Chemotherapy-Induced Apoptosis and Bcl-2 Levels Correlate with Breast Cancer Response to Chemotherapy.
Buchholz, Thomas A. MD a; Davis, Darren W PhD b; McConkey, David J. PhD b; Symmans, W Fraser MD c; Valero, Vicente MD d; Jhingran, Anuja MD a; Tucker, Susan L. PhD e; Pusztai, Lajos MD, PhD d; Cristofanilli, Massimo MD d; Esteva, Francisco J. MD d; Hortobagyi, Gabriel N. MD d; Sahin, Aysegul A. MD c
9(1):33-41, January/February 2003.
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PURPOSE: The relevance of apoptosis to breast cancer response to chemotherapy is unclear. We investigated whether changes in tumor cell apoptosis and Bcl-2 expression immediately after chemotherapy correlated with response to breast cancer treatment.
PATIENTS AND METHODS: Serial core biopsies of 25 breast cancer primary tumors were performed at either two or three time points: before treatment (N = 24) and approximately 24 hours (N = 22) and/or 48 hours (N = 19) after the initiation of the first cycle of chemotherapy. Apoptosis levels were quantified by use of a fluorescent terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) stain, and Bcl-2 and Bax were measured by semiquantitative immunohistochemical assays. All calculated P values were two sided.
RESULTS: The apoptosis level at 48 hours was significantly higher in the tumors with pathological complete response or < 1 cm of residual disease (median, 22%; range, 6%-51%) than in the tumors with > 1 cm residual disease (median, 7%; range, 1%-36%); Mann-Whitney test. This difference was also present in the subgroup of 16 tumors treated with docetaxel/doxorubicin chemotherapy (25% vs 4%, respectively). A decrease in Bcl-2 expression after chemotherapy relative to the expression from the pretreatment sample also correlated with disease response. Specifically, three of the nine tumors with a decrease in Bcl-2 had a pathological complete response, compared with 0 of the 15 tumors with stable levels of Bcl-2 (Fisher's exact test). There was no relationship between serial measurements of Bax and response.
DISCUSSION: These data suggest that apoptosis may play an important role in determining breast cancer response to chemotherapy and that the level of treatment-induced apoptosis may have some value as a predictive marker.
(C) 2003 Lippincott Williams & Wilkins, Inc.