Prognostic Value of Baseline Sarcopenia and Adipose Tissue Indices in HR+/HER2− Metastatic Breast Cancer Treated with CDK4/6 Inhibitors: A Retrospective Cohort Study

TL;DR

This study finds that low muscle mass (sarcopenia) at diagnosis is linked to worse outcomes in breast cancer patients treated with CDK4/6 inhibitors.

Contribution

The study is the first to show that non-sarcopenia and de novo metastasis predict better survival in CDK4/6 inhibitor-treated breast cancer patients.

Findings

Patients with sarcopenia had shorter progression-free survival compared to non-sarcopenic patients.

Non-sarcopenia and de novo metastatic disease were independent predictors of longer progression-free survival.

Adipose tissue indices and BMI were not associated with survival outcomes.

Abstract

Background/Objectives: Sarcopenia, defined by reduced skeletal muscle mass, may have prognostic relevance in metastatic breast cancer. Muscle quality, reflected by adipose tissue indices, could also influence outcomes, but evidence in CDK4/6 (cyclin-dependent kinase)-inhibitor-treated patients is limited. We therefore evaluated the prognostic impact of baseline sarcopenia and adipose tissue distribution indices in this population. Methods: We retrospectively analyzed 156 women with HR+/HER2− MBC (hormone-receptor-positive, Her2-negative metastatic breast cancer) who initiated ribociclib or palbociclib plus endocrine therapy between May 2020 and January 2024. Association between L3 computed tomography (CT)-derived skeletal muscle index (SMI) and adipose tissue indices was evaluated with univariable and multivariable analyses. Sarcopenia was defined as SMI < 41 cm2/m2. Results: Median age was 57.6 years; 75% of patients were postmenopausal, and 48% of the cohort were sarcopenic. Median progression-free survival (PFS) for the entire cohort was 24.7 months (95% CI: 20.3–29.2). Patients with baseline sarcopenia had substantially shorter PFS compared to those without sarcopenia (21.5 months (95% CI: 10.9–32.1), versus 27.1 months (95% CI: 15.2–39; p = 0.016). Multivariable Cox regression analyses identified two independent predictors of prolonged PFS: non-sarcopenia (SMI ≥ 41 cm2/m2) and de novo metastatic disease. BMI (body mass index) and all adipose indices were not associated with PFS. Conclusions: Baseline non-sarcopenia and de novo metastatic disease independently predict longer PFS on CDK4/6 inhibitors, whereas adiposity measures and BMI are not prognostic. Routine body composition assessment may refine risk stratification and identify candidates for supportive interventions. Prospective studies are needed to validate these findings.

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