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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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“Two percent (3) of women with bilateral prophylactic mastectomy and 4% (23) of women with contralateral prophylactic mastectomy made comments that described the peace of mind prophylactic mastectomy brought them:”
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“Some of the difference between the Meijers-Heijboer et al. study and the current series may be due to the younger mean age at PM in The Netherlands study (37.7 years vs. 41.5 years) and to the higher percentage of women in that study who had undergone a premenopausal oophorectomy before PM (58% vs. 29%).”
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Confronting Genetic Testing Disparities
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Risk reducing mastectomy: outcomes in 10 European centres
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Selective use of sentinel lymph node surgery during prophylactic mastectomy
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“of women requiring reoperations 0 282 (48) 317 (63) 181 (58) 136 (70) 300 (94) 1 311 (52) 189 (37) 130 (43) 59 (30) 18 (6) 1 152 (26) 142 (28) 94 (30) 48 (25) 13 (4) 2 79 (13) 28 (6) 21 (7) 7 (4) 3 (1) 3 45 (8) 14 (3) 11 (4) 3 (2) 2 (1) 4 35 (6) 5 (1) 4 (1) 1 ( 1) 0 Total no.”
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Barton, M. B. (2005) · JNCI Monographs · doi:10.1093/jncimonographs/lgi039 · Cited by 78
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Self-citationClinical management of BRCA1 and BRCA2 mutation carriers
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“Subsequently, several groups have confirmed that PM reduces breast cancer risk in mutation carriers by 90% (Hartmann et al., 2001; Meijers-Heijboer et al., 2001; Rebbeck et al., 2004) .”
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Impact of screening for breast cancer in high-risk women on health-related quality of life
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“Several strategies to reduce the risk of breast cancer or breast cancer death may be discussed with BRCA 1/2 mutation carriers and women with a strong family history, such as intensive surveillance, chemoprevention (Cuzick et al, 2003) and prophylactic mastectomy (Meijers-Heijboer et al, 2001).”
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Prophylactic and Therapeutic Mastectomy in BRCA Mutation Carriers: Can the Nipple Be Preserved?
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“9 years, though these were not NSM procedures.(35) These studies substantiate a high degree of risk reduction in women with BRCA mutation who elect to undergo bilateral prophylactic mastectomy.”
Backgroundvan Dijk, S., Otten, W., Zoeteweij, M. W., Timmermans, D. R. M., van Asperen, C. J., Breuning, M. H., Tollenaar, R. A. �. �., & Kievit, J. (2003) · British Journal of Cancer · doi:10.1038/sj.bjc.6600988 · Cited by 75
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“These include chemoprevention (including tamoxifen) (2, 3) or prophylactic surgery [mastectomy (4, 5) or oophorectomy (6, 7)].”
BackgroundRole of Surgery in the Prophylaxis of Hereditary Cancer Syndromes
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A Cost-Effectiveness Evaluation of Germline BRCA1 and BRCA2 Testing in UK Women with Ovarian Cancer
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Risk-reducing strategies for women carrying brca1/2 mutations with a focus on prophylactic surgery
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“Furthermore, in a prospective study of 139 women with BRCA1 or BRCA2 mutations, after a mean follow-up of 3 years, breast cancer developed in 8 of 63 women who had elected surveillance, but in none of the 76 BRCA mutations carriers who had undergone prophylactic surgery [73].”
BackgroundWhat Women Wish They Knew Before Prophylactic Mastectomy
Rolnick, S. J., Altschuler, A., Nekhlyudov, L., Elmore, J. G., Greene, S. M., Harris, E. L., Herrinton, L. J., Barton, M. B., Geiger, A. M., & Fletcher, S. W. (2007) · Cancer Nursing · doi:10.1097/01.ncc.0000281733.40856.c4 · Cited by 70
“It may also provide gains in life expectancy.(4,8,11) Thus, although the surgery is invasive and irreversible, the risk reduction it affords is often appealing.”
BackgroundRisk assessment and management of high risk familial breast cancer
Evans, D. G., & Lalloo, F. I. (2002) · Journal of Medical Genetics · doi:10.1136/jmg.39.12.865 · Cited by 69
Wu, S., Weinstein, S. P., Deleo, M. J., Conant, E. F., Chen, J., Domchek, S. M., & Despina Kontos, B. (2015) · Breast Cancer Research · doi:10.1186/s13058-015-0577-0 · Cited by 68
“Several risk reduction interventions are currently being used clinically, ranging from the less aggressive, such as lifestyle changes [5] and chemoprevention [6, 7], to those that are more aggressive, such as oophorectomy [8] and prophylactic mastectomy [9].”
