Expression of ERCC1 in triple-negative breast cancer.

Abstract

e11064 Background: Triple-negative breast cancer (TNBC) comprises 15% of breast cancers. Since TNBC lack the available targets of treatment, cytotoxic therapy is the standard approach. Platinum-based chemotherapy regimens seem promising in this setting. Excision repair cross-complementation group 1 (ERCC1) which is a component of nucleotide excision repair (NER) pathway removes platinum induced DNA adducts. Over expression of ERCC1 has been associated with resistance to platinum-based chemotherapy in ovarian and lung cancers. Detecting ERCC1 over expression is important in planning treatment options for TNBC and conducting trials that are investigating specific chemotherapy regimen for TNBC. Methods: Monoclonal antibody against ERCC1 (clone 8F1, Neomarkers) was used for analyzing immunohistochemical expression of ERCC1. Two experienced pathologists blinded to clinical data evaluated ERCC1 expression in 45 TNBC patients' tumor samples. A semi-quantitative H score was calculated by multiplying staining intensity with extent score. Tumors with H-score ≥ 1 classified as ERCC1 positive. Results: Positive ERCC1 expression was found in 73.3% of the tumor samples with an H score ≥ 1 and 26.7% of the tumor samples stained negative with an H score less than 1. 15.5% of the tumor samples stained diffusely and intensively with ERCC1 antibody. Higher ERCC1 expression tended to be correlated with tumor grade (Pearson's correlation coefficient, 0.22; p = 0.14) and family history of cancer (Pearson's correlation coefficient, 0.29; p = 0.053). ERCC1 expression was not correlated with any of the following clinical parameters; age at diagnosis, menopausal status, stage, history of cancer, recurrence in follow-up period. Conclusions: Our results demonstrate that about two thirds of the TNBC showed a relevant expression of ERCC1 that may be predictive of a poor response to platinum-based chemotherapies. Dysfunction of other DNA repair enzymes such as inactivation of BRCA-1 may explain higher sensitivity to cisplatin in TNBC patients. No significant financial relationships to disclose.