Schettini Francesco, Chic Nuria, Brasó-Maristany Fara, Paré Laia, Pascual Tomás, Conte Benedetta, Martínez-Sáez Olga, Adamo Barbara, Vidal Maria, Barnadas Esther, Fernández-Martinez Aranzazu, González-Farre Blanca, Sanfeliu Esther, Cejalvo Juan Miguel, Perrone Giuseppe, Sabarese Giovanna, Zalfa Francesca, Peg Vicente, Fasani Roberta, Villagrasa Patricia, Gavilá Joaquín, Barrios Carlos H, Lluch Ana, Martín Miguel, Locci Mariavittoria, De Placido Sabino, Prat Aleix
Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.
Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain.
NPJ Breast Cancer. 2021 Jan 4;7(1):1. doi: 10.1038/s41523-020-00208-2.
Novel antibody-drug conjugates against HER2 are showing high activity in HER2-negative breast cancer (BC) with low HER2 expression (i.e., 1+ or 2+ and lack of ERBB2 amplification). However, the clinical and molecular features of HER2-low BC are yet to be elucidated. Here, we collected retrospective clinicopathological and PAM50 data from 3,689 patients with HER2-negative disease and made the following observations. First, the proportion of HER2-low was higher in HR-positive disease (65.4%) than triple-negative BC (TNBC, 36.6%). Second, within HR-positive disease, ERBB2 and luminal-related genes were more expressed in HER2-low than HER2 0. In contrast, no gene was found differentially expressed in TNBC according to HER2 expression. Third, within HER2-low, ERBB2 levels were higher in HR-positive disease than TNBC. Fourth, HER2-low was not associated with overall survival in HR-positive disease and TNBC. Finally, the reproducibility of HER2-low among pathologists was suboptimal. This study emphasizes the large biological heterogeneity of HER2-low BC, and the need to implement reproducible and sensitive assays to measure low HER2 expression.
新型抗HER2抗体药物偶联物在HER2低表达（即1+或2+且无ERBB2扩增）的HER2阴性乳腺癌（BC）中显示出高活性。然而，HER2低表达BC的临床和分子特征尚待阐明。在此，我们收集了3689例HER2阴性疾病患者的回顾性临床病理和PAM50数据，并得出以下观察结果。首先，HR阳性疾病中HER2低表达的比例（65.4%）高于三阴性乳腺癌（TNBC，36.6%）。其次，在HR阳性疾病中，HER2低表达组中ERBB2和管腔相关基因的表达高于HER2 0组。相比之下，在TNBC中未发现根据HER2表达有差异表达的基因。第三，在HER2低表达组中，HR阳性疾病的ERBB2水平高于TNBC。第四，HER2低表达与HR阳性疾病和TNBC的总生存期无关。最后，病理学家之间HER2低表达的可重复性欠佳。本研究强调了HER2低表达BC存在较大的生物学异质性，以及需要实施可重复且敏感的检测方法来测量低HER2表达。
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