Lifestyle and chemotherapy shape functional aging trajectories in older breast cancer survivors and matched...

Breast cancer and its treatment may contribute to premature aging, but long-term evidence regarding risk factors for functional decline is limited among the growing population of older survivors.

In the Women's Health Initiative (n = 45 530; median age at index or diagnosis = 72 years), we compared repeated RAND Short Form 36 (SF-36) physical function scores (0-100) among women with localized (n = 6462) or regional breast cancer (n = 1872) to age-matched, cancer-free comparators (n = 37 196) over 15 years. We tested effect modification by treatment (including agent class), age, and prediagnosis lifestyle behaviors (diet, physical activity, and smoking). Physical performance (grip strength, walking pace) was evaluated in a subset (1045 survivors; 1970 comparators).

Survivors experienced acute postdiagnosis declines followed by incomplete recovery leading to a persistent SF-36 deficit relative to age-matched comparators. Regional disease showed larger deficits (-6.8 at year 1; -5.3 at year 10), with the steepest early declines among chemotherapy recipients (-7.1 at year 1), consistent across agents. Grip strength and walking pace showed trends similar to SF-36 deficits. Deficits relative to cancer-free comparators were greater and sustained among older individuals, whereas those aged younger than 70 years showed lesser differences after an early postdiagnosis drop. Among women with lower-risk lifestyle, survivors remained lower than comparators early after diagnosis but showed greater recovery over time; women with higher-risk lifestyles had persistently lower function overall with lesser differences by cancer status.

Breast cancer, especially with chemotherapy, was associated with durable functional deficits among older women. Healthier prediagnosis lifestyles are associated with greater functional reserve and better recovery trajectories, suggesting intervention targets for aging survivors.