589 Background: Only 20% of patients with breast cancer (BC) benefit from their treatment and there is an urgent need to identify biological markers which could be used to tailor treatment to individual patients, thereby avoiding unnecessary toxicity. Most chemotherapy agents preferentially target continuously cycling cells, which results in mitotic catastrophe and apoptosis. We therefore hypothesized that the level of Bcl2 protein, which is a cell cycle/apoptosis regulator, could predict response and clinical outcome, following chemotherapy for BC.
METHODS
Bcl2 expression was immunohistochemically evaluated in 2650 patients with primary BC, who received neoadjuvant and/or adjuvant therapy, from four independent series; a) 240 locally advanced primary BC patients treated with an anthracycline-based combination b) 245 BC patients treated with surgery followed by anthracycline-based chemotherapy, c) 145 patients with BC with HER-2 overexpression treated with surgery followed by trastuzumab and d) 2000 consecutive cases of primary BC in which adjuvant CMF and/or tamoxifen therapies were prescribed.
RESULTS
Low Bcl2 expression was associated with poor clinical outcome in patients who received CMF, tamoxifen and/or trastuzumab compared to high Bcl2 expression (p=0.01). After anthracycline-based neo-adjuvant chemotherapy, 18/58 (31%) of low Bcl2 expression BC achieved pCR vs. 8/97 (8%) of high Bcl2 expression BC (p=0.00023). In a multivariate analysis, Bcl2 expression remained an independent predictor for pCR (p<0.02). In the ER+ subgroup, 4/11 (36%) of low Bcl2 expression BC achieved a pCR compared to 3/70 (4%) of high Bcl2 expression BC (p=0.0004) and the progression free survival of low and high Bcl2 expression BC was similar despite on-going treatment with adjuvant hormonal therapy.
CONCLUSIONS
Anthracycline based neo-adjuvant chemotherapy is an effective treatment for low Bcl2 expression BC, even in ER+ tumours. Bcl2 expression should be included in the prognostic and predictive panel of markers for management of BC. Clinical trials based on Bcl2 expression are warranted.