Triglyceride-glucose index: A candidate prognostic marker in HR-positive/HER2-negative metastatic breast cancer patients treated with CDK4/6 inhibitors

Abstract

Aims and ObjectivesAlthough cyclin-dependent kinase 4/6 inhibitors (CDK 4/6i) are a vital part of the treatment of hormone receptor (HR)-positive/HER-2-negative metastatic breast cancer (BC), individuals have different sensitivities to CDK4/6i, indicating the need for biomarkers. The fasting triglyceride glucose (TyG) index is an easily accessible surrogate marker of insulin resistance (IR). Herein, we investigated the prognostic significance of the fasting triglyceride glucose (TyG) index in HR+/HER2- metastatic BC patients treated with CDK4/6i plus endocrine therapy (ET). Methods333 patients with HR+/HER2-metastatic BC treated with CDK4/6i plus ET were analyzed retrospectively. The TyG index was calculated within three months before the initiation of CDK4/6i plus ET. The median value of 8.43 was taken as the cutoff for the TyG index. ResultsThe median overall survival (OS) was 73.6 months (95% CI, 66.0-81.1) in the whole cohort. The progression-free survival (PFS) was significantly longer in the low-TyG subgroup than in the high-TyG subgroup (30.1 vs. 21.3 months, multivariate adjusted [HR]=0.666, 95% CI=0.450-0.987, p=0.043). While the median OS was not reached in the low TyG subgroup, it was 69.0 months in the high TyG subgroup (multivariate-adjusted HR=0.513, 95% CI=0.281-0.936, p=0.030). Although the ORR and DCR were numerically greater in the low-TyG subgroup, no significant differences were observed between the low-TyG subgroup and high-TyG subgroup [28.1% vs. 24.7%, p=0.476; 83.2% vs. 80.1%, p=0.463, respectively]. ConclusionsThese data imply that the TyG index could be a predictive biomarker for the therapeutic efficacy of CDK4/6is. Extensive prospective studies are needed to confirm these findings. Micro AbstractAims and Objectives: Herein, we investigated the prognostic significance of the fasting triglyceride glucose (TyG) index in HR+/HER2- metastatic BC patients treated with CDK4/6i plus endocrine therapy (ET).Methods: A total of 333 patients with HR+/HER2- metastatic BC treated with CDK4/6i plus ET were retrospectively analyzed. The TyG index was calculated before the initiation of CDK4/6i plus ET.Results: The median overall survival (OS) was 73.6 months (95% CI, 66.0-81.1) in the whole cohort. The progression-free survival (PFS) was significantly longer in the low-TyG subgroup than in the high-TyG subgroup (30.1 vs. 21.3 months, multivariate adjusted [HR]=0.666, 95% CI=0.450-0.987, p=0.043). While the median OS was not reached in the low TyG subgroup, it was 69.0 months in the high TyG subgroup (multivariate-adjusted HR=0.513, 95% CI=0.281-0.936, p=0.030).Conclusions: These data imply that the TyG index could be a predictive biomarker for the therapeutic efficacy of CDK4/6is.