Adverse childhood experiences, adult adiposity, and risk of young-onset breast cancer subtypes in a population-based case-control study

Purpose Adverse childhood experiences (ACEs) are hypothesized to increase breast cancer risk via social and physiological pathways, yet associations between ACEs and young-onset breast cancer (BC) subtypes–and potential mediators (e.g., adiposity) of these associations–are largely unstudied. We sought to evaluate associations between ACEs and young-onset BC molecular subtypes, and the potential mediating effects of adiposity, in a population-based case–control study of invasive young-onset BC. Methods Cases (n = 1,754) were identified from the Los Angeles County and Metropolitan Detroit SEER registries, 2010–2015, and area-based, frequency-matched controls (n = 1,350) sampled from the 2010 Census. Associations between ACEs aged < 18 years and young-onset BC (diagnosed ages 20 to < 50 years), overall and by subtype (luminal A, luminal B, HER2 + , triple negative [TN]), were examined using weighted logistic regression. Adult adiposity (i.e., body mass index 12 months before diagnosis, waist circumference at interview) was evaluated as a mediator of these associations using weighted path analyses. Results ACEs (≥ 1 vs 0) were not significantly associated with young-onset BC (all p trend > 0.10); however, reporting one ACE (vs 0) was associated with TN (odds ratio [OR] = 1.85 [95% confidence interval [95%CI] = 1.08–3.16]). For individual ACEs, death of a loved one (vs 0 ACEs) was associated with HER2 + (OR = 2.50 [95%CI = 1.06–5.88]) and potentially TN (OR = 1.72 [95%CI = 0.96–3.10]) young-onset BC; other associations were non-significant. In path analyses, ACEs had a significant total effect on luminal A (β = 0.08, p = 0.03) and TN (β = 0.13, p < 0.01) tumors, with adiposity mitigating this association for luminal A tumors (β = -0.01, p = 0.04; TN β = 0.00, p > 0.05). Conclusions Bereavement during childhood was associated with higher odds of HER2 + young-onset BC, and there was some evidence of an association between ACEs and other young-onset BC subtypes, particularly TN.