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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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“A prophylactic bilateral mastectomy has shown to decrease the lifetime risk of breast cancer up to 90% (41-43).”
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“The effectiveness of bilateral prophylactic mastectomy in carriers of BRCA mutations was demonstrated in a recent study from the Netherlands (7).”
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Culler, D., Grimes, S. J., Acheson, L. S., & Wiesner, G. L. (2004) · Primary Care Clinics in Office Practice · doi:10.1016/j.pop.2004.05.001 · Cited by 8
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“Previous studies conducted in unaffected BRCA mutation carriers have indicated that prophylactic mastectomy effectively reduces the residual lifetime risk of breast cancer to < 5% [1,3-5].”
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Tang, R., Kelly, B. N., Smith, B. L., Lanahan, C. R., Brown, C. L., Gadd, M. A., Hughes, K. S., Oseni, T. O., McGugin, C., Specht, M. C., et al. (2019) · Clinical Breast Cancer · doi:10.1016/j.clbc.2019.03.003 · Cited by 7
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“수술적방법을적용할수록공격적이나보다궁극적인예방 이라고 할 수 있는데, 예방적 유방절제술은 유방암을 90% 정도 예방하며예방적난소절제술은난소암의위험을95% 이상, 유방 암의위험도또한50% 정도줄일수있는것으로알려져있다.(11, 21,22) 본연구에서질환발현보인자의관리현황을살펴보면, 유 방암조기진단을위해서적극적감시만을받는군이89.”
High-Risk Lesions in High-Risk Women
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Prognostic and Predictive Factors and Targets for Therapy in Breast Cancer
Klijn, J. G. M., Berns, E. M. J. J., & Foekens, J. A. (2002) · CRC Press eBooks · doi:10.1201/b14039-5 · Cited by 7
Self-citationGenetic Testing for Cancer Susceptibility
Stadler, Z. K., & Schrag, D. (2023) · JAMA · doi:10.1001/jama.2023.9474 · Cited by 7
Apostol, A. I., Gronwald, J., Cybulski, C., Kim, R. H., Møller, P., Karlan, B. Y., Bordeleau, L. J., Schrader, I., y Cajal, T. R., Pal, T., et al. (2026) · Journal of Clinical Oncology · doi:10.1200/jco-25-01648 · Cited by 6
Risk-reducing Surgery in Women at Risk for Familial Breast or Ovarian Cancer
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Chiarella, L. S., Huelsboemer, L. F., Diatta, F. H., Klimitz, F. J., Kammien, A. J., Kochen, A., Boroumand, S., Allam, O., Kauke‐Navarro, M., & Pomahač, B. (2025) · Annals of Surgical Oncology · doi:10.1245/s10434-025-17105-2 · Cited by 6
Prophylactic Mastectomy: An Appraisal
Zagouri, F., Chrysikos, D., Sergentanis, T. Ν., Γιαννακοπούλου, Γ., Zografos, C. G., PAPADIMITRIOU, C. A., & Zografos, G. (2013) · The American Surgeon · doi:10.1177/000313481307900233 · Cited by 6
The Angelina Jolie Effect in Jewish Law: Prophylactic Mastectomy and Oophorectomy in BRCA Carriers
Grossman, S. G. (2015) · Rambam Maimonides Medical Journal · doi:10.5041/rmmj.10222 · Cited by 6
Jeon, H. J., Park, H. S., Park, J. S., Nam, E. J., Lee, S., & Han, J. (2019) · Annals of Surgical Treatment and Research · doi:10.4174/astr.2019.97.3.113 · Cited by 6
“The advantages of CPM are a 95% reduction of risk for contralateral BC development in patients with BRCA mutations and a 90% reduction of risk in women with a strong family history [8,9].”
