Whole-transcriptome analysis links trastuzumab sensitivity of breast tumors to both HER2 dependence and immune cell infiltration.

Oncotarget
Tiziana TriulziElda Tagliabue

Abstract

While results thus far demonstrate the clinical benefit of trastuzumab, some patients do not respond to this therapy. To identify a molecular predictor of trastuzumab benefit, we conducted whole-transcriptome analysis of primary HER2+ breast carcinomas obtained from patients treated with trastuzumab-containing therapies and correlated the molecular portrait with treatment benefit. The estimated association between gene expression and relapse-free survival allowed development of a trastuzumab risk model (TRAR), with ERBB2 and ESR1 expression as core elements, able to identify patients with high and low risk of relapse. Application of the TRAR model to 24 HER2+ core biopsies from patients treated with neo-adjuvant trastuzumab indicated that it is predictive of trastuzumab response. Examination of TRAR in available whole-transcriptome datasets indicated that this model stratifies patients according to response to trastuzumab-based neo-adjuvant treatment but not to chemotherapy alone. Pathway analysis revealed that TRAR-low tumors expressed genes of the immune response, with higher numbers of CD8-positive cells detected immunohistochemically compared to TRAR-high tumors. The TRAR model identifies tumors that benefit from trastuzuma...Continue Reading

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Citations

Feb 7, 2018·Disease Markers·Martina Di ModicaTiziana Triulzi
Aug 23, 2018·Journal of Cellular Physiology·Lorenzo CastagnoliSerenella M Pupa
Dec 14, 2018·Oncoimmunology·Tiziana TriulziElda Tagliabue
May 7, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sandra M SwainNorman Wolmark
Jul 10, 2019·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Serena Di CosimoElda Tagliabue

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Datasets Mentioned

BETA
GSE22358
GSE50948
GSE41656
GSE55348

Methods Mentioned

BETA
biopsies
biopsy
chips

Software Mentioned

BrB
TRAR
GSEA
pcaMethods R
package
ArrayTool
Collapse Dataset
R
R package superpc
BioConductor

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