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.