From Pages to Practice

By Lisa Caulley, MD, MPH, FRCSC

Published December 6, 2017


Modern medicine and the development of contemporary hormonal contraceptives have allowed an estimated 140 million women to prevent unplanned pregnancies and modify their hormonal cycles. The options for hormonal contraceptives now include oral, injectable, transdermal, and intrauterine devices, with formulations that vary from combination estrogen and progestin to progestin-only. Studies have shown an association between the use of exogenous estrogen and progestin and increased risk for breast cancer. However, these studies have had inconsistent findings and have focused on older women who initiate therapy at a later age. Further, these findings cannot be assumed to translate to risk in younger women, leading to the question of how the wide range of hormonal contraceptives affects the risk of breast cancer in the 25-year-old patient who presents to your office to initiate hormonal contraception.

In this week’s issue of NEJM, MØrch and colleagues used national registry data from Denmark to examine the association between the use of hormonal contraception and the risk of breast cancer in 1.8 million women aged 15 to 49 with no prior history of cancer, venous thrombosis, or infertility treatments. The researchers examined incident breast cancers in the Danish Cancer Registry as a function of type and duration of hormonal contraception use. Women were categorized as never users of hormonal contraceptives, current or recent users (cessation within 6 months), or previous users (cessation >6 months ago).

During a mean follow-up of 10.9 years (19.6 million person-years), 11, 517 cases of breast cancers were identified. The age-adjusted absolute risk difference for breast cancer between women who had never used hormonal contraception and current and recent users of any type of hormonal contraception was 13 (95% CI, 10 to 16) per 100,000 person-years. This translates to approximately one extra breast cancer diagnosis for every 7690 women using hormonal contraception for 1 year. For women younger than 35, the absolute risk difference decreased to 2 per 100,000 women.

The adjusted relative risk of breast cancer in current and recent users as compared to never users was 1.20 (95% CI, 1.14-1.26). The risk increased with duration of use from 1.09 (95% CI, 0.96-1.23) for <1 year of use to 1.38 (95% CI, 1.26-1.51) for >10 years of use. Among woman who had previously used hormonal contraception for more than 5 years, the risk of breast cancer remained increased for more than 5 years after discontinuation (relative risk, 1.16; 95% CI, 1.02-1.33). In addition, users of the levonorgestrel intrauterine device had a significantly higher risk of breast cancer 1.21 (95% CI, 1.11-1.33).

In this large cohort study, the authors integrated time-varying exposure information and type of contraception to validate previous findings of an increased risk of breast cancer associated with hormonal contraception use. In an accompanying editorial, David J. Hunter, an NEJM statistical consultant highlights the low absolute risks associated with hormonal contraception among young women, and notes that benefits, including reductions in dysmenorrhea and menorrhagia and reduced risks of ovarian, endometrial, and colorectal cancer, must be weighed against this risk. Nevertheless, given the large number of young women using these products, he notes, “these data suggest that the search for an oral contraceptive that does not elevate risk of breast cancer needs to continue.”

Patients considering contemporary hormonal contraception should be counselled about risks and benefits in the context of their planned duration of use, type of contraception, and risk of adverse events. For the 25-year-old woman in your office who would like to initiate hormonal contraception, she should be informed that this study suggests that her risk of additional breast cancers attributable to hormonal contraception is low, particularly if she is planning only short-term use.

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Lisa is a 2017-2018 NEJM Editorial Fellow. An otolaryngologist-head and neck surgeon by training, she graduated from the University of Toronto Medical School and completed her residency training at the University of Ottawa. She has a Master's in Public Health from the Harvard T. H. Chan School of Public Health.