Abstract
BACKGROUND: Gynecologic surgery is hypothesized to reduce risk of breast cancer; however, associations may be modified by subsequent hormone use. Our objective was to examine the association between gynecologic surgery and breast cancer incidence considering the use of hormone therapy. METHODS: The Sister Study is a prospective cohort of initially breast cancer-free women aged 35-74 years with a sister who had breast cancer. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between gynecologic surgery (no surgery, hysterectomy only, bilateral oophorectomy with or without hysterectomy) and incident breast cancer among 50 701 women. RESULTS: History of gynecologic surgery was common, with 13.8% reporting hysterectomy only and 18.1% reporting bilateral oophorectomy with or without hysterectomy. During follow-up (median = 11.4 years), 3948 cases were diagnosed. Compared with no surgery, bilateral oophorectomy was inversely associated with breast cancer (HR = 0.91, 95% CI = 0.83 to 1.00), and hysterectomy alone was positively associated (HR = 1.12, 95% CI = 1.02 to 1.23). Compared with no surgery and no hormone therapy, bilateral oophorectomy combined with estrogen only therapy (HR = 0.83, 95% CI = 0.74 to 0.94) was inversely associated with breast cancer, while hysterectomy combined with estrogen plus progestin therapy was positively associated with breast cancer (HR = 1.25, 95% CI = 1.01 to 1.55). CONCLUSIONS: We observed an inverse association between bilateral oophorectomy and breast cancer risk. The positive association between hysterectomy and breast cancer may be due to concomitant estrogen plus progestin therapy.