Pathological Complete Response to Neoadjuvant Trastuzumab Is Dependent on HER2/CEP17 Ratio in HER2-Amplified Early Breast Cancer.

Purpose: To evaluate whether pathological complete response (pCR) to neoadjuvant trastuzumab is dependent on the level of HER2 amplification. Patients and methods: 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 ISH 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, while only 39.1%, and 38.3% with low-level amplification achieved pCR (p=0.002 and p 6 in the pre-therapeutic tumor biopsy is associated with a significantly higher pCR rate, particularly in HER2/HR co-positive tumors, and can be used as a biomarker to predict response before neoadjuvant trastuzumab is initiated.