Prognostic value of Bcl-2 in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy

VARGAS ROIG L. M.; CUELLO CARRIÓN F. D.; FERNÁNDEZ ESCOBAR N.; DAGUERRE P.; LEUZZI M.; IBARRA J.; GAGO F. E.; NADIN S. B.; CIOCCA D. R.

Chicago, IL, USA

Congreso; 44rd American Society of Clinical Oncology Annual Meeting; 2008

Americam Society of Clinical Oncology

Background: Bcl-2 has important roles in apoptosis, cell proliferation and cell differentiation in breast cancer. The value of Bcl-2 protein as predictive/prognostic factor to adjuvant treatment in breast cancer has been investigated. However, there are few analyses in a homogeneous group of patients treated with neoadjuvant chemotherapy. We analyzed Bcl-2 in pre- and post-chemotherapy biopsies and correlated its expression with clinical and pathological response, and with disease-free survival (DFS) and overall survival (OS) in patients treated with neoadjuvant chemotherapy. Methods: One hundred and ten patients were submitted to two different chemotherapeutic regimens: a) fluorouracil, doxorubicin or epirubicin, and cyclophosphamide (FAC/FEC) during 2 to 6 cycles before surgery and 3 or 4 additional cycles of FAC/FEC after surgery (n = 40) and b) doxorubicin (D) 75 mg/m2 or epirubicin (E) 120 mg/m2 during 4 cycles before surgery, and 6 cycles of cyclophosphamide, methotrexate, and fluorouracil after surgey (n = 70). Pre- and post-chemotherapy samples were immediately fixed and embedded in paraffin for studies (H&E, immunohistochemistry, TUNEL). Kaplan-Meier method, Wilcoxon signed rank test, Spearman´ s rank correlation coefficient, Fisher´s exact test, logistic regression and Cox models were used. Results: Bcl-2 expression did not change significantly after chemotherapy and was not related to clinical/pathologic response. The expression of Bcl-2, Bax and p53 evaluated before chemotherapy did not correlate with the clinical and pathologic response. In FAC/FEC group, Bcl-2 expression after chemotherapy correlated with better DFS and OS (P = 0.008 and P = 0.001), and ERalfa expression showed a tendency to correlate with longer DFS (P = 0.052) but not with OS (P = 0.08). In D/E group, Bcl-2 correlated with better DFS and OS (P = 0.03 and P = 0.054) in the post-chemotherapy biopsies, and ERalfa was associated with longer DFS (P = 0.004) and OS (P = 0.04). An unusual nuclear localization of Bax was observed in some biopsies, but this localization did not correlate with the tumor response or outcome of the patients. Conclusions: A high Bcl-2 expression had prognostic value in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy.