Apoptosis and Expression of Bcl-2 and Bax Proteins in Breast Cancer Patients Treated with Induction Chemotherapy

VARGAS ROIG, L.M.; FERNANDEZ-ESCOBAR, N.; GAGO, F.E.; CIOCCA, D.R.

New Orleans

Congreso; 92nd Annual Meeting of the American Association for Cancer Research; 2001

American Association for Cancer Research

Apoptosis is one of the main mechanisms of tumor cell death induced by chemotherapeutics agents and alterations of this process may confer drug resistance. In this study we have analyzed whether the apoptotic index and the expression of Bcl-2 and Bax proteins may be determinants of tumor sensitivity/resistance in locally advanced breast cancer patients (n=29) treated with induction chemotherapy. All patients received FAC or FEC (5-fluorouracil, adryamicin or epirubicin, and ciclophosphamide), the follow-up was 7-60 months (median=30 months). Apoptosis was evaluated in paired pre- and post-chemotherapy biopsies (n=16) and in post-chemotherapy biopsies (n=13) by digoxigenin-labeled genomic DNA and by cell morphology. Immunohistochemistry was performed to evaluate expression of Bcl-2 and Bax. We did not find significant changes in the apoptotic index and in the expression of the proteins after chemotherapy (biopsies taken about 20 days after the last chemotherapy). Distant metastases (study end-point) were observed in 64% (14/22) of patients. Elevated Bcl-2 protein expression was found in 100% of disease free patients; in contrast, high Bcl-2 was noted in 58% of patients with distant metastasis (p=0.04, Fisher test) and in 37.5% of the patients who died (p=0.002). Disease free survival (DFS) and overall survival (OS) curves between Bcl-2 positive and Bcl-2 negative patients were statistically significant (p<0.0001). No correlation between apoptotic index, Bax expression or Bcl-2/Bax with DFS or OS was found. These results suggest that Bcl-2 protein expression is associated with drug sensitivity in patients treated with induction chemotherapy receiving relatively high doses of anthracyclines.