p53 and bcl-2 expression correlates with clinical outcome in a series of node-positive breast cancer patients

Background and Purpose: The tumor-suppressor gene TP53 and the proto-oncogene bcl-2 encode, respectively, for a nuclear phosphoprotein and for a mitochondrial protein involved in multiple cellular functions, The proteins provide prognostic information in node-negative breast cancer and are supposed to influence treatment responsiveness. We analyzed the predictive role of p53 and bcl-2 expression, alone and in association with other variables, in postmenopausal women with node-positive, estrogen receptor-positive (ER+) breast cancers treated with radical or conservative surgery plus radiotherapy and adjuvant tamoxifen for at least 1 year. Patients and Methods: On 240 resectable cancers, we determined the expression of p53 and bcl-2, using immuno-histochemistry, cell proliferation (H-3-thymidine labeling index [H-3-dT LI]), and ER and progesterone receptors (PgR). Results: p53 expression and 3H-dT LI were weakly related to one another and both were unrelated to bcl-2, Relapse-free and distant metastasis-free survival at 5 years were significantly lower for patients with tumors that highly expressed p53 (P = .0001) and for those that weakly expressed or did not express bcl-2 (P = .02). However, p53, but not bcl-2, provided prognostic information independent of tumor size, axillary node involvement, steroid receptors, and H-3-dT LI. Moreover, the simultaneous p53 overexpression and lack of PgR identified patients at maximum risk of relapse, whereas bcl-2 overexpression, associated with a low 3H-dT LI or the presence of PgR, improved the prognostic resolution for low-risk patients. Conclusion: p53 expression appears to be indicative of clinical outcome in postmenopausal patients treated with tamoxifen, Whether p53 overexpression and weak bcl-2 expression are indicators of biologic aggressiveness, regardless of treatment, or of hormone resistance remains to be defined. (C) 1996 by American Society of Clinical Oncology.