Abstract 621: Changes in the senescence biomarker p16INK4a among older adults with early breast cancer treated with and without chemotherapy and non-cancer controls

Abstract Background: Our group previously showed that p16INK4a (p16) expression, a biomarker of senescence (a fundamental process of aging), increases after adjuvant breast cancer chemo. However, no study has examined whether this increase in p16 is driven by cancer, chemo, or both. Here, we compare the change in p16 between older adults with early breast cancer who receive chemo, those who do not, and those without cancer. Methods: We prospectively recruited 701 adults age ≥65 with stage I-III breast cancer (composed of three age-matched cohorts: 501 treated with chemo [BC chemo], 100 treated without chemo [BC control]), and 100 without cancer (NC control). Sociodemographic, functional, and clinical characteristics were collected at baseline. The p16 level in peripheral blood CD3+ T lymphocytes was obtained at two time points: ≤14 days pre-chemo (T1) and ≤30 days post-chemo (or at matched time points in the BC and NC control groups, T2). The primary endpoint was the mean ∆p16 level from T1 to T2. Data was analyzed using descriptive statistics, t-tests, and analysis of variance (ANOVA). Results: There were no differences in T1 age, race/ethnicity, education, comorbidities, or functional status across the three groups. At T1, there was no difference in mean p16 levels across the three groups (p=0.06) (Table). At T2, the BC chemo group had a significantly higher mean p16 level compared to the BC and NC control groups (p<0.01). The mean ∆p16 levels from T1 to T2 were significantly different among the three groups (p=0.04). The BC chemo group had a 15% increase in mean ∆p16 from T1 to T2 (p<0.01), while the BC and NC control groups had no significant change. Conclusions: In a cohort of older adults with early breast cancer, the combination of breast cancer and chemo led to increases in p16 levels. Further independent validation of these findings is needed to understand the role of senescence in older adults with early breast cancer treated with chemo. Citation Format: Chaiyaporn C. Vatanatham, Jingran Ji, Canlan Sun, Marla D. Lipsyc-Sharf, Nikita V. Baclig, Yuliya A. Zektser, Ali Al Saleem, Joseph D. Olivera, Kelly S. Synold, Lauren R. Zelman, Hyman B. Muss, Mina S. Sedrak. Changes in the senescence biomarker p16INK4a among older adults with early breast cancer treated with and without chemotherapy and non-cancer controls [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 621.