Survival after bilateral risk-reducing mastectomy in healthy BRCA1 and BRCA2 mutation carriers
Heemskerk-Gerritsen, Bernadette A.M.; Jager, Agnes; Koppert, Linetta B.; Obdeijn, A. Inge Marie; Collée, Margriet; Meijers-Heijboer, Hanne E.J.; Jenner, Denise J.; Oldenburg, Hester S.A.; van Engelen, Klaartje; de Vries, Jakob; van Asperen, Christi J.; Devilee, Peter; Blok, Marinus J.; Kets, C. Marleen; Ausems, Margreet G.E.M.; Seynaeve, Caroline; Rookus, Matti A.; Hooning, Maartje J.
(2019) Breast Cancer Research and Treatment, volume 177, issue 3, pp. 723 - 733
(Article)
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
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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.
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Keywords: Bilateral risk-reducing mastectomy, BRCA1/2, Prevention, Surveillance, Survival, Oncology, Cancer Research
ISSN: 0167-6806
Publisher: Springer New York
Note: Funding Information: This work was supported by a Grant from the Dutch Pink Ribbon foundation (Grant No. 2016-209). Funding Information: We thank the Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) for providing the data. The HEBON consists of the following Collaborating Centers: Netherlands Cancer Institute (coordinating center), Amsterdam, NL: M.A. Rookus, F.B.L. Hogervorst, F.E. van Leeuwen, M.A. Adank, M.K. Schmidt, N.S. Russell, D.J. Jenner; Erasmus Medical Center, Rotterdam, NL: J.M. Collée, A.M.W. van den Ouweland, M.J. Hooning, C. Seynaeve, C.H.M. van Deurzen, I.M. Obdeijn; Leiden University Medical Center, NL: C.J. van Asperen, J.T. Wijnen, R.A.E.M. Tollenaar, P. Devilee, T.C.T.E.F. van Cronenburg; Radboud University Nijmegen Medical Center, NL: C.M. Kets, A.R. Mensenkamp; University Medical Center Utrecht, NL: M.G.E.M. Ausems, R.B. van der Luijt; Amsterdam Medical Center, NL: C.M. Aalfs, H.E.J. Meijers-Heijboer, T.A.M. van Os; VU University Medical Center, Amsterdam, NL: K. van Engelen, J.J.P. Gille, Q. Waisfisz; Maastricht University Medical Center, NL: E.B. Gómez-Garcia, M.J. Blok; University of Groningen, NL: J.C. Oosterwijk, A.H. van der Hout, M.J. Mourits, G.H. de Bock; The Netherlands Comprehensive Cancer Organisation (IKNL): S. Siesling, J.Verloop; The nationwide network and registry of histo- and cytopathology in The Netherlands (PALGA): L.I.H. Overbeek. The HEBON study is supported by the Dutch Cancer Society [Grant Nos. NKI1998-1854, NKI2004-3088, NKI2007-3756], the Netherlands Organisation of Scientific Research [Grant No. NWO 91109024], the Dutch Pink Ribbon foundation [Grant Nos. 110005 and 2014-187.WO76], BBMRI [Grant No. NWO 184.021.007/CP46] and Transcan [Grant No. JTC 2012 Cancer 12-054]. HEBON thanks the study participants and the registration teams of IKNL and PALGA for part of the data collection. Funding Information: We thank the Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) for providing the data. The HEBON consists of the following Collaborating Centers: Netherlands Cancer Institute (coordinating center), Amsterdam, NL: M.A. Rookus, F.B.L. Hogervorst, F.E. van Leeuwen, M.A. Adank, M.K. Schmidt, N.S. Russell, D.J. Jenner; Erasmus Medical Center, Rotterdam, NL: J.M. Coll?e, A.M.W. van den Ouweland, M.J. Hooning, C. Seynaeve, C.H.M. van Deurzen, I.M. Obdeijn; Leiden University Medical Center, NL: C.J. van Asperen, J.T. Wijnen, R.A.E.M. Tollenaar, P. Devilee, T.C.T.E.F. van Cronenburg; Radboud University Nijmegen Medical Center, NL: C.M. Kets, A.R. Mensenkamp; University Medical Center Utrecht, NL: M.G.E.M. Ausems, R.B. van der Luijt; Amsterdam Medical Center, NL: C.M. Aalfs, H.E.J. Meijers-Heijboer, T.A.M. van Os; VU University Medical Center, Amsterdam, NL: K. van Engelen, J.J.P. Gille, Q. Waisfisz; Maastricht University Medical Center, NL: E.B. G?mez-Garcia, M.J. Blok; University of Groningen, NL: J.C. Oosterwijk, A.H. van der Hout, M.J. Mourits, G.H. de Bock; The Netherlands Comprehensive Cancer Organisation (IKNL): S. Siesling, J.Verloop; The nationwide network and registry of histo- and cytopathology in The Netherlands (PALGA): L.I.H. Overbeek. The HEBON study is supported by the Dutch Cancer Society [Grant Nos. NKI1998-1854, NKI2004-3088, NKI2007-3756], the Netherlands Organisation of Scientific Research [Grant No. NWO 91109024], the Dutch Pink Ribbon foundation [Grant Nos. 110005 and 2014-187.WO76], BBMRI [Grant No. NWO 184.021.007/CP46] and Transcan [Grant No. JTC 2012 Cancer 12-054]. HEBON thanks the study participants and the registration teams of IKNL and PALGA for part of the data collection. Publisher Copyright: © 2019, The Author(s).
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