Abstract 623: Epigenetic age acceleration measures and chemotoxicity in older adults with early breast cancer

Abstract Background: Older adults with early breast cancer can have very different risks of chemotoxicity despite similar chronological age. This heterogeneity may be due to differences in biological age. However, few studies have evaluated whether epigenetic indicators of biological age can stratify the risk of chemotoxicity in older adults with early breast cancer. Methods: In a prospective multicenter study of 394 adults age >65 with stage I-III breast cancer treated with neo/adjuvant chemo, we analyzed DNA methylation patterns from peripheral blood to estimate epigenetic age acceleration (EAA) prior to chemo. We tested three generations of epigenetic age algorithms (1st gen: Horvath and Hannum; 2nd gen: PhenoAge and GrimAge; 3rd gen: DunedinPACE). We calculated EAA as the residual that results from regressing epigenetic age on chronological age. The primary endpoint was grade 2+ chemotoxicity (yes/no, yes defined as any grade 2+ toxicity attributed to chemo). Using multivariable logistic regression, we examined the association between EAA (analyzed as continuous and categorical [quartiles] variables) and grade 2+ chemotoxicity, adjusting for demographic, geriatric, and clinical covariates. Results: The median (range) pre-treatment chronological age was 70 (65-85), 65% had stage II/III disease, 38% had anthracycline, and 75% received G-CSF prophylaxis. A total of 334 (84.8%) participants experienced a grade 2+ toxicity. After adjusting for age, cell composition, stage, race/ethnicity, education, regimen, organ function, and geriatric assessment variables, there was no significant association between the measures of EAA and grade 2+ chemotoxicity (Table). Conclusions: In this cohort of older adults with early breast cancer, there was no significant association between pre-treatment EAA and grade 2+ chemotoxicity. Further research is needed to examine how measures of biological age can be translated to the clinical care of older patients with breast cancer. Citation Format: Jingran Ji, Canlan Sun, Marla Lipsyc-Sharf, Nikita V. Baclig, Yulia A. Zektser, Ali Al Saleem, Joseph D. Olivera, Kelly S. Synold, Lauren R. Zelman, Alexandra M. Binder, Mina S. Sedrak. Epigenetic age acceleration measures and chemotoxicity in older adults with early breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 623.