Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer

Francesco Schettini, Nuria Chic, Fara Brasó-Maristany, Laia Paré, Tomás Pascual, Benedetta Conte, Olga Martínez-Sáez, Barbara Adamo, Maria Vidal, Esther Barnadas, Aranzazu Fernández-Martinez, Blanca González-Farre, Esther Sanfeliu, Juan Miguel Cejalvo, Giuseppe Perrone, Giovanna Sabarese, Francesca Zalfa, Vicente Peg, Roberta Fasani, Patricia VillagrasaJoaquín Gavilá, Carlos H. Barrios, Ana Lluch, Miguel Martín, Mariavittoria Locci, Sabino De Placido, Aleix Prat

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number1
Journalnpj Breast Cancer
Issue number1
Publication statusPublished - Dec 2021
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology (medical)

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