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SHR Neuro Cancer Cardio Lipid Metab Microb

Singer, CF; Tan, YY; Fitzal, F; Steger, GG; Egle, D; Reiner, A; Rudas, M; Moinfar, F; Gruber, C; Petru, E; Bartsch, R; Tendl, KA; Fuchs, D; Seifert, M; Exner, R; Balic, M; Bago-Horvath, Z; Filipits, M; Gnant, M; Austrian Breast and Colorectal Cancer Study Group.
Pathological Complete Response to Neoadjuvant Trastuzumab Is Dependent on HER2/CEP17 Ratio in HER2-Amplified Early Breast Cancer.
Clin Cancer Res. 2017; 23(14):3676-3683 Doi: 10.1158/1078-0432.CCR-16-2373 [OPEN ACCESS]
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Co-authors Med Uni Graz: Balic Marija; Moinfar Farid; Petru Edgar
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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. ©2017 American Association for Cancer Research.
Find related publications in this database (using NLM MeSH Indexing): Adult -; Aged -; Biomarkers, Pharmacological -; Breast Neoplasms - drug therapy; 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; Receptor, ErbB-2 - genetics; Trastuzumab - administration & dosage; Trastuzumab - adverse effects