Combined effect of oral contraceptive use and hormone replacement therapy on breast cancer risk in postmenopausal women

Objective: We examined breast cancer risk related to lifetime exposure to oral contraceptives (OCs) and hormone replacement therapy (HRT) in postmenopausal women. Methods: The Women's Contraceptive and Reproductive Experiences (CARE) Study was a population-based case–control study that included 1847 postmenopausal women with incident invasive breast cancer, and 1932 control subjects, identified using random digit dialing. Results: 45% of cases and 49% of controls used both OCs and HRT. OC users were not at increased risk regardless of subsequent HRT exposure. HRT users who had used OCs previously did not have a higher risk of breast cancer than women with no exposure to OCs. We observed a negative interaction (p-value: 0.032) of combined hormone replacement therapy (CHRT) and past OC use. The increase in risk with CHRT was stronger in women who had never used OCs in the past (odds ratio: 1.05; 95% confidence interval: 1.01–1.10 per year of exclusive CHRT use) than in women who had used OCs (odds ratio: 1.00; 95% confidence interval: 0.97–1.03). Conclusions: We found no indication that adverse effects of exposure to OCs or HRT appeared only in the presence of the other hormone or were exacerbated by exposure to the other hormone.