Evolution of low HER2 expression between early and advanced-stage breast cancer. (March 2022)

• Record Type: Journal Article
• Authors: Tarantino, Paolo; Gandini, Sara; Nicolò, Eleonora; Trillo, Pamela; Giugliano, Federica; Zagami, Paola; Vivanet, Grazia; Bellerba, Federica; Trapani, Dario; Marra, Antonio; Esposito, Angela; Criscitiello, Carmen; Viale, Giuseppe; Curigliano, Giuseppe
• Is Part Of: European journal of cancer. Volume 163(2022)
• Page Start: 35
• Page End: 43
• Publication Date: 2022-03
• Subjects: HER2 expression -- HER2-Low -- HER2 dynamics -- Breast cancer -- Antibody-drug conjugates; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2021.12.022
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Background: Low human epidermal growth factor receptor 2 (HER2) expression is emerging as an actionable biomarker for the treatment of breast cancer (BC) with novel anti-HER2 drugs. However, the evolution of this biomarker during the course of disease is still poorly characterised, and controversial data exist on its prognostic implications. Methods: We reviewed data of patients with HER2-negative BC according to the latest ASCO/CAP guidelines referred between January 2014 and December 2020. We grouped patients based on the immunohistochemistry (IHC) expression of HER2, HER2-zero (IHC 0) and HER2-low subgroup (IHC 1+ or 2+/ISH-negative) and evaluated the evolution of HER2 expression between the primary tumour and the first biopsy collected in the advanced setting. Disease-free survival, overall survival and progression-free survival were compared between patients with HER2-zero and HER2-low expression on the primary tumour. Results: 232 patients were included in the analysis. Among the overall population, there was a relevant discordance in HER2 expression between the primary tumour and the matched biopsy (K = 0.33, 95%CI 0.21–0.44): 44% of the HER2-zero primary tumour showed an increased HER2 score on biopsy, and 22% of the HER2-low primary tumours turned into HER2-IHC 0. The findings in the sub-populations of hormone-receptors positive (K = 0.32, 95%CI 0.19–0.45) and triple-negative tumours (K = 0.18, 95%CI -0.09-0.46) were consistent with the primary analysis. No difference in survival outcomes was observed between HER2-low and HER2-zero primary tumours. Conclusions: HER2-low expression is dynamic in BC and may be enriched in the advanced-stage setting. No prognostic significance was demonstrated for HER2-low expression. Highlights: HER2-low expression is emerging as an actionable biomarker in breast cancer. HER2 IHC score increased from primary to metastatic tumour in 44% of the patients. HER2-low to HER2-zero evolution was observed in 22% of the patients. HER2-low expression is dynamic and may be enriched in the advanced-stage setting.