Menopausal Hormone Therapy and Subsequent Risk of Specific Invasive Breast Cancer Subtypes in the California Teachers Study

Abstract

Although it is well established that combined estrogen-progestin therapy (EPT) increases breast cancer risk, questions remain regarding the effect of different formulations of hormones, whether certain women are at particularly high risk, and whether risk varies by tumor subtype. We investigated hormone therapy (HT) use in relation to breast cancer risk in the California Teachers Study cohort; after a mean follow-up of 9.8 years, 2,857 invasive breast cancers were diagnosed. Compared with women who had never used HT, women who reported 15 or more years of estrogen therapy (ET) use had a 19% greater risk of breast cancer (95% confidence interval, 1.03-1.37), whereas women using EPT for 15 or more years had an 83% greater risk (95% confidence interval, 1.48-2.26). Breast cancer risk was highest among women using continuous combined EPT regimens. Risks associated with EPT and ET use were increased with duration of HT use for women with a body mass index (BMI) of <29.9 kg/m(2) but not for women with BMI of >or=30 kg/m(2). Elevated risks associated with EPT and ET use were confined to tumors that were positive for both estrogen and progesterone receptors and those that were HER2+ but were slightly diminished for HER2- tumors. Breast cancer risks increased with longer duration of ET and EPT use, and risks were highest for continuous-combined EPT use. Furthermore, risks varied by BMI and tumor subtype. These findings underscore the need for personalized risk-benefit discussions with women contemplating HT use.