ERBB2 mRNA Expression and Response to Ado-Trastuzumab Emtansine (T-DM1) in HER2-Positive Breast Cancer

Cancers
Gaia GriguoloAleix Prat

Abstract

Trastuzumab emtansine (T-DM1) is approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive (HER2+) metastatic breast cancer (BC) and for residual disease after neoadjuvant therapy; however, not all patients benefit. Here, we hypothesized that the heterogeneity in the response seen in patients is partly explained by the levels of human epidermal growth factor receptor 2 gene (ERBB2) mRNA. We analyzed ERBB2 expression using a clinically applicable assay in formalin-fixed paraffin-embedded (FFPE) tumors (primary or metastatic) from a retrospective series of 77 patients with advanced HER2+ BC treated with T-DM1. The association of ERBB2 levels and response was further validated in 161 baseline tumors from the West German Study (WGS) Group ADAPT phase II trial exploring neoadjuvant T-DM1 and 9 in vitro BC cell lines. Finally, ERBB2 expression was explored in 392 BCs from an in-house dataset, 368 primary BCs from The Cancer Genome Atlas (TCGA) dataset and 10,071 tumors representing 33 cancer types from the PanCancer TCGA dataset. High ERBB2 mRNA was found associated with better response and progression-free survival in the metastatic setting and higher rates of pathological complete response in the neoadj...Continue Reading

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Citations

Jan 6, 2021·NPJ Breast Cancer·Francesco SchettiniAleix Prat
Jun 3, 2021·JCO Oncology Practice·Olga Martínez-Sáez, Aleix Prat
May 30, 2021·Molecular Oncology·Fara Brasó-MaristanyAleix Prat
Jul 3, 2021·Cancers·Chiara CortiGiuseppe Curigliano
Jul 3, 2021·Cancers·Elisa AgostinettoEvandro de Azambuja
Aug 16, 2021·The Breast : Official Journal of the European Society of Mastology·Francesco Schettini, Aleix Prat

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Methods Mentioned

BETA
biopsy
Assay

Software Mentioned

R
nCounter
GraphPad Prism
nSolver

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