The study, led by Professor Anne May, a distinguished Clinical Epidemiologist specialized in Cancer Survivorship at the University Medical Center Utrecht and the Netherlands Cancer Institute, specifically targeted patients with stage IV metastatic breast cancer. This cohort, often experiencing debilitating side effects including fatigue, nausea, pain, and muscle wasting, was enrolled in a comprehensive nine-month exercise program designed to address declines in skeletal muscle mass and functional capacity. The exercise intervention combined aerobic, resistance, and balance training, tailored and supervised by expert trainers to suit individual patient capabilities and treatment statuses.

Skeletal muscle mass, particularly in the arms and legs, is critically linked to mobility, functional independence, and resistance to falls—concerns acutely magnified in breast cancer patients with metastatic spread, especially those with bone metastases. The PREFERABLE-EFFECT study intricately measured whole-body lean mass, a primary indicator of muscle health, and found that participants undergoing supervised exercise experienced an average increase of 0.79 kilograms after three months and maintained a muscle mass retention advantage at six months compared to controls. These findings represent a pivotal shift from previous assumptions that advanced cancer and its treatments irreversibly diminish physical function and muscle integrity.

Notably, the study’s rigorous randomized controlled design spanned multiple international centers, including Germany, Poland, Spain, Sweden, The Netherlands, and Australia, enrolling 357 participants between 2019 and 2022. Such diversity enhances the generalizability of the results, reflecting a broad spectrum of metastatic breast cancer patients mostly undergoing first or second-line therapies. Importantly, most participants presented with bone metastases, a factor compounding their risk for fractures and functional decline, thereby underscoring the critical nature of the exercise intervention’s impact on balance and musculoskeletal strength.

Muscle mass gains observed were not uniform throughout the body but concentrated in limbs instrumental for daily activities and weight-bearing functions. The study reports statistically significant improvements in skeletal muscle mass index (SMI), an analogue to body mass index for musculature, with increases of 0.22 kg/m^2 at three months and sustained improvement at six months in the exercise group. Conversely, the control group experienced declines in both muscle mass and SMI, highlighting the natural trajectory of muscle degradation in untreated metastatic breast cancer patients.

Beyond mass accrual, functional assessments revealed enhanced physical performance, including improved balance and muscle strength, which directly correlate with decreased fall risk. This is especially salient given that neuropathy induced by chemotherapy can exacerbate balance deficits and frailty. One patient’s anecdote vividly illustrates these gains—initial incapacity to safely use public transportation was reversed through commitment to the exercise program, enabling renewed community engagement and autonomy.

While the exercise intervention robustly augmented lean muscle mass and strength, no significant differences were observed between groups in terms of whole-body fat percentage. This specificity suggests that exercise predominantly mitigates cancer-and-therapy-induced muscle wasting rather than inducing broad body composition shifts, a nuanced finding that informs future intervention targets.

The mechanistic underpinnings of these improvements likely extend beyond physiological alterations alone. Strengthened musculature is associated with better treatment tolerability, potentially reducing the incidence of dose-limiting toxicities and enabling adherence to full therapeutic regimens. Additionally, increased muscle strength has been linked to improved survival outcomes and enhanced quality of life metrics, encompassing physical, psychological, and social dimensions for patients often facing chronic disease trajectories.

This study represents a significant paradigm shift. Historically, patients with metastatic breast cancer were frequently excluded from exercise trials due to concerns about safety and efficacy. The PREFERABLE-EFFECT study’s success challenges this notion, advocating for the integration of supervised, comprehensive exercise programs as standard-of-care components. The resistance training element is especially emphasized, given its effectiveness in combating muscle atrophy.

Looking forward, the ABC Global Alliance plans to launch a Physical Activity Resource Hub by early 2026, providing tailored exercise resources for patients, caregivers, and healthcare professionals. This digital platform will incorporate instructional videos, customizable exercise guides, and evidence-based guidance to accommodate varying metastases locations, symptom burdens, and fitness levels. The initiative is spearheaded by experts including cancer physiotherapist Isabelle Aloi-Timeus and patient advocate Eva Schumacher-Wulf, ensuring the hub’s practicality and relevance.

The broader oncology community and cancer care providers increasingly recognize that effective cancer management encompasses not only oncologic control but also the preservation and enhancement of functional status and life quality. Professor Fatima Cardoso, President of ABC Global Alliance, underscores this ethos, emphasizing that empowering patients through supervised exercise constitutes a vital therapeutic adjunct, enabling patients to regain agency over their health and daily lives.

In sum, the PREFERABLE-EFFECT study solidifies the role of exercise as a potent, evidence-based intervention mitigating muscle wasting, enhancing physical performance, and ultimately improving the lived experience of patients with metastatic breast cancer. This milestone advances a holistic model of cancer care, positioning physical activity as indispensable in the continuum of treatment and survivorship.

Subject of Research: People

Article Title: Exercise and body composition

News Publication Date: 7-Nov-2025

References:

[1] Anne May, “Exercise and body composition”, Presentation at the Advanced Breast Cancer Eighth International Consensus Conference (ABC8), 7 November 2025.

[2] PREFERABLE-EFFECT study: Project on Exercise for Fatigue Eradication in Advanced Breast to improve quality of Life – Effects of exercise in patients with metastatic breast cancer.

Image Credits: Anne May

Keywords: Breast cancer, Breast carcinoma, Cancer, Cancer relapse, Health care, Physical exercise, Health counseling

Sarcopenia, characterized by the progressive loss of skeletal muscle mass and strength, presents a significant risk factor for adverse clinical outcomes in cancer patients. Particularly in breast cancer patients receiving neoadjuvant chemotherapy, where systemic toxicity often exacerbates muscle degradation, sarcopenia can compromise both treatment tolerance and overall survival. This research protocol outlines a carefully designed randomized controlled trial intending to evaluate the efficacy of structured resistance training as a therapeutic adjunct.

