Molecular and Clinical Effects of Aromatase Inhibitor Therapy on Skeletal Muscle Function in Early-Stage Breast Cancer

Authors

Tara A Seibert
Lei Shi
Sandra Althouse
Richard Hoffman
Bryan P Schneider
Kristen A Russ
Cody A Altherr
Stuart J Warden
Theresa A Guise
Andrew R Coggan
Tarah J Ballinger

Publication Date

1-10-2024

Journal

Scientific Reports

Abstract

We evaluated biochemical changes in skeletal muscle of women with breast cancer initiating aromatase inhibitors (AI), including oxidation of ryanodine receptor RyR1 and loss of stabilizing protein calstabin1, and detailed measures of muscle function. Fifteen postmenopausal women with stage I-III breast cancer planning to initiate AI enrolled. Quadriceps muscle biopsy, dual-energy x-ray absorptiometry, isokinetic dynamometry, Short Physical Performance Battery, grip strength, 6-min walk, patient-reported outcomes, and serologic measures of bone turnover were assessed before and after 6 months of AI. Post-AI exposure, oxidation of RyR1 significantly increased (0.23 ± 0.37 vs. 0.88 ± 0.80, p <  0.001) and RyR1-bound calstabin1 significantly decreased (1.69 ± 1.53 vs. 0.74 ± 0.85, p <  0.001), consistent with dysfunctional calcium channels in skeletal muscle. Grip strength significantly decreased at 6 months. No significant differences were seen in isokinetic dynamometry measures of muscle contractility, fatigue resistance, or muscle recovery post-AI exposure. However, there was significant correlation between oxidation of RyR1 with muscle power (r = 0.60, p = 0.02) and muscle fatigue (r = 0.57, p = 0.03). Estrogen deprivation therapy for breast cancer resulted in maladaptive changes in skeletal muscle, consistent with the biochemical signature of dysfunctional RyR1 calcium channels. Future studies will evaluate longer trajectories of muscle function change and include other high bone turnover states, such as bone metastases.

Keywords

Female, Humans, Ryanodine Receptor Calcium Release Channel, Aromatase Inhibitors, Breast Neoplasms, Muscle, Skeletal, Walking

DOI

10.1038/s41598-024-51751-y

PMID

38200207

PMCID

PMC10781701

PubMedCentral® Posted Date

1-10-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes