Kelly-Anne Phillips on Hormonal Contraceptives and BRCA1/2 Mutations (2025)

In women with BRCA1 mutations, hormonal contraceptives were associated with a significantly higher risk for breast cancer in a dose-response relationship, researchers reported in an observational study in the Journal of Clinical Oncology.

Kelly-Anne Phillips, MD, of the Peter MacCallum Cancer Centre of the University of Melbourne in Australia, and colleagues pooled data on 3,882 women from four cohort studies who were followed for an average of 6 years. Women who had ever used hormonal contraceptives had a 29% relative increase in the risk of developing breast cancer (HR 1.29, P=0.02) compared with those who had not. The relative risk increased by 3% with each additional year of contraceptive use.

There was no increased risk in the 1,509 women with BRCA2 mutations, although the team said the smaller sample size and relatively small number of new breast cancer cases may have limited the power of the study to detect additional risk in this group.

"Our findings are consistent with hormonal contraceptive use in BRCA1 mutation carriers being associated with similar increases in the relative risk of breast cancer as seen in the general population," the investigators wrote. They noted, however, that the higher baseline risk for BRCA1 mutation carriers means the relative risks translate into even higher absolute risks for carriers than for the general population.

"Decisions about use of hormonal contraceptives in women at increased risk for breast cancer due to BRCA1 mutations need to carefully weigh the absolute risks and benefits," the researchers advised, "While shorter-term use may result in only small increases, prolonged cumulative use may result in larger increases in absolute breast cancer risk that may not be acceptable to some women."

In the following interview, Phillips, who is also co-lead of breast medical oncology and a senior strategic research leader, discussed methods to determine a specific patient's absolute risk and how to effectively counsel patients.

Your paper noted that determining absolute risk associated with hormonal contraceptives is more useful than relative risk. How can oncologists provide BRCA1 carriers with personalized risk estimates?

Phillips: It is hoped that these research findings will be incorporated into risk-prediction models. Until then, clinicians should first estimate the absolute baseline breast cancer risk for the individual woman, using a validated tool such as CanRisk or iPrevent. Then the relative risk increase can be applied to estimate the increase in absolute risk that could be expected with use of hormonal contraceptives, based on the planned age at commencement and duration of use.

Once personalized risk is determined, do you have advice for the best way to counsel women with BRCA1 mutations about hormone contraceptive use?

Phillips: Hormonal contraceptives have important benefits as well as risks. Nuanced discussion of these with each woman is essential to ensure that decisions made about hormonal contraceptives are adequately informed and consistent with the woman's personal circumstances and values. The planned age of use and duration of use are essential considerations, as well as what alternative contraceptives are available and their comparative efficacy and risks.

And what about women with BRCA2 mutations?

Phillips: Given that some other studies have suggested an association between the oral contraceptive pill and increased breast cancer risk for BRCA2 mutation carriers, women should be advised that hormonal contraceptives may increase their breast cancer risk.

Do you have any thoughts about the effect of oral contraceptives on tubo-ovarian cancer risk in BRCA1/2 mutation carriers?

Phillips: BRCA1 and BRCA2 mutation carriers also have very high lifetime risks of tubo-ovarian cancer. Oral contraceptives are associated with substantial reductions in tubo-ovarian cancer risk for BRCA1 and BRCA2 mutation carriers.

Based on the observed age of onset of these tubo-ovarian cancers, most guidelines recommend bilateral salpingo-oophorectomy by age 35-40 years for BRCA1 mutation carriers and 40-45 years for BRCA2. This virtually eliminates tubo-ovarian cancer risk.

Thus, the benefit of oral contraceptives in terms of reducing tubo-ovarian cancer risk is essentially redundant unless women delay bilateral salpingo-oophorectomy beyond the recommended age.

Is there anything else you want to make sure oncologists understand about this study or this topic?

Phillips: It is important to recognize that, due to its observational design, this study may have important biases that could have affected the findings. However, there are no relevant randomized studies, and randomized studies are unlikely to be feasible.

Read the study here.