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Breast Cancer after Prophylactic Bilateral Mastectomy in Women with a BRCA1 or BRCA2 Mutation
Open accessAbstract
BACKGROUND: Women with a BRCA1 or BRCA2 mutation have a high risk of breast cancer and may choose to undergo prophylactic bilateral total mastectomy. We investigated the efficacy of this procedure in such women. METHODS: We conducted a prospective study of 139 women with a pathogenic BRCA1 or BRCA2 mutation who were enrolled in a breast-cancer surveillance program at the Rotterdam Family Cancer Clinic. At the time of enrollment, none of the women had a history of breast cancer. Seventy-six of these women eventually underwent prophylactic mastectomy, and the other 63 remained under regular surveillance. The effect of mastectomy on the incidence of breast cancer was analyzed by the Cox proportional-hazards method in which mastectomy was modeled as a time-dependent covariate. RESULTS: No cases of breast cancer were observed after prophylactic mastectomy after a mean (+/-SE) follow-up of 2.9+/-1.4 years, whereas eight breast cancers developed in women under regular surveillance after a mean follow-up of 3.0+/-1.5 years (P=0.003; hazard ratio, 0; 95 percent confidence interval, 0 to 0.36). The actuarial mean five-year incidence of breast cancer among all women in the surveillance group was 17+/-7 percent. On the basis of an exponential model, the yearly incidence of breast cancer in this group was 2.5 percent. The observed number of breast cancers in the surveillance group was consistent with the expected number (ratio of observed to expected cases, 1.2; 95 percent confidence interval, 0.4 to 3.7; P=0.80). CONCLUSIONS: In women with a BRCA1 or BRCA2 mutation, prophylactic bilateral total mastectomy reduces the incidence of breast cancer at three years of follow-up.
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“Studies on PM consistently show a risk reduction of breast cancer of at least 90% [1,2]”
From Standard psychological consultations and follow up for women at increased risk of hereditary breast cancer considering prophylactic mastectomy (2009) · cites this paper as [2]
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“which has been shown to reduce the incidence of breast cancer by approximately 90% [57-59]”
From Screening, Risk Reduction Strategies, and Clinical Management of Unaffected Carriers of BRCA1 or BRCA2 Pathogenic Variants (2026) · cites this paper as [58]
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“Meijers-Heijboer’s later study (5) in the NEJM along with other publications (6-9) then proved the advantages of risk reducing mastectomy in BRCA patients.”
BackgroundKoil, C., Everett, J. N., Hoechstetter, L., Ricer, R., & Huelsman, K. M. (2003) · Genetics in Medicine · doi:10.1097/01.gim.0000086477.00766.c9 · Cited by 46
Genetic Counseling and Testing for Common Hereditary Breast Cancer Syndromes
Allain, D. C. (2008) · Journal of Molecular Diagnostics · doi:10.2353/jmoldx.2008.070161 · Cited by 37
Bilateral Implant Breast Reconstruction
Antony, A. K., McCarthy, C. M., Disa, J. J., & Mehrara, B. J. (2013) · Annals of Plastic Surgery · doi:10.1097/sap.0b013e31826af03e · Cited by 37
Plasma osteoprotegerin and breast cancer risk in BRCA1 and BRCA2 mutation carriers
Odén, L., Akbari, M. R., Zaman, T., Singer, C. F., Sun, P., Narod, S. A., Salmena, L., & Kotsopoulos, J. (2016) · Oncotarget · doi:10.18632/oncotarget.13417 · Cited by 37
Ball, S., Arevalo, M., Juarez, E., Payne, J. D., & Jones, C. (2019) · Preventive Medicine · doi:10.1016/j.ypmed.2019.105834 · Cited by 37
Gramling, R. E., Nash, J. M., Siren, K., & Culpepper, L. (2003) · Genetics in Medicine · doi:10.1097/01.gim.0000068986.03217.bb · Cited by 37
Gray, S. W., O'Grady, C., Karp, L., Smith, D. R., Schwartz, J. S., Hornik, R., & Armstrong, K. (2009) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-08-0825 · Cited by 37
“In addition, there is ample literature suggesting that genetic testing is underutilized despite the fact that mutation carriers and other high-risk women have good options for cancer risk reduction (35, 50-59).”
