We thank Dr Zhang and colleagues for their thoughtful commentary on our recent work examining the association between changes in physical activity and cardiovascular disease (CVD) risk among cancer survivors, 1 and welcome the opportunity to further clarify and expand upon our study’s implications.
Our findings raise an important research question regarding the physiological and molecular pathways that mediate the sustained benefits of prediagnosis physical activity. We agree that the residual cardioprotective effect observed among individuals who were active before diagnosis but became inactive afterwards warrants additional mechanistic investigation. Although our claim-based database does not allow biomarker analyses, future prospective cohort studies could systematically measure biological markers at regular intervals to determine and clarify the role of prediagnosis physical activity.
Evaluating the effect size among smaller subpopulations—such as those with hematologic malignancies (eg, lymphoma, multiple myeloma, and leukemia)—was challenging. Our stratified analyses did not reveal a significant association between changes in physical activity and cardiovascular disease, 1 but these findings were likely limited by small subgroup sizes and a lack of detailed treatment-specific data. Given the substantial cardiovascular burden of cancer treatment for these malignancies, further studies targeting cancer types with larger sample sizes are warranted.
We acknowledge the inherent difficulty of promoting sustained behavior change, especially among cancer survivors who may experience fatigue, treatment-related adverse events, and psychosocial stressors. 2 , 3 To address these barriers, structured exercise interventions embedded within oncological care, combined with multidisciplinary support, are needed. 4 Recent evidence suggests that financial incentives and gamification strategies can enhance adherence to physical activity programs. 5 Targeted trials specifically focusing on cancer survivors may yield effective, scalable interventions to improve both short- and long-term cardiovascular outcomes in this growing population.
We hope that our findings will assist clinicians, researchers, and policy makers in developing strategies that integrate exercise and related behavioral interventions into standard oncological care. Through collaborative efforts, we can continue to advance the science of cardio-oncology and improve survivorship outcomes.
Footnotes
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center .
References
1. Jung W., Cho I.Y., Jung J., et al. Changes in physical activity and cardiovascular disease risk in cancer survivors: a nationwide cohort study. JACC CardioOncol. 2024;6:879–889. doi: 10.1016/j.jaccao.2024.09.013.
2. Bellissimo M.P., Canada J.M., Jordan J.H., et al. Physical activity during breast cancer therapy associates with preserved exercise capacity and cardiac function (WF97415) JACC CardioOncol. 2023;5:641–652. doi: 10.1016/j.jaccao.2022.12.011.
3. Cespedes Feliciano E.M., Vasan S., Luo J., et al. Long-term trajectories of physical function decline in women with and without cancer. JAMA Oncol. 2023;9:395–403. doi: 10.1001/jamaoncol.2022.6881.
4. Fanaroff A.C., Orr J.A., Anucha C., et al. A randomized controlled trial of gamification to increase physical activity among black and Hispanic breast and prostate cancer survivors: rationale and design of the ALLSTAR clinical trial. Am Heart J. 2025;280:42–51. doi: 10.1016/j.ahj.2024.10.021.
5. Fanaroff A.C., Patel M.S., Chokshi N., et al. Effect of gamification, financial incentives, or both to increase physical activity among patients at high risk of cardiovascular events: the BE ACTIVE randomized controlled trial. Circulation. 2024;149:1639–1649. doi: 10.1161/CIRCULATIONAHA.124.069531.