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Open AccessFeature PaperArticle

Extracellular Matrix Features Discriminate Aggressive HER2-Positive Breast Cancer Patients Who Benefit from Trastuzumab Treatment

1
Molecular Targeting Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
2
Data Methods and Systems Statistical Laboratory, University of Brescia, 25121 Brescia, Italy
3
Platform of Integrated Biology, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
4
Genomic Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
5
Anatomic Pathology A Unit, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
6
Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, 20133 Milan, Italy
*
Author to whom correspondence should be addressed.
Cells 2020, 9(2), 434; https://doi.org/10.3390/cells9020434 (registering DOI)
Received: 15 January 2020 / Revised: 10 February 2020 / Accepted: 11 February 2020 / Published: 13 February 2020
(This article belongs to the Special Issue Extracellular Matrix Remodeling 2019)
We previously identified an extracellular matrix (ECM) gene expression pattern in breast cancer (BC), called ECM3, characterized by a high expression of genes encoding structural ECM proteins. Since ECM is reportedly implicated in response to therapy of BCs, the aim of this work is to investigate the prognostic and predictive value of ECM3 molecular classification in HER2-positive BCs. ECM3 resulted in a robust cluster that identified a subset of 25–37% of HER2-positive tumors with molecular aggressive features. ECM3 was significantly associated with worse prognosis in two datasets of HER2-positive BCs untreated with adjuvant therapy. Analyses carried out on two of our cohorts of patients treated or not with adjuvant trastuzumab showed association of ECM3 with worse prognosis only in patients not treated with trastuzumab. Moreover, investigating a dataset that includes gene profile data of tumors treated with neoadjuvant trastuzumab plus chemotherapy or chemotherapy alone, ECM3 was associated with increased pathological complete response if treated with trastuzumab. In the in vivo experiments, increased diffusion and trastuzumab activity were found in tumors derived from injection of HER2-positive cells with Matrigel that creates an ECM-rich tumor environment. Taken together, these results indicate that HER2-positive BCs classified as ECM3 have an aggressive phenotype but they are sensitive to trastuzumab treatment. View Full-Text
Keywords: extracellular matrix; HER2 positive breast cancer; gene expression; ECM3; collagen; trastuzumab extracellular matrix; HER2 positive breast cancer; gene expression; ECM3; collagen; trastuzumab
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Rybinska, I.; Sandri, M.; Bianchi, F.; Orlandi, R.; De Cecco, L.; Gasparini, P.; Campiglio, M.; Paolini, B.; Sfondrini, L.; Tagliabue, E.; Triulzi, T. Extracellular Matrix Features Discriminate Aggressive HER2-Positive Breast Cancer Patients Who Benefit from Trastuzumab Treatment. Cells 2020, 9, 434.

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