Abstract P5-02-43: Incidence of HER2-low Expression in HR-positive/HER2-negative and Triple-Negative Breast Cancers in the Integra Connect Database
Authors: Fares Marielle , Gart Mike , Blanc Simon , Zheng Jia , Saunders William , Smith Robert , Vasudevan Anupama , English Sandy 
Published: March 2023

Abstract
Approximately half of primary breast cancers exhibit low levels of human epidermal growth factor receptor 2 (HER2), defined as a score of 1+ on immunohistochemical (IHC) analysis or a score of 2+ on IHC and lack of HER2 gene amplification on in situ hybridization (ISH). Tumors classified as HER2-low represent a target for novel antibody-drug conjugates. In addition, HER2-low expression accounts for about 60% of HER2-negative breast cancers (BC). Real-world studies noted that HER2-low represents 47-54% of hormone positive (HR-positive)/HER2-negative breast cancers, a percentage higher than in the triple negative subgroup, reported at 35%.   The goal of this study was to determine the frequency of HER2-low expression in patients with HR-positive/HER2-negative and triple-negative breast cancers (TNBCs) in the real-world and compare it with the published literature.  The IntegraConnect (IC) real-world database of 330 thousand breast cancer patients was used for this analysis. Within the IC database, a subgroup of 387 patients with HR-positive/HER2-negative breast cancer and 618 patients with TNBC were abstracted with medical chart curation. The mean age at diagnosis for each group was 56 years and most patients had an ECOG performance status of 0-1. The statistical tests used were the Mann-Whitney test for age at diagnosis and the Chi-squared test for race, major stage, and ECOG at diagnosis. Differences were considered significant at P &lt; .05.   In the HR-positive/HER2-negative subgroup (n=387), 327 patients were tested by IHC and ISH. Sixty patients were tested by ISH only and were removed as they did not fit the definition of HER2-low. Of the 327 HER2-negative patients, 199 patients exhibited low HER2 expression (IHC1+, n=138 patients; IHC2+/ISH-negative, n=61), accounting for 61% (199/327) of HR-positive/HER2-negative breast cancers. In this group, numerically more patients were HER2-low than HER2-negative across all race subgroups. In the TNBC patient group (n=618), 546 patients tested HER2-negative by ICH and ISH. Patients testing HER2-negative by ISH only were removed (n=72) from the analysis. Of 546 patients with TNBC, HER2-low expression accounted for 42% (227/546) [IHC1+, n=168; IHC2+/ISH-negative, n=59].   In the Black or AA patients with TNBC subgroup, 37.2% (N=129) were HER2-low compared with 44% (N=353) in White patients. In all TNBC race subgroups, numerically more patients were HER2-negative compared with HER2-low.   In addition, the proportion of HER2-low expression was higher in the HR+/HER2-negative subgroup (N=327) than in TNBC (N=546) (61% vs 42%, respectively), corroborating literature reports. In conclusion, analysis of the IC database showed HER2-low expression in 61% of HR-positive/HER2-negative breast cancers and in 42% of TNBC patients. Approximately 37% of Black or African Americans (AA) patients with TNBC expressed low levels of HER2. The frequency of HER2-low expression in TNBC in the IC database at 42% is slightly higher than previous studies that estimate HER2-low expression at 35% of TNBC. The percentage of HER2-low in HR+/HER2-negative breast cancers at 61% is higher than previous reports, which estimate low HER2 expression in patients with primary and recurrent HR+/HER2-negative breast cancers at 47 and 54%, respectively.
Citation Format: Marielle Fares, Mike Gart, Simon Blanc, Jia Zheng, William Saunders, Robert Smith, Anupama Vasudevan, Sandy English. Incidence of HER2-low Expression in HR-positive/HER2-negative and Triple-Negative Breast Cancers in the Integra Connect Database [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-02-43.