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

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 metastotic breast cancer. Methods: A total of 205 paraffin-embedded tumor blocks were evaluated far nuclear p53 (a marker of p53 inactivation) and cytoplasmic bcl-2 by immunohistochemistry (IHC). All patients received tamoxifen as initial therapy for metastotic disease. The study began in 1982 and follow-up duration of the 24 patients lost known alive is 8 years. Results: Response to tamoxifen andtimetotreatment 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 tomoxifen (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 ore 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. (C) 1997 by American Society of Clinical Oncology.