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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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“In this view, NSM as a risk-reducing procedure for BRCA-mutation carriers appears to be an oncologically safe procedure, comparable to the standard modified radical mastectomy [30], with better patient-reported outcomes.”
Taira, N., Arai, M., Ikeda, M., Iwasaki, M., Okamura, H., Takamatsu, K., Nomura, T., Yamamoto, S., Ito, Y., & Mukai, H. (2016) · Breast Cancer · doi:10.1007/s12282-016-0673-8 · Cited by 22
Malhotra, H., Kowtal, P., Mehra, N., Pramank, R., Sarin, R., Rajkumar, T., Gupta, S., Bapna, A., Bhattacharyya, G. S., Gupta, S., et al. (2020) · JCO Global Oncology · doi:10.1200/jgo.19.00381 · Cited by 22
LoPiccolo, J., Ballas, M. S., & Dennis, P. A. (2007) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2007.06.002 · Cited by 21
de Leeuw, J. R. J., van Vliet, M. J., & Ausems, M. G. E. M. (2008) · Familial Cancer · doi:10.1007/s10689-008-9189-5 · Cited by 21
“The uptake rates of PM and BPSO seem to differ between different countries [28, 37].”
BackgroundRosenthal, M. S., & Pierce, H. (2005) · Thyroid · doi:10.1089/thy.2005.15.140 · Cited by 21
“…mutations in BRCA1 or BRCA2 and high penetrance in their family, elect to have prophylactic mastec-tomies, the surgery does not completely eliminate the risk of developing breast cancer (20), and there are risks of surgical complications (21) and a likely need for reconstructive surgeries (22).”
Prophylactic Mastectomy: Obstacles and Benefits
Lynch, H. T., Lynch, J. F., & Rubinstein, W. S. (2001) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/93.21.1586 · Cited by 21
Risk Management in BRCA1 and BRCA2 Mutation Carriers: Lessons Learned, Challenges Posed
DeMichele, A. M., & Weber, B. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.2002.20.5.1164 · Cited by 21
BRCA and Breast Cancer-Related High-Penetrance Genes
Han, S., & Kim, S. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-981-32-9620-6_25 · Cited by 22
Recent Advances in Breast Cancer Genetics
Pasche, B. (2007) · Cancer treatment and research · doi:10.1007/978-0-387-73161-2_1 · Cited by 20
Impact of Prophylactic Mastectomy in BRCA1/2 Mutation Carriers
Rhiem, K., & Schmutzler, R. K. (2014) · Breast Care · doi:10.1159/000369592 · Cited by 20
Vadaparampil, S. T., Quinn, G. P., Brzosowicz, J., & Miree, C. A. (2008) · Journal of Psychosocial Oncology · doi:10.1080/07347330802359586 · Cited by 20
“…and bilateral prophylactic mastectomy in reducing breast cancer risk in mutation carriers (Hartmann et al., 1999; Hartmann, et al., 2001; Meijers-Heijboer et al., 2001; Rebbeck et al., 2004), high-risk breast cancer patients may want genetic-risk information prior to making a definitive…”
BackgroundEldor, L., & Spiegel, A. J. (2009) · The Breast Journal · doi:10.1111/j.1524-4741.2009.00797.x · Cited by 20
Somashekhar, S. P., Agarwal, G., Deo, S. V. S., Chintamani, C., Ram, P. R., Sarkar, D. K., & Parmar, V. V. (2017) · Indian Journal of Surgery · doi:10.1007/s12262-017-1666-3 · Cited by 20
Molecular comparison of interval and screen‐detected breast cancers
Cheasley, D. A., Li, N., Rowley, S. M., Elder, K., Mann, G. B., Loi, S., Savas, P. S., Goode, D. L., Kader, T., Zethoven, M., et al. (2019) · The Journal of Pathology · doi:10.1002/path.5251 · Cited by 20
Scott, C. L., Iorgulescu, D., Thorne, H., Henderson, M., & Phillips, K. (2003) · Clinical Genetics · doi:10.1034/j.1399-0004.2003.00097.x · Cited by 20
“Two prospective studies, both of which were small, single-institution observational studies with limited follow-up, also showed a reduction in BC risk for BPM vs surveillance in women known to carry a mutation in either BRCA1 or BRCA2 (23, 24).”
ResultProphylactic mastectomy: ethical issues
Eisinger, F. (2007) · British Medical Bulletin · doi:10.1093/bmb/ldm003 · Cited by 20
The prevention of breast cancer
Prichard, R. S., Hill, A. D. K., Dijkstra, B., McDermott, E. W. M., & O’Higgins, N. J. (2003) · British journal of surgery · doi:10.1002/bjs.4218 · Cited by 20
Georgia Primary Care Providers’ Knowledge of Hereditary Breast and Ovarian Cancer Syndrome
Nair, N., Bellcross, C. A., Haddad, L. B., Martin, M. L., Matthews, R., Gabram‐Mendola, S., Crane, B. E., & Meaney‐Delman, D. M. (2015) · Journal of Cancer Education · doi:10.1007/s13187-015-0950-9 · Cited by 19
“The identification of BRCA mutation carriers, coupled with risk reduction strategies, has been shown to lower the incidence of both breast and ovarian cancer, as well as cancer specific and all-cause mortality [10–16].”
BackgroundAhmadloo, S., Nakaoka, H., Hayano, T., Hosomichi, K., You, H., Utsuno, E., Sangai, T., Nishimura, M., Matsushita, K., Hata, A., et al. (2017) · Journal of Human Genetics · doi:10.1038/jhg.2017.5 · Cited by 21
Gamble, C. R., Havrilesky, L. J., Myers, E. R., Chino, J., Hollenbeck, S. T., Plichta, J. K., Marcom, P. K., Hwang, E. S., Kauff, N. D., & Greenup, R. A. (2017) · Annals of Surgical Oncology · doi:10.1245/s10434-017-5995-z · Cited by 20
Strach, M. C., Prasanna, T., Kirova, Y., Alran, S., O'Toole, S. A., Beith, J. M., Poortmans, P. M., McNeil, C. M., & Carroll, S. L. (2018) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2018.11.007 · Cited by 21
Dominguez, F. J., Jones, J. L., Calvillo, K. Z., Smith, B. L., Gadd, M. A., Specht, M., Kopans, D. B., Moore, R. H., Michaelson, J. S., & Hughes, K. S. (2005) · Cancer · doi:10.1002/cncr.21393 · Cited by 19
Reeder, J. G., & Vogel, V. G. (2007) · Clinical Breast Cancer · doi:10.3816/cbc.2007.n.047 · Cited by 19
Silva, E., Gatalica, Z., Snyder, C., Vranić, S., Lynch, J. F., & Lynch, H. T. (2008) · The Breast Journal · doi:10.1111/j.1524-4741.2007.00516.x · Cited by 19
“The appropriately counseled BRCA mutation carrier who undergoes a bilateral prophylactic mastectomy will decrease her risk of breast cancer by 96% (50,51).”
BackgroundSchlehe, B., & Schmutzler, R. K. (2008) · Der Chirurg · doi:10.1007/s00104-008-1556-0 · Cited by 21
Who is prone to high levels of distress after prophylactic mastectomy and/or salpingo-ovariectomy?
Bresser, P. J. C., Van Gool, A. R., Seynaeve, C., Duivenvoorden, H. J., Niermeijer, M. F., van Geel, A. N., Menke, M., Klijn, J. G. M., & Tibben, A. (2007) · Annals of Oncology · doi:10.1093/annonc/mdm274 · Cited by 18
Self-citationKang, H. P., Maguire, J., Chu, C. S., Haque, I. S., Lai, H., Mar‐Heyming, R., Ready, K. J., Vysotskaia, V. S., & Evans, E. (2016) · PeerJ · doi:10.7717/peerj.2162 · Cited by 18
“Risk management options Effectiveness Prophylactic mastectomy Up to 90% reduction in breast cancer risk (Hartmann et al., 1999, 2001;Meijers-Heijboer et al., 2001) Prophylactic oophorectomy ∼50% reduction in breast cancer risk when performed premenopausally (more pronounced effect for BRCA2mutation…”
Background
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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