Impact of lifestyle and chemotherapy on functional aging trajectories in older breast cancer survivors and matched comparators

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), repeated RAND SF-36 physical function scores (0-100) were compared among women with localized (n=6462) or regional breast cancer (n=1972) to age-matched, cancer-free comparators (n=37 196) over 15 years. Effect modification was tested by treatment (including agent class), age, and prediagnosis lifestyle (diet, physical activity, and smoking). Physical performance (grip strength, walking pace) was evaluated in a subset of 1045 survivors and 1970 comparators. Survivors experienced acute postdiagnosis declines, followed by incomplet recovery leading to a persistent SF-36 deficit relative to age-matched comparators. Regional disease showed larger deficits (-6.8 at year one; -5.3 at year ten), with the steepest early declines among chemotherapy recipients (-7.1 at year one), consistent across agents. Grip strength and walking pace showed similar trends. 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. The authors conclude that breast cancer, especially with chemotherapy, was associated with durable functional deficits among older women, while healthier prediagnosis lifestyles were associated with greater functional reserve and better recovery trajectories.