Anthracyclines, including doxorubicin and epirubicin, are among the most effective chemotherapy agents available for breast cancer, but they carry a well-documented risk of cardiotoxicity. These drugs interfere with topoisomerase II and generate reactive oxygen species within cardiac mitochondria, leading to progressive myocyte injury, cell death, and ultimately a decline in left ventricular function. Cancer therapy-related cardiac dysfunction, abbreviated CTRCD, can manifest during treatment or emerge years later, significantly increasing cardiovascular morbidity and mortality among cancer survivors. Because breast cancer patients frequently receive anthracycline regimens and often live decades beyond their diagnosis, preventing even subtle early cardiac damage has become a central goal of cardio-oncology care.

Exercise has emerged as a candidate intervention precisely because it counteracts several of the mechanisms through which anthracyclines injure the heart. Preclinical research suggests that regular physical activity improves mitochondrial function, enhances antioxidant defenses, and promotes angiogenesis, all of which may buffer cardiomyocytes against chemotherapy-induced stress. Clinical guidelines from the European Society of Cardiology on cardio-oncology acknowledge the theoretical rationale for exercise-based cardioprotection, yet previous reviews have largely examined heterogeneous cancer populations receiving varied treatments, making it difficult to isolate the specific effect of exercise on anthracycline-induced cardiac dysfunction in breast cancer patients. The Spanish research team set out to close that gap with a rigorously focused analysis.

To do so, the investigators conducted a comprehensive search of PubMed, Scopus, the Cochrane Central Register of Controlled Trials, and Web of Science. They applied strict eligibility criteria: studies had to be randomized controlled trials including breast cancer patients undergoing anthracycline-based chemotherapy, the exercise intervention had to last at least twelve weeks with at least one session per week, and each trial had to report at least one of five prespecified outcomes. Those outcomes were left ventricular ejection fraction, global longitudinal strain, cardiac troponin I, cardiac troponin T, and N-terminal prohormone of brain natriuretic peptide, commonly known as NT-proBNP. Together, these markers capture different dimensions of cardiac injury, from pumping capacity and myocardial deformation to biochemical evidence of myocyte damage and neurohormonal activation.

After screening and quality assessment, six randomized controlled trials totaling 360 participants met the inclusion criteria. The meta-analysis revealed that exercise significantly attenuated the elevation of cardiac troponin I compared with usual cancer care, with a standardized mean difference of −0.50 and a 95 percent confidence interval spanning −0.93 to −0.06, yielding a p value of 0.02. Cardiac troponin I is a protein released when heart muscle cells are injured, and elevated levels during chemotherapy are among the earliest biochemical indicators of myocardial damage. The fact that exercising patients showed measurably lower troponin I elevations suggests that physical training may genuinely reduce the degree of acute myocyte injury caused by anthracyclines, rather than merely masking symptoms after damage has occurred.

However, the picture becomes more complicated when the other outcomes are considered. The analysis found no statistically significant between-group differences for left ventricular ejection fraction, the standard echocardiographic measure of pumping efficiency; for global longitudinal strain, a more sensitive deformation-based imaging metric; for cardiac troponin T, a related but structurally distinct isoform; or for NT-proBNP, a hormone released when the heart is under hemodynamic stress. This pattern is intriguing from a mechanistic standpoint. Troponin I reflects early cellular injury, whereas ejection fraction and strain measure functional consequences that may take longer to develop or may require larger sample sizes to detect reliably. It is possible that exercise protects cardiomyocytes at the biochemical level before those protective effects translate into measurable preservation of pump function, but the current evidence cannot confirm that sequence.

The authors are careful to frame their conclusion appropriately. They state that the cardioprotective role of exercise during anthracycline treatment remains uncertain, though the attenuation of cardiac troponin I elevation suggests a potential protective signal warranting further investigation. This nuanced position reflects the realities of the underlying evidence base. Six trials with 360 participants is a modest foundation for meta-analysis, and the individual studies varied in exercise modality, intensity, duration, and supervision. Some trials employed supervised aerobic training, others combined aerobic and resistance elements, and the timing of assessments relative to chemotherapy cycles differed across studies. Such heterogeneity, even among trials meeting strict inclusion criteria, can dilute true effects and widen confidence intervals.

The broader context of cardio-oncology research reinforces both the promise and the limitations of these findings. Earlier systematic reviews, including work by Zhang and colleagues in 2025 and Murray and colleagues in 2022, have generally reported favorable trends for exercise on cardiac outcomes in breast cancer patients, but they too have been constrained by small sample sizes and inconsistent outcome definitions. The European Society of Cardiology guidelines published in 2022 established biomarker criteria for diagnosing CTRCD, and subsequent research by Mecinaj and colleagues in 2024 demonstrated that applying those criteria changes the apparent incidence of cardiac dysfunction in treated populations. Standardization of both imaging and biomarker endpoints remains an unfinished project, and until it is completed, meta-analyses will continue to grapple with heterogeneous data.

What makes the current study particularly valuable is its exclusive focus on anthracycline-treated breast cancer patients, a population in which the cardiotoxic insult is relatively well characterized and the therapeutic window for intervention is clearly defined. By restricting inclusion to trials with interventions lasting at least twelve weeks and comparing exercise against usual cancer care, the Spanish team reduced some sources of noise that have plagued earlier reviews. The finding that troponin I, arguably the most mechanistically proximal biomarker of anthracycline injury, responded to exercise while more distal functional measures did not is biologically plausible and consistent with the understanding that subcellular damage precedes overt systolic dysfunction, sometimes by years.

Looking forward, the authors call for larger, standardized trials employing advanced assessment modalities and longer follow-up periods. Techniques such as stress echocardiography, cardiac magnetic resonance imaging with T1 mapping, and high-sensitivity troponin assays could detect subtler degrees of myocardial injury and dysfunction than conventional resting echocardiography. Longer follow-up is equally critical, because anthracycline cardiotoxicity can progress insidiously over a decade or more after exposure. Meanwhile, the ICOS-CORE working group, an international collaboration focused on cardio-oncology rehabilitation and exercise, published evidence priorities in 2025 aimed at establishing research standards for the field, signaling growing momentum behind precisely the kind of rigorous investigation this meta-analysis advocates. For now, breast cancer patients receiving anthracyclines should discuss exercise with their oncology and cardiology teams, balancing the encouraging troponin I signal against the honest uncertainty that still surrounds exercise as a proven cardioprotective therapy.

Subject of Research: Exercise training as a cardioprotective intervention against anthracycline-induced cardiac dysfunction in breast cancer patients

Article Title: Exercise for the mitigation of cancer therapy-related cardiac dysfunction in breast cancer patients treated with anthracyclines: a systematic review and meta-analysis

Article References: Marín, A. J., García-Coll, M. V., Moraleda, E. M., Castellanos-Montealegre, M., & Laín, S. A. (2026). Exercise for the mitigation of cancer therapy-related cardiac dysfunction in breast cancer patients treated with anthracyclines: a systematic review and meta-analysis. Supportive Care in Cancer, 34(10), Article 928. https://doi.org/10.1007/s00520-026-11085-z

Image Credits: AI Generated

DOI: 10.1007/s00520-026-11085-z

Keywords: breast cancer, anthracyclines, cardiotoxicity, exercise, cardiac troponin I, cancer therapy-related cardiac dysfunction, cardio-oncology, meta-analysis, left ventricular ejection fraction, global longitudinal strain, NT-proBNP, chemotherapy