Do Combined Resistance and Aerobic Exercise Programs Cause an Interference Effect in Women with Breast Cancer? A Systematic Review and Network Meta-analysis

BACKGROUND: Exercise medicine has gained significant recognition owing to its demonstrated benefits throughout the breast cancer treatment continuum. While resistance exercise (RE) promotes improvements in lean mass and muscle strength, aerobic exercise (AE) enhances cardiorespiratory fitness, with several studies investigating both exercise modes in patients with breast cancer. However, because of an effect often referred to as interference effect, it is hypothesised that combining resistance and aerobic exercise (COMB) may compromise gains in lean mass and muscle strength and other outcomes in cancer populations. OBJECTIVE: This study aims to investigate the presence of an interference effect from prescribing COMB compared with RE on fatigue, lean mass, physical function and muscle strength in women with breast cancer. In addition, it examines a range of demographic, clinical and exercise prescription moderators within this population. METHODS: We searched seven databases from inception to January 2024 (PROSPERO CRD42023491118), with an updated search in April 2025. Eligible trials examined the effects of RE, AE and/or COMB in women diagnosed with breast cancer. The primary outcomes for this review were cancer-related fatigue, lean mass, physical function and/or lower-limb muscle strength. A random-effects network meta-analysis was undertaken to examine the effect of different exercise programs and controls, with specific focus on the comparisons between RE and COMB. Differences between RE and COMB above 0.20 standardised mean difference (SMD) were an indicative of a potential interference effect. RESULTS: We included a total of 131 articles describing 116 randomised trials (n = 9206). Both RE (SMD - 0.52, 95% CI - 0.83 to - 0.21, p = 0.001) and COMB (SMD - 0.47, 95% CI - 0.65 to - 0.29, p < 0.001) similarly reduced fatigue compared with controls. However, a potential interference effect was observed on fatigue during surgery (SMD - 0.23, 95% CI - 0.58 to 0.12, p = 0.191) and chemotherapy (SMD - 0.22, 95% CI - 0.59 to 0.16, p = 0.257), with RE showing greater benefits than COMB. For physical function, both RE (SMD 0.86, 95% CI 0.41-1.30, p < 0.001) and COMB (SMD 0.90, 95% CI 0.58-1.22, p < 0.001) improved outcomes compared with controls, though RE was superior to COMB in patients receiving hormone therapy (SMD 0.62, 95% CI - 0.56 to 1.81, p = 0.303). Differences between RE and COMB in lean mass (MD 0.18 kg, 95% CI - 0.17-0.53 kg, p = 0.303) and muscle strength (SMD 0.43, 95% CI - 0.01-0.86, p = 0.056) were not significant in the main analyses; however, sensitivity analyses omitting the outliers indicated significant differences favouring RE for lean mass (MD 0.36 kg, 95% CI 0.15-0.57 kg, p < 0.001) and muscle strength (SMD 0.40, 95% CI 0.08-0.71, p = 0.014). CONCLUSIONS: Our findings emphasise the importance of personalised exercise medicine targeted to treatment characteristics in women with breast cancer. While COMB may offer benefits across the outcomes investigated, prescribing RE alone may be preferable to minimize potential interference effects on lean mass and muscle strength, regardless of demographic, clinical and exercise prescription characteristics, as well as fatigue and physical function tests, particularly during adjuvant and hormonal therapies.