Muscle Fiber Morphological and Molecular (mal)Adaptations in Early Stage Breast Cancer

The 5-year survival rate for localized breast cancer (BC) is >99%, due in large part to established screening and surveillance criteria. While this success is undeniable, millions of women survive BC and spend their post-treatment years enduring fatigue that negatively affects their quality of life. The goal of our laboratory has been to develop supportive therapies to alleviate breast cancer-associated muscle fatigue which are complimentary to standard-of-care therapies.  The central research hypothesis that has been driving this goal is that early stage breast cancer is associated with a clinically relevant phenotype of muscle fatigue in the absence of muscle wasting (i.e., cachexia).  Data from our laboratory in the breast cancer patient-derived orthotopic xenograft (BC-PDOX) mouse model has supported this hypothesis.  Specifically, muscles from these mice fatigue at a greater rate during a repeated stimulation protocol, while muscle mass and tumor-free body mass are not different from tumor naive mice.  In addition, bulk RNA-sequencing profiles of muscles from BC-PDOX mice are strikingly similar to the transcriptional profile of skeletal muscles from patients with early stage breast cancer.  Therefore, this model has been used for preclinical studies aimed at restoring dysfunctional molecular patterns within skeletal muscle which are associated with a fatigable phenotype.  However, our recent data analyzing muscle from patients with early stage breast cancer, using spatial transcriptomics and muscle morphological assessments, has caused our laboratory to reconsider the central research hypothesis.  This seminar will include unpublished data to highlight molecular and morphological changes of muscle in early-stage breast cancer and our thoughts on strategies for treating this phenotype clinically. 

Learning Objectives:

1. Interpret the changes in muscle morphology that occur in weight-stable patients with early stable breast cancer.

2. Understand the underlying molecular adaptations that occur in skeletal muscles of patients with early stage breast cancer.

3. Determine practical therapeutic interventions aimed at alleviating muscle fatigue in patients with early stage breast cancer.