BackgroundHigh Prevalence of Preinvasive Lesions Adjacent to BRCA1/2-Associated Breast Cancers
Arun, B., Vogel, K. J., López, A., Hernández, M., Atchley, D. P., Broglio, K. R., Amos, C. I., Meric‐Bernstam, F., Kuerer, H. M., Hortobágyi, G. N., et al. (2009) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-08-0050 · Cited by 37
Physicians’ Experiences With BRCA1/2 Testing in Community Settings
Keating, N. L., Stoeckert, K. A., Regan, M. M., DiGianni, L. M., & Garber, J. E. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.17.8053 · Cited by 37
Familial non-BRCA1/BRCA2-associated breast cancer
Eccles, D., & Pichert, G. (2005) · The Lancet Oncology · doi:10.1016/s1470-2045(05)70318-1 · Cited by 38
Guidelines for the management of women at increased familial risk of breast cancer.
Sauven, P. (2004) · European Journal of Cancer · doi:10.1016/j.ejca.2003.10.028 · Cited by 36
High satisfaction rate ten years after bilateral prophylactic mastectomy - a longitudinal study
Wasteson, E., Sandelin, K., Brandberg, Y., Wickman, M., & Arver, B. W. (2010) · European Journal of Cancer Care · doi:10.1111/j.1365-2354.2010.01204.x · Cited by 36
Brandberg, Y., Arver, B. W., Johansson, H., Wickman, M., Sandelin, K., & Liljegren, A. (2011) · European Journal of Surgical Oncology · doi:10.1016/j.ejso.2011.10.010 · Cited by 36
Provider Discussions of Genetic Tests With U.S. Women at Risk for a BRCA Mutation
Hull, L. E., Haas, J. S., & Simon, S. R. (2017) · American Journal of Preventive Medicine · doi:10.1016/j.amepre.2017.10.015 · Cited by 36
Breast and ovarian cancer risk and risk reduction in Jewish BRCA1/2 mutation carriers.
Finkelman, B., Rubinstein, W., Friedman, S., Friebel, T., Dubitsky, S., Schonberger, N., Shoretz, R., Singer, C., Blum, J., Tung, N., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.37.8133 · Cited by 39
Brandberg, Y., Arver, B. W., Lindblom, A., Sandelin, K., Wickman, M., & Hall, P. N. (2003) · European Journal of Cancer · doi:10.1016/j.ejca.2003.08.026 · Cited by 36
Therapeutic Approaches for Women Predisposed to Breast Cancer
Nathanson, K. L., & Domchek, S. M. (2010) · Annual Review of Medicine · doi:10.1146/annurev-med-010910-110221 · Cited by 35
Nipple-sparing mastectomy: A contemporary perspective
Sisco, M., & Yao, K. A. (2016) · Journal of Surgical Oncology · doi:10.1002/jso.24209 · Cited by 35
“Prophylactic skin-sparing mastectomy reduces the risk of breast cancer in BRCAcarriers by at least 95% [29,30] and it is expected”
BackgroundGrobmyer, S. R., Pederson, H. J., Valente, S. A., Al‐Hilli, Z., Radford, D. M., Djohan, R. S., Yetman, R. J., Eng, C., & Crowe, J. P. (2018) · BJS Open · doi:10.1002/bjs5.50117 · Cited by 35
Verkooijen, H. M., Chappuis, P. O., Rapiti, E., Vlastos, G., Fioretta, G., Sarp, S., Sappino, A. P., Schubert, H., & Bouchardy, C. (2005) · British Journal of Cancer · doi:10.1038/sj.bjc.6602914 · Cited by 35
“Some studies have shown improved survival rates among breast cancer patients with affected relatives compared to those without a family history (Malone et al, 1996; Mohammed et al, 1998), some reported poorer survival rates (Slattery et al, 1993; Gonzalez-Angulo et al, 2005), and others did not…”
BackgroundScreening for breast cancer post reduction mammoplasty
Muir, T., Tresham, J. J., Fritschi, L., & Wylie, E. J. (2010) · Clinical Radiology · doi:10.1016/j.crad.2009.09.015 · Cited by 35
An Update in Breast Cancer Screening and Management
Warrier, S. K., Tapia, G., Goltsman, D., & Beith, J. M. (2015) · Women s Health · doi:10.2217/whe.15.105 · Cited by 38
Elsayegh, N., Webster, R. D., Gutierrez‐Barrera, A. M., Lin, H. Y., Kuerer, H. M., Litton, J. K., Bedrosian, I., & Arun, B. (2018) · Cancer Medicine · doi:10.1002/cam4.1519 · Cited by 34
Management Updates for Women with a BRCA1 or BRCA2 Mutation
Nusbaum, R. H., & Isaacs, C. J. (2007) · Molecular Diagnosis & Therapy · doi:10.1007/bf03256234 · Cited by 33
Fryzek, J. P., Ye, W., Nyrén, O., Tarone, R. E., Lipworth, L. P., & McLaughlin, J. K. (2005) · Breast Cancer Research and Treatment · doi:10.1007/s10549-005-9099-2 · Cited by 33
“High-risk women who elect to undergo prophylactic bilateral mastectomy reportedly have a 90% or higher reduction in breast cancer risk [1,2].”
