Clinicopathologic Significance of Excision Repair Cross-Complementation 1 Expression in Patients Treated With Breast-Conserving Surgery and Radiation Therapy

Purpose: The excision repair cross-complementation 1 (ERCC1) enzyme plays a rate-limiting role in the nucleotide excision repair pathway and is associated with resistance to platinum-based chemotherapy in cancers of the head and neck and the lung. The purpose of this study was to evaluate the clinicopathologic and prognostic significance of ERCC1 expression in a cohort of early-stage breast cancer patients treated with breast conservation therapy. Methods and Materials: Paraffin specimens from 504 women with early-stage breast cancer treated with breast conservation therapy were constructed into tissue microarrays. The array was stained for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) and ERCC1. This was then correlated with clinicopathologic factors and outcomes data. Results: ERCC-1 expression was evaluable in 366 cases (72%). In this group, 32% and 38% of patients received adjuvant chemotherapy and hormonal therapy, respectively. Increased ERCC-1 expression was found to be correlated with ER positivity (p \u3c 0.005), lower T stage (p \u3c 0.017), nodal negativity (p \u3c 0.013), age \u3e50 (p \u3c 0.006), reduced use of adjuvant chemotherapy (p \u3c 0.02), and increased use of adjuvant hormonal therapy (p \u3c 0.004). ERCC1 expression did not correlate with locoregional recurrence-free survival, distant metastasis-free survival, cause-specific survival, or overall survival. In patients who were both ERCC1-negative and -positive, the use of chemotherapy predicted for worse distant metastasis-free survival (p = 0.05 and p = 0.07, respectively) but not cause-specific survival or overall survival. Conclusions: Although ERCC1 expression did not predict for outcome measures in this dataset, overexpression correlated with favorable prognostic factors such as ER positivity, lower T stage, nodal negativity, and age \u3e50. To our knowledge, this is the first study investigating ERCC1 expression in patients receiving adjuvant radiation therapy for breast cancer. © 2010 Elsevier Inc. All rights reserved