bcl-2, p53, and response to tamoxifen in estrogen receptor-positive metastatic breast cancer: A Southwest Oncology Group Study

R. M. Elledge, S. Green, L. Howes, G. M. Clark, M. Berardo, D. C. Allred, R. Pugh, D. Ciocca, P. Ravdin, J. O'Sullivan, S. Rivkin, S. Martino, C. K. Osborne

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126 Scopus citations

Abstract

Purpose: To test the hypothesis that high bcl-2 expression and accumulation of p53 protein, both of which should inhibit apoptosis, are associated with a poorer tamoxifen response and a more aggressive clinical course in estrogen receptor (ER)-positive metastatic breast cancer. Methods: A total of 205 paraffin-embedded tumor blacks were evaluated for nuclear p53 (a marker of p53 inactivation) and cytoplasmic bcl-2 by immunohistochemistry (IHC). All patients received tamoxifen as initial therapy for metastatic disease. The study began in 1982 and follow-up duration of the 24 patients last known alive is 8 years. Results: Response to tamoxifen and time to treatment failure (TTF) were not significantly associated with p53 status, although patients with higher p53 had a worse survival (P = .008; median, 36 v 20 months). Higher bcl-2 expression was associated with higher levels of ER (P= .02), better response to tamoxifen (62% v 49%; P = .07), longer TTF (median, 9 v 5 months; P = .002), and better survival (median, 40 months v 25 months; P = .009), in multivariate analyses, including ER, progesterone receptor (PgR), and p53, high bcl-2 remained significantly associated with a longer TTF (P = .007) and survival (P = .07). p53 status was a significant factor for shorter survival (P = .05), but not for TTF (P = .61). Conclusion: p53 status, as determined by IHC is not significantly-associated with response to tamoxifen, although tumors with altered p53 protein are inherently more aggressive. Contrary to expectation, high bcl-2 identifies a relatively indolent phenotype of ER-positive metastatic breast cancer, in which patients experience a better clinical response to tamoxifen and a longer survival.

Original languageEnglish (US)
Pages (from-to)1916-1922
Number of pages7
JournalJournal of Clinical Oncology
Volume15
Issue number5
DOIs
StatePublished - May 1997

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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