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

Thomas A. Buchholz, Darren W. Davis, David J. McConkey, W. Fraser Symmans, Vicente Valero, Anuja Jhingran, Susan L. Tucker, Lajos Pusztai, Massimo Cristofanilli, Francisco J. Esteva, Gabriel N. Hortobagyi, Aysegul A. Sahin

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Pages (from-to)33-41
Number of pages9
JournalCancer Journal
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

Keywords

  • Apoptosis
  • Bcl-2
  • Breast cancer
  • Docetaxel
  • Doxorubicin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Buchholz, T. A., Davis, D. W., McConkey, D. J., Symmans, W. F., Valero, V., Jhingran, A., Tucker, S. L., Pusztai, L., Cristofanilli, M., Esteva, F. J., Hortobagyi, G. N., & Sahin, A. A. (2003). Chemotherapy-induced apoptosis and Bcl-2 levels correlate with breast cancer response to chemotherapy. Cancer Journal, 9(1), 33-41. https://doi.org/10.1097/00130404-200301000-00007