Study Finds Link Between Hormonal Contraceptives and Higher Breast Cancer Risk in BRCA1 Carriers

Use of hormonal contraceptives (HCs) was associated with a higher-than-average risk of breast cancer (BC) in individuals who carry germline BRCA1 mutations, according to findings published in the Journal of Clinical Oncology.¹

Samples with BRCA1 and BRCA2 mutations | Image Credit: © Saiful52 - stock.adobe.com

Women with germline BRCA1 or BRCA2 mutations have an approximate 70% lifetime risk of developing BC, of which most occur before 50 years of age. Thereby, comprehensive monitoring, as well as identification of preventative strategies and risk factors, are crucial to prevent development of BC in these individuals.¹

Many premenopausal women use HCs as a method to prevent pregnancy, as well as to treat a variety of conditions such as polycystic ovary syndrome or endometriosis. Historically, use of HCs, particularly prolonged use, has been a topic of controversy due to concerns of its consequences for fertility. Although this has been largely disproven, emerging evidence suggests potential risks associated with HC use specifically in patients with BRCA1 mutations.²

In the study, the researchers used pooled observational data from 4 prospective cohort studies to determine associations between HC use and BC risk for unaffected female BRCA1 and BRCA2 mutation carriers. Their assessment included 3882 BRCA1 and 1509 BRCA2 mutation carriers, of which 53% and 71% had ever used HCs for at least 1 year, respectively. The median cumulative duration of use was 4.8 years for BRCA1 carriers and 5.7 years for BRCA2 carriers.¹

During the follow-up period, 488 women with a BRCA1 mutation and 191 women with a BRCA2 mutation were diagnosed with BC, of which 440 of the cases in BRCA1 carriers and 151 in BRCA2 carriers were identified as invasive cancers. In women with a BRCA1 mutation, any use of hormonal birth control was linked to a 29% relative increase in BC risk, with an additional 3% increase in risk for each year of use (1% to 5%, P = .002). However, there was no observed link between HC use and BC risk for women with a BRCA2 mutation (HR, 0.70 [95% CI, 0.33 to 1.47], P = .3 and 1.07 [0.73 to 1.57], P = .7, respectively).¹

Absolute risk, which reflects an individual’s personal likelihood of developing breast cancer, varies significantly. The average woman faces a 13% lifetime risk, while women with a BRCA1 mutation have up to a 72% risk. To determine the impact of HCs on absolute risk, researchers estimated the risk for an average woman with a BRCA1 mutation who began using hormonal birth control at age 18.³

By age 58, a woman who never used hormonal birth control would have a 51.3% risk of developing BC. For those who used HC for 5, 10, or 15 years, the risk increased to 56.6%, 62%, and 67.3%, respectively. While short-term use of hormonal birth control causes a small increase in absolute risk, long-term use results in a more substantial increase.³

The findings underscore the importance of personalized risk assessment for women with BRCA1 mutations considering HC use. Although HCs are widely used, the observed association between their use and an increased risk of BC in BRCA1 carriers highlights the need for careful evaluation of the benefits and risks in this population.

REFERENCES

1. Phillips K, Kotsopoulos J, Domchek S, et al. Hormonal contraception and breast cancer risk for carriers of germline mutations in BRCA1 and BRCA2. J Clin Oncol. October 2, 2024. doi:10.1200/JCO.24.00176

2. Does birth control affect fertility long-term. Beaufort Memorial Hospital. March 30, 2021. Accessed January 14, 2025. https://www.bmhsc.org/blog/does-birth-control-affect-fertility-long-term#

3. Hormonal birth control ups breast cancer risk in women with BRCA1 mutations. Breastcancer.org. October 23, 2024. Accessed January 14, 2025. https://www.breastcancer.org/research-news/hormonal-birth-control-ups-breast-cancer-risk-brca1-mutation