EXPRESSION OF BCL-2 PROTEIN PREDICTS EFFICACY OF ADJUVANT TREATMENTS IN OPERABLE NODE-POSITIVE BREAST-CANCER

The proto-oncogene bcl-2 encodes a protein that inhibits apoptosis, a common mechanism of cell death caused by hormone and chemotherapy, We have analyzed bcl-2 protein expression by immunocytochemistry in prima ry node-positive breast cancers in two groups of patients (for a total of 180 cases), One group received adjuvant hormone therapy, the other chemotherapy (cyclophosphamide, methotrexate, and fluorouracil), and both groups were followed for a median time of 63 months, We compared our findings with conventional clinicopathological indicators [menopau sal status, number of axillary nodes, histological grade, tumor size a nd type, estrogen receptor (ER), and progesterone receptor] and with p 53 protein expression, bcl-2 protein was present in 65% of the carcino mas (117/180) and it was significantly associated with ER and progeste rone receptor and inversely associated with p53 in both the groups of patients treated with adjuvant chemotherapy and tamoxifen, In patients treated either with adjuvant chemotherapy or tamoxifen, relapse-free survival at 5 years was significantly better among patients with bcl-2 -positive tumors than in those with bcl-2 negative ones (P = 0.05 and 0.02, respectively), As far as overall survival is concerned, patients with bcl-2-positive tumors had a significantly better outcome in the group treated with adjuvant chemotherapy (P = 0.03), Multivariate anal yses were performed for the two treatment groups, In the group treated with tamoxifen, lack of expression of ER and of bcl-2 was the only si gnificant and independent predictor for poor relapse-free survival (P < 0.01), A number of nodes above 3 was the only significant and indepe ndent predictor for poor overall survival (P < 0.01), In the cyclophos phamide-methotrexate-fluorouracil-treated group, bcl-2 absence was sig nificant for poor overall survival (P = 0.02) as well as a number of n odes above 3 (P = 0.01) and a tumor size above 2 cm (P = 0.05), For po or relapse-free survival only a number of nodes above 3 (P < 0.01) and progesterone negativity (P = 0.02) were significant and independent p redictors of a higher probability of relapse, Thus, in contrast to iii vitro data on drug resistance, bcl-2 expression was associated with b etter outcomes in patients treated,vith hormone and chemotherapy, Over all, these results suggest that expression of bcl-2 protein and the nu mber of metastatic lymph nodes are independent features predictive of clinical outcome in patients with node-positive breast cancer, irrespe ctive of the type of adjuvant treatment, The determination of bcl-2 pr otein may prove to be a useful tool to distinguish patients for whom c onventional forms of adjuvant therapy are beneficial from those with b cl-2 negative and ER-negative tumors for whom novel therapeutic strate gies are needed.