EXPRESSION OF BCL-2 IN NODE-NEGATIVE BREAST-CANCER IS ASSOCIATED WITHVARIOUS PROGNOSTIC FACTORS, BUT DOES NOT PREDICT RESPONSE TO ONE COURSE OF PERIOPERATIVE CHEMOTHERAPY

The aim of this study was to assess relationships between Bcl-2 expres sion, response to chemotherapy and a number of pathological and biolog ical tumour parameters in premenopausal, lymph node-negative breast ca ncer patients. Expression of Bcl-2 was determined using immunohistoche mistry on paraffin-embedded sections in a series of 441 premenopausal, lymph node-negative breast cancers of patients randomised to receive perioperative chemotherapy (5-fluorouracil, doxorubicin, cyclophospham ide) or no perioperative chemotherapy. Immunohistochemistry of Bcl-2 w as evaluated by scoring both staining intensity (0-3) and number of po sitive cells (0-2). Using these scores tumours were grouped into categ ories 0-6. It was found that 9.2% of the rumours were completely negat ive (0), 17.2% weakly (1 + 2), 41.6% moderately (3 + 4) and 31.9% stro ngly positive (5 + 6) for Bcl-2. A positive correlation was found betw een high Bcl-2 expression and oestrogen (P < 0.001) and progesterone r eceptor positivity (P < 0.001) and low tumour grade (P < 0.001), where as high Bcl-2 expression was negatively correlated with p53 (P < 0.001 ) and c-erb-B-2 positivity (P < 0.001), high Ki-67 index (P < 0.001), mitotic index (P < 0.001) and large tumour size (P = 0.006). Patients with tumours expressing high levels of Bcl-2 (overall score 3-6) had a significantly batter disease-free (P = 0.004) and overall (P = 0.009) survival. However, in a multivariate model this association no longer remained significant. There was a trend for an effect of adjuvant che motherapy on disease-free survival both for patients with Bcl-2-positi ve (HR-0.61, 95% CI 0.35-1.06, P = 0.07) and negative (HR = 0.55, 95% CI 0.27-1.12, P = 0.09) breast tumours at a median Follow-up of 49 mon ths. The level of Bcl-2 expression does not seem to predict response t o perioperative chemotherapy in premenopausal, lymph node-negative bre ast cancer patients. High levels of Bcl-2 are preferentially expressed in well-differentiated tumours and are associated with favourable pro gnosis. However, Bcl-2 expression is not an independent prognostic fac tor in this patient series.