From sedentary to survival: exercise intervention as a precision supportive care strategy in triple-negative breast cancer—a scoping review

Abstract

Triple-negative breast cancer (TNBC) carries a poor prognosis with limited therapeutic options beyond conventional chemotherapy. This scoping review synthesizes evidence on exercise-induced mechanisms, clinical outcomes, and implementation strategies for patients with TNBC. Exercise appears to engage multiple pathways with potential anti-tumor relevance, including myokine-mediated natural killer cell activation, AMPK/mTOR inhibition, nuclear factor-kappa B suppression, and epigenetic modifications. Emerging evidence suggests that aerobic and resistance training may improve quality of life, reduce cancer-related fatigue, help preserve physical function, and support maintenance of chemotherapy dose intensity in some patient subgroups. In a randomized controlled trial of aerobic and resistance training during neoadjuvant chemotherapy (n = 180), which included hormone receptor-negative patients inclusive of TNBC, both modalities significantly reduced premature chemotherapy discontinuation, with no severe exercise-related adverse events reported in this trial—offering preliminary support for the short-term safety, feasibility, and clinical relevance of supervised exercise during active chemotherapy. Preclinical and translational studies suggest that exercise-induced circulating factors may suppress TNBC cell growth and enhance anti-tumor immunity, though clinical replication in TNBC-specific populations remains limited. The central proposition of this review is that TNBC’s defining molecular vulnerabilities—including immune evasion, constitutive inflammatory signaling, and hyperactivated PI3K/Akt/mTOR signaling—may plausibly align with the biological adaptations induced by exercise, suggesting a subtype-specific mechanistic rationale for exercise in TNBC that could be biologically distinct from hormone receptor-positive disease. However, evidence remains limited for metastatic disease and long-term oncologic outcomes, underscoring the need for TNBC-targeted trials with immune and metabolic biomarkers as primary outcome domains.