Evolution of HER2-low expression from primary to recurrent breast cancer

• Published in: NPJ breast cancer Vol. 7; no. 1; pp. 137 - 8
• Main Authors: Miglietta, Federica, Griguolo, Gaia, Bottosso, Michele, Giarratano, Tommaso, Lo Mele, Marcello, Fassan, Matteo, Cacciatore, Matilde, Genovesi, Elisa, De Bartolo, Debora, Vernaci, Grazia, Amato, Ottavia, Conte, PierFranco, Guarneri, Valentina, Dieci, Maria Vittoria
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.10.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 692/4028/67/1347; 692/4028/67/1857; 692/4028/67/322; Biomedical and Life Sciences; Biomedicine; Biopsy; Breast cancer; Cancer Research; Cancer therapies; Cell Biology; Chemotherapy; Clinical medicine; Evolution; Gene amplification; Gene expression; Genotype & phenotype; Human Genetics; Medical research; Metastasis; Oncology; Pathology; Tumors
• ISSN: 2374-4677; 2374-4677
• DOI: 10.1038/s41523-021-00343-4

About a half of HER2-negative breast cancer (BC) show HER2-low expression that can be targeted by new antibody-drug conjugates. The main aim of this study is to describe the evolution of HER2 expression from primary BC to relapse by including HER2-low category in both primary and recurrent BC samples. Patients with matched primary and relapse BC samples were included. HER2 was evaluated according to ASCO/CAP recommendations in place at the time of diagnosis. A cutoff of >10% cells staining for HER2-positivity was applied. HER2-negative cases were sub-classified as HER2-low (IHC = 1 + /2+ and ISH not amplified), or HER2-0 (IHC-0). 547 patients were included. The proportion of HER2-low cases was 34.2% on the primary tumor and 37.3% on the relapse samples. Among HER2-negative cases, HER2-low status was more frequent in HR-positive vs triple-negative tumors (47.3% vs 35.4% on primary tumor samples, 53.8% vs 36.2% on relapse samples). The overall rate of HER2 discordance was 38.0%, mostly represented by HER2-0 switching to HER2-low (15%) and HER2-low switching to HER2-0 (14%). Among patients with a primary HER2-negative tumor, the rate of HER2 discordance was higher in HR-positive/HER2-negative vs triple-negative cases (45.5% vs 36.7% p  = 0.170). This difference was mostly driven by cases switching from HER2-0 to HER2-low. HER2-low expression is highly unstable during disease evolution. Relapse biopsy in case of a primary HER2-0 tumor may open new therapeutic opportunities in a relevant proportion of patients.