The intervention focuses on resistance exercise targeting muscle groups most affected by cancer-induced cachexia. Resistance training is hypothesized to counteract muscle atrophy by stimulating anabolic pathways, enhancing muscle protein synthesis, and improving neuromuscular function. Moreover, it may confer systemic benefits by modulating inflammatory cytokines and improving metabolic profiles, which are often deranged during chemotherapy regimens.

Participants in the trial will be rigorously selected breast cancer patients slated for neoadjuvant chemotherapy. The study envisages detailed baseline assessments encompassing muscle mass quantification through imaging modalities, strength testing, and functional performance measures. Subsequently, the exercise intervention group will engage in supervised resistance training sessions, tailored in intensity and volume, while a control group undergoes standard care without added exercise.

Prevailing literature endorses exercise oncology as a transformative adjunct therapy; however, few studies have systematically focused on resistance training in the neoadjuvant setting specifically targeting sarcopenia. This protocol addresses that gap by integrating oncological parameters with exercise physiology principles, thereby offering insights into how muscle preservation might directly impact chemotherapy efficacy and patient quality of life.

Critically, the study protocol underlines the meticulous approach to intervention fidelity and adherence monitoring, recognizing that exercise compliance significantly influences outcome validity. Parameters such as progressive overload, periodization, and individualization are embedded into the program design, ensuring that patients receive optimal dosing of resistance stimuli even amidst the challenges of active chemotherapy.

Another essential aspect highlighted in the protocol is the multidisciplinary collaboration. Integrating expertise from nursing research, surgical oncology, exercise medicine, and biobehavioral sciences, the study framework exemplifies an interdisciplinary strategy essential for addressing complex oncological challenges. Such comprehensive integration facilitates not only intervention design but also holistic patient support and outcome measurement.

Additionally, the trial encompasses a range of secondary endpoints, including treatment-related toxicity, inflammatory markers, physical function, and psychological well-being. These parameters are expected to elucidate the broader systemic effects of resistance exercise beyond mere muscle mass increments, encompassing dimensions of survivorship that are often neglected in clinical trials.

This correction notice, while primarily technical, signifies the ongoing refinement and validation of the study framework. Accurate study protocols are the bedrock of scientific rigor, and amendments such as this ensure reproducibility and transparency—qualities critical to advancing exercise oncology into routine clinical practice.

Resistance exercise, particularly in the context of sarcopenia associated with cancer treatment, represents a promising non-pharmacologic strategy. By mitigating muscle loss, resistance training has the potential to enhance physical resilience, improve metabolic homeostasis, and possibly amplify therapeutic responses to chemotherapy, thereby shifting paradigms in supportive cancer care.

The study also raises broader implications about personalized medicine in oncology. As muscle wasting varies significantly among patients due to genetic, metabolic, and treatment-related factors, tailored exercise prescriptions could become an indispensable component of individualized cancer management approaches.

Moreover, this research aligns with growing global awareness regarding the importance of physical activity in chronic disease modulation. Cancer survivorship increasingly demands integrative frameworks that encompass lifestyle factors alongside conventional therapies, positioning exercise as a cornerstone intervention with multifaceted benefits.

On a mechanistic level, resistance exercise likely impacts cellular signaling pathways such as mTOR, AMPK, and ubiquitin-proteasome systems—key regulators of muscle protein turnover. Understanding these pathways in the context of chemotherapy-induced muscle catabolism could illuminate novel targets for adjunctive therapies and optimize exercise prescriptions.

Furthermore, the psychological impact of engaging in a structured resistance exercise program during chemotherapy cannot be overstated. Empowering patients with active roles in their treatment journey may alleviate depression and anxiety commonly associated with cancer diagnosis and treatment side effects.

While the protocol emphasizes resistance exercise, integration with nutritional interventions remains a potential area for future exploration. Synergistic effects of combined exercise and protein supplementation could further enhance muscle anabolism and functional recovery in this vulnerable population.

As this trial progresses, its findings promise to refine clinical guidelines and inform oncology rehabilitation practices worldwide. The anticipation surrounding its results underscores the urgent need for evidence-based strategies that address sarcopenia’s multifactorial etiology and enhance patients’ capacity to withstand aggressive cancer therapies.

In conclusion, the corrected study protocol published in BMC Cancer advances a critical frontier in oncology research. Its focus on resistance exercise as a mediator against chemotherapy-associated sarcopenia in breast cancer patients encapsulates an innovative approach merging physical therapy and oncology. The outcomes could redefine supportive care paradigms, ushering in an era where exercise not only complements but actively potentiates the effectiveness of cancer treatment.

Subject of Research:
Effects of resistance exercise interventions on sarcopenia in breast cancer patients undergoing neoadjuvant chemotherapy.

Article Title:
Correction: Evaluating the effects of a resistance exercise intervention for sarcopenia in patients receiving neoadjuvant chemotherapy for breast cancer: study protocol for a randomized controlled trial.

Article References:
Jang, M.K., Park, S., Jeon, J.Y. et al. Correction: Evaluating the effects of a resistance exercise intervention for sarcopenia in patients receiving neoadjuvant chemotherapy for breast cancer: study protocol for a randomized controlled trial. BMC Cancer 25, 1422 (2025). https://doi.org/10.1186/s12885-025-15003-0

Image Credits:
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