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Purpose <p>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.</p> Methods <p>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 &lt; 18&#xa0;years and young-onset BC (diagnosed ages 20 to &lt; 50&#xa0;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&#xa0;months before diagnosis, waist circumference at interview) was evaluated as a mediator of these associations using weighted path analyses.</p> Results <p>ACEs (≥ 1 vs 0) were not significantly associated with young-onset BC (all p<sub>trend</sub> &gt; 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, <i>death of a loved one</i> (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 &lt; 0.01) tumors, with adiposity mitigating this association for luminal A tumors&#xa0;(β = -0.01, p = 0.04; TN β = 0.00, p &gt; 0.05).</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月26日

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  • Lydia Marcus Post,
  • Young Ik Cho,
  • James Topitzes,
  • DPhuong Do,
  • Dorothy R. Pathak,
  • Ann S. Hamilton,
  • Amani M. Nuru-Jeter,
  • Kelly A. Hirko,
  • Jamila L. Kwarteng,
  • Richard Houang,
  • Ann G. Schwartz,
  • Ellen M. Velie

摘要

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 ptrend > 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.