ERCC1 is a predictor of anthracycline resistance and taxane sensitivity in early stage or locally advanced breast cancers

Abdel-Fatah, T.M.A., Ali, R., Sadiq, M., Moseley, P.M., Mesquita, K.A., Ball, G. ORCID: 0000-0001-5828-7129, Green, A.R., Rakha, E.A., Chan, S.Y.T. and Madhusudan, S., 2019. ERCC1 is a predictor of anthracycline resistance and taxane sensitivity in early stage or locally advanced breast cancers. Cancers, 11 (8): 1149. ISSN 2072-6694

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Abstract

Genomic instability could be a beneficial predictor for anthracycline or taxane chemotherapy. We interrogated 188 DNA repair genes in the METABRIC cohort (n = 1980) to identify genes that influence overall survival (OS). We then evaluated the clinicopathological significance of ERCC1 in early stage breast cancer (BC) (mRNA expression (n = 4640) and protein level, n = 1650 (test set), and n = 252 (validation)) and in locally advanced BC (LABC) (mRNA expression, test set (n = 2340) and validation (TOP clinical trial cohort, n = 120); and protein level (n = 120)). In the multivariate model, ERCC1 was independently associated with OS in the METABRIC cohort. In ER+ tumours, low ERCC1 transcript or protein level was associated with increased distant relapse risk (DRR). In ER−tumours, low ERCC1 transcript or protein level was linked to decreased DRR, especially in patients who received anthracycline chemotherapy. In LABC patients who received neoadjuvant anthracycline, low ERCC1 transcript was associated with higher pCR (pathological complete response) and decreased DRR. However, in patients with ER−tumours who received additional neoadjuvant taxane, high ERCC1 transcript was associated with a higher pCR and decreased DRR. High ERCC1 transcript was also linked to decreased DRR in ER+ LABC that received additional neoadjuvant taxane. ERCC1 based stratification is an attractive strategy for breast cancers.

Item Type: Journal article
Publication Title: Cancers
Creators: Abdel-Fatah, T.M.A., Ali, R., Sadiq, M., Moseley, P.M., Mesquita, K.A., Ball, G., Green, A.R., Rakha, E.A., Chan, S.Y.T. and Madhusudan, S.
Publisher: MDPI
Date: 10 August 2019
Volume: 11
Number: 8
ISSN: 2072-6694
Identifiers:
NumberType
10.3390/cancers11081149DOI
1348755Other
Divisions: Schools > School of Science and Technology
Record created by: Jonathan Gallacher
Date Added: 03 Aug 2020 15:17
Last Modified: 03 Aug 2020 15:17
URI: http://irep.ntu.ac.uk/id/eprint/40305

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