Invasive Breast Cancer Treated with Taxol and Epirubicin Neo-adjuvant Chemotherapy: The Role in the Outcome of the “Crosstalk” between Erb Receptors and p53

Abstract

Purpose: To correlate p53 and ErbB receptors status with disease-free survival (DFS) and overall survival (OS) in locally advanced breast cancer. Patients and Methods: Sixty patients were included in a single-center, open-label, phase II trial (1998-2003). Analysis of Erb receptors and p53 status and estrogen receptor/progesterone receptor data were available for 33 patients. Neoadjuvant epirubicin 75 mg/m² and paclitaxel 175-200 mg/m² were administered every 21 days. The patients underwent surgery and radiation therapy and adjuvant chemo/hormonotherapy. Results: Approximately two thirds of the patients demonstrated overexpression of ErbB receptors and had mutant p53 overexpression. The disease recurred in 11/33 patients and 7 died (median follow-up 56 months). Detrimental effects on OS were established in cases of combined defective p53 expression and ErbB1-ErbB3 heterodimeric receptor overexpression. In contrast, normal p53 together with the same overexpressed heterodimeric combination of ErbB receptors showed no statistically significant effect. Conclusion: In terms of the clinical impact of combinations of ErbB receptors with or without mutant p53, only the overexpressed various ErbB1-ErbB3 dimeric combinations and the ErbB1/ErbB2/ErbB3 triplet combination with mutated p53 were related to a significantly poorer outcome. This observation may help in the development of new strategies required for blocking these molecular pathways and improving the outcome of patients with locally advanced breast cancer.