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

Bernadette A. M. Heemskerk-Gerritsen; Agnes Jager; Linetta B. Koppert; A. Inge-Marie Obdeijn; Margriet Collee; Hanne E. J. Meijers-Heijboer; Denise J. Jenner; Hester S. A. Oldenburg; Klaartje van Engelen; Jakob de Vries; Christi J. van Asperen; Peter Devilee; Marinus J. Blok; C. Marleen Kets; Margreet G. E. M. Ausems; Caroline Seynaeve; Matti A. Rookus; Maartje J. Hooning

doi:10.1007/s10549-019-05345-2

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

Bernadette A. M. Heemskerk-Gerritsen^*, Agnes Jager, Linetta B. Koppert, A. Inge-Marie Obdeijn, Margriet Collee, Hanne E. J. Meijers-Heijboer, Denise J. Jenner, Hester S. A. Oldenburg, Klaartje van Engelen, Jakob de Vries, Christi J. van Asperen, Peter Devilee, Marinus J. Blok, C. Marleen Kets, Margreet G. E. M. Ausems, Caroline Seynaeve, Matti A. Rookus, Maartje J. Hooning

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	723-733
Number of pages	11
Journal	Breast Cancer Research and Treatment
Volume	177
Issue number	3
DOIs	https://doi.org/10.1007/s10549-019-05345-2
Publication status	Published - Oct 2019

Keywords

BRCA1
2
Bilateral risk-reducing mastectomy
Prevention
Surveillance
Survival
CONTRALATERAL BREAST-CANCER
OVARIAN-CANCER
PROPHYLACTIC MASTECTOMY
SURGERY
STRATEGIES
EFFICACY
FAMILIES
SERIES
WOMEN
TIME

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Heemskerk-Gerritsen, B. A. M., Jager, A., Koppert, L. B., Obdeijn, A. I.-M., Collee, M., Meijers-Heijboer, H. E. J., Jenner, D. J., Oldenburg, H. S. A., van Engelen, K., de Vries, J., van Asperen, C. J., Devilee, P., Blok, M. J., Kets, C. M., Ausems, M. G. E. M., Seynaeve, C., Rookus, M. A., & Hooning, M. J. (2019). Survival after bilateral risk-reducing mastectomy in healthy BRCA1 and BRCA2 mutation carriers. Breast Cancer Research and Treatment, 177(3), 723-733. https://doi.org/10.1007/s10549-019-05345-2

@article{e551ef12cff44d58bfe0930def67213b,

title = "Survival after bilateral risk-reducing mastectomy in healthy BRCA1 and BRCA2 mutation carriers",

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, CONTRALATERAL BREAST-CANCER, OVARIAN-CANCER, PROPHYLACTIC MASTECTOMY, SURGERY, STRATEGIES, EFFICACY, FAMILIES, SERIES, WOMEN, TIME",

author = "Heemskerk-Gerritsen, {Bernadette A. M.} and Agnes Jager and Koppert, {Linetta B.} and Obdeijn, {A. Inge-Marie} and Margriet Collee and Meijers-Heijboer, {Hanne E. J.} and Jenner, {Denise J.} and Oldenburg, {Hester S. A.} and {van Engelen}, Klaartje and {de Vries}, Jakob and {van Asperen}, {Christi J.} and Peter Devilee and Blok, {Marinus J.} and Kets, {C. Marleen} and Ausems, {Margreet G. E. M.} and Caroline Seynaeve and Rookus, {Matti A.} and Hooning, {Maartje J.}",

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. Coll{\'e}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{\'o}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. 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: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = oct,

doi = "10.1007/s10549-019-05345-2",

language = "English",

volume = "177",

pages = "723--733",

journal = "Breast Cancer Research and Treatment",

issn = "0167-6806",

publisher = "Springer",

number = "3",

}

Heemskerk-Gerritsen, BAM, Jager, A, Koppert, LB, Obdeijn, AI-M, Collee, M, Meijers-Heijboer, HEJ, Jenner, DJ, Oldenburg, HSA, van Engelen, K, de Vries, J, van Asperen, CJ, Devilee, P, Blok, MJ, Kets, CM, Ausems, MGEM, Seynaeve, C, Rookus, MA & Hooning, MJ 2019, 'Survival after bilateral risk-reducing mastectomy in healthy BRCA1 and BRCA2 mutation carriers', Breast Cancer Research and Treatment, vol. 177, no. 3, pp. 723-733. https://doi.org/10.1007/s10549-019-05345-2

TY - JOUR

T1 - Survival after bilateral risk-reducing mastectomy in healthy BRCA1 and BRCA2 mutation carriers

AU - Heemskerk-Gerritsen, Bernadette A. M.

AU - Jager, Agnes

AU - Koppert, Linetta B.

AU - Obdeijn, A. Inge-Marie

AU - Collee, Margriet

AU - Meijers-Heijboer, Hanne E. J.

AU - Jenner, Denise J.

AU - Oldenburg, Hester S. A.

AU - van Engelen, Klaartje

AU - de Vries, Jakob

AU - van Asperen, Christi J.

AU - Devilee, Peter

AU - Blok, Marinus J.

AU - Kets, C. Marleen

AU - Ausems, Margreet G. E. M.

AU - Seynaeve, Caroline

AU - Rookus, Matti A.

AU - Hooning, Maartje J.

N1 - 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).

PY - 2019/10

Y1 - 2019/10

N2 - 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.

AB - 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.

KW - BRCA1

KW - 2

KW - Bilateral risk-reducing mastectomy

KW - Prevention

KW - Surveillance

KW - Survival

KW - CONTRALATERAL BREAST-CANCER

KW - OVARIAN-CANCER

KW - PROPHYLACTIC MASTECTOMY

KW - SURGERY

KW - STRATEGIES

KW - EFFICACY

KW - FAMILIES

KW - SERIES

KW - WOMEN

KW - TIME

U2 - 10.1007/s10549-019-05345-2

DO - 10.1007/s10549-019-05345-2

M3 - Article

C2 - 31302855

SN - 0167-6806

VL - 177

SP - 723

EP - 733

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

IS - 3

ER -

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

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Keywords

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