Are modern hormonal contraceptives associated with an increased risk of breast cancer?

In this large, well-executed, prospective cohort study, longer exposure to hormonal contraceptives (HCs) was associated with an increased incidence of breast cancer. The dose-response relationship, biological plausability, and coherence with other research argues that this association is causal. However, the absolute risk increase is small—approximately 13 additional breast cancers per 100,000 person-years (number needed to treat to harm = 7690)—and must be balanced against the important benefits of contraception and the maternal mortality rate of 26 per 100,000 pregnancies in the United States, which is the highest in the developed world. (LOE = 2b)

Mørch LS, Skovlund CW, Hannaford PC, Iversen L, Fielding S, Lidegaard Ø. Contemporary hormonal contraception and the risk of breast cancer. N Engl J Med 2017;377(23):2228-2239.  [PMID:29211679]

Cohort (prospective)

Industry

Population-based

Studies have identified an association between HC use and breast cancer, but most of these data are older and are based on higher estrogen doses, were limited to oral contraceptives, and did not study newer progestins. The current study used data from all women in Denmark between the ages of 15 years and 49 years in 1995, and any women who turned 15 before 2012 were included. Those with a history of cancer, venous thromboembolism, or infertility were excluded, leaving nearly 1.8 million women in the final study cohort. Cases of cancer were identified using a national cancer registry, and HC use was culled from the national prescribing database. HC use was defined as current use or recent use (discontinued within the past 6 months) or previous use (discontinued more than 6 months ago). The analysis was adjusted for education, parity, endometriosis, polycystic ovarian syndrome, smoking, body mass index, and a family history of breast or ovarian cancer. The mean duration of follow-up was approximately 11 years, with a total of 19.6 million person-years of follow-up. There were 14 million person-years of follow-up for the first HC used by women, and during that time there were 9101 breast cancers. Overall, the risk of having a diagnosis of breast cancer was significantly higher among recent or current users of HC than among never users (relative risk 1.20; 95% CI 1.14 - 1.26). There was a dose-response relationship between years of exposure to HC and the relative risk of breast cancer, with the relative risk increasing from 1.09 with less than a year of use to 1.38 with more than 10 years of use. The increased risk persisted, especially for women who had taken HC for longer than 5 years.