Hormonal Contraception and the Risk of Breast Cancer

By Pelin Batur, MD

A 44-year-old woman presents to your office for an annual visit. She is sexually active but does not wish to become pregnant. She has a family history of breast cancer: her mother was diagnosed at age 53. She is interested in an oral contraceptive to prevent pregnancy and acne. However, she is nervous about being on any contraceptive that may increase her risk of breast cancer.

To date, studies assessing the effect of hormonal contraception on the risk of breast cancer have produced inconsistent results. Although most studies have shown no associated risk, a few have shown a temporary 20% to 30% increased risk of breast cancer during use.1-2 Case-controlled studies that reported an association between hormonal contraception and breast cancer included populations taking higher-dose combination pills, which are no longer prescribed. Most studies do not evaluate specific formulations of hormonal contraception, and little is known about effects associated with intrauterine devices or progestin-only contraception.

Further research warranted

A prospective study performed by Morch et al1 followed more than 1 million reproductive-aged women for a mean of 10.9 years. The Danish Cancer Registry was used to identify cases of invasive breast cancer. Women who used hormonal contraceptives had a relative risk of breast cancer of 1.20 compared with women not on hormonal contraception (95% CI 1.14–1.26). The study suggested that those who had been on contraceptive agents for more than five years had an increased risk and that this risk remained for five years after the agents were discontinued. Conversely, no increased risk of cancer was noted in those who used hormonal contraception for less than five years. No notable differences were seen among various formulations.

For women using the levonorgestrel-containing intrauterine device, the relative risk of breast cancer was 1.21 (95% CI 1.11–1.33). A few cancers were noted in those who used the progestin-only implant or those using depot medroxyprogesterone acetate. While the study showed an increased relative risk of breast cancer, the absolute risk was low — 13 cases per 100,000, or approximately one additional case of breast cancer per 7,690 per year.1

This study had several important limitations. The authors did not adjust for common breast cancer risk factors including age at menarche, alcohol use or breastfeeding. Additionally, the study did not account for the use of hormonal contraception before the study period and conversely, did not account for women who may have stopped taking their contraceptive despite their prescribed duration. The frequency of mammography was not explicitly noted, which could have shifted results for women who had more aggressive screening.

It is also noteworthy that the use of high-dose systemic progestins was not associated with an increased risk, whereas the levonorgestrel intrauterine device, which contains only 1/20th the dose of a low-dose oral contraceptive pill, was associated with an increased risk. This discrepancy in risk warrants further investigation, and clinicians should be aware that this inconsistency needs validation before changing clinical practice.

In an observational cohort study,3 more than 100,000 women ages 50 to 71 were followed prospectively for 15 years to evaluate the association between hormonal contraceptive use and the risk of gynecologic and breast cancers. In this study, the duration of hormonal contraceptive use, smoking status, alcohol use, body mass index, physical activity and family history of cancer were recorded. Long-term hormonal contraceptive use reduced ovarian and endometrial cancer risks by 40% and 34%, respectively, with no increase in breast cancer risk regardless of family history.

How would you counsel the patient?

The patient should be educated on the benefits of hormonal contraception that extend beyond pregnancy prevention, including regulation of menses, improved acne, decreased risk of endometrial and ovarian cancer, and likely reductions in colorectal cancer and overall mortality risk.1-4 Further, after their own systematic review of the data assessing risk of breast cancer with hormonal contraception, the US Centers for Disease Control and Prevention state in their guidelines that all contraceptives may be used without limitation in those who have a family history of breast cancer.5 Any potential increased risk of breast cancer in women using hormonal contraception is small and would not outweigh the benefits associated with use.

One must consider the impact of an unintended pregnancy in such women, including effects on the health of the fetus and mother. Recent reports on the increasing rates of maternal death in the US (23.8 of 100,000 live births) serve as a reminder of the complications that can arise with pregnancy, especially if a mother’s health is not optimized before conception.6

References

1. 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.
2. Batur P, Sikka S, McNamara M. Contraception update: extended use of long acting methods, hormonal contraception risks, and over the counter access. J Womens Health (Larchmt). 2018 Oct 6. [Epub ahead of print]
3. Michels KA, Pfeiffer RM, Brinton LA, Trabert B. Modification of the associations between duration of oral contraceptive use and ovarian, endometrial, breast and colorectal cancers. JAMA Oncol. 2018;4(4):516–521.
4. Iversen L, Fielding S, Lidegaard Ø, Mørch LS, Skovlund CW, Hannaford PC. Association between contemporary hormonal contraception and ovarian cancer in women of reproductive age in Denmark: prospective, nationwide cohort study. BMJ. 2018;362:k3609.
5. Curtis KM, Tepper NK, Jatlaoui TC, et al. US Medical eligibility criteria for contraceptive use, 2016. MMWR Recomm Rep. 2016;65(3):1–103.
6. MacDorman MF, Declercq E, Cabral H, Morton C. Recent increases in the US maternal mortality rate: disentangling trends from measurement issues. Obstet Gynecol. 2016; 128(3):447–455.

Note: This is an abridged version of an article originally published in the Cleveland Clinic Journal of Medicine.