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Breast Cancer Research
Published in: Breast Cancer Research 1/2018

Open Access 01-12-2018 | Research article

Novel 18-gene signature for predicting relapse in ER-positive, HER2-negative breast cancer

Authors: Richard Buus, Belinda Yeo, Adam R. Brentnall, Marie Klintman, Maggie Chon U. Cheang, Komel Khabra, Ivana Sestak, Qiong Gao, Jack Cuzick, Mitch Dowsett

Published in: Breast Cancer Research | Issue 1/2018

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.
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Metadata
Title
Novel 18-gene signature for predicting relapse in ER-positive, HER2-negative breast cancer
Authors
Richard Buus
Belinda Yeo
Adam R. Brentnall
Marie Klintman
Maggie Chon U. Cheang
Komel Khabra
Ivana Sestak
Qiong Gao
Jack Cuzick
Mitch Dowsett
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2018
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-018-1040-9

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