Beyond Weight Loss: A Clinical Framework for Preserving Physiological Reserve During GLP-1 Receptor Agonist Therapy in Breast Cancer Survivorship

Kathy M. Mahalati MD, PhD, Douglas L. Forman MD, FACS and John O. Collins MD

Department of Obstetrics and Gynecology, University of Maryland Medical Systems, USA Department of Plastic Surgery, Georgetown University School of Medicine and Department of Plastic and Reconstructive Surgery, Johns Hopkins University, USA Dupont Integrative Neurological Center/ Fort Wayne Neuro Center Associates, USA

^*Correspondance to: Kathy M. Mahalati 

 PDF  Full Text Review Article | Open Access

Abstract:

Breast cancer survivors frequently experience obesity, adverse alterations in body composition, skeletal muscle loss, bone deterioration, metabolic dysfunction, and progressive declines in physical function that collectively compromise long-term health, independence, and quality of life. The expanding use of glucagon-like peptide-1 (GLP-1) receptor agonists has generated growing interest in their role within survivorship care. Although these therapies provide well-established benefits for obesity, type 2 diabetes, and cardiometabolic disease, their incorporation into breast cancer survivorship requires a broader perspective that extends beyond weight reduction alone. This review proposes a clinically applicable framework centered on the preservation of physiological reserve. Rather than focusing exclusively on weight loss, the framework integrates metabolic therapy with comprehensive assessment of body composition, musculoskeletal health, nutrition, exercise, functional performance, and principles of healthy aging to support long-term survivorship. Evidence from oncology, endocrinology, metabolism, musculoskeletal biology, nutrition, exercise science, rehabilitation, immunometabolism, and mitochondrial biology was critically synthesized to examine the complex relationships between GLP-1 receptor agonist therapy, body composition, skeletal muscle, bone health, and long-term survivorship outcomes. Current evidence suggests that successful integration of GLP-1 receptor agonists should extend beyond traditional metabolic endpoints to include preservation of skeletal muscle, protection of bone health, optimization of nutritional status, resistance exercise, body composition monitoring, and comprehensive functional assessment. Emerging mechanistic evidence further highlights the interconnected roles of metabolism, musculoskeletal biology, mitochondrial function, inflammation, and immunometabolism in supporting recovery, resilience, and healthy aging. GLP-1 receptor agonists represent an important component of contemporary metabolic management for appropriately selected breast cancer survivors but should be incorporated within a comprehensive survivorship strategy aimed at preserving physiological reserve. An integrated approach combining individualized nutrition, structured exercise, body composition assessment, bone health surveillance, and longitudinal functional evaluation has the potential to optimize longterm health beyond what weight reduction alone can achieve. Future prospective studies should evaluate multidimensional survivorship outcomes to determine how best to integrate metabolic therapies into personalized survivorship care models that prioritize functional independence, healthy aging, and quality of life.

Keywords:

Breast cancer survivorship; GLP-1 receptor agonists; Physiological reserve; Body composition; Musculoskeletal health; Healthy aging

Cite the Article:

Mahalati KM, Forman DL, Collins JO. Beyond Weight Loss: A Clinical Framework for Preserving Physiological Reserve During GLP-1 Receptor Agonist Therapy in Breast Cancer Survivorship. Ann Clin Case Rep. 2026; 11: 2852.