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ERCC1 Is a Predictor of Anthracycline Resistance and Taxane Sensitivity in Early Stage or Locally Advanced Breast Cancers - PubMed

  • ️Tue Jan 01 2019

ERCC1 Is a Predictor of Anthracycline Resistance and Taxane Sensitivity in Early Stage or Locally Advanced Breast Cancers

Tarek M A Abdel-Fatah et al. Cancers (Basel). 2019.

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.

Keywords: ERCC1; anthracycline resistance; taxane sensitivity.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1

ERCC1, adjuvant chemotherapy and survival. (A) Kaplan Meier curves showing BCSS (Breast cancer specific survival) based on ERCC1 mRNA expression in ER+ METABRIC cohort. (B) Kaplan Meier curves showing BCSS (Breast cancer specific survival) based on ERCC1 mRNA expression in ER− METABRIC cohort. (C) Kaplan Meier curves showing disease specific survival based on ERCC1 mRNA expression in ER+ Multicentre Adjuvant (Adj MC) cohort. (D) Kaplan Meier curves showing disease specific survival based on ERCC1 mRNA expression in ER− Adj MC cohort. (E) Kaplan Meier curves showing disease specific survival based on ERCC1 protein level in ER+ Adj MC cohort. (F) Kaplan Meier curves showing disease specific survival based on ERCC1 protein level in ER− Adj MC cohort.

Figure 2
Figure 2

ERCC1 and neoadjuvant chemotherapy. (A) Pathological complete response (pCR) based on ERCC1 mRNA expression in ER+ tumours (neoadjuvant anthracycline based (Neo-Adj) MC cohort) that received neoadjuvant AC or AC+T or AC+T+H chemotherapy. (B) Pathological complete response (pCR) based on ERCC1 mRNA expression in ER− tumours (Neo-Adj MC cohort) who received neoadjuvant AC or AC+T or AC+T+H chemotherapy. (C) Disease free survival based on ERCC1 mRNA expression in TOP1 cohort patients who received neoadjuvant AC chemotherapy. (D) Disease free survival based in ER− Neo-Adj MC cohort who received neoadjuvant AC+T chemotherapy. (E) Disease free survival based in ER+ Neo-Adj MC cohort who received neoadjuvant AC+T chemotherapy.

Figure 3
Figure 3

Consort diagram summarizing patient cohorts investigated in the current study.

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