In a study reported in the Journal of Clinical Oncology, Phillips et al found that carriers of BRCA1—but not BRCA2—germline mutations who used hormonal contraception were at increased risk for developing breast cancer.
Study Details
The investigators used pooled data from four prospective cohort studies including women from Australia, New Zealand, Europe, Canada, and the United States with a germline mutation in BRCA1 or BRCA2 who were enrolled between December 1991 and August 2019. Women who were carriers of both mutations were analyzed as BRCA1 carriers.
Key Findings
Overall, 53% of 3,882 BRCA1 carriers and 71% of 1,509 BRCA2 carriers had used hormonal contraceptives for at least 1 year, with median cumulative use of 4.8 and 5.7 years, respectively. Incident breast cancer was diagnosed in 488 BRCA1 carriers and 191 BRCA2 carriers over a median follow-up of 5.9 and 5.6 years, respectively.
Among BRCA1 mutation carriers, no significant association with breast cancer risk was observed for current or past use of hormonal contraceptives for at least 1 year: hazard ratios (HRs) were 1.40 (95% confidence interval [CI] = 0.94–2.08, P = .10) for current use; 1.16 (95% CI = 0.80–1.69, P = .4) for past use over 1 to 5 years; 1.40 (95% CI = 0.99–1.97, P = .05) for past use over 6 to 10 years; and 1.27 (95% CI = 0.98–1.63, P = .07) for past use over more than 10 years. However, ever use for at least 1 year was associated with a significantly increased risk of breast cancer (HR = 1.29, 95% CI = 1.04–1.60, P = .02). Risk significantly increased with longer cumulative duration of use, with a risk increase of 3% (95% CI = 1%–5%, P = .002) for each additional year of use.
Among BRCA2 mutation carriers, neither current use (HR = 0.70, 95% CI = 0.33–1.47, P = .3) nor ever use of hormonal contraceptives (HR = 1.07, 95% CI = 0.73–1.57, P = .7) was associated with an increased risk of breast cancer.
The investigators concluded: “Hormonal contraceptives were associated with increased [breast cancer] risk for BRCA1 mutation carriers, especially if used for longer durations. Decisions about their use in women with BRCA1 mutations should carefully weigh the risks and benefits for each individual.”
Kelly-Anne Phillips, MD, MBBS, of Peter MacCallum Cancer Centre, Melbourne, Australia, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Australian National Health and Medical Research Council. Canadian Cancer Society Research Institute, U.S. National Institutes of Health, and others. For full disclosures of the study authors, visit ascopubs.org.
