TY - JOUR
T1 - Decrease in bcl-2 expression shortly after neoadjuvant chemotherapy predicts primary breast cancer response to treatment
AU - Buchholz, T. A.
AU - Valero, V.
AU - Gilcrease, M.
AU - Symmans, W. F.
AU - Tucker, S. L.
AU - McConkey, D. J.
AU - Pusztai, L.
AU - Davis, D.
AU - Hortobagyi, G. N.
AU - Sahin, A.
N1 - Copyright:
Copyright 2006 Elsevier B.V., All rights reserved.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33749110614&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33749110614&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:33749110614
SN - 0167-6806
VL - 69
SP - 244
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 3
ER -