Abstract C129: Lifetime cumulative cigarette exposure and young-onset breast cancer risk by subtype in the Young Women’s Health History Study
Authors: Ihenacho Ugonna , Hamilton Ann S. , Mack Wendy J. , Wu Anna H. , Unger Jennifer B. , Pathak Dorothy R. , Hirko Kelly A. , Houang Richard T. , Press Michael F. , Schwartz Kendra L. , Marcus Lydia R. , Velie Ellen M. 
Published: January 2023

Abstract
Few studies have described the association between lifetime smoking exposures and young-onset breast cancer (YOBC) risk by BC subtypes including the human epidermal growth factor receptor 2 (HER2) subtype. This study explored associations between lifetime cumulative cigarette smoking exposure from both secondhand smoke (SHS) and personal smoking exposures and YOBC risk, overall and by BC subtype. Data are from the Young Women’s Health History Study, a population-based, case-control study of BC in non-Hispanic Black and White women 20-49 years of age. Invasive BC cases were identified in the Los Angeles County and Metropolitan Detroit Surveillance, Epidemiology, and End Results (SEER) registry areas, 2010-2015 (n=1,812). Controls were identified through area-based sampling and frequency matched to cases by study site, race and age (n=1,381). Lifetime cumulative cigarette exposure (LCCE) was categorized as no personal or SHS exposure, only SHS exposure in childhood, only SHS exposure in adulthood, SHS exposure in childhood & adulthood, and ever personally smoked (with or without SHS exposure). BC subtypes were defined as Luminal A, Luminal B, HER2-type, and triple negative (TN) BC. We conducted multivariable adjusted sample-weighted logistic regression analysis to estimate the association between LCCE and YOBC risk among all participants and then among women who never personally smoked by duration of SHS exposure (&lt;15 and ≥15 years). We also conducted adjusted polytomous logistic regression analyses and the Wald test to assess heterogeneity by BC subtype. Lifetime cumulative SHS exposure only was reported by 42% of participants, and an additional 37% reported personally smoking. In adjusted models, compared to no SHS, LCCE was not significantly associated with overall YOBC risk. Suggestive differences in YOBC risk by BC subtype were observed, however (P heterogeneity=0.04), with a suggestive increased odds of HER2-type BC with ever smoking (adjusted odds ratio [aOR] 1.61; 95% confidence interval [CI] 0.91, 2.86). Among participants who never smoked, duration of childhood SHS exposure was associated with differences in YOBC risk by subtype (P heterogeneity=0.01); childhood SHS exposure of ≥15 years compared to no childhood SHS was associated with a significantly decreased odds of HER2-type BC (aOR 0.31; 95% CI 0.12, 0.83) and a suggestive increased odds of TNBC (aOR 1.43; 95% CI 0.95, 2.16) while childhood SHS exposure of &lt;15 years compared to no childhood SHS was associated with a suggestive decreased odds of Luminal A BC (aOR 0.74; 95% CI 0.54, 1.03); the latter two findings did not reach statistical significance. Our results suggest that LCCE is associated with differences in risk of YOBC by BC subtype where personal cigarette smoking may be associated with an increased risk for HER2 type YOBC while childhood SHS exposure for ≥15 years may be associated with a decreased risk of HER2 type YOBC and an increased risk of TN YOBC. These findings warrant further examination.
Citation Format: Ugonna Ihenacho, Ann S. Hamilton, Wendy J. Mack, Anna H. Wu, Jennifer B. Unger, Dorothy R. Pathak, Kelly A. Hirko, Richard T. Houang, Michael F. Press, Kendra L. Schwartz, Lydia R. Marcus, Ellen M. Velie. Lifetime cumulative cigarette exposure and young-onset breast cancer risk by subtype in the Young Women’s Health History Study [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C129.