Tailored Exercise Strategies and Mortality Among Breast Cancer Survivors.

Importance: Guidelines recommend tailored (ie, individualized) exercise strategies for cancer survivors. However, there are limited data on the effects of these strategies on long-term mortality outcomes among breast cancer survivors. Objective: To estimate the effect of tailored exercise strategies on mortality for breast cancer survivors. Design, Setting, and Participants: In this cohort study, a target trial protocol was first specified to approximately mirror the Colon Health and Lifelong Exercise Change (CHALLENGE) trial among breast cancer survivors. Observational data from the Pathways Study were used to emulate this first target trial. These results were then extended by emulating a second target trial of more pragmatic, tailored exercise strategies applied to a broader population of breast cancer survivors. Women enrolled in the Kaiser Permanente Northern California health plan were recruited from January 2006 to December 2013, and were followed up through December 2021. Analyses were performed between September 2024 and September 2025. Exposures: Tailored exercise strategies adaptively modified based on evolving characteristics. Main Outcomes and Measures: All-cause and breast cancer-specific mortality. Results: In the first target trial, there were 959 eligible women (mean [SD] age, 58.3 [12.5] years) and 183 deaths. Compared with a strategy similar to the health education intervention of the CHALLENGE trial, an aerobic exercise strategy was associated with an 8.0 (95% CI, 3.4-13.3)-percentage point lower 8-year all-cause mortality risk, which was compatible with the CHALLENGE trial (7.1 [95% CI, 1.8-12.3]-percentage point lower risk). In the second target trial, there were 2107 eligible women (mean [SD] age, 60.1 [12.1] years) and 321 deaths. Estimated 10-year all-cause mortality ranged from 18.1% to 21.2%. Breast cancer-specific mortality ranged from 7.6% to 10.0%. Compared with no intervention, engaging in a tailored strategy requiring an increase of 60 minutes of vigorous or 120 minutes of moderate aerobic exercise per week was associated with a 3.1 (95% CI, 2.0-4.6)-percentage point lower 10-year all-cause mortality risk and a 2.4 (95% CI, 1.2-3.5)-percentage point lower 10-year breast cancer-specific mortality risk. Conclusions and Relevance: In this cohort study using a target trial emulation design, tailored exercise strategies were associated with reductions in 10-year mortality among breast cancer survivors. A randomized trial is warranted to confirm these findings.