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 accumul ation of p53 protein, both of which should inhibit apoptosis, are asso ciated with a poorer tamoxifen response and a more aggressive clinical course in estrogen receptor (ER)-positive metastotic breast cancer. M ethods: A total of 205 paraffin-embedded tumor blocks were evaluated f ar nuclear p53 (a marker of p53 inactivation) and cytoplasmic bcl-2 by immunohistochemistry (IHC). All patients received tamoxifen as initia l therapy for metastotic disease. The study began in 1982 and follow-u p duration of the 24 patients lost known alive is 8 years. Results: Re sponse to tamoxifen andtimetotreatment failure (TTF) were not signific antly associated with p53 status, although patients with higher p53 ha d a worse survival (P=.008; median, 36 v 20 months). Higher bcl-2 expr ession was associated with higher levels of ER (P=.02), better respons e 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: p5 3 status, as determined by IHC is not significantly associated with re sponse to tamoxifen, although tumors with altered p53 protein ore inhe rently more aggressive. Contrary to expectation, high bcl-2 identifies a relatively indolent phenotype of ER-positive metastatic breast canc er, in which patients experience a better clinical response to tamoxif en and a longer survival. (C) 1997 by American Society of Clinical Onc ology.