Total Lesion Glycolysis Levels as Predictive Indicators in Patients With Metastatic and Recurrent Breast Cancer Undergoing Endocrine Therapy With or Without CDK4/6 Inhibitor

Abstract

Background/Aim: Endocrine therapy (ET) with or without CDK4/6 inhibitors is the primary treatment choice for patients with estrogen receptor (ER)-positive and HER2-negative subtype of metastatic breast cancer (MBC). We examined the metabolic parameters identified using 18 Ffluorodeoxyglucose-positron emission tomography (FDG-PET) in terms of sensitivity, since no predictive factors exist. Patients and Methods: We included 136 patients with MBC treated with ET alone (n=107) or combined with CDK4/6 inhibitor (n=29) and examined using FDG-PET before treatment began. The highest maximum value of the standard uptake value (SUVmax), whole-body metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated. Results: Progression-free survival (PFS) was significantly longer in patients with low levels of MTV, TLG, and SUVmax than those with higher levels (median PFS 49.5 vs. 20.7 months, p=0.001 for MTV, 49.5 vs. 20.7 months, p=0.0016 for TLG, 37.0 vs. 20.7 months, p=0.012 for SUVmax). Multivariable analysis revealed that TLG (hazard ratio=6.383, 95% confidence interval=1.167-34.913, p=0.033) was independently and significantly associated with PFS. The relationship between TLG levels and PFS was significant in patients treated with ET with (p=0.0054) and without (p=0.0188) CDK4/6 inhibitor. Conclusion: TLG at baseline was a significant predictor for sensitivity to ET alone or combined with CDK4/6 inhibitor. These data may be useful to identify patients that would benefit from ET.Cyclin-dependent kinase 4/6 (CDK4/6) inhibitor plus endocrine therapy (ET) is recommended as the first-line therapy for patients with estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC), except for those with visceral crisis (1, 2). From 2017 to 2018, 9.3% and 64.3% of patients with ER-positive/ HER2-negative MBC were treated with ET alone and the combination of ET with CDK4/6 inhibitor, respectively, as first-line therapy (3). However, predictive factors for ET with or without CDK4/6 inhibitor have yet to be identified. Clinically useful biomarkers that can be used in daily practice as alternatives to ER or HER2 status to select agents that would serve as effective treatments are urgently needed.Clinicopathological factors including tumor grade, ER, progesterone receptor (PgR), HER2, and Ki67 are considered as prognostic factors; however, only ER is a significant predictive factor for ET (4). In the phase III FALCON study, which compared first-line treatment with anastrozole and fulvestrant for patients with MBC, longer progression-free survival (PFS) was demonstrated in the fulvestrant arm. Interestingly, in the subgroup analysis, improved PFS was consistently recognized in the non-visceral diseases, but not visceral diseases [hazard ratio (HR)=0.59, 95% confidence interval (95%CI)=0.42-0.84, median PFS 13.8 vs. 22.3 months for non-visceral diseases; HR=0.99, 95%CI=0.74-4813

Advances in PET/CT Imaging for Breast Cancer Patients and Beyond

“…Cyclin-dependent 4/6 kinase inhibitors plus endocrine therapy is considered the gold standard treatment for individuals with hormone receptor-positive Human epidermal growth factor receptor 2 (HER2-positive) breast cancer [ 11 ]. According to previous studies, low levels of whole-body metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) on [18F]FDG PET/CT are significantly associated with prolonged progression-free survival and overall survival in patients treated with endocrine therapy alone or in combination with Cyclin-dependent Kinase 4/6 (CDK 4/6) inhibitors [ 12 ].…”