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Research Paper|Volume 17, Issue 3|pp 643—656

Accelerated aging associated with cancer characteristics and treatments among breast cancer survivors

Cong Wang1, Jill B. De Vis2, Kirsten Nguyen3, Brigitte Jia3, Mason Alford3, Marjan Rafat2,4,5, Bapsi Chakravarthy2, Xiao-Ou Shu1
  • 1Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37235, USA
  • 2Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN 37235, USA
  • 3Vanderbilt University School of Medicine, Nashville, TN 37235, USA
  • 4Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN 37235, USA
  • 5Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA
Received: July 3, 2024Accepted: February 20, 2025Published: March 7, 2025
https://doi.org/10.18632/aging.206218

Copyright: © 2025 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Breast cancer (BC) survivors may experience accelerated aging due to detrimental effects of BC and/or its treatments. Our study aims to evaluate Phenotypic Age Acceleration (PAA), a biological age measure, among BC patients and assess its associations with cancer characteristics and treatments. In this study including 1264 BC patients (age 54.7±11.7) and 429 cancer-free controls (age 49.9±12.4), we evaluated the differences in PAA (ΔPAA) by BC characteristics and treatments at multiple time points using linear mixed models. Overall, BC survivors had a higher PAA than controls at diagnosis (ΔPAA=3.73, p<0.001), 1-year (ΔPAA=1.68, p=0.001), and 10-year (ΔPAA=1.16, p=0.03) post-diagnosis. At 10-year post-diagnosis, stage III/IV (vs 0), intermediate- and high- (vs low-) grade BC were associated with a higher PAA of 4.48 (p<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 patients receiving surgery with or without radiotherapy, higher PAA was observed at 1-year post-diagnosis among those receiving additional chemotherapy (ΔPAA=4.26, p<0.001) and at 10-year post-diagnosis for endocrine therapy (ΔPAA=2.89, p=0.001). In conclusion, BC patients had accelerated aging up to 10 years post-diagnosis, especially among those with stage III/IV and high/intermediate-grade BC, and receiving systemic treatment.