Immune gene expression and response to chemotherapy in advanced breast cancer.

Autor: Foukakis T; Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet and University Hospital, Stockholm 17176, Sweden., Lövrot J; Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet and University Hospital, Stockholm 17176, Sweden., Matikas A; Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet and University Hospital, Stockholm 17176, Sweden., Zerdes I; Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet and University Hospital, Stockholm 17176, Sweden., Lorent J; Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet and University Hospital, Stockholm 17176, Sweden., Tobin N; Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet and University Hospital, Stockholm 17176, Sweden., Suzuki C; Department of Radiology and Nuclear Medicine, Karolinska Institutet and University Hospital, Stockholm 17176, Sweden., Brage SE; Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet and University Hospital, Stockholm 17176, Sweden., Carlsson L; Department of Oncology, Sundsvall General Hospital, Sundsvall 85643, Sweden., Einbeigi Z; Department of Oncology, Sahlgrenska University Hospital, Gothenborg 41345, Sweden., Linderholm B; Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet and University Hospital, Stockholm 17176, Sweden.; Department of Oncology, Sahlgrenska University Hospital, Gothenborg 41345, Sweden., Loman N; Department of Oncology, Skåne University Hospital, Lund 22241, Sweden., Malmberg M; Department of Oncology, Helsingborg General Hospital, Helsingborg 25187, Sweden., Fernö M; Department of Oncology, Skåne University Hospital, Lund 22241, Sweden., Skoog L; Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet and University Hospital, Stockholm 17176, Sweden., Bergh J; Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet and University Hospital, Stockholm 17176, Sweden., Hatschek T; Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet and University Hospital, Stockholm 17176, Sweden.
Jazyk: angličtina
Zdroj: British journal of cancer [Br J Cancer] 2018 Feb 20; Vol. 118 (4), pp. 480-488. Date of Electronic Publication: 2018 Jan 25.
DOI: 10.1038/bjc.2017.446
Abstrakt: 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.
Databáze: MEDLINE
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