IMPORTANCE: Women with a history of breast cancer (BC) experience greater physical health decline compared with age-matched women without cancer. However, whether this decline differs in patients who received chemotherapy and endocrine therapy is not well understood. OBJECTIVE: To investigate physical health decline in BC survivors who received chemotherapy or endocrine therapy compared with age-matched women without cancer. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was conducted as part of the Cancer Prevention Study-3, a prospective US cohort study that enrolled participants in 35 states, the District of Columbia, and Puerto Rico between 2006 and 2013. Follow-up for this analysis was through April 1, 2020. Statistical analyses were conducted between May 2023 and December 2024. Female participants diagnosed with nonmetastatic BC who returned a survey at least 90 days after their diagnosis were matched on age and year of survey return with up to 5 women without cancer. EXPOSURE: Cancer status and treatment information. MAIN OUTCOMES AND MEASURES: Outcomes of interest were measures of physical health, assessed using the Patient-Reported Outcomes Measurement Information System Global Health Scale instrument. Linear regression was used to estimate associations (β) and 95% CIs of treatment with physical health. RESULTS: This analysis included 2566 individuals diagnosed with BC and 12 826 age-matched women without cancer. Median (IQR) age at diagnosis was 56.3 (49.9-61.9) years. Of women with BC, 1223 (47.7%) received endocrine therapy, 276 (10.8%) received chemotherapy, and 634 (24.7%) received both. Compared with women without cancer, there was a greater physical health decline within 2 years of diagnosis for BC survivors receiving endocrine therapy (β = -1.12
95% CI, -1.64 to -0.60), chemotherapy (β = -3.13
95% CI, -4.19 to -2.07), or both (β = -3.26
95% CI, -3.97 to -2.55). The decline among endocrine therapy users was restricted to women receiving aromatase inhibitors. More than 2 years after diagnosis, the decline was only observed in women who received chemotherapy. CONCLUSIONS AND RELEVANCE: In this cohort study of 15 392 BC survivors and age-matched women without cancer, BC survivors who received chemotherapy had a long-lasting physical health decline, unlike survivors who received endocrine therapy without chemotherapy. Further studies are needed to confirm these results and to better understand the health consequences of these treatments.