Abstract P3-08-33: Intermediate HER2 expression predicts poor prognosis in ER (+) breast cancer patients aged 55 and older
Authors: Kim Min Hwan , Kim Gun Min , Kim Jee Hung , Kim Ji Ye , Park Hyung Seok , Park Seho , Cho Young Up , Park Byeong Woo , Kim Seung Il , Sohn Joo-Hyuk 
Published: March 2020

Abstract
Background The antibody-drug conjugate targeting HER2, DS8201 has shown clinical activity against breast cancer with low-level HER2 expression in early clinical trial. In this study, we investigated the clinical implication and prognostic impact of intermediate HER2 expression in the prospectively collected ER (+) early breast cancer (EBC) and metastatic breast cancer (MBC) cohorts. Methods We analyzed the prospectively collected database of EBC and MBC cohort patients in Yonsei Cancer Center. We defined patients with HER2 immunohistochemistry (IHC) 0~1+ as HER2-negative group, and IHC 2+ and in situ hybridization (ISH) negative as HER2-intermediate group. Only ER (+) patients with complete HER2 IHC and ISH status were selected, excluding HER2 IHC 3+ or ISH+ patients. A total of 2,657 early breast cancer and 535 metastatic breast cancer patients were finally analyzed. The clinical and pathological characteristics and survival outcome of the patients were compared between HER2-negative and HER2-intermediate group in each cohort. Results The 654 (24.6%) EBC patients and 166 (31.0%) MBC patients were classified as HER2-intermediate group. The HER2-intermediate patients were more common in PR negative (30.4% versus 22.6%, p&lt; 0.001) and higher nuclear grade (grade 2 or 3) patients (25.7% versus 17.4%, p = 0.001) in EBC cohort and in age ≥ 55 patients (36.7% versus 27.4%, p = 0.001) in MBC cohort. Other characteristics were not different between two groups in both cohorts. The HER2-intermediate patients showed significantly poorer recurrence-free survival (RFS) than HER2-negative patients in EBC patients (p = 0.044), although the prognostic impact was not significant in the multivariate analysis. Of note, intermediate HER2 expression was associated with significantly poorer RFS in EBC patients (p = 0.007) of age ≥ 55, but did not affect the RFS in patients of age &lt; 55. The intermediate HER2 expression independently predicted poorer RFS of EBC patients of age ≥ 55 (Hazard ratio [HR], 1.95; 95% Confidence interval [CI], 1.03-3.73; p = 0.042) in multivariate Cox regression analysis with adjustment of other prognostic factors, T stage, N stage, PR status, and histologic grade. In line with result of EBC cohort, intermediate HER2 expression was associated with poorer overall survival (OS) in MBC patients of age ≥ 55 (p = 0.037), not affecting OS in MBC patients of age &lt; 55. Intermediate HER2 expression predicted significantly poorer OS in MBC patients of age ≥ 55 (HR, 1.45; 95% CI, 1.01-2.07; p = 0.044) independent from PR status, disease status (recurrent versus de novo stage IV), and visceral metastasis. Conclusion Our analysis demonstrates intermediate HER2 expression as an independent poor prognostic factor for ER (+) breast cancer patients with age ≥ 55 in both EBC and MBC cohorts. The clinical efficacy of new HER2-targeting antibody-drug conjugates needs to be validated in this high-risk subset of ER (+) breast cancer patients.
Citation Format: Min Hwan Kim, Gun Min Kim, Jee Hung Kim, Ji Ye Kim, Hyung Seok Park, Seho Park, Young Up Cho, Byeong Woo Park, Seung Il Kim, Joo-Hyuk Sohn. Intermediate HER2 expression predicts poor prognosis in ER (+) breast cancer patients aged 55 and older [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 P3-08-33.