Abstract
<div>Abstract<p><b>Purpose:</b> To evaluate whether pathologic complete response (pCR) to neoadjuvant trastuzumab is dependent on the level of HER2 amplification.</p><p><b>Experimental Design:</b> 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 <i>in situ</i> 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).</p><p><b>Results:</b> 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; <i>P</i> = 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 (<i>P</i> = 0.002 and <i>P</i> < 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; <i>P</i> = 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%, <i>P</i> = 0.014; ypT0/is ypN0: 75.0% vs. 28.0%, <i>P</i> = 0.005; and ypT0/is: 87.5% vs. 28.0%, <i>P</i> < 0.001), and was largely absent in HR-negative tumors.</p><p><b>Conclusions:</b> 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. <i>Clin Cancer Res; 23(14); 3676–83. ©2017 AACR</i>.</p></div>
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