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

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.