Reference
Soldato D, Michiels S, Havas J, et al. Dose/exposure relationship of exercise and distant recurrence in primary breast cancer. J Clin Oncol. 2024;42(25)3022-3032.
Study Objective
To evaluate the impact and dose-response relationship of exercise and distant recurrence in patients with primary breast cancer
Key Takeaway
Moderate exercise at the time of breast cancer diagnosis is associated with a lower risk of distant recurrence, particularly for premenopausal women with hormone receptor–negative subtype tumors.
Design
Multicenter, prospective cohort analysis
Participants
The study included 10,359 female patients diagnosed with stage I to III breast cancer at 26 institutions in France. The mean age was 56.3 ± 11.2 years. At diagnosis, 38.7% were premenopausal, and 61.3% were menopausal; 57.1% of participants adhered to the World Health Organization (WHO) recommendations for exercise, and 42.9% did not.
Intervention
Investigators enrolled patients between 2012 and 2018 and followed them until October 2021.
Study Parameters Assessed
Investigators assessed patients at time of diagnosis and then 1, 2, 4, and 6 years post treatment. At each assessment, subjects received a physical activity questionnaire that looked at exercise intensity, from which investigators calculated a metabolic equivalent of task (MET). The questionnaire also looked at frequency and duration of exercise, from which investigators calculated a total MET-hours/week.
Primary Outcome
The primary outcome this study assessed was distant recurrence-free interval (DRFI).
Key Findings
During the period of this study, 5-year DRFI was statistically significantly improved in the following subcohorts:
Hormone receptor–negative (HR–)/human epidermal growth factor receptor 2–negative (HER2–): The 5-year DRFI was 86.6% for less than 5 MET-h/week vs 91.6% for greater than or equal to 5 MET-h/week, with a hazard ratio (HR) of 0.60 (95% CI).
HR–/HER2+: The 5-year DRFI was 90.0% for less than 5 MET-h/week vs 96.2% for greater than or equal to 5 MET-h/week, with a HR of 0.37 (95% CI).
Premenopausal cohort: For the entire cohort, the 5-year DRFI was 93.1% for less than 5 MET-h/week vs 95.4% for greater than 5 MET-h/week, with a HR of 0.64 (95% CI). In the premenopausal cohort, investigators observed a higher magnitude of benefit in the HR–/HER2– subtypes.
No significant relationship was found between exercise and DRFI in the postmenopausal cohort or for HR+ tumors.
Transparency
This study was primarily funded by the French government under the Investment for the Future program, as well as the Prism project and the MyPROBE Program.
Authors also received support from Odysséa, Foundation Gustave Roussy, Career Pathway Grant in Symptom Management from Conquer Cancer, American Society of Clinical Oncology (ASCO), the Rising Tide Foundation for Clinical Cancer Research, the Fondation ARC pour la Recherche sur le Cancer, the Breast Cancer Research Foundation, the National Cancer Institute, AKTIV Against Cancer, the Kavli Trust, and the Memorial Sloan Kettering Cancer Center Support Grant/Core Grant.
Practice Implications & Limitations
This study asks 2 important questions: Does exercise decrease the likelihood of distant recurrence of breast cancer? And if so, how much is optimal? The authors’ observations are somewhat surprising. The first interesting outcome of this study is that the impact of exercise on distant recurrence differs between subgroups of women. In this cohort, increased exercise improved the DRFI only in women with hormone receptor–negative (HR–) subtype tumors. Additionally, the benefit of exercise on DRFI was found only in premenopausal, but not postmenopausal, women. The other interesting outcome of this study is that it found an inverse association between amount of exercise and recurrence rate but only up to a certain threshold of exercise—with no additional benefit for those who exercised more and only for those who exercised at the time of diagnosis.
So, how do we use this data in clinical practice? Does this mean that we tell our postmenopausal, hormone receptor–positive breast cancer patients and survivors who didn’t pick up an exercise regimen until later to forget it and just retire to the couch? Even with these surprising data about exercise and recurrence rate, there is no question that exercise is beneficial for women who have been diagnosed with breast cancer. The first great reason to recommend moderate exercise to our patients is decreased mortality rates from breast cancer and all-cause mortality,1,2,3 as well as increased survival time for women diagnosed with stage IV breast cancer.4
Exercise can also improve the efficacy of cancer therapy, as well as recovery. Regular exercise has been shown to reduce cancer-related fatigue.5,6 Postsurgical exercises are crucial to retain mobility, promote healing, and prevent lymphedema, as well as reduce postsurgical pain.7 Possibly the biggest impact of exercise in breast cancer survivors is maintenance and improvement of physical fitness and quality of life.8-11 It can decrease fatigue and depression and improve sleep.12 Not only is exercise useful for improving quality of life and mental health during chemotherapy,13 but women going through chemotherapy for breast cancer who were assigned to a home-based nutrition and exercise program were also more likely to have a pathologically complete response to their treatment regimen.14
The benefits of exercise, of course, extend beyond cancer specifically, to improving the overall health of breast cancer survivors. Exercise improves metabolic syndrome and cardiovascular health markers, which can be significant concerns for all postmenopausal women but particularly for breast cancer survivors.5,15 Survivors who exercise moderately show increased lean muscle mass, decreased adipose tissue, and decreased insulin and leptin.9,16 Exercise can also decrease bone loss related to breast cancer treatment in premenopausal women.17
So what is the ideal amount of exercise for women diagnosed with breast cancer? In this study, the amount of exercise necessary to show a significant decrease in distant recurrence starts at 5 MET-h/week and extends to 25 MET-h/week, with no additional benefit beyond this amount. For our patients who aren’t used to exercise or have trouble with movement, this is good news. Five MET-h/week is equivalent to walking 2 mph for 15 min/day, 5 days/week, an amount achievable by almost any mobile person. For patients who were active before diagnosis or who are very motivated to do everything they can to prevent recurrence, they may find that adding intensity or duration to their workouts may be unnecessary, since 25 MET-h/week is equivalent to walking 4 mph for 60 min/day, 5 days/week, or running 6 mph for 30 min/day, 5 days per week.18
This study is 1 example of several that show that there is benefit up to a certain amount of exercise each week, with little benefit beyond the upper limit of that window. WHO states that there is a decrease in all-cause mortality for breast cancer survivors with up to 10 to 15 MET-h/week, or 150 minutes of moderate-to-vigorous exercise each week.3 A large meta-analysis found a similar optimal benefit window for all-cause mortality as well as breast cancer–specific mortality, with greater benefit for those who exercise postdiagnosis rather than prediagnosis.1 Also, a cohort of nearly 80,000 breast cancer survivors showed decreased all-cause mortality for those who ran or walked at least 7.5 MET-h/week.2
So the bottom line is: Advise your patients to exercise regularly before, during, and after breast cancer treatment. It’s critical for mental health, improves overall health, and decreases all-cause and cancer-specific mortality rates in women with breast cancer. Exercise has the added benefit of decreasing distant recurrence rates in premenopausal women with hormone receptor–negative tumors. But you can also let your patients know that more isn’t always better, and they can derive benefit from even small amounts of exercise. For women who are not active at the time of diagnosis, even adding a short, slow walk each day will make a significant difference. For women who are already active, letting them know there is an upper ceiling of potential benefit from exercise can help ease anxiety about how much they need to do.
