Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Oct;177(3):723-733.
doi: 10.1007/s10549-019-05345-2. Epub 2019 Jul 13.

Survival after bilateral risk-reducing mastectomy in healthy BRCA1 and BRCA2 mutation carriers

Bernadette A M Heemskerk-Gerritsen  1 , Agnes Jager  2 , Linetta B Koppert  3 , A Inge-Marie Obdeijn  4 , Margriet Collée  5 , Hanne E J Meijers-Heijboer  6 , Denise J Jenner  7 , Hester S A Oldenburg  8 , Klaartje van Engelen  9 , Jakob de Vries  10 , Christi J van Asperen  11 , Peter Devilee  12 , Marinus J Blok  13 , C Marleen Kets  14 , Margreet G E M Ausems  15 , Caroline Seynaeve  2 , Matti A Rookus  7 , Maartje J Hooning  2
Affiliations

Survival after bilateral risk-reducing mastectomy in healthy BRCA1 and BRCA2 mutation carriers

Bernadette A M Heemskerk-Gerritsen et al. Breast Cancer Res Treat. 2019 Oct.

Abstract

Background: In healthy BRCA1/2 mutation carriers, bilateral risk-reducing mastectomy (BRRM) strongly reduces the risk of developing breast cancer (BC); however, no clear survival benefit of BRRM over BC surveillance has been reported yet.

Methods: In this Dutch multicenter cohort study, we used multivariable Cox models with BRRM as a time-dependent covariable to estimate the associations between BRRM and the overall and BC-specific mortality rates, separately for BRCA1 and BRCA2 mutation carriers.

Results: During a mean follow-up of 10.3 years, 722 out of 1712 BRCA1 (42%) and 406 out of 1145 BRCA2 (35%) mutation carriers underwent BRRM. For BRCA1 mutation carriers, we observed 52 deaths (20 from BC) in the surveillance group, and 10 deaths (one from BC) after BRRM. The hazard ratios were 0.40 (95% CI 0.20-0.90) for overall mortality and 0.06 (95% CI 0.01-0.46) for BC-specific mortality. BC-specific survival at age 65 was 93% for surveillance and 99.7% for BRRM. For BRCA2 mutation carriers, we observed 29 deaths (7 from BC) in the surveillance group, and 4 deaths (no BC) after BRRM. The hazard ratio for overall mortality was 0.45 (95% CI 0.15-1.36). BC-specific survival at age 65 was 98% for surveillance and 100% for BRRM.

Conclusion: BRRM was associated with lower mortality than surveillance for BRCA1 mutation carriers, but for BRCA2 mutation carriers, BRRM may lead to similar BC-specific survival as surveillance. Our findings support a more individualized counseling based on BRCA mutation type.

Keywords: BRCA1/2; Bilateral risk-reducing mastectomy; Prevention; Surveillance; Survival.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Flowchart of inclusion of participants (a) and Design of the analytic method and allocation of person-years of observation (b). DNA date of DNA test result, CE censoring event, BRRM bilateral risk-reducing mastectomy, BC first breast cancer. As visualized in b, observation started at the age at DNA test result, or age 25, whichever came last. For women not opting for BRRM, we allocated all person-years of observation (PYO) to the surveillance group (solid lines; scenarios 1, 3, 4, 7). For women opting for BRRM, we allocated PYO before surgery to the surveillance group, and PYO after surgery to the BRRM group (dashed lines; scenarios 2, 5, 6, and 8). The observation ended on the age of death (any cause), or age at study closing date (i.e., December 31, 2016), whichever came first
Fig. 2
Fig. 2
Overall survival curves for BRCA1 (a) and BRCA2 (b) mutation carriers and breast cancer-specific survival curves for BRCA1 (c) and BRCA2 (d) mutation carriers opting for bilateral risk-reducing mastectomy (BRRM) versus staying under surveillance, using the Simon and Makuch method—which takes into account the change in an individual’s variable status over time—with chronological age as the time variable
See this image and copyright information in PMC

Comment in

References

    1. van der Kolk DM, de Bock GH, Leegte BK, Schaapveld M, Mourits MJ, de Vries J, van der Hout AH, Oosterwijk JC. Penetrance of breast cancer, ovarian cancer and contralateral breast cancer in BRCA1 and BRCA2 families: high cancer incidence at older age. Breast Cancer Res Treat. 2010;124(3):643–651. doi: 10.1007/s10549-010-0805-3. - DOI - PubMed
    1. Mavaddat N, Peock S, Frost D, Ellis S, Platte R, Fineberg E, Evans DG, Izatt L, Eeles RA, Adlard J, Davidson R, Eccles D, Cole T, Cook J, Brewer C, Tischkowitz M, Douglas F, Hodgson S, Walker L, Porteous ME, Morrison PJ, Side LE, Kennedy MJ, Houghton C, Donaldson A, Rogers MT, Dorkins H, Miedzybrodzka Z, Gregory H, Eason J, Barwell J, McCann E, Murray A, Antoniou AC, Easton DF, Embrace Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE. J Natl Cancer Inst. 2013;105(11):812–822. doi: 10.1093/jnci/djt095. - DOI - PubMed
    1. Brohet RM, Velthuizen ME, Hogervorst FBL, Meijers-Heijboer HEJ, Seynaeve C, Collee MJ, Verhoef S, Ausems MGEM, Hoogerbrugge N, van Asperen CJ, Garcia EG, Menko F, Oosterwijk JC, Devilee P, van’t Veer LJ, van Leeuwen FE, Easton DF, Rookus MA, Antoniou AC, Resource H Breast and ovarian cancer risks in a large series of clinically ascertained families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations. J Med Genet. 2014;51(2):98–107. doi: 10.1136/jmedgenet-2013-101974. - DOI - PubMed
    1. Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips KA, Mooij TM, Roos-Blom MJ, Jervis S, van Leeuwen FE, Milne RL, Andrieu N, Goldgar DE, Terry MB, Rookus MA, Easton DF, Antoniou AC, Brca, Consortium BC. McGuffog L, Evans DG, Barrowdale D, Frost D, Adlard J, Ong KR, Izatt L, Tischkowitz M, Eeles R, Davidson R, Hodgson S, Ellis S, Nogues C, Lasset C, Stoppa-Lyonnet D, Fricker JP, Faivre L, Berthet P, Hooning MJ, van der Kolk LE, Kets CM, Adank MA, John EM, Chung WK, Andrulis IL, Southey M, Daly MB, Buys SS, Osorio A, Engel C, Kast K, Schmutzler RK, Caldes T, Jakubowska A, Simard J, Friedlander ML, McLachlan SA, Machackova E, Foretova L, Tan YY, Singer CF, Olah E, Gerdes AM, Arver B, Olsson H. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA. 2017;317(23):2402–2416. doi: 10.1001/jama.2017.7112. - DOI - PubMed
    1. Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol. 2007;25(11):1329–1333. doi: 10.1200/JCO.2006.09.1066. - DOI - PMC - PubMed