Abstract P1-09-10: Pathological complete response to neoadjuvant trastuzumab is dependent on HER2/CEP17 ratio in HER2-amplified early breast cancer

Abstract

Abstract Purpose To evaluate whether pathological complete response to neoadjuvant trastuzumab is dependent on the level of HER2 amplification. Patients and Methods 114 women with HER2-overexpressing early breast cancer who had received neo-adjuvant trastuzumab in the prospective ABCSG-24 and ABCSG-32 trials, and for whom the HER2/CEP17 ratio was available, were included in this analysis. The ratio was correlated with tumor response as measured by the three most commonly used definitions of pathological complete response: ypT0 ypN0, ypT0/is ypN0, and ypT0/is. Results In trastuzumab-treated patients, ypT0 pN0 was achieved in 69.0% of patients with a HER2/CEP17 ratio of >6, but only in 30.4% of tumors with a ratio of ≤6 (p=0.001, Chi Square test). When pCR was defined by ypT0/is pN0 or by ypTis, 75.9% and 82.8% of tumors with a high ratio had a complete remission, while only 39.1%, and 38.3% with a low ratio achieved a pCR (p=0.002 and p<0.001, respectively). Logistic regression revealed that tumors with a higher HER2/CEP17 ratio had a significantly higher probability to achieve ypT0 ypN0 (OR: 5.08, 95% CI 1.86-13.90; p=0.002) than tumors with a low ratio, while none of the other clinicopathological parameters was predictive of pCR. The association between high HER2 amplification and pCR was almost exclusively confined to HR positive tumors (62.5% vs. 24.0%, 75.0% vs. 28.0%, and 87.5% vs. 28.0%, for ypT0 ypN0, ypT0/is ypN0, and ypT0/is; p=0.014, p=0.005, and p<0.001), and was largely absent in HR negative tumors. Conclusion A HER2/CEP17 ratio of >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 to predict outcome before neoadjuvant trastuzumab is initiated. Citation Format: Singer CF, Tan YY, Fitzal F, Steger GG, Egle D, Reiner A, Rudas M, Gruber C, Bartsch R, Fridrik M, Seifert M, Exner R, Balic M, Bago-Horvath Z, Filipits M, Gnant M, For the 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 [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-09-10.