BackgroundProphylactic Surgery: For Whom, When and How
Mau, C. Y., & Untch, M. (2017) · Breast Care · doi:10.1159/000485830 · Cited by 33
International Perspectives on Genetic Counseling and Testing for Breast Cancer Risk
Meiser, B., Gaff, C., Julian‐Reynier, C., Biesecker, B. B., Esplen, M. J., Vodermaier, A., & Tibben, A. (2007) · Breast Disease · doi:10.3233/bd-2007-27107 · Cited by 33
Kim, S. I., Lim, M. C., Lee, D. O., Kong, S., Seo, S., Kang, S., Lee, E. S., & Park, S. (2015) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-015-2051-x · Cited by 33
Francken, A. B., Schouten, P. C., Bleiker, E. M. A., Linn, S. C., & Rutgers, E. J. T. (2013) · The Breast · doi:10.1016/j.breast.2013.07.045 · Cited by 34
“As a result of this increased risk, the rate of risk reduction by performing prophylactic mastectomy of the contralateral breast is about 97% [29,32,33].”
BackgroundSoran, A., Falk, J. S., Bonaventura, M., Keenan, D., Ahrendt, G. M., & Johnson, R. R. (2006) · Annals of Surgical Oncology · doi:10.1245/s10434-006-9264-9 · Cited by 33
Breast Cancer Risk Reduction: Strategies for Women at Increased Risk
Chlebowski, R. T. (2002) · Annual Review of Medicine · doi:10.1146/annurev.med.53.082901.103925 · Cited by 33
Hereditary breast cancer: from bench to bedside
Grève, J. D., Sermijn, E., Brakeleer, S. D., Ren, Z., & Teugels, E. (2008) · Current Opinion in Oncology · doi:10.1097/cco.0b013e3283139173 · Cited by 32
Grinstein, O., Krug, B., Hellmic, M., Siedek, F., Malter, W., Burke, C., Schmutzler, R. K., Maintz, D. C., & Rhiem, K. (2019) · Surgical Oncology · doi:10.1016/j.suronc.2019.04.009 · Cited by 32
Breast Cancer Prevention: Patient Decision Making and Risk Communication in the High Risk Setting
Ozanne, E. M., Wittenberg, E., Garber, J. E., & Weeks, J. C. (2009) · The Breast Journal · doi:10.1111/j.1524-4741.2009.00857.x · Cited by 32
Metadata
- Authors
- Meijers-Heijboer, H., van Geel, B., van Putten, W. L. J., Henzen-Logmans, S. C., Seynaeve, C., Menke-Pluymers, M. B. E., Bartels, C. C. M., Verhoog, L. C., van den Ouweland, A. M. W., Niermeijer, M. F., Brekelmans, C. T. M., & Klijn, J. G. M.
- Affiliations
- Erasmus MC (NL)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2001-07-19
- Volume
- 345
- Issue
- 3
- Pages
- 159-164
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2046809735
- Cited by
- 973
- References
- 33
- Citations by year
- 2026: 15 · 2025: 14 · 2024: 14 · 2023: 18 · 2022: 18 · 2021: 24 · 2020: 23 · 2019: 30 · 2018: 21 · 2017: 37 · 2016: 42 · 2015: 28 · 2014: 34 · 2013: 29 · 2012: 42
- FWCI
- 35.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (acceptedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Women's cancer prevention and management
- Health Sciences › Medicine › Pathology and Forensic Medicine › Breast Lesions and Carcinomas
- Keywords
- breast cancer, bilateral prophylactic mastectomy, BRCA1 mutation, BRCA2 mutation, hereditary breast cancer, breast cancer incidence, breast cancer surveillance, genetic susceptibility to cancer
- MeSH terms
- Adult, Breast Neoplasms, Female, Humans, Middle Aged, Mutation, Neoplasm Proteins, Prospective Studies, Transcription Factors, Mastectomy, Simple, Proportional Hazards Models, Genes, BRCA1, BRCA2 Protein
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