BackgroundTesting for Inherited Susceptibility to Breast Cancer
Robson, M. E. (2022) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2022.08.003 · Cited by 6
Emerging Technologies for Improved Stratification of Cancer Patients
Lamlertthon, W., Hayward, M. C., & Hayes, D. N. (2011) · The Cancer Journal · doi:10.1097/ppo.0b013e31823bd1f8 · Cited by 6
Complication rates among women undergoing preventive mastectomy: An Austrian registry
Leser, C., Deutschmann, C., Dorffner, G., Gschwantler‐Kaulich, D., König-Castillo, D. M., Abayev, S., Stübler, M., Reitsamer, R., & Singer, C. F. (2020) · The Breast Journal · doi:10.1111/tbj.13877 · Cited by 6
“Of the 54 patients, 46 underwent surgery at the General Hospital of Vienna at the Department of Gynecology and General Surgery (Medical University of Vienna; 31 bilateral mastectomy only, 13 bilateral mastectomy and bilateral salpingo-oophorectomy; data on salpingo-oophorectomy were missing in two patients), one under…”
BackgroundMexican consensus on breast cancer diagnosis and treatment
Cárdenas-Sánchez, J. (2021) · Gaceta Mexicana de Oncología · doi:10.24875/j.gamo.m21000215 · Cited by 6
Genetic Factors: Hereditary Cancer Predisposition Syndromes
Offit, K., Thom, P., & Bernstein, D. B. (2008) · Elsevier eBooks · doi:10.1016/b978-0-443-06694-8.50015-4 · Cited by 7
Applications of Advances in Molecular Biology and Genomics to Clinical Cancer Care
Loud, J. T., Peters, J. A., Fraser, M. C., & Jenkins, J. (2002) · Cancer Nursing · doi:10.1097/00002820-200204000-00007 · Cited by 6
Cabaret, A.-S., Lévêque, J., Dugast, C., Blanchot, J., & Grall, J. Y. (2003) · Gynécologie Obstétrique & Fertilité · doi:10.1016/s1297-9589(03)00058-4 · Cited by 6
Personalized medicine: The future is not what it used to be
Demeure, M. J. (2009) · Surgery · doi:10.1016/j.surg.2009.10.023 · Cited by 6
Breast cancer prevention in women with a BRCA1 or BRCA2 mutation.
Metcalfe, K. A., & Narod, S. A. (2007) · PubMed Central · Cited by 6
Expanding Eligibility Criteria for Nipple-Sparing Mastectomy
Orcutt, S. T., O’Donoghue, C., Smith, P. D., & Laronga, C. (2017) · Southern Medical Journal · doi:10.14423/smj.0000000000000707 · Cited by 6
Chung, M. A., & Cady, B. (2004) · The Breast Journal · doi:10.1111/j.1075-122x.2004.21666.x · Cited by 6
“Bilateral mastectomy, in addition to treating the index cancer, is a good cancer preventive strategy and will decrease the risk of developing future breast cancers by about 90% (6).”
BackgroundWeighing Options for Cancer Risk Reduction in Carriers of BRCA1 and BRCA2 Mutations
Stadler, Z. K., & Kauff, N. D. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.25.6875 · Cited by 6
Clinical Approaches to Discovering and Testing New Breast Cancer Prevention Drugs
Fabian, C., Kimler, B., Mayo, M., Grizzle, W., Masood, S., & Ursin, G. (2005) · Humana Press eBooks · doi:10.1007/978-1-59259-768-0_17 · Cited by 6
Onkoplasztikai szemlélet az emlőrák sebészetében – új kihívás a jövő emlősebészeinek?r
Romics, L., Weiler-Mithoff, E. M., Cooke, T. G., & George, W. D. (2008) · Magyar Sebészet (Hungarian Journal of Surgery) · doi:10.1556/maseb.61.2008.1.2 · Cited by 5
Boeri, L., Canzonieri, C., Cagioni, C., Ornati, F., & Danesino, C. (2011) · Journal of Ultrasound · doi:10.1016/j.jus.2011.10.002 · Cited by 5
Contralateral Prophylactic Mastectomy
Rai, S. S., Mahabir, R. C., Roberts, J. W., Song, J., Hamid, K. S., & White, R. R. (2011) · Annals of Plastic Surgery · doi:10.1097/sap.0b013e3181fabc4c · Cited by 5
Consenso Nacional Intersociedades sobre Alto Riesgo para Cáncer de Mama. Octubre de 2014
Intersociedades, P. N. D. C., Oncológicas, P. N. D. C. I. P. A. D. C. D. E., Argentina, A. M., del Cáncer, I. N., de Genética, S. A., de Patología, S. A., de Mastología, S. A., de Radiología, S. A., de Cancerología, S. A., Roffo, I. D. O. Á. H., et al. (2016) · Revista Argentina de Radiología / Argentinian Journal of Radiology · doi:10.1016/j.rard.2016.06.002 · Cited by 5
Prophylactic Surgery in the BRCA+ Patient: Do Women Develop Breast Cancer While Waiting?
Macadam, S. A., Slater, K., Cheifetz, R. E., Jansen, L. A., Chia, S., Brasher, P. M. A., & Bovill, E. S. (2021) · Current Oncology · doi:10.3390/curroncol28010069 · Cited by 5
Taliaferro, A. S., Price, E. R., Hayward, J. H., Wong, J., Balassanian, R., Fay, J. S., Freimanis, R. I., Joe, B. N., & Lee, A. Y. (2021) · American Journal of Roentgenology · doi:10.2214/ajr.21.26561 · Cited by 5
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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