Chemotherapy-Induced Apoptosis and Bcl-2 Levels Correlate with Breast Cancer Response to Chemotherapy


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Abstract

PURPOSEThe 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 METHODSSerial 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.RESULTSThe 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.DISCUSSIONThese 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.

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