Exercise During Chemotherapy Fails to Boost Tumor Response Across Cancer Types, Meta-Analysis Finds

Exercise has long been promoted as one of the most powerful tools in cancer care, with mounting evidence that physical activity improves survival, reduces recurrence risk, and eases the punishing side effects of treatment. But a new systematic review and meta-analysis published in Supportive Care in Cancer delivers a sobering reality check: when it comes to one of the most clinically meaningful short-term markers of chemotherapy success, exercise alone may not move the needle across all cancer types. The findings, however, hint at a tantalizing exception that could reshape how oncologists think about exercise prescriptions for specific tumor subtypes.

A team of Portuguese researchers led by Nuno Dias Rato of the University of Maia set out to answer a deceptively simple question: does exercising during neoadjuvant chemotherapy actually help tumors respond better to the drugs? Neoadjuvant chemotherapy, given before surgery, is a standard approach for several cancers including breast, esophageal, gastric, and rectal tumors. The goal is to shrink the tumor before an operation, and the gold standard of success is what oncologists call pathologic complete response, or pCR, the complete disappearance of invasive cancer in tissue examined under the microscope after surgery.

The researchers systematically searched four electronic databases for randomized controlled trials testing physical exercise during neoadjuvant chemotherapy, with studies published through May 2025. They assessed the methodological quality of each trial using the Cochrane Risk of Bias 2.0 tool and the TESTEX scale, which is specifically designed to evaluate exercise training studies. To pool the results, they employed a random-effects meta-analysis using the inverse variance method, quantifying heterogeneity between studies with the I-squared and chi-squared statistics. The effect size was expressed as a risk ratio, comparing the proportion of patients achieving pCR in exercise groups versus control groups.

Eight studies involving 504 patients with breast, esophageal, gastric, or rectal cancer made it into the final analysis. The exercise interventions across these trials consisted of aerobic training, resistance training, or combinations of both, delivered during the chemotherapy period. When the data were pooled, the result was unambiguous: there were no significant differences between the exercise and control groups in the rate of pathologic complete response. The pooled risk ratio was 1.08 with a 95 percent confidence interval spanning 0.82 to 1.43, a Z statistic of 0.56, and a p value of 0.58. In plain terms, exercise during chemotherapy did not improve the likelihood of achieving a complete tumor response across the cancer types studied.

That headline result, however, is not the whole story. When the researchers drilled down into the breast cancer subset, which comprised four studies and 367 participants, the exploratory meta-regression analysis suggested something intriguing. Exercise may be associated with enhanced tumor response to neoadjuvant chemotherapy in patients with hormone receptor-positive, HER2-negative breast cancer, one of the most common molecular subtypes of the disease. The regression coefficient was 0.83 with a confidence interval of negative 0.00 to 1.67 and a p value of exactly 0.05, sitting right at the conventional threshold of statistical significance.

The biological plausibility behind this subtype-specific signal is grounded in a growing body of mechanistic research. Preclinical studies have shown that exercise can suppress tumor growth through epinephrine- and interleukin-6-dependent mobilization of natural killer cells, and that cytotoxic T cells mediate exercise-induced reductions in tumor growth. Human studies have demonstrated that serum drawn after acute exercise can reduce cancer cell proliferation in laboratory settings. For hormone receptor-positive breast cancers in particular, exercise is known to influence sex steroid hormones, which drive tumor proliferation in this subtype, offering a plausible pathway by which physical activity might sensitize these tumors to chemotherapy.

The authors themselves urge caution in interpreting these findings. The meta-regression result comes from a small number of studies, and the certainty of the evidence was rated as low. The confidence interval for the regression coefficient barely touches the null value, meaning the association could plausibly reflect chance rather than a true biological effect. With only eight trials and 504 patients spread across four different cancer types, the analysis was never powered to detect subtle subtype-specific differences with confidence. Larger, adequately powered randomized trials focused specifically on molecular subtypes will be needed before any clinical recommendation can be made.

Still, the study arrives at a moment of remarkable momentum for exercise oncology. Recent landmark work, including a randomized trial published in the New England Journal of Medicine showing that structured exercise after adjuvant chemotherapy for colon cancer improved disease-free survival, has cemented physical activity as a legitimate component of cancer care rather than a mere lifestyle add-on. International consensus statements and clinical guidelines from organizations such as the American Society of Clinical Oncology now formally recommend exercise during and after cancer treatment. The question has shifted from whether exercise helps cancer patients to precisely how, when, and for whom it delivers the greatest benefit.

The new meta-analysis adds an important nuance to that conversation. While exercise reliably improves fitness, quality of life, treatment completion rates, and fatigue during chemotherapy, its ability to directly enhance tumor killing, as measured by pathologic complete response, appears limited when all cancer types are considered together. The possible exception in hormone receptor-positive, HER2-negative breast cancer suggests that the tumor microenvironment and hormonal context may determine whether exercise can act as a true anti-cancer agent rather than a supportive one. If future trials confirm this signal, exercise prescriptions could eventually be tailored not just to a patient’s overall health but to the molecular fingerprint of their tumor.

For now, the practical message for patients and clinicians remains unchanged: exercise during neoadjuvant chemotherapy is safe, feasible, and beneficial for many aspects of health and well-being, but patients should not expect it to guarantee a complete tumor response. The Portuguese team’s work, funded by the Foundation for Science and Technology, underscores both the promise and the limitations of lifestyle interventions in precision oncology. As the field moves toward larger subtype-stratified trials, the dream of exercise as a tumor-sensitizing therapy lives on, but the evidence so far suggests it will be a targeted tool rather than a universal one.

Subject of Research: The effect of exercise during neoadjuvant chemotherapy on pathologic complete response in solid tumors

Article Title: Exercise and pathologic complete response to cancer treatment: a systematic review and meta-analysis

Article References: Dias Rato, N., Garcia, C., Pinto, D., Guedes, H., Joaquim, A., Viamonte, S., Helguero, L., Viana, J., & Alves, A. (2026). Exercise and pathologic complete response to cancer treatment: a systematic review and meta-analysis. Supportive Care in Cancer, 34(10), Article 948. https://doi.org/10.1007/s00520-026-11156-1

Image Credits: AI Generated

DOI: 10.1007/s00520-026-11156-1

Keywords: exercise oncology, neoadjuvant chemotherapy, pathologic complete response, breast cancer, meta-analysis, randomized controlled trials, tumor response, hormone receptor-positive, HER2-negative, supportive care, physical activity, cancer treatment