Abstract P3-05-26: Association of muscle mass and density with outcomes in patients with ER positive metastatic breast cancer: correlative analysis of ECOG-ACRIN 2112
Authors: Ballinger Tarah J. , Xue Gloria , Marques Helga S. , Gatsonis Constantine , Hoffman Richard , Miller Kathy D. , Zhao Fengmin , Sparano Joseph , Connolly Roisin 
Published: March 2023

Introduction: Observational data investigating the relationship between body habitus and survival or toxicity in breast cancer has been largely centered in the curative setting and focused on weight- based metrics, with variable and inconsistent results. Muscle is a large, active endocrine organ that affects physical function, drug metabolism, inflammation, and quality of life, but is not adequately measured by body weight alone. Very few studies have evaluated muscle measures in metastatic breast cancer (MBC) and have been focused on patients receiving cytotoxic chemotherapy. Here, we evaluate the impact of muscle mass and muscle density measured on CT scan on outcomes in patients with MBC receiving endocrine- based therapy. Methods: Baseline CT scans done at the time of study enrollment were centrally collected from participants in ECOG-ACRIN E2112, a randomized phase III study of exemestane with or without entinostat in MBC, which ultimately did not impact survival. A transverse cut at the L3 level was extracted and processed using semi-automated SliceOmatic software (Tomovision) by two independent investigators to obtain total body skeletal muscle mass and muscle attenuation. Low muscle mass was defined as skeletal muscle index (SMI, lean muscle area/height, cm2/m2) less than 41 and low skeletal muscle attenuation (SMA) was defined as average muscle density less than 41 HU, or less than 33 HU if the patient is overweight or obese by BMI. Chi-square tests were used to determine the association between SMI and SMA and other clinical characteristics, including body weight, race, and performance status. Multivariable Cox proportional hazard models were used to determine the association between low SMI or low SMA and overall survival (OS), progression free survival (PFS), and patient- reported outcomes. Results: Of the 608 patients randomized in E2112, 546 had analyzable CT scans and follow up data available. 45% (n=246) of participants had obesity by BMI (≥30); 39% (n=212) had low SMI and 56% (n=305) had low SMA. Obese patients were more likely to have higher SMI (p&lt; 0.001); however, 9.5% (n=52) of the study population had both obesity and low SMI. Low SMA was associated with higher rate of obesity and worse performance status (p&lt; 0.001), consistent with muscle quality being a predictor of functional status. Low SMI was not associated with survival outcomes (OS HR 1.04 95%CI 0.83-1.30, PFS HR 1.12 95% CI 0.92-1.36), nor was low SMA (OS HR 1.02 95%CI 0.81-1.28; PFS HR 1.02 95%CI 0.84-1.23). In addition, BMI was not related to survival outcomes. Conclusions: Low muscle mass and low muscle density are prevalent in estrogen receptor positive MBC patients. Muscle measures correlated with obesity and performance status; however, neither low SMI nor low SMA were associated with worse prognosis in this population. Further work is needed to refine body composition measurements and select optimal cutoffs and meaningful endpoints in specific breast cancer populations, particularly in those living with metastatic disease.

Citation Format: Tarah J. Ballinger, Gloria Xue, Helga S. Marques, Constantine Gatsonis, Richard Hoffman, Kathy D. Miller, Fengmin Zhao, Joseph Sparano, Roisin Connolly. Association of muscle mass and density with outcomes in patients with ER positive metastatic breast cancer: correlative analysis of ECOG-ACRIN 2112 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-26.