Exercise is a promising strategy associated with improved cancer-related outcomes through multiple biological mechanisms. However, current exercise guidelines largely adopt a one-size-fits-all approach and overlook inter-individual variability in response. Given the heterogeneity of breast cancer, precision exercise prescriptions may better target biological pathways linked to therapeutic efficacy and long-term prognosis. Observational studies consistently show that higher physical activity levels are associated with improved survival outcomes, including reduced all-cause and breast cancer-specific mortality. In contrast, evidence from interventional trials remains limited and inconsistent, with effects on tumour response and survival largely derived from secondary or exploratory analyses. These discrepancies likely reflect differences in study design, exercise dose, adherence and treatment-related factors, and may indicate that null findings are partly attributable to an insufficient or inconsistent exercise stimulus rather than a true biological non-response. Exercise influences key pathways involved in tumour progression and treatment response, including immune function, inflammation, metabolism, tumour perfusion and the gut microbiome. As these responses may vary according to tumour subtype, treatment context and host characteristics, a uniform approach to exercise prescription may fail to optimise its therapeutic potential. This review proposes a precision exercise framework that integrates tumour, treatment and patient-specific factors such as genetic and epigenetic profiles, metabolic status and body composition, systemic inflammation and the gut microbiome to guide precision exercise strategies. It also highlights the potential of digital tools, including wearable technologies and artificial intelligence, to enable data-driven personalisation and real-time adaptation, alongside key considerations for safe clinical implementation. While this framework is supported by biological plausibility, whether variability in these upstream biological responses translates into differences in cancer-related outcomes remains unknown. As such, this approach remains hypothesis generating. Future research should focus on adequately powered trials and mechanistic studies to determine whether precision exercise can meaningfully improve cancer-related outcomes in breast cancer.
Crespo-Garcia et al. (Tue,) studied this question.