Published in Contemporary OB/GYN, December 14, 2017
Results of a prospective cohort study by Danish investigators suggest that current or recent use of hormonal contraceptives may be associated with an increased risk of breast cancer. The researchers caution, however, that the risk is low and must be weighed against the important benefits of taking the drugs, including their efficacy and reduced risks of ovarian, endometrial, and perhaps colorectal cancer.
Published in The New England Journal of Medicine, the findings reflect data from 1.8 million women aged 15 to 49 who were followed for 10.9 years, or equal to 19.6 million person-years of use of contraception. During that time, 11,517 cases of breast cancer were diagnosed in the cohort.
A relative risk (RR) of breast cancer of 1.20 was seen among all current and recent users of hormonal contraception (95% confidence interval [CI], 1.14 to 1.26) compared with women who had never used the drugs. The RR increased from 1.09 (95% CI, 0.96 to 1.23) with < 1 year of use to 1.38 (95% CI, 1.26 to 1.51) with > 10 years of use (P = 0.002). After discontinuation of hormonal contraception, risk of breast cancer was still higher among women who had used hormonal contraception for 5 years or more than in those who had not used the drugs.
RRs for breast cancer associated with triphasic and monophasic levonorgestrel-containing oral contraceptives (OCs) were similar (1.21 and 1.45, respectively). No major differences were seen when the authors compared various combined OCs and after adjustment for multiple testing, they were no longer significant. Contraceptives studied included norethisterone, levonorgestrel, norgestimate, desogestrel, gestodene, drospirenone and cyproterone combined with 20 to 40 µg estradiol, the progestin-only implant, depot medroxyprogesterone acetate, and the levonorgestrel-releasing intrauterine device (IUD). Adjustment of analyses for estrogen dose attenuated overall relative risk of breast cancer with current or recent use.
The data, taken from nationwide registries, were fully adjusted for level of education, parity, polycystic ovary syndrome, endometriosis, and family history of breast or ovarian cancer. Adjustment also was made for body mass index (in parous women only), smoking status, and age of the women at first delivery when this information was available for parous women. The authors were not able to adjust for age at menarche, breastfeeding, alcohol consumption or physical activity.
“Our results,” the authors said, “suggest the rapid disappearance of excess risk of breast cancer after discontinuation of use among women who have used hormonal contraceptives for short periods, whereas the risk among women who have used these contraceptives for longer periods may persist for a least 5 years after discontinuation.”
This study provides important information regarding the risks of breast cancer associated with newer, low-dose combination OCs (notably lower doses of estrogen), non-oral hormonal contraception such as implants, the vaginal ring, and the levonorgestrel IUD, and different formulations of progestins. Older studies have suggested that there is an association between the older formulations of OCs and breast cancer risk, but there has been little data on the newer, and non-oral forms of hormonal contraception. The new findings suggest that contemporary hormonal contraception does not decrease the risk of breast cancer and there is a dose-response effect with higher risk associated with longer use. The study does not adjust for some of the important factors that affect breast cancer risk, such as physical activity, breastfeeding or alcohol use. It also does not report on long-term risk of breast cancer > 10 years after discontinuation of use of hormonal contraception, which are important data, given the young age of women using hormonal contraception and the older age at which most women are diagnosed with breast cancer. Nonetheless, the data suggest that current hormonal contraception, both with lower doses of hormones and non-oral formulations, are associated with a small, but significant risk of breast cancer.~ Ilana Cass, MD, Editorial Board Member, Contemporary OB/GYN