Abstract P3-08-63: Predictors of pathologic complete response in HER2 positive breast cancer patients treated with neoadjuvant targeted therapy
Authors: Rosario Mariela Huerta , Sahoo Sunati 
Published: March 2020

Abstract
Background: Anti-HER2 therapy is a standard treatment for HER2-positive tumors, however, the response to targeted therapy varies with a pathologic complete response rate of approximately 40%. Additionally, the relationship between the level of HER2 gene amplification and the clinical outcome is unclear.
Purpose: The aim of this study was to determine clinico-pathologic predictors of pathologic complete response after neoadjuvant targeted therapy in HER2 positive breast cancers.
Materials and Methods: We performed a retrospective review of HER2-positive breast cancer patients treated with Neoadjuvant Systemic Therapy (NST). PCR was defined as no residual invasive carcinoma in the breast and axillary lymph nodes (ypT0/is, pN0). We divided our cohort into two groups: patient with pathologic complete response (pCR) and patients without complete responses (non-pCR). We compared the HER2 copy number, HER2/CEP-17 ratio, and clinical and pathologic features using univariate and multivariate analyses.
Results: A total of 163 patients with HER2 gene amplification (copy number ≥4) or HER2/CEP17 ratio ≥ 2.0 who received neoadjuvant chemotherapy along with Trastuzumab or Trastuzumab-Pertuzumab therapy were included in the study. Only 33.3% of patients achieved pCR. Patients who achieved pCR had tumors with higher HER2 copy numbers (median: 19.1, range: 4.5 - 45.6), compared to those who did not achieve pCR (median:15.22, range: 4.12 - 35.0, p=0.003). The HER2/CEP17 ratio was higher in the pCR group (median 7.43, range 2.1 - 17.94) compared with non-pCR group (median 6.1, range 1.72 - 12.6, p= 0.32). A receiver operating characteristic curve (ROC) to identify the optimal cutoff point to predict pCR revealed the area under the curve for HER2 copy number and HER2/CEP17 ratio to be 0.639 and 0.600, respectively. Univariate analysis showed significant correlation of pCR with HER2 copy number of ≥14 (p=0.003) and an HER2/CEP17 ratio of 4 or greater (p=0.044), and Ki-67 ≥ 40 % (p=0.002). Consistent with previous studies, tumors with negative hormone receptor (HR) statuses had higher pCR rates (p&lt;0.005). In contrast, variables including age (&lt;50 years), and tumor size (&gt;5cm), were not associated with pCR. In our study, all patients with who negative lymph nodes, achieved pCR. In multivariate regression analysis, only HR negativity (OR=2.60, p=0.008), Ki-67 ≥ 40 % (p=0.015 OR=2.625) and HER 2 copy number ≥14 (p=0.009 OR=2.689) remained as a significant factors associated with pCR.
Conclusion: Patients with PCR tend to have higher HER/CEP-17 ratios, smaller tumors and negative nodal statuses. Based on our result, HER2 copy number, negative HR status and high KiI-67 are one of the strongest predictors of pCR in HER2 positive tumors.
Citation Format: Mariela Huerta Rosario, Sunati Sahoo. Predictors of pathologic complete response in HER2 positive breast cancer patients treated with neoadjuvant targeted therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-63.