Environmental exposures and breast cancer risk in the context of underlying susceptibility: A systematic review of the epidemiological literature

Background: The evidence evaluating environmental chemical exposures (ECE) and breast cancer (BC) risk is heterogeneous which may stem in part as few studies measure ECE during key BC windows of susceptibility (WOS). Another possibility may be that most BC studies are skewed towards individuals at average risk, which may limit the ability to detect signals from ECE. Objectives: We reviewed the literature on ECE and BC focusing on three types of studies or subgroup analyses based on higher absolute BC risk: BC family history (Type 1); early onset BC (Type 2); and/or genetic susceptibility (Type 3). Methods:We systematically searched the PubMed database to identify epidemiologic studies examining ECE and BC risk published through June 1, 2019. Results: We identified 100 publications in 56 unique epidemiologic studies. Of these 56 studies, only 2 (3.6%) were enriched with BC family history and only 11% of studies (6/56) were specifically enriched with early onset cases. 80% of the publications from these 8 enriched studies (Type 1: 8/10 publications; Type 2: 8/10 publications) supported a statistically significant association between ECE and BC risk including studies of PAH, indoor cooking, NO2, DDT; PCBs, PFOSA; metals; personal care products; and occupational exposure to industrial dyes. 74% of Type 3 publications (20/27) supported statistically significant associations for PAHs, traffic-related air pollution, PCBs, phthalates, and PFOSAs in subgroups of women with greater genetic susceptibility due to variants in carcinogen metabolism, DNA repair, oxidative stress, cellular apoptosis and tumor suppressor genes. Discussion: Studies enriched for women at higher BC risk through family history, younger age of onset and/or genetic susceptibility consistently support an association between an ECE and BC risk. In addition to measuring exposures during WOS, designing studies that are enriched with women at higher absolute risk are necessary to robustly measure the role of ECE on BC risk.