Immune gene expression and response to chemotherapy in advanced breast cancer

Theodoros Foukakis, John Lövrot, Alexios Matikas, Ioannis Zerdes, Julie Lorent, Nick Tobin, Chikako Suzuki, Suzanne Egyházi Brage, Lena Carlsson, Zakaria Einbeigi, Barbro Linderholm, Niklas Loman, Martin Malmberg, Mårten Fernö, Lambert Skoog, Jonas Bergh, Thomas Hatschek, TEX Study Group

Research output: Contribution to journalArticlepeer-review

Abstract

Background:Transcriptomic profiles have shown promise as predictors of response to neoadjuvant chemotherapy in breast cancer (BC). This study aimed to explore their predictive value in the advanced BC (ABC) setting.Methods:In a Phase 3 trial of first-line chemotherapy in ABC, a fine needle aspiration biopsy (FNAB) was obtained at baseline. Intrinsic molecular subtypes and gene modules related to immune response, proliferation, oestrogen receptor (ER) signalling and recurring genetic alterations were analysed for association with objective response to chemotherapy. Gene-set enrichment analysis (GSEA) of responders vs non-responders was performed independently. Lymphocytes were enumerated in FNAB smears and the absolute abundance of immune cell types was calculated using the Microenvironment Cell Populations counter method.Results:Gene expression data were available for 109 patients. Objective response to chemotherapy was statistically significantly associated with an immune module score (odds ratio (OR)=1.62; 95% confidence interval (CI), 1.03-2.64; P=0.04). Subgroup analysis showed that this association was restricted to patients with ER-positive or luminal tumours (OR=3.54; 95%, 1.43-10.86; P=0.012 and P for interaction=0.04). Gene-set enrichment analysis confirmed that in these subgroups, immune-related gene sets were enriched in responders.Conclusions:Immune-related transcriptional signatures may predict response to chemotherapy in ER-positive and luminal ABC.

Original languageEnglish
Pages (from-to)480-488
JournalBritish Journal of Cancer
Volume118
Issue number4
DOIs
Publication statusPublished - 2018 Feb 20

Subject classification (UKÄ)

  • Cancer and Oncology

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