In situ protein expression of RRM1, ERCC1, and BRCA1 in metastatic breast cancer patients treated with gemcitabine-including chemotherapy

Abstract

1129 Background: Ribonucleotide reductase 1 (RRM1) is a determinant of gemcitabine efficacy in non-small cell lung cancer (NSCLC) and pancreatic cancer. We investigated the tumoral levels of RRM1 in a population of metastatic breast cancer (MBC) patients treated with gemcitabine-based regimens. The protein levels of the excision repair cross-complementation group 1 (ERCC1) and breast and ovarian cancer susceptibility gene 1 (BRCA1) were also measured. Methods: Fifty-five patients were treated and followed prospectively from September 2004 to December 2007. Treatment consisted of gemcitabine plus a taxane in 46 patients and gemcitabine plus pegylated liposomal doxorubicin in 9 patients. RRM1, ERCC1, and BRCA1 were determined by automated in situ protein quantification (AQUA v1.6) on a tissue microarray containing triplicate tumor specimens. Results: The average scores for RRM1, ERCC1, and BRCA1 ranged from 245.6–2, 774.1, 74.0–410.3, and 54.4–1, 833.1, respectively. A statistically significant correlation between the levels of expression of all three markers (Spearman's rho > .36; P < 0.007) was observed. There was no significant association between RRM1, ERCC1, or BRCA1 levels and disease response, progression free survival, or overall survival. Conclusions: In tumor specimens from patients with MBC, RRM1, and BRCA1 had a range of expression and pattern of distribution that makes these markers potentially suitable for clinical decision making. In contrast, the relatively narrow range of ERCC1 expression might signify that ERCC1 protein levels are not useful predictors of platinum efficacy in MBC. Consistent with what has been shown in NSCLC, RRM1, ERCC1, and BRCA1 levels were significantly correlated, suggesting that the coexpression of such DNA repair proteins may be universal to epithelial malignancies. The lack of correlation between marker levels and clinical outcome may be explained by the specific chemotherapy combinations used. No significant financial relationships to disclose.