ABSTRACT
Breast cancers (BC) can mutate, allowing metastatic tumors (MT) to sometimes differ to primary tumors (PT) in gene expression. Despite contemporary metastatic breast cancer (MBC) therapy, subtype conversion seems prognostically disadvantageous. We strived to determine the influence of mRNA-assessed intrinsic subtype stability comparing PT and MT biopsies and circulating tumor cell (CTC)-based liquid biopsies on progression free survival (PFS) and overall survival (OS). Additional analyzed prognostic factors were PT subtype, MT subtype and hormone receptor loss. Kaplan-Meier curves and the log rank tests were used to compare PFSs and OSs. The proportions of luminal B and triple negative subtype MTs were increased compared to those observed in PTs. Fifteen patients were found to have tumors that underwent intrinsic subtype conversion and their OS was significantly decreased (p = 0.038). No such difference was observed when it comes to PFS. The majority of these tumors switched to a more aggressive intrinsic subtype. No significant differences in PFSs or OSs were observed between subtype converters with triple negative PTs compared to those with luminal subtype PTs. The same is true of subtype stable patients. Total CTC, iCTC and aCTC counts decreased with therapy, but there were no significant differences between subtype converters and subtype stable patients. Our data confirm a poorer overall survival of the intrinsic subtype converters and emphasize the importance of acquiring biopsies and re-biopsies of all available metastatic lesions alongside with CTC-based liquid biopsies for earlier recognition of patients with poorer prognosis and in need of altered individualized therapy regimens.
ABSTRACT
BACKGROUND: Autonomic dysfunction is an emerging non-traditional cardiovascular risk factor that correlates with obesity, components of metabolic syndrome, as well as cardiorespiratory fitness. As a simple and validated index of autonomic balance, heart rate recovery (HRR) has been reported as a useful biomarker for predicting cardiovascular morbidity and mortality. OBJECTIVES: The aim of this study was to compare HRR in metabolically healthy vs. metabolically unhealthy obese children. METHODS: A total of 56 obese children of whom 31 had metabolic syndrome were examined. All the participants underwent the multistage submaximal cycle ergometer test and HRR was determined one minute after the test. RESULTS: The HRR was significantly lower (18.9 ± 3.7) in a group of metabolically unhealthy obese children compared to metabolically healthy obese children (24 ± 4.1) p < 0.001. Logistic regression analysis showed that reduction in HRR was also influenced by higher BMI. CONCLUSION: Our findings implicate the presence of the autonomic dysfunction as reflected by impaired heart rate recovery (HRR) in obese children with metabolic syndrome.
