Chemotherapy-induced apoptosis and Bcl-2 levels correlate with breast cancer response to chemotherapy

Cancer J. Jan-Feb 2003;9(1):33-41. doi: 10.1097/00130404-200301000-00007.

Abstract

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 Bcl2 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Apoptosis / drug effects*
  • Biomarkers, Tumor / metabolism
  • Biopsy / methods
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery
  • Docetaxel
  • Doxorubicin / therapeutic use*
  • Female
  • Humans
  • In Situ Nick-End Labeling
  • Middle Aged
  • Neoplasm, Residual / drug therapy
  • Neoplasm, Residual / pathology
  • Neoplasm, Residual / surgery
  • Paclitaxel / analogs & derivatives*
  • Paclitaxel / therapeutic use*
  • Predictive Value of Tests
  • Prospective Studies
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Taxoids*
  • Time Factors

Substances

  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-bcl-2
  • Taxoids
  • Docetaxel
  • Doxorubicin
  • Paclitaxel