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Immune gene expression and response to chemotherapy in advanced breast cancer

Foukakis, Theodoros; Lövrot, John; Matikas, Alexios; Zerdes, Ioannis; Lorent, Julie; Tobin, Nick LU ; Suzuki, Chikako; Brage, Suzanne Egyházi; Carlsson, Lena and Einbeigi, Zakaria, et al. (2018) In British Journal of Cancer 118(4). p.480-488
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... (More)

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.

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Contribution to journal
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published
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British Journal of Cancer
volume
118
issue
4
pages
480 - 488
publisher
Nature Publishing Group
external identifiers
  • scopus:85042377834
ISSN
0007-0920
DOI
10.1038/bjc.2017.446
language
English
LU publication?
yes
id
656f8ef8-e184-4c86-93e9-17a6027884d4
date added to LUP
2018-03-12 10:04:12
date last changed
2018-08-12 04:43:02
@article{656f8ef8-e184-4c86-93e9-17a6027884d4,
  abstract     = {<p>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.</p>},
  author       = {Foukakis, Theodoros and Lövrot, John and Matikas, Alexios and Zerdes, Ioannis and Lorent, Julie and Tobin, Nick and Suzuki, Chikako and Brage, Suzanne Egyházi and Carlsson, Lena and Einbeigi, Zakaria and Linderholm, Barbro and Loman, Niklas and Malmberg, Martin and Fernö, Mårten and Skoog, Lambert and Bergh, Jonas and Hatschek, Thomas and , },
  issn         = {0007-0920},
  language     = {eng},
  month        = {02},
  number       = {4},
  pages        = {480--488},
  publisher    = {Nature Publishing Group},
  series       = {British Journal of Cancer},
  title        = {Immune gene expression and response to chemotherapy in advanced breast cancer},
  url          = {http://dx.doi.org/10.1038/bjc.2017.446},
  volume       = {118},
  year         = {2018},
}