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 met astases from 206 consecutive patients in a population-based cohort wer e investigated with regard to the presence of an intact p53 gene using a cDNA based sequencing method. Clinical follow-up data and outcome o f node-negative patients without any adjuvant systemic therapy (n = 16 8)were related to locoregional radiotherapy and p53 status. Results: M utations in p53 occurred in 31 node-negative breast cancer patients wh o did not receive any systemic adjuvant treatment, but were treated wi th postoperative locoregional radiotherapy or nothing. Node-negative b reast cancer patients with p53 mutations had significantly improved re lapse-free survival (P = .0007), breast cancer corrected survival (P = .01), and overall survival (P = .02) rates when treated with locoregi onal radiotherapy. In node-negative breast cancer patients with wild-t ype 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 radiotherap y and that response to radiotherapy is qualitatively different in tumo rs with p53 mutations compared with those with wild-type p53. Conclusi on: Our clinical findings define a group of breast cancer patients in whom locoregional radiotherapy improves relapse-free, breast cancer-co rrected, and overall survival. The outcome for irradiated node-negativ e breast cancer patients with p53 alterations indicates that irradiati on can induce cell death even in the presence of p53 mutations. (C) 19 95 by American Society of Clinical Oncology.