Breast cancer still a small risk with some hormonal contraceptives


What does the new study showing a link between low-dose hormonal contraceptives and breast cancer really tell us in practical terms? First, that the risk has not gone away with the introduction of pills delivering newer and lower formulations, and second, that the risk is significant at the population level but tiny at the individual level.[1] It is important to unpack the study’s findings to really put them into perspective.

It has been decades since we learned that women who used combined oral contraceptives had an increased risk of developing breast cancer. What the researchers conducting the most recent study wanted to know was whether women using the newer forms of hormonal contraceptives—low-dose pills, progestin-containing IUDs, patches, rings, implants, and injectables—had enough hormonal exposure to continue to be at to a risk for breast cancer. Many researchers and providers have speculated that women exposed to lower doses or newer progestins might be less likely to develop breast cancer.

The prospective cohort study examined data on 1,797,932 Danish reproductive-age women from 1995 through 2012. The cohort accumulated 14 million person-years and 9,101 incident breast cancers. The average length of follow up was 11 years. Information on confounding factors was also collected: age, body mass index (BMI), smoking status, previous pregnancies, family history of breast cancer, history of endometriosis and PCOS, and education.

Women who were using hormonal contraceptives pills or IUDs, had an increased relative risk of developing breast cancer, RR 1.20, compared with women who had never used them. The findings were similar to those reported two decades ago,[2] surprising those who had expected that lower doses of hormone would result in a smaller risk. In the current study, the risk was similar across different preparations for combined pills. There were no findings that reach significance among women who had used progestin-only pills, patches, rings, implants or injectables, because it did not accumulate enough users or incident cases of breast cancer.

Women who used pills or IUDs for more than 10 years were 40% more likely to develop breast cancer. Among women who used the hormones for 5 years, the increased risk persisted for at least 5 years after they discontinued use, a finding not seen in previous studies, though those studies had not analyzed a 5-year minimum for use. The researchers said that the risk decreased rapidly among women who used hormonal contraceptives for less than 5 years.

More important to clinical decision-making, however, is the absolute risk for breast cancer. While relative risk describes a group’s risk compared to another group, absolute risk describes an individual’s risk.  And that risk is what would occur above and beyond the baseline risk for women not exposed. In this study, the overall absolute risk among current and recent users was 13 cases per 100,000 person-years. The researchers estimated that the hormonal contraceptive use could result in 1 additional case of breast cancer for every 7,690 women using a hormonal method for 1 year. This is a small increase in risk. An individual woman’s absolute risk will vary according to her age and other characteristics. Younger women will have a fraction of the risk that older women will have.

How solid are these findings? As with all studies, there were limitations that could have introduced bias, ranging from incomplete information on confounders and other data to relying on prescription databases that cannot tell us whether a filled prescription was actually used correctly or used at all. The researchers were not able to adjust for age at menarche, breastfeeding, alcohol consumption or physical activity, and they had BMI measures for parous women only. And of course, this was a cohort study, which can show associations but not cause and effect.

Women who wish to reduce their exposure to the potential for risk can select nonhormonal contraceptives as complete childbearing or approach age 40, along with modifying known other risk factors. But for most women, their individual increased risk for breast cancer will be small and that risk may well be outweighed by the benefits of hormonal contraception, including the associated reduced risks for cancers of the ovary and endometrium and, possibly, the colon and rectum.

[1] Mørch LS, Skovlund CW, Hannford PC, et al. Contemporary hormonal contraception and the risk of breast cancer. N Engl J Med 2017:377:2228-39.

[2] Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53,297 women with breast cancer and 100,239 without breast cancer from 54 epidemiological studies. Lancet 1996;347:1713-27.