Low Skeletal Muscle Radiodensity Predicts Response to CDK4/6 Inhibitors Plus Aromatase Inhibitors in Advanced Breast Cancer

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 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 retrospective cohort of patients with ABC at the Yonsei Cancer Center who received CDK4/6i and aromatase inhibitors as first-line therapy between January 2017 and October 2020. Body composition parameters were estimated from the non-enhanced CT images of the third lumbar spine by commercialized deep learning software. Patients with low skeletal muscle radiodensity (SMD) were defined as patients with SMD of low tertile (≤ 28.7 Hounsfield Units). The primary outcome was progression-free survival (PFS).

Results: Among the 247 female participants (median age, 53 years; mean body mass index [BMI], 23.7 kg/m²), 45.7% had disease progression or death during a median follow-up of 36.4 months. After adjusting for age and visceral metastasis, SMD was the only independent predictor among body composition parameters for worse PFS (adjusted hazard ratio [HR] = 1.20 per standard deviation decrement, 95% CI: 1.01-1.42, p = 0.041), whereas BMI, muscle area, and fat area were not. Participants with low SMD had a higher risk of progression than those without (PFS, 27.2 vs. 51.1 months, p = 0.009; adjusted HR 1.84, 95% CI: 1.22-2.76, p = 0.003). Strong associations between low SMD and poor PFS were observed in groups with pre-menopause status (HR, 3.04 vs. 1.19 in post-menopause; 95% CI: 1.54-5.99, p for interaction < 0.05) and without visceral metastases (HR, 2.95 vs. 1.19 in with visceral metastases; 95% CI: 1.59-5.49, p for interaction < 0.05).

Conclusions: CT-defined low SMD predicts poor treatment outcomes in patients with ABC undergoing first-line treatment with aromatase inhibitors and CDK4/6i.