Myosteatosis on computed tomography as a predictor of therapeutic response to CDK4/6 inhibitors plus aromatase inhibitors in patients with advanced breast cancer

Abstract

Background: Recent evidence indicates that a dysregulated host metabolism influences treatment outcomes in patients with breast cancer. We investigated the association of computed tomography (CT)-derived body composition indices as imaging biomarkers of host metabolic status with therapeutic responses in patients with hormone receptor-positive, HER2-negative advanced breast cancer (ABC) on endocrine plus CDK4/6 inhibitor (CDK4/6i) treatment. Methods: The study involved a prospective cohort of patients with ABC at the Yonsei Cancer Center who received CDK4/6i and aromatase inhibitors as first-line therapy. Body composition parameters were estimated from the pretreatment non-enhanced CT images of the third lumbar spine. Myosteatosis was defined as skeletal muscle radiodensity (SMD) of low tertile (#28.7 Hounsfield Units). The primary outcome was progression-free survival (PFS). Results: Among the 247 participants (mean age, 54.8 years; body mass index [BMI], 23.7 kg/m2), 45.7% had events during a median follow-up of 36.4 months. Low SMD was an independent predictor of worse PFS after adjusting for age and visceral metastases (adjusted hazard ratio [HR]=1.20 per standard deviation decrement, p=0.041), whereas BMI, muscle area, and fat area did not. Participants with myosteatosis had a higher risk of progression than those without (PFS, 27.2 vs. 51.1 months; p=0.009; adjusted HR 1.84, p=0.003). Strong associations between myosteatosis and poor PFS were observed in groups with pre-menopause status (HR, 3.04 vs. 1.19 in post-menopause; p for interaction,0.05) and without visceral metastases (HR, 2.95 vs. 1.19 in with visceral metastases; p for interaction,0.05). Conclusions: CT-derived myosteatosis predicts poor treatment outcomes in patients with ABC undergoing first-line treatment with aromatase inhibitors and CDK4/6i. Research Sponsor: Severance Hospital; Korea Health Industry Development Institute; Ministry of Science and ICT; RS-2023-00231864. © (2024), (Lippincott Williams and Wilkins). All rights reserved.