P53 STATUS PREDICTS SURVIVAL IN BREAST-CANCER PATIENTS TREATED WITH OR WITHOUT POSTOPERATIVE RADIOTHERAPY - A NOVEL HYPOTHESIS BASED ON CLINICAL FINDINGS

Purpose and Methods: Primary breast cancer tumors without axillary metastases from 206 consecutive patients in a population-based cohort were investigated with regard to the presence of an intact p53 gene using a cDNA based sequencing method. Clinical follow-up data and outcome of node-negative patients without any adjuvant systemic therapy (n = 168)were related to locoregional radiotherapy and p53 status. Results: Mutations in p53 occurred in 31 node-negative breast cancer patients who did not receive any systemic adjuvant treatment, but were treated with postoperative locoregional radiotherapy or nothing. Node-negative breast cancer patients with p53 mutations had significantly improved relapse-free survival (P = .0007), breast cancer corrected survival (P = .01), and overall survival (P = .02) rates when treated with locoregional radiotherapy. In node-negative breast cancer patients with wild-type p53, there was no statistically significant difference in outcome between patients who received lo coregional radiotherapy and those who did not. Cox proportional hazards models indicate that mutant p53 is associated with worse prognosis independent of response to radiotherapy and that response to radiotherapy is qualitatively different in tumors with p53 mutations compared with those with wild-type p53. Conclusion: Our clinical findings define a group of breast cancer patients in whom locoregional radiotherapy improves relapse-free, breast cancer-corrected, and overall survival. The outcome for irradiated node-negative breast cancer patients with p53 alterations indicates that irradiation can induce cell death even in the presence of p53 mutations. (C) 1995 by American Society of Clinical Oncology.