Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/19513
Title: Novel 18-gene signature for predicting relapse in ER-positive, HER2-negative breast cancer.
Authors: Buus, Richard;Yeo, Belinda;Brentnall, Adam R;Klintman, Marie;Cheang, Maggie Chon U;Khabra, Komel;Sestak, Ivana;Gao, Qiong;Cuzick, Jack;Dowsett, Mitch
Affiliation: Ralph Lauren Centre for Breast Cancer Research, Royal Marsden Hospital, London, UK
Clinical Trials and Statistic Unit, The Institute of Cancer Research, London, UK
Research Data Management and Statistics Unit, Royal Marsden Hospital, London, UK
The Breast Cancer Now Toby Robins Research Centre at the Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Austin Health, Heidelberg, Victoria, Australia
Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK
Lund University, Skane University Hospital, Faculty of Medicine, Department of Clinical Sciences Lund, Oncology and Pathology, Lund, Sweden
Issue Date: 4-Sep-2018
EDate: 2018-09-04
Citation: Breast cancer research : BCR 2018; 20(1): 103
Abstract: Several prognostic signatures for early oestrogen receptor-positive (ER+) breast cancer have been established with a 10-year follow-up. We tested the hypothesis that signatures optimised for 0-5-year and 5-10-year follow-up separately are more prognostic than a single signature optimised for 10 years. Genes previously identified as prognostic or associated with endocrine resistance were tested in publicly available microarray data set using Cox regression of 747 ER+/HER2- samples from post-menopausal patients treated with 5 years of endocrine therapy. RNA expression of the selected genes was assayed in primary ER+/HER2- tumours from 948 post-menopausal patients treated with 5 years of anastrozole or tamoxifen in the TransATAC cohort. Prognostic signatures for 0-10, 0-5 and 5-10 years were derived using a penalised Cox regression (elastic net). Signature comparison was performed with likelihood ratio statistics. Validation was done by a case-control (POLAR) study in 422 samples derived from a cohort of 1449. Ninety-three genes were selected by the modelling of microarray data; 63 of these were significantly prognostic in TransATAC, most similarly across each time period. Contrary to our hypothesis, the derived early and late signatures were not significantly more prognostic than the 18-gene 10-year signature. The 18-gene 10-year signature was internally validated in the TransATAC validation set, showing prognostic information similar to that of Oncotype DX Recurrence Score, PAM50 risk of recurrence score, Breast Cancer Index and IHC4 (score based on four IHC markers), as well as in the external POLAR case-control set. The derived 10-year signature predicts risk of metastasis in patients with ER+/HER2- breast cancer similar to commercial signatures. The hypothesis that early and late prognostic signatures are significantly more informative than a single signature was rejected.
URI: http://ahro.austin.org.au/austinjspui/handle/1/19513
DOI: 10.1186/s13058-018-1040-9
ORCID: 0000-0002-3386-3465
0000-0002-9218-9917
PubMed URL: 30180877
Type: Journal Article
Subjects: Biomarkers
Breast cancer
Late recurrence
Oestrogen receptor
Prognostic tests
Appears in Collections:Journal articles

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