Progestin-only and combined oral contraceptives and receptor-defined premenopausal breast cancer risk: The Norwegian Women and Cancer Study

Receptor-defined subtypes of breast cancer represent distinct cancer types and have differences in risk factors. Whether the two main hormonal forms of oral contraceptives (OCs); i.e. progestin-only (POC) and combined oral contraceptives (COC), are differentially associated with these subtypes are not well known. The aim of our study was to assess the effect of POC and COC use on hormone receptor-defined breast cancer risk in premenopausal women in a prospective population-based cohort - The Norwegian Women and Cancer Study (NOWAC). Information on OC use was collected from 74,862 premenopausal women at baseline. Updated information was applied when follow-up information became available. Multiple imputation was performed to handle missing data, and multivariable Cox regression models were used to calculate hazard ratios (HR) for breast cancer. 1,245 incident invasive breast cancer cases occurred. POC use 5 years was associated with ER+ (HR=1.59, 95% CI 1.09- 2.32, p(trend)=0.03) and ER+/PR+ cancer (HR=1.63, 95% CI 1.07-2.48, p(trend)=0.05), and was not associated with ER- (p(heterogeneity)=0.36) or ER-/PR- (p(heterogeneity)=0.49) cancer. COC use was associated with ER- and ER-/PR- cancer, but did not increase risk of ER+ and ER+/PR+ cancer. Current COC use gave different estimates for ER/PR-defined subtypes (p(heterogeneity)=0.04). This is the first study to show significant associations between POC use and hormone receptor-positive breast cancer. The lack of power to distinguish effects of POC use on subtype development calls for the need of larger studies to confirm our finding. What's new? Use of combined oral contraceptives (COC) is associated with an increased risk of breast cancer and, predominantly, its hormone receptor-negative subtypes. Whether progestin-only contraceptives (POC) are also associated with elevated risk of receptor-defined subtypes of breast cancer is unknown. In this prospective, population-based study in Norway, POC use for five or more years was associated with estrogen receptor-positive and estrogen receptor-positive/progesterone receptor-positive but not estrogen receptor-negative or estrogen receptor-negative/progesterone receptor-negative breast cancer subtypes in premenopausal women. The associations contrast with those found for COC use, suggesting that estrogen and progestin serve dissimilar roles in subtype carcinogenesis.