An estimated 140 million women worldwide use hormonal contraception, which account for approximately 13% of women between the ages of 15 and 49 years.1 In the past, oral contraceptives had a higher dose of estrogen than they do today. Higher estrogen dose in estrogen-progestin oral contraceptives has been associated with a higher risk for breast cancer. 2,3 Based on this finding, lower-dose hormonal contraceptive options were developed.
A recent analysis of data from the Danish Sex Hormone Register Study was published by Mørch and colleagues in the New England Journal of Medicine.1 The registry collects data on Danish women aged 15 to 79 years to assess the risks associated with the use of hormones.
Women from the registry who were living in Denmark and who were between 15 and 49 years of age on January 1, 1995, and those who were 15 years of age before December 31, 2012, were eligible (unless they immigrated to Denmark after 1995). Women were excluded if they had cancer (except nonmelanoma skin cancer), venous thromboembolism, or had received treatment for infertility. Cancers were identified through the Danish Cancer Registry.1
A total of 1,797,932 women were included in the analysis. Among the women included in the analysis with a mean follow-up of 10.9 ± 5.8 years and a total of 19.6 million person-years, there were 11,517 incidents of breast cancers. The relative risk of the disease among all current or recent users of any hormonal contraceptive or those who had discontinued hormonal contraceptive use within the previous 6 months was 20% higher compared with women who had never used hormonal contraceptives.1,4
Longer duration of hormonal contraceptive use significantly increased the risk for breast cancer from 1.09 (with <1 year of use) to 1.38 (with >10 years of use [P = .002]). Additionally, women who never used hormonal contraceptives had a lower risk for breast cancer than women who used hormonal contraceptives for ≥5 years. Even after discontinuing hormonal contraceptives, the risk remained elevated for ≥5 years. Shorter duration (<5 years) use of hormonal contraceptives was not associated with elevated risk for breast cancer.1
When evaluating the use of specific types of hormonal contraception, use of the levonorgestrel-releasing intrauterine system had a similar risk to oral products containing levonorgestrel alone (relative risk of 1.21 for the intrauterine system).1 This has been referred to as “the most important subgroup analysis” in the study because it evaluated the use of various formulations and found that no hormonal contraceptive is risk-free.4
Mørch and colleagues concluded that, “The current or recent use of hormonal contraception was associated with a higher risk of breast cancer than the risk among women who had never used hormonal contraceptives, with little evidence of major differences between specific combined oral contraceptives. The risk increased with the duration of use.”
In an editorial in the same issue of The New England Journal of Medicine, 3 important implications of this study were discussed.4 First, the absolute increase in the risk for developing breast cancer in women taking hormonal contraceptives is 13 per 100,000 women overall, but only 2 per 100,000 in women younger than 35 years of age. Second, the risk for breast cancer needs to be balanced against the benefits of the use of oral contraceptives, including the fact that their use benefits women with dysmenorrhea or menorrhagia and is associated with reductions in risks for ovarian, endometrial, and colorectal cancers later in life. Finally, the data presented by Mørch and colleagues suggest that the search for an oral contraceptive that does not elevate the risk for breast cancer needs to continue.
1. Mørch LS, Skovlund CW, Hannaford PC, et al. Contemporary hormonal contraception and the risk of breast cancer. N Engl J Med. 2017;377:2228-2239.
2. Pasqualini JR. Progestins and breast cancer. Gynecol Endocrinol. 2007;23(Suppl 1):32-41.
3. 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 women without breast cancer from 54 epidemiological studies. Lancet. 1996;347:1713-1727.
4. Hunter DJ. Oral contraceptives and the small increased risk of breast cancer. N Engl J Med. 2017;377:2276-2277.