Effects of chemotherapy on contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers: A nationwide cohort study.

Autor: Akdeniz D; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., van Barele M; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Heemskerk-Gerritsen BAM; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Steyerberg EW; Department of Public Health, Erasmus MC, Rotterdam, the Netherlands; Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, the Netherlands., Hauptmann M; Institute of Biostatistics and Registry Research, Brandenburg Medical School Theodor Fontane, Neuroppin, Germany., van de Beek I; Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., van Engelen K; Department of Clinical Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands., Wevers MR; Department for Clinical Genetics, Radboud University Medical Centre, Nijmegen, Netherlands., Gómez García EB; Department of Genetics, Maastricht University Medical Centre, Maastricht, Netherlands., Ausems MGEM; Division of Laboratories, Pharmacy and Biomedical Genetics, Department of Genetics, University Medical Centre Utrecht, Utrecht, Netherlands., Berger LPV; Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands., van Asperen CJ; Department of Clinical Genetics, Leiden University Medical Centre, Leiden, the Netherlands., Adank MA; Family Cancer Clinic, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands., Collée MJ; Department of Clinical Genetics, Erasmus University Medical Centre, Rotterdam, the Netherlands., Stommel-Jenner DJ; Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands., Jager A; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Schmidt MK; Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands; Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands., Hooning MJ; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands. Electronic address: m.hooning@erasmusmc.nl.
Jazyk: angličtina
Zdroj: Breast (Edinburgh, Scotland) [Breast] 2022 Feb; Vol. 61, pp. 98-107. Date of Electronic Publication: 2021 Dec 14.
DOI: 10.1016/j.breast.2021.12.007
Abstrakt: Aim: BRCA1/2 mutation carriers with primary breast cancer (PBC) are at high risk of contralateral breast cancer (CBC). In a nationwide cohort, we investigated the effects of chemotherapeutic agents given for PBC on CBC risk separately in BRCA1 and BRCA2 mutation carriers.
Patients and Methods: BRCA1 or BRCA2 mutation carriers with an invasive PBC diagnosis from 1990 to 2017 were selected from a Dutch cohort. We estimated cumulative CBC incidence using competing risks analysis. Hazard ratios (HR) for the effect of neo-adjuvant or adjuvant chemotherapy and different chemotherapeutic agents on CBC risk were estimated using Cox regression.
Results: We included 1090 BRCA1 and 568 BRCA2 mutation carriers; median follow-up was 8.9 and 8.4 years, respectively. Ten-year cumulative CBC incidence for treatment with and without chemotherapy was 6.7% [95%CI: 5.1-8.6] and 16.7% [95%CI: 10.8-23.7] in BRCA1 and 4.8% [95%CI: 2.7-7.8] and 16.0% [95%CI: 9.3-24.4] in BRCA2 mutation carriers, respectively. Chemotherapy was associated with reduced CBC risk in BRCA1 (multivariable HR: 0.46, 95%CI: 0.29-0.74); a similar trend was observed in BRCA2 mutation carriers (HR: 0.63, 95%CI: 0.29-1.39). In BRCA1, risk reduction was most pronounced in the first 5 years (HR: 0.32, 95%CI: 0.17-0.61). Anthracyclines and the combination of anthracyclines with taxanes were associated with substantial CBC risk reduction in BRCA1 carriers (HR: 0.34, 95%CI: 0.17-0.68 and HR: 0.22, 95%CI: 0.08-0.62, respectively).
Conclusion: Risk-reducing effects of chemotherapy are substantial for at least 5 years and may be used in personalised CBC risk prediction in any case for BRCA1 mutation carriers.
Competing Interests: Declaration of competing interest None. For Fig. A.2, A.3A and A.3B below colour should be used in print.
(Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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