Human breast cancer susceptibility to paclitaxel therapy is independent of Bcl-2 expression

Susan M. Poelman, Moses O. Adeyanju, Maria Antonia Robertson, Wendy M. Recant, Theodore Karrison, Gini F. Fleming, Olufunmilayo I. Olopade, Suzanne D. Conzen

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Abstract

In laboratory studies, ectopic overexpression of the antiapoptotic protein Bcl-2 has been shown to result in resistance to the cytotoxic effects of many chemotherapeutic drugs. Furthermore, posttranslational modification of moderately expressed endogenous Bcl-2 has been correlated with susceptibility to paclitaxel treatment in vitro. To determine whether tumor expression of Bcl-2 protein correlates with response and ultimate outcome in vivo, we quantified Bcl-2 expression by immunohistochemical analysis of archived biopsy specimens from metastatic breast cancer patients treated with single-agent paclitaxel. The statistical association between the degree of Bcl-2 expression, objective tumor response, and clinical outcome was then determined. In patients (n = 39) whose tumors had low (≤10% cells positive) Bcl-2 levels by immunohistochemical analysis, the overall response (complete response + partial response) rate was 21% versus an overall response rate of 22% in patients (n = 36) with high (>10% cells positive) Bcl-2 expression (P = 0.92). In patients with low Bcl-2 expression, the median time to progression was 126 days [95% confidence interval (CI), 63-160 days]. This was not significantly different than the 105 days for patients with high tumor Bcl-2 expression (95% CI, 84-214 days). The median survival time from initiation of paclitaxel therapy for patients with low Bcl-2 expression was 663 days (95% CI, 456-1119 days) and was not significantly different than the 450 days (95% CI, 239-1058 days) observed for patients with high Bcl-2 expression. In conclusion, we found that in metastatic breast cancer, there is no significant association between tumor Bcl-2 expression and response to paclitaxel, median time to progression, or survival, suggesting that the main mechanism of paclitaxel-induced cytotoxicity in breast tumors is independent of Bcl-2 expression.

Original languageEnglish (US)
Pages (from-to)4043-4048
Number of pages6
JournalClinical Cancer Research
Volume6
Issue number10
StatePublished - Jan 1 2000

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Poelman, S. M., Adeyanju, M. O., Robertson, M. A., Recant, W. M., Karrison, T., Fleming, G. F., Olopade, O. I., & Conzen, S. D. (2000). Human breast cancer susceptibility to paclitaxel therapy is independent of Bcl-2 expression. Clinical Cancer Research, 6(10), 4043-4048.