Oral contraceptive use by formulation and breast cancer risk by subtype in the Nurses' Health Study II: a prospective cohort study.

Overview

abstract

BACKGROUND: Oral contraceptive (OC) use has been associated with higher breast cancer risk; however, evidence on the associations between different OC formulations and breast cancer risk, especially by disease subtype, is limited. OBJECTIVE: To evaluate associations between OC use by formulation and breast cancer risk by disease subtype. STUDY DESIGN: This prospective cohort study included 107,069 women from the Nurses' Health Study II with recalled OC use from age 13 to baseline (1989) and updated data on OC use until 2009 collected via biennial questionnaires. A total of 5,799 breast cancer cases were identified through 2017. Multivariable Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals [95% CI] for associations between OC use and breast cancer risk, overall and by estrogen and progesterone receptor and HER2 status. OC use was evaluated by status of use (current, former, and never), duration of and time since last use independently and cross-classified, and formulation (i.e., estrogen and progestin type). RESULTS: Current OC use was associated with higher risk of invasive breast cancer (HR 1.31 (95% CI 1.09-1.58), vs. never use), with stronger associations with longer duration of current use (>5 years, 1.56 (1.23-1.99); ≤5 years, 1.19 (0.95-1.49)). From >5 years since cessation, risk among former and never users was similar (e.g., >5-10 years since cessation, 0.99 (0.88-1.11)). Associations did not differ significantly by tumor subtype. In analyses by formulation, current use of formulations containing levonorgestrel in triphasic (2.83 (1.98-4.03)) and extended cycle regimens (3.49 (1.28-9.53)), and norgestrel in monophasic regimen (1.91 (1.19-3.06); vs. never OC users), all combined with ethinyl estradiol, was associated with higher breast cancer risk. No association was observed with current use of the other progestin types evaluated (norethindrone, norethindrone acetate, ethynodiol diacetate, desogestrel, norgestimate, and drospirenone), though sample sizes were relatively small for some of the subgroups, limiting these analyses. CONCLUSIONS: Current OC use was associated with higher risk of invasive breast cancer regardless of disease subtype, though risk was comparable to never users 5 years after cessation. In analyses by progestin type, associations were observed for select formulations including levonorgestrel and norgestrel. Assessment of the associations for newer progestin types (desogestrel, norgestimate, drospirenone) was limited by sample size, and further research on more recently introduced progestins is warranted.