Abstract 2244: Accelerated aging associated with cancer characteristics and treatments among breast cancer survivors
Authors: Wang Cong , De Vis Jill B. , Nguyen Kirsten , Jia Brigitte , Alford Mason , Chakravarthy Anuradha Bapsi , Shu Xiao-Ou 
Published: March 2024

Abstract
There are currently approximately four million breast cancer (BC) survivors in the US. BC survivors may experience accelerated aging, with greater physical dysfunction and cognitive decline than cancer-free women, potentially due to the detrimental effects of BC and/or its treatments (Tx). However, the aging trajectory after BC diagnosis has not been fully elucidated. A biological age measure, PhenoAge acceleration (PAA), derived from chronological age and nine clinical blood chemistry biomarkers, has been associated with aging-related health outcomes and mortality in the general population. Our study aims to evaluate PAA among BC patients by clinical characteristics, cancer Tx, and medications (chemotherapy and endocrine therapy drugs). The study included 1264 BC patients (age 54.7±11.7) recruited at Vanderbilt University Medical Center in 2004-2021. BC-related information and lab test results were obtained from the tumor registry and electronic health records. The differences in PAA (ΔPAA) by BC stage, grade, subtype, Tx, and medications at multiple time points were evaluated using linear mixed models, with the time interval between diagnosis and PAA assessments as a natural spline, and its interaction with the exposures under study as covariates. Associations of PAA with Tx and medications were estimated with adjustment for other Tx and medications. At 10 years post-diagnosis, stage III/IV (vs 0) and intermediate- and high- (vs low-) grade BC were associated with a higher PAA of 4.48 (p&lt;0.001), 1.26 (p=0.03), and 1.95 (p=0.001), respectively; triple-negative (vs hormone receptor+/Her2-) BC was associated with a lower PAA (ΔPAA=-1.96, p=0.004). Compared with surgery, alone or with radiotherapy, surgery plus chemotherapy was associated with a higher PAA at 1 year (ΔPAA ranging from 1.96, p=0.03 to 4.61, p&lt;0.001), while surgery plus endocrine therapy was associated with a higher PAA at 10 years post-diagnosis (ΔPAA ranging from 1.70, p=0.04 to 2.75, p=0.006). The associations of PAA with most chemotherapy agents diminished over time, reverting to negative or null at 10 years. Antimetabolites, on the other hand, were associated with an increased PAA at 2 years (ΔPAA=2.62, p&lt;0.001) which increased further at 10 years post-diagnosis (ΔPAA=7.26, p&lt;0.001). Endocrine therapy and PAA association at 10 years post-diagnosis was likely driven by aromatase inhibitors (AI) (ΔPAA=1.53, p&lt;0.001). Selective estrogen receptor modulators were inversely associated with PAA at year 10 (ΔPAA=-1.03, p=0.01). Additional adjustment for BC stage, grade, and subtype did not materially change the results for Tx and medications. Our study found that BC patients had accelerated aging up to 10 years post-diagnosis, especially those with stage III/IV and high/intermediate-grade BC. The aging trajectory varied by cancer Tx and medications; antimetabolites and AI might accelerate aging in long term BC survivors.
Citation Format: Cong Wang, Jill B. De Vis, Kirsten Nguyen, Brigitte Jia, Mason Alford, Anuradha Bapsi Chakravarthy, Xiao-Ou Shu. Accelerated aging associated with cancer characteristics and treatments among breast cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2244.