ERCC1 expression affects outcome in metastatic pancreatic carcinoma treated with FOLFIRINOX: A single institution analysis.

INTRODUCTION: No clinically useful predictive factor has been yet identified for treatment of metastatic pancreatic cancer (mPC). It is noteworthy that FOLFIRINOX, despite its high toxicity, is effective only in some patients. We retrospectively analyzed expression of excision repair cross-complementing group-1 (ERCC1) - involved in the repair of platinum induced damage - in patients affected by mPC treated with FOLFIRINOX in order to evaluate its predictive role. RESULTS: FOLFIRINOX resulted more effective in patients with normal ERCC1 levels than in those with ERCC1 hyper-expression. Median progression free survival (PFS) was 11 vs. 4 months (HR 0.26; 95% CI 0.14-0.50; p<.0001), median overall survival (OS) 16 vs. 8 months (HR 0.23; 95% CI 0.12-0.46; p<.0001) and disease control rate (DCR) 93% vs. 50% (p=0.00006). The advantage was confirmed at univariate and multivariate analysis. PATIENTS AND METHODS: 71 patients with histologically proven mPC and treated with FOLFIRINOX as first-line therapy were considered eligible. mRNA ERCC1 expression was determined using RT-PCR analysis. DISCUSSION: ERCC1 might be an effective predictor of response to FOLFIRINOX in mPC. Patients overexpressing ERCC1 should be excluded by this often toxic therapy and referred to an alternative treatment.

Hormone Receptor Status and HER2 Expression in Primary Breast Cancer Compared With Synchronous Axillary Metastases or Recurrent Metastatic Disease.

Estrogen receptor (ER), progesterone receptor (PR), and HER2/neu are the most important tissue markers in the management of breast cancer, in the adjuvant setting and in the setting of metastatic disease. Many studies have demonstrated a discordance of expression between primary breast cancer, synchronous axillary metastases, and metastatic sites. The aim of this article is to review studies on discordance of expression of these predictive parameters to better understand the importance of a reassessment of biomolecular status to modify treatment strategies. We performed a literature review to identify studies that assessed ER, PR, and HER2 discordance between primary breast cancer, synchronous axillary lymph node metastasis, and other metastatic sites. We reviewed these data related to (1) relevance of discordance rates in clinical practice and (2) therapeutic consequences of discordance rate. Results were analyzed qualitatively. Changes in ER and particularly in PR are observed in locoregional and in distant metastases reaching a rate of 10% to 30% for ER and 20% to 50% for PR. The loss of PR is more frequent than ER loss. High HER2 concordance between primary tumors and axillary lymph node or distant metastases has been demonstrated in many studies; in the discordant cases, it is more frequent to have HER2-positive metastases with negative primary tumors than the opposite. A reassessment of biomolecular status in residual tumors after neoadjuvant treatment or in metastatic sites is advisable, whenever it is possible, to correct/modify the treatment schedule and to estimate the actual prognosis.