ABSTRACT
PURPOSE: Endocrine therapy (ET) in combination with CDK 4/6 inhibitors (CDK 4/6i) is the standard treatment modality for hormone receptor (HR)-positive and HER2-negative metastatic breast cancer (mBC). There is uncertainty about the prognostic and predictive value of HER2-low status and whether HER2-low BC is an individual biologic subtype. In this study, we aimed to investigate the prognostic effect of HER2 expression status on survival in mBC patients treated with first-line ET plus CDK 4/6i. METHODS: This multicenter retrospective study included patients with HR + /HER2-negative mBC cancer who were treated with first-line CDK 4/6i in combination with ET from January 2016 to March 2023. Patients were divided into two groups (HER2-low and zero), and survival and safety analyses were performed. RESULTS: A total of 201 patients were included in this study; of these, 73 (36.3%) had HER2-low disease and 128 (63.7%) had HER2-zero. There were 135 patients (67.2%) treated with ribociclib and 66 (32.8%) with palbociclib. Most of the patients (75.1%) received aromatase inhibitors as combination-endocrine therapy. Baseline characteristics were similar between the two groups. The median follow-up was 19.1 months (range: 2.5-78.4). The most common side effect was neutropenia (22.4%). The frequency of grade 3-4 toxicity was similar between the HER2-zero and low patients (32% vs 31.5%; p = 0.939). Visceral metastases were present in 44.8% of patients. Between the HER2-low and zero groups, median PFS (25.2 vs 22.6 months, p = 0.972) and OS (not reached vs 37.5 months, p = 0.707) showed no statistically significant differences. CONCLUSION: The prognostic value of HER2-low status remains controversial. Our study showed no significant effect of HER2 low expression on survival in patients receiving CDK 4/6i plus ET.
Subject(s)
Breast Neoplasms , Cyclin-Dependent Kinase 4 , Cyclin-Dependent Kinase 6 , Protein Kinase Inhibitors , Receptor, ErbB-2 , Humans , Female , Receptor, ErbB-2/metabolism , Breast Neoplasms/drug therapy , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Retrospective Studies , Middle Aged , Cyclin-Dependent Kinase 4/antagonists & inhibitors , Cyclin-Dependent Kinase 6/antagonists & inhibitors , Aged , Protein Kinase Inhibitors/therapeutic use , Adult , Prognosis , Pyridines/therapeutic use , Pyridines/administration & dosage , Piperazines/therapeutic use , Piperazines/administration & dosage , Purines/therapeutic use , Purines/administration & dosage , Neoplasm Metastasis , Aminopyridines/therapeutic use , Aminopyridines/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Aged, 80 and over , Biomarkers, Tumor/metabolismABSTRACT
INTRODUCTION: We aimed to investigate the effect of glycemic impairment in prediabetes on cognitive impairment and the impact of glycemic control on cognitive function in patients with diabetes. MATERIALS AND METHODS: This age- and sex-matched case-control study included a total of 80 individuals: 20 patients with prediabetes, 20 patients with well-controlled type 2 diabetes mellitus (T2DM) (HbA1C < %7.5), 20 patients with poorly controlled T2DM (HbA1C >% 7.5), and 20 healthy controls. RESULTS: The poorly controlled T2DM patients performed significantly worse than controls and patients with prediabetes in the verbal memory process test (p = 0.041). In Trail Making Test B, the well-controlled and poorly-controlled groups with diabetes performed significantly worse (p = 0.015) than patients with prediabetes and controls, and in the Wisconsin Card Sorting Test (WCST), all three patient groups performed significantly worse (p = 0.007) than controls. CONCLUSION: T2DM causes early brain aging and declines cognitive functions since the prediabetic stage. Poor glycemic control in T2DM patients contributes to cognitive impairments, especially in learning.
