Retrospective study to estimate the prevalence of HER2-low breast cancer (BC) and describe its clinicopathological characteristics.

Abstract

1087 Background: Approximately 50% of BCs traditionally categorized as HER2 negative (HER2-neg) express low levels of HER2 (IHC 1+ or IHC 2+/ISH-; Miglietta, NPJ Breast Cancer 2021). HER2-targeted therapies for HER2-low metastatic BC (mBC) are under investigation (eg, T-DXd in the phase 3 DESTINY-Breast04 study; NCT03734029), but HER2 assays currently used to select patients (pts) for approved anti-HER2 therapies are optimized for high HER2 expression and are not validated for HER2-low detection. A recent study found relatively poor agreement (<70% interrater agreement) in evaluation of IHC scores of 0 and 1+ using current HER2 assays (Fernandez, JAMA Oncol 2022). Our objectives were to assess the prevalence of HER2-low among HER2-neg based on rescored HER2 IHC slides after training on low-end expression scoring and to describe pt characteristics of HER2-low vs HER2 IHC 0 mBC. Preliminary results are reported for 233 of 1000 planned pts. Methods: This multicenter, retrospective study (NCT04807595) included pts with confirmed HER2-neg unresectable/mBC diagnosed between 2015 and 2017. Local laboratories, blinded to historical HER2 scores, rescored HER2 IHC-stained slides. HER2 was assessed using Ventana 4B5 and other assays. BCs were categorized as HER2-low or HER2 IHC 0. The prevalence of HER2-low BC among pts originally scored as HER2-neg was measured. Demographics (eg, age, country, race) and clinicopathological characteristics were examined via medical charts/electronic health records. Concordance between historical HER2 scores and rescores was assessed. Results: HER2 rescores were obtained for 233 pts (mean age, 54 y). HER2-low prevalence was 63.2% overall and numerically greater in hormone receptor (HR)–positive vs HR-negative subgroups (66.1% vs 54.8%; Table). No notable differences in prevalence were seen among different HER2 assays or in demographic/baseline disease characteristics between the HER2-low and HER2 IHC 0 groups. Concordance rate between historical and rescored slides for HER2-status classification was 82.3%. The presentation will include an expanded data set (≈400 pts) with additional results. Conclusions: Data on HER2-low prevalence in BC is limited. Preliminary data from this study of mBC samples suggest a somewhat higher prevalence estimate (≈63%) than a previous study of primary BC samples (≈50%). Concordance was 82%; ongoing analyses with updated data will clarify the concordance between rescored and historical HER2 slides. These data can support development of best practices for identifying pts with HER2-low expression who may benefit from HER2-targeted therapies. Clinical trial information: NCT04807595. [Table: see text]