BackgroundPhillips, K., Jenkins, M. A., Lindeman, G. J., McLachlan, S., McKinley, J. M., Weideman, P. C., Hopper, J. L., Friedlander, M., & kConFab Investigators (2006) · Clinical Genetics · doi:10.1111/j.1399-0004.2006.00665.x · Cited by 68
Early detection of breast and ovarian cancer in families with BRCA mutations
Vasen, H. F. A., Tesfay, E. B., Boonstra, H., Mourits, M. J. E., Rutgers, E. J. T., Verheyen, R., Oosterwijk, J. C., & Beex, L. V. A. M. (2005) · European Journal of Cancer · doi:10.1016/j.ejca.2004.10.029 · Cited by 69
“The only study performed in mutation carriers showed that none of 76 carriers developed breast cancer after a mean follow-up of three years after surgery [14].”
BackgroundEffectiveness of preventive interventions in BRCA1/2 gene mutation carriers: A systematic review
Bermejo-Pérez, M. J., Márquez-Calderón, S., & Llanos-Méndez, A. (2007) · International Journal of Cancer · doi:10.1002/ijc.22817 · Cited by 67
“Only one of the deaths was due to breast cancer.(11)”
BackgroundResultBRCA Mutation Testing in Determining Breast Cancer Therapy
Smith, K. L., & Isaacs, C. J. (2011) · The Cancer Journal · doi:10.1097/ppo.0b013e318238f579 · Cited by 67
Zon, R. T., Goss, E., Vogel, V. G., Chlebowski, R. T., Jatoi, I., Robson, M. E., Wollins, D. S., Garber, J. E., Brown, P. H., & Kramer, B. S. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.16.3691 · Cited by 67
van Dijk, S., van Roosmalen, M. S., Otten, W., & Stalmeier, P. F. M. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2006.10.5494 · Cited by 67
Roukos, D. H., Agnanti, N., Paraskevaidis, E. A., & Kappas, A. M. (2002) · Annals of Surgical Oncology · doi:10.1007/bf02574510 · Cited by 67
Breast Cancer Risk – Genes, Environment and Clinics
Fasching, P. A., Ekici, A. B., Adamietz, B. R., Wachter, D. L., Hein, A., Bayer, C., Häberle, L., Loehberg, C. R., Jud, S. M., Heusinger, K., et al. (2011) · Geburtshilfe und Frauenheilkunde · doi:10.1055/s-0031-1280437 · Cited by 66
Breast cancer after bilateral risk-reducing mastectomy
Skytte, A., Crüger, D. G., Gerster, M., Lænkholm, A., Lang, C., Brøndum‐Nielsen, K., Andersen, M., Sunde, L., Kølvraa, S., & Gerdes, A. (2011) · Clinical Genetics · doi:10.1111/j.1399-0004.2010.01604.x · Cited by 66
Cancer: A disease at the crossroads of trade‐offs
Jacqueline, C. M., Biro, P. A., Beckmann, C., Møller, A. P., Renaud, F., Sorci, G., Tasiemski, A., Újvári, B., & Frédéric Thomas, A. (2016) · Evolutionary Applications · doi:10.1111/eva.12444 · Cited by 69
Quality of Life After Bilateral Prophylactic Mastectomy
Geiger, A. M., Nekhlyudov, L., Herrinton, L. J., Rolnick, S. J., Greene, S. M., West, C. N., Harris, E. L., Elmore, J. G., Altschuler, A., Liu, I.-L. A., et al. (2006) · Annals of Surgical Oncology · doi:10.1245/s10434-006-9206-6 · Cited by 66
Risk-Reduction Mastectomy: Clinical Issues and Research Needs
Stefanek, M. E., Hartmann, L. C., & Nelson, W. (2001) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/93.17.1297 · Cited by 66
Löwy, I., & Gaudillière, J. (2008) · Science Technology & Human Values · doi:10.1177/0162243907306855 · Cited by 65
“By contrast, while preventive mastectomy is seen by professionals as highly efficient in limiting cancer risk (Meijers-Heijboer et al. 2001; Hartmann et al. 2001), opinions on its use vary.”
