CT-defined sarcopenia and outcomes in HR+/HER2− metastatic breast cancer treated with CDK4/6 inhibitors
- 1Istanbul Medeniyet University Göztepe Prof Dr Süleyman Yalçın City Hospital, Department of Medical Oncology, İstanbul, Türkiye
- 2Bezmialem Vakif University Hospital, Department of Medical Oncology, İstanbul, Türkiye
- 3Bezmialem Vakif University Hospital, Department of Radiology, İstanbul, Türkiye
Abstract
BackgroundSarcopenia is increasingly recognized as a potential prognostic factor in patients with cancer, but its clinical significance in HR+/HER2− metastatic breast cancer treated with CDK4/6 inhibitors remains uncertain. This study investigated the association between CT-defined sarcopenia and clinical outcomes in this population.MethodsThis retrospective multicenter study included 94 patients with HR+/HER2− metastatic breast cancer who received ribociclib or palbociclib plus endocrine therapy between January 2021 and March 2024. Baseline sarcopenia was defined using the skeletal muscle index measured on CT at the third lumbar vertebral level (L3). Progression-free survival (PFS) was estimated using the Kaplan–Meier method. Cox proportional hazards regression was used to identify prognostic factors for PFS, with CT-defined sarcopenia, continuous skeletal muscle index (SMI), and total muscle area (TMA) evaluated in separate multivariable models.ResultsCT-defined sarcopenia was present in 37 patients (39.4%). Median PFS was markedly shorter in patients with sarcopenia than in those without sarcopenia (15.2 vs. 26.6 months; log-rank p < 0.001). At 1 and 2 years, PFS rates were 57.6% and 15.2% in patients with sarcopenia versus 84.1% and 56.0% in those without sarcopenia, respectively. In separate multivariable models, CT-defined sarcopenia remained independently associated with shorter PFS (HR, 3.22; 95% CI, 1.86–5.59; p < 0.001), whereas higher continuous SMI (HR, 0.93; 95% CI, 0.89–0.97; p = 0.001) and TMA (HR, 0.97; 95% CI, 0.96–0.99; p = 0.002) were independently associated with longer PFS. Higher Ki-67 expression and second-line CDK4/6 inhibitor therapy also remained significantly associated with shorter PFS across all three models.ConclusionsCT-defined sarcopenia was an independent prognostic factor of inferior PFS in patients with HR+/HER2− metastatic breast cancer receiving CDK4/6 inhibitor-based therapy. Assessment of skeletal muscle mass on routinely acquired baseline CT scans may offer a practical tool for risk stratification and may help identify patients requiring more intensive follow-up and supportive care.
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BibTeX
@article{topcu2026ctdefined,
title = {{CT-defined sarcopenia and outcomes in HR+/HER2− metastatic breast cancer treated with CDK4/6 inhibitors}},
author = {Zeynep Alaca Topcu and Zehra Sucuoglu Isleyen and Ismail Yurtsever and Bugra Oztosun and Engin Erdemoglu and Mehmet Besiroglu and Haci Mehmet Turk and Mahmut Gumus},
journal = {Frontiers in Medicine},
year = {2026},
month = oct,
doi = {10.3389/fmed.2026.1943515},
url = {https://doi.org/10.3389/fmed.2026.1943515},
note = {CC BY},
}
RIS
TY - JOUR
TI - CT-defined sarcopenia and outcomes in HR+/HER2− metastatic breast cancer treated with CDK4/6 inhibitors
AU - Zeynep Alaca Topcu
AU - Zehra Sucuoglu Isleyen
AU - Ismail Yurtsever
AU - Bugra Oztosun
AU - Engin Erdemoglu
AU - Mehmet Besiroglu
AU - Haci Mehmet Turk
AU - Mahmut Gumus
PY - 2026
DA - 2026/10/28
JO - Frontiers in Medicine
DO - 10.3389/fmed.2026.1943515
UR - https://doi.org/10.3389/fmed.2026.1943515
AB - BackgroundSarcopenia is increasingly recognized as a potential prognostic factor in patients with cancer, but its clinical significance in HR+/HER2− metastatic breast cancer treated with CDK4/6 inhibitors remains uncertain. This study investigated the association between CT-defined sarcopenia and clinical outcomes in this population.MethodsThis retrospective multicenter study included 94 patients with HR+/HER2− metastatic breast cancer who received ribociclib or palbociclib plus endocrine therapy between January 2021 and March 2024. Baseline sarcopenia was defined using the skeletal muscle index measured on CT at the third lumbar vertebral level (L3). Progression-free survival (PFS) was estimated using the Kaplan–Meier method. Cox proportional hazards regression was used to identify prognostic factors for PFS, with CT-defined sarcopenia, continuous skeletal muscle index (SMI), and total muscle area (TMA) evaluated in separate multivariable models.ResultsCT-defined sarcopenia was present in 37 patients (39.4%). Median PFS was markedly shorter in patients with sarcopenia than in those without sarcopenia (15.2 vs. 26.6 months; log-rank p < 0.001). At 1 and 2 years, PFS rates were 57.6% and 15.2% in patients with sarcopenia versus 84.1% and 56.0% in those without sarcopenia, respectively. In separate multivariable models, CT-defined sarcopenia remained independently associated with shorter PFS (HR, 3.22; 95% CI, 1.86–5.59; p < 0.001), whereas higher continuous SMI (HR, 0.93; 95% CI, 0.89–0.97; p = 0.001) and TMA (HR, 0.97; 95% CI, 0.96–0.99; p = 0.002) were independently associated with longer PFS. Higher Ki-67 expression and second-line CDK4/6 inhibitor therapy also remained significantly associated with shorter PFS across all three models.ConclusionsCT-defined sarcopenia was an independent prognostic factor of inferior PFS in patients with HR+/HER2− metastatic breast cancer receiving CDK4/6 inhibitor-based therapy. Assessment of skeletal muscle mass on routinely acquired baseline CT scans may offer a practical tool for risk stratification and may help identify patients requiring more intensive follow-up and supportive care.
SN - 2296-858X
ER -