Decrease in bcl-2 expression shortly after neoadjuvant chemotherapy predicts primary breast cancer response to treatment

Molecular events immediately after chemotherapy may affect breast cancer response to treatment. Previous in vivo data from our institution suggested that the degree of therapy-induced apoptosis, measured within 72 hours after treatment, correlated with breast cancer response to taxane chemotherapy. We performed this study to investigate whether apoptosis-related biomarkers can be used to predict treatment response in breast cancer patients treated with neoadjuvant chemotherapy. Methods: Biomarker data were available on 25 out of the 30 patients with locally advanced breast cancer who underwent serial core biopsies of the primary tumor at 3 time points: pretreatment, 24 hours after chemotherapy and 48 hours after chemotherapy. The neoadjuvant chemotherapy was docetaxel/ doxorubicin in 16 patients, single-agent paclitaxel in 8 patients, and 5-flourouracil, doxorubicin, cyclophosphamide in 1 patient. Bcl-2, bax, and p53 were studied with immunohistochemistry using semi-quantitative values. Results: After the neoadjuvant chemotherapy. 4 patients had a pathological complete response (CR) of the primary tumor, 7 additional patients had disease measuring <1 cm, and the remaining 14 had >1cm of residual disease. There was no correlation of response to pretreatment measurements of p53, bcl-2, or bax. However, a decrease in bcl-2 expression after chemotherapy relative to the expression from the pretreatment sample correlated with a favorable pathological response (CR versus non-CR, p=0.010 - Fisher's exact test). (CR + <1cm versus >1cm, p=0.026). There was no relationship between the serial measurements of bax and disease response. Conclusion: We demonstrated that a decrease in bcl-2 expression immediately after treatment predicts response of breast cancer to neoadjuvant chemotherapy. These data suggest that apoptosis may play an important role in determining breast cancer response to chemotherapy.