Abstract HER2-15: HER2-15 Retrospective Study to Estimate the Prevalence and Describe the Clinicopathological Characteristics, Treatment Patterns, and Outcomes of HER2-Low Breast Cancer
Authors: Viale Giuseppe , Basik Mark , Niikura Naoki , Tokunaga Eriko , Brucker Sara , Penault-Llorca Frédérique , Hayashi Naoki , Sohn Joo Hyuk , de Sousa Rita Teixeira , Brufsky Adam M. , O’Brien Ciara S. , Schmitt Fernando , Higgins Gavin , Varghese Della , James Gareth D. , Moh Akira , Livingston Andrew , de Giorgio-Miller Victoria 
Published: March 2023

Abstract
Background: About 60% of breast cancers (BCs) traditionally categorized as HER2 negative (HER2-neg; immunohistochemistry [IHC] 0, IHC 1+ or IHC 2+/in situ hybridization [ISH]–) express low levels of HER2 (HER2-low; IHC 1+ or IHC 2+/ISH–; Schettini, NPJ Breast Cancer 2021). In the phase 3 DESTINY-Breast04 trial (NCT03734029), trastuzumab deruxtecan (T-DXd) showed significantly longer progression-free survival and overall survival (OS) vs physician’s choice of chemotherapy in patients (pts) with HER2-low metastatic BC (mBC) who previously received chemotherapy (Modi, NEJM 2022). As HER2-low becomes a clinically relevant HER2 status among pts with BC, greater understanding of pts with HER2-low disease is needed, including identification of these pts using conventional IHC assays. Our objectives were to assess the prevalence of HER2-low among HER2-neg mBC based on rescored HER2 IHC slides, to describe characteristics of pts with HER2-low mBC, and to characterize concordance between historical HER2 scores and rescores. Methods: This global, multicenter, retrospective study (NCT04807595) included pts with confirmed HER2-neg (HER2 IHC 0, 1+, or 2+/ISH−) unresectable/mBC diagnosed from 2014 through 2017. HER2 IHC-stained slides were rescored after training on low-end expression scoring using Ventana 4B5 and other assays by local laboratories at 13 sites in 10 countries blinded to historical HER2 scores. BCs were categorized as HER2-low (IHC 1+ or IHC 2+/ISH−) or HER2 IHC 0 (IHC 0 or &gt;0&lt; 1+). Prevalence of HER2-low and concordance between historical HER2 scores and rescores were assessed. Demographics, clinicopathological characteristics, treatment patterns, and outcomes were examined via data from medical charts/health records. Results: HER2 rescores were obtained for 781 pts with HER2-neg mBC. HER2-low prevalence was 67.1% overall; 71.1% in hormone receptor (HR)–positive (HR+) and 52.5% in HR–negative (HR−) subgroups. There were no notable differences in characteristics (Table) or treatment patterns between pts with HER2-low and HER2 IHC 0. The most frequent therapies used in the first treatment in the metastatic setting were endocrine therapy (64.1%) for pts with HR+ mBC and chemotherapy (94.4%) for pts with HR− mBC. Among pts with HR+ mBC, 10.2% received cyclin-dependent kinase 4/6 inhibitors as part of their first treatment. There were no statistically significant differences in clinical outcomes between the HER2-low and HER2 IHC 0 groups within each HR subgroup. For pts with HR+ mBC, median time to first subsequent treatment was 10 and 8 months for the HER2-low and HER2 IHC 0 groups, respectively. Overall, concordance was 81.2% (kappa=0.582). Concordance between historical HER2 scores and rescores was 87.3% for HER2-low and 70.1% for HER2 IHC 0 samples. Conclusions: The prevalence of HER2-low (67.1%) among pts previously categorized as HER2-neg mBC in this study was similar to that of an earlier study (≈60%). No obvious differences in patient characteristics or clinical presentation were seen between pts with HER2-low and HER2 IHC 0 mBC. Overall percentage agreement between rescored and historical HER2 scores was 81.2%; agreement was numerically greater for HER2-low than HER2 IHC 0. As HER2-targeted therapies such as T-DXd for the treatment of pts with HER2-low BC are emerging, a greater understanding of pts with HER2-low expression who may benefit from these therapies is important.
Citation Format: Giuseppe Viale, Mark Basik, Naoki Niikura, Eriko Tokunaga, Sara Brucker, Frédérique Penault-Llorca, Naoki Hayashi, Joo Hyuk Sohn, Rita Teixeira de Sousa, Adam M. Brufsky, Ciara S. O’Brien, Fernando Schmitt, Gavin Higgins, Della Varghese, Gareth D. James, Akira Moh, Andrew Livingston, Victoria de Giorgio-Miller. HER2-15 Retrospective Study to Estimate the Prevalence and Describe the Clinicopathological Characteristics, Treatment Patterns, and Outcomes of HER2-Low Breast Cancer [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 HER2-15.