ESTABLISHMENT OF HISTOLOGICAL CRITERIA FOR HIGH-RISK NODE-NEGATIVE BREAST-CARCINOMA FOR A MULTIINSTITUTIONAL RANDOMIZED CLINICAL-TRIAL OF ADJUVANT THERAPY

Background: A multi-institutional randomized clinical trial of adjuvan t therapy for patients with high-risk node-negative (n0) breast cancer has been undertaken in Japan. The pathology panel was organized in or der to establish histological criteria to identify patient groups with higher rates of recurrence. Methods: Initially, three pathologists in dependently judged the nuclear grade, composed of nuclear atypia and m itotic counts, of 100 n0 invasive ductal carcinomas, focusing on inter observer variation of the nuclear grade and its correlation with patie nt prognosis. These pathologists then gave consensus histological type s and nuclear grades for 130 other n0 breast carcinomas and examined t he prognostic significance of the grade. Results: In the first study, nuclear grade 2-3 significantly identified a patient group with a rate of recurrence of 17-20% by any pathologists and the degree of agreeme nt for the grade was fair. In the second study the consensus type and nuclear grade identified a group (n = 66) with a 22% recurrence rate a nd another group (n = 64) with a 3.6% recurrence rate at 10 years. In 12 tumors, the resection-fixation interval of the tumor did not genera te any significant difference in mitotic counts. Conclusions: The hist ological type and the nuclear grade clearly identified a higher-risk p atient group with n0 breast carcinoma, and may be applied to the multi -institutional protocol study when the criteria have been well standar dized by the pathologists.