Establishment of histological criteria for high-risk node-negative breast carcinoma for a multi-institutional randomized clinical trial of adjuvant therapy. Japan National Surgical Adjuvant Study of Breast Cancer (NSAS-BC) Pathology Section

BACKGROUND: A