associated breast cancer
Verhoog, L., Brekelmans, C., Seynaeve, C., Meijers-Heijboer, E., & Klijn, J. (2000) · British Journal of Cancer · doi:10.1054/bjoc.2000.1239 · Cited by 135 · cited 1×
“…lifetime risk of breast cancer (Ford et al, 1998) and, once diagnosed with breast cancer, face a high risk of second primary cancer in the contralateral breast (Robson et al, 1998; Verhoog et al, 1998, 2000; Haffty et al, 2002; Metcalfe et al, 2004; Brekelmans et al, 2007; Graeser et al, 2009).”
BackgroundFamily History of Cancer and Cancer Risks in Women with BRCA1 or BRCA2 Mutations
Metcalfe, K. A., Lubiński, J., Lynch, H. T., Ghadirian, P., Foulkes, W. D., Kim‐Sing, C., Neuhausen, S. L., Tung, N., Rosen, B. P., Gronwald, J., et al. (2010) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djq443 · Cited by 110 · cited 1×
“We have recently reported that a family history of cancer influences breast cancer risk in women with a BRCA1 or BRCA2 mutation (Metcalfe et al, 2010).”
BackgroundSelf-citationChang-Claude, J. C., Andrieu, N., Rookus, M. A., Brohet, R. M., Antoniou, A. C., Peock, S., Davidson, R., Izatt, L., Cole, T. R. P., Noguès, C., et al. (2007) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-06-0829 · Cited by 88
The WECARE Collaborative Study Group, Reding, K. W., Bernstein, J. L., Langholz, B. M., Bernstein, L., Haile, R. W., Begg, C. B., Lynch, C. F., CONCANNON, P. J., Borg, Å., et al. (2010) · Breast Cancer Research and Treatment · doi:10.1007/s10549-010-0769-3 · Cited by 62
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Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers
Kuchenbaecker, K. B., Hopper, J. L., Barnes, D. R., Phillips, K.-A., Mooij, T. M., Roos-Blom, M.-J., Jervis, S., van Leeuwen, F. E., Milne, R. L., Andrieu, N., et al. (2017) · JAMA · doi:10.1001/jama.2017.7112 · Cited by 2,954
Cancer Risks for BRCA1 and BRCA2 Mutation Carriers: Results From Prospective Analysis of EMBRACE
Mavaddat, N., Peock, S., Frost, D., Ellis, S., Platte, R., Fineberg, E., Evans, D. G., Izatt, L., Eeles, R. A., Adlard, J., et al. (2013) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djt095 · Cited by 951
Tung, N., Boughey, J. C., Pierce, L. J., Robson, M. E., Bedrosian, I., Dietz, J. R., Dragun, A. J., Balmañà, J., Hofstatter, E. W., Isaacs, C. J., et al. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.20.00299 · Cited by 335
Self-citationSecond Malignant Neoplasms: Assessment and Strategies for Risk Reduction
Wood, M. E., Vogel, V. G., Ng, A. K., Foxhall, L. E., Goodwin, P. J., & Travis, L. B. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2012.41.8681 · Cited by 325
“Mutations in BRCA1 and BRCA2 are associated with high risks of second primary breast cancer or ovarian cancer.(11,12) Mutations in mismatch repair genes (MLH1, MSH2, PMS1, MSH6) confer an increased risk of a variety of cancers including second primary colon cancers, other gastrointestinal and gynecologic cancers.”
BackgroundMetcalfe, K. A., Gershman, S., Ghadirian, P., Lynch, H. T., Snyder, C., Tung, N., Kim‐Sing, C., Eisen, A. F., Foulkes, W. D., Rosen, B. P., et al. (2014) · BMJ · doi:10.1136/bmj.g226 · Cited by 311
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Metadata
- Authors
- Metcalfe, K., Gershman, S., Lynch, H. T., Ghadirian, P., Tung, N., Kim-Sing, C., Olopade, O. I., Domchek, S., McLennan, J., Eisen, A., Foulkes, W. D., Rosen, B., Sun, P., & Narod, S. A.
- Affiliations
- University of Toronto (CA)
- Creighton University (US)
- Centre Hospitalier de l’Université de Montréal (CA)
- Beth Israel Deaconess Medical Center (US)
- University of Chicago (US)
- University of Pennsylvania (US)
- University of California, San Francisco (US)
- Sunnybrook Health Science Centre (CA)
- McGill University (CA)
- University Health Network (CA)
- Women’s College Hospital Research and Innovation Institute (CA)
- Corresponding author
- Narod, S A
- Venue
- British Journal of Cancer
- Published
- 2011-04
- Volume
- 104
- Issue
- 9
- Pages
- 1384-1392
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC3101934
- OpenAlex
- W2002561481
- Cited by
- 232
- References
- 15
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 12 · 2023: 11 · 2022: 15 · 2021: 21 · 2020: 31 · 2019: 13 · 2018: 9 · 2017: 12 · 2016: 17 · 2015: 20 · 2014: 18 · 2013: 21 · 2012: 16
- FWCI
- 11.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- www.springer.com/tdm (unspecified)
- Locations
- British Journal of Cancer (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Epidemiology › Multiple and Secondary Primary Cancers
- Health Sciences › Medicine › Pathology and Forensic Medicine › Breast Lesions and Carcinomas
- Keywords
- contralateral breast cancer, BRCA1 mutation, BRCA2 mutation, hereditary breast cancer, oophorectomy, age at diagnosis, family history (medicine), first-degree relatives, early-onset breast cancer, risk factors, young women
- MeSH terms
- Adult, Age Factors, Aged, Breast Neoplasms, Female, Heterozygote, Humans, Middle Aged, Mutation, Ovariectomy, Predictive Value of Tests, Risk Factors, Cohort Studies, Odds Ratio, Survival Analysis, Neoplasms, Second Primary, Risk Assessment, Genes, BRCA1, Genetic Predisposition to Disease, Genes, BRCA2
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