Re-Evaluating the Association Between Hormonal Contraception and Breast Cancer Risk

Abstract

This review aims to summarize and assess key studies investigating the relationship between hormonal contraception and breast cancer risk. Approximately two-thirds of breast cancers express the estrogen receptor, and long-term exposure to estrogen is a debated risk factor for breast cancer development. This hypothesis is based on prior studies looking at reproductive risk factors (endogenous estrogen exposure) along with hormone replacement therapy (exogenous hormone exposure). Historically accepted reproductive risk factors include age at menarche, age at first delivery, and parity. Exogenous hormone exposure encompasses both receipt of hormonal contraception and menopausal hormone replacement therapy. This review highlights the reported risks associated with the most common hormonal contraception methods including oral, transdermal, and transvaginal routes. Large observational studies of the past and more recent works are summarized highlighting gaps in knowledge. Several themes emerge: difficulty accounting for well-established risk factors in analyses of epidemiologic studies, challenges determining whether associations between hormonal contraception and breast cancer are due to the exogenous hormones themselves or to increased engagement with the medical system, and discrepancies between statistically significant and clinically significant risk, odds, and hazard ratios. Understanding the strengths and limitations of these studies will help providers in and outside of oncology support women making decisions regarding both cancer risk-reduction and family planning.