Education level and risk of breast cancer by tumor subtype in the EPIC cohort

Abstract

Breast cancer (BC) is a heterogeneous disease with subtypes based on receptor status (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor 2 [HER2]), influencing prognosis and treatment. A higher socioeconomic position (SEP) is associated with an increased BC risk, but its relation to BC subtypes is less clear. This study analyzed 311,631 women from the EPIC cohort, focusing on the incidence of in situ and invasive BC (overall and by receptor status and subtype). Educational attainment was used as a proxy for SEP, and hazard ratios (HRs) were calculated using Cox regression models. Mediation analyses were performed to evaluate the extent to which selected risk factors explained the educational gradient. Over 14 years, 14,432 BC cases were identified, including 12,863 invasive cases. Lower education was associated with a reduced risk of both in situ and invasive BCs. The HRs for primary versus tertiary education were 0.61 (95% CI 0.49-0.73) for in situ and 0.81 (95% CI 0.75-0.87) for invasive BC overall, with similar reductions across ER-positive, PR-positive, HER2-positive, Luminal A, BH-, and BH+. No significant association was found between education and ER-negative, and HER2-enriched BCs. Reproductive and lifestyle factors explained 20-40% of the educational differences in BC risk. While many of the risk factors through which education impacts the development of subtype-specific BC were identified, others remain to be fully elucidated. Differences in screening attendance could partially explain the higher ER-positive BC risk among highly educated; this study further contributes to the understanding of the complex nature of BC in terms of its social gradient and aetiology.

Keywords: breast cancer risk; education level; estrogen receptor; molecular subtypes.