BackgroundThe impact of proband mediated information dissemination in families with a BRCA1/2 gene mutation
Sermijn, E., Goelen, G., Teugels, E., Kaufman, L., Bonduelle, M., Neyns, B., Poppe, B., Paepe, A. D., & Grève, J. D. (2004) · Journal of Medical Genetics · doi:10.1136/jmg.2003.011353 · Cited by 64
Bresser, P. J. C., Seynaeve, C., Gool, A. R. V., Niermeijer, M. F., Duivenvoorden, H. J., van Dooren, S., van Geel, A. N., Menke‐Pluijmers, M. B. E., Klijn, J. G. M., & Tibben, A. (2006) · European Journal of Cancer · doi:10.1016/j.ejca.2006.09.009 · Cited by 63
Self-citationProphylactic Mastectomy and Reconstruction: Clinical Outcomes and Patient Satisfaction
Spear, S. L., Schwarz, K. A., Venturi, M. L., Barbosa, T., & Alattar, A. A. (2008) · Plastic & Reconstructive Surgery · doi:10.1097/prs.0b013e318177415e · Cited by 63
Surgical risk reduction: Prophylactic salpingo-oophorectomy and prophylactic mastectomy
Dowdy, S. C., Stefanek, M., & Hartmann, L. C. (2004) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2004.04.028 · Cited by 61
Jones, L. P., Li, M., Halama, E. D., Ma, Y., Lubet, R. A., Grubbs, C. J., Deng, C., Rosen, E. M., & Furth, P. A. (2005) · Oncogene · doi:10.1038/sj.onc.1208426 · Cited by 62
“First, a number of studies have shown that ovariectomy, with follow-ups of 6–10 years, decreases the occurrence of breast cancer almost 50% (Metcalfe et al., 2004) and greater degrees of protection are found when it is performed at younger ages (Meijers-Heijboer et al., 2001; Rebbeck et al., 2002).”
BackgroundEvaluation of models to predict BRCA germline mutations
kConFab Investigators, Kang, H. H., Williams, R., Leary, J., Ringland, C. L., Kirk, J., & Ward, R. L. (2006) · British Journal of Cancer · doi:10.1038/sj.bjc.6603358 · Cited by 62
Bilateral Prophylactic Mastectomy in Swedish Women at High Risk of Breast Cancer
Arver, B. W., Isaksson, K., Atterhem, H., Baan, A., Bergkvist, L., Brandberg, Y., Ehrencrona, H., Emanuelsson, M., Hellborg, H., Henriksson, K. M., et al. (2011) · Annals of Surgery · doi:10.1097/sla.0b013e318214b55a · Cited by 61
Sermijn, E., Delesie, L. M., Deschepper, E., Pauwels, I., Bonduelle, M., Teugels, E., & Grève, J. D. (2016) · Familial Cancer · doi:10.1007/s10689-015-9854-4 · Cited by 61
“Mean (SD) [min–max] [18–77] [18–77] [18–75]”
BRCA1 and BRCA2: The genetic testing and the current management options for mutation carriers
Palma, M., Ristori, E., Ricevuto, E., Giannini, G., & Gulino, A. (2005) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2005.05.003 · Cited by 61
ASCO/SSO Review of Current Role of Risk-Reducing Surgery in Common Hereditary Cancer Syndromes
Guillem, J., Wood, W., Moley, J., Berchuck, A., Karlan, B., Mutch, D., Gagel, R., Weitzel, J., Morrow, M., Weber, B., et al. (2006) · Annals of Surgical Oncology · doi:10.1245/s10434-006-9036-6 · Cited by 177
“several studies have recently emerged comparing mutation carriers who elected prophylactic bilateral mastectomy with those who did not.(20) Reassuringly, this also demonstrated a risk reduction of at least 90%.”
