ABSTRACT
Purpose: To evaluate whether pathologic complete response (pCR) to neoadjuvant trastuzumab is dependent on the level of HER2 amplification.Experimental Design: 114 HER2-overexpressing early breast cancer patients who had received neoadjuvant trastuzumab were included in this study. Absolute HER2 and chromosome 17 centromere (CEP17) were measured by in situ hybridization analysis, and associations were examined between HER2/CEP17 ratio and tumor pCR status (commonly defined by ypT0 ypN0, ypT0/is ypN0, and ypT0/is).Results: In trastuzumab-treated patients, ypT0 ypN0 was achieved in 69.0% of patients with high-level amplification (HER2/CEP17 ratio > 6), but only in 30.4% of tumors with low-level amplification (ratio ≤ 6; P = 0.001). When pCR was defined by ypT0/is ypN0 or ypTis, 75.9% and 82.8% of tumors with high-level amplification had a complete response, whereas only 39.1%, and 38.3% with low-level amplification achieved pCR (P = 0.002 and P < 0.001, respectively). Logistic regression revealed that tumors with high-level amplification had a significantly higher probability achieving ypT0 ypN0 (OR, 5.08; 95% confidence interval, 1.86-13.90; P = 0.002) than tumors with low-level amplification, whereas no other clinicopathologic parameters were predictive of pCR. The association between high-level HER2 amplification and pCR was almost exclusively confined to hormone receptor (HR)-positive tumors (ypT0 ypN0: 62.5% vs. 24.0%, P = 0.014; ypT0/is ypN0: 75.0% vs. 28.0%, P = 0.005; and ypT0/is: 87.5% vs. 28.0%, P < 0.001), and was largely absent in HR-negative tumors.Conclusions: An HER2/CEP17 ratio of >6 in the pretherapeutic tumor biopsy is associated with a significantly higher pCR rate, particularly in HER2/HR copositive tumors, and can be used as a biomarker to predict response before neoadjuvant trastuzumab is initiated. Clin Cancer Res; 23(14); 3676-83. ©2017 AACR.
Subject(s)
Biomarkers, Pharmacological , Breast Neoplasms/drug therapy , Receptor, ErbB-2/genetics , Trastuzumab/administration & dosage , Adult , Aged , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Centromere/genetics , Chromosomes, Human, Pair 17/genetics , Disease-Free Survival , Female , Humans , In Situ Hybridization, Fluorescence , Middle Aged , Neoadjuvant Therapy/adverse effects , Trastuzumab/adverse effectsABSTRACT
Diagnosis of bacterial sepsis in preterm neonates can be difficult when using serum markers that rely on physiological changes because these changes may not necessarily be the result of bacterial infections alone. This retrospective investigation explores the potential use of the DNA methylation pattern of CpG sites in the promoter region of the calcitonin-related polypeptide α (CALCA) gene as an epigenetic biomarker for bacterial sepsis in preterm newborns. Four novel changes in the DNA methylation of eight CpG sites were detected in this gene and are present only in neonates with bacterial sepsis: (1) partial methylation at -769 CpG in gram-negative or gram-positive early onset sepsis (EOS) and late onset sepsis (LOS) episodes; (2) demethylation of 8 CpGs in gram-negative EOS followed by LOS (ELS) and in gram-negative EOS; (3) demethylation of 7 CpGs in gram-positive ELS and gram-positive EOS; (4) -771 C:G>T:A; 5' de novo -778 CpG mutation on both alleles in EOS. These changes were not detected in birth weight and gestational age matched controls or in newborns with isolated infections. Our results indicate that the DNA methylation pattern of the promoter region of the CALCA gene varies in different types of bacterial preterm sepsis, thus suggesting a potential use as an epigenetic biomarker. A prospective confirmation of these results is essential.
Subject(s)
Bacteremia/metabolism , Calcitonin/genetics , DNA Methylation , Epigenesis, Genetic , Infant, Premature, Diseases/metabolism , Protein Precursors/genetics , Sepsis/metabolism , Bacteremia/diagnosis , Bacteremia/microbiology , Biomarkers/blood , Calcitonin/metabolism , Calcitonin Gene-Related Peptide , CpG Islands , Humans , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases/diagnosis , Infant, Premature, Diseases/microbiology , Promoter Regions, Genetic , Protein Precursors/metabolism , Retrospective Studies , Sepsis/diagnosis , Sepsis/microbiologyABSTRACT
BACKGROUND: Monitoring of blood glucose in neonatal intensive care unit (NICU) patients is important in maintaining normoglycaemia and reducing the risk of hypoglycaemia. Point-of-care testing (POCT) glucose meters provide short turnaround times but some have been reported to be affected by haematocrit interference and other biochemical or biological substances in their accuracy and performance. The aim of this study was to assess the performance of a new POCT glucose meter in a challenging preterm neonatal population. METHODS: The new Nova Biomedical StatStrip™ (Nova Biomedical) was tested on 159 heparinised whole blood samples from NICU patients obtained for blood gas analysis. Accuracy (bias) of the meter and analytical interferences were evaluated by comparing the results of the meter with the results of the blood gas analyser routinely used for glucose measurements in this NICU setting. RESULTS: The results of the StatStrip glucose meter correlated very well with the reference routine method across a wide glucose concentration range (13-389 mg/dL) and were not affected by the level of haematocrit, by sample pH or by medication. CONCLUSIONS: The StatStrip meter showed good clinical accuracy and performance for measuring and monitoring glucose levels in NICU patients, with special respect to preterm infants, and therefore can act as a perfect alternative to a blood gas analyser for measuring blood glucose in NICU patients.