BackgroundInfluentialInherited predisposition to cancer: A historical overview
Lynch, H. T., Shaw, T. G., & Lynch, J. F. (2004) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.30026 · Cited by 60
“We believe these findings [Hartmann et al., 1999, 2001; Meijers-Heijboer et al., 2001; Rebbeck et al., 1999, 2002] indicate that third-party carriers should defray the expenses of not only surveillance but, moreover, prophylactic mastectomy and prophylactic salpingo-oophorectomy, in women at…”
ResultEvaluation of the Validity and Utility of Genetic Testing for Rare Diseases
Grosse, S. D., Kalman, L. V., & Khoury, M. J. (2010) · Advances in experimental medicine and biology · doi:10.1007/978-90-481-9485-8_8 · Cited by 59
Breast cancer susceptibility testing: past, present and future
Goldberg, J., & Borgen, P. I. (2006) · Expert Review of Anticancer Therapy · doi:10.1586/14737140.6.8.1205 · Cited by 58
Ager, B., Butow, P. N., Jansen, J., Phillips, K., & Porter, D. J. T. (2016) · The Breast · doi:10.1016/j.breast.2016.04.005 · Cited by 58
“CPM reduces risk of CBC by 90e95% [5,6].”
BackgroundUtilization of BRCA1/2 genetic testing in the clinical setting
Lee, S.-C., Bernhardt, B. A., & Helzlsouer, K. (2002) · Cancer · doi:10.1002/cncr.10420 · Cited by 62
Prevention and genetic testing for breast cancer: variations in medical decisions.
Bouchard, L., Blancquaert, I., Eisinger, F., Foulkes, W., Evans, G., Sobol, H., & Julian-reynier, C. (2004) · Social Science & Medicine (1967) · doi:10.1016/s0277-9536(03)00263-6 · Cited by 66
Delayed Nipple-Sparing Modified Subcutaneous Mastectomy: Rationale and Technique
Palmieri, B., Baitchev, G., Grappolini, S., Costa, A., & Benuzzi, G. (2005) · The Breast Journal · doi:10.1111/j.1075-122x.2005.21520.x · Cited by 56
Genetic Testing for Inherited Breast Cancer Risk in African Americans
Halbert, C. H., Kessler, L. J., & Mitchell, E. P. (2005) · Cancer Investigation · doi:10.1081/cnv-58819 · Cited by 56
Geiger, A. M. (2005) · Archives of Internal Medicine · doi:10.1001/archinte.165.5.516 · Cited by 56
Scheuner, M. T., Yoon, P. W., & Khoury, M. J. (2004) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.30008 · Cited by 56
Breast MRI for Women With Hereditary Cancer Risk
Robson, M. E. (2004) · JAMA · doi:10.1001/jama.292.11.1368 · Cited by 56
Does the Diagnosis of Breast or Ovarian Cancer Trigger Referral to Genetic Counseling?
Powell, C. B., Littell, R. D., Hoodfar, E., Sinclair, F., & Pressman, A. R. (2013) · International Journal of Gynecological Cancer · doi:10.1097/igc.0b013e318280f2b4 · Cited by 55
Evidence-based management options for women at increased breast/ovarian cancer risk
Pichert, G., Bolliger, B., Buser, K., & Pagani, O. (2002) · Annals of Oncology · doi:10.1093/annonc/mdg030 · Cited by 55
“[53] conducted the first prospective study of 139 women with BRCA1 and BRCA2 mutations.”
BackgroundProphylactic Mastectomy for BRCA1/2 Carriers: Progress and More Questions
Hartmann, L. C., Degnim, A. C., & Schaid, D. J. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.01.925 · Cited by 55
“The Rotterdam group published a prospective study of prophylactic mastectomy in BRCA1/2 carriers in 2001 [8].”
BackgroundInfluentialRisk‐Reduction Surgery Decisions in High‐Risk Women Seen for Genetic Counseling
Ray, J. A., Loescher, L. J., & Brewer, M. (2005) · Journal of Genetic Counseling · doi:10.1007/s10897-005-5833-5 · Cited by 53
“Retrospective studies comparing conditions of RRM to clinical surveillance showed 0% breast cancers in BRCA carriers who underwent RRM and 13% incidence in carriers in the surveillance group (Meijers-Heijboer et al., 2001).”
MethodResultEvron, E., Ben-David, A., Goldberg, H., Fried, G., Kaufman, B., Catane, R., Pfeffer, M. R., Geffen, D. B., Chernobelsky, P., Karni, T., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy515 · Cited by 54
The Role of Prophylactic Surgery in Cancer Prevention
You, Y. N., Lakhani, V. T., & Wells, S. A. (2007) · World Journal of Surgery · doi:10.1007/s00268-006-0616-1 · Cited by 54
“003).(16) In another study of 26 BRCA mutation carriers, no cancer occurred after PM with a median follow-up of 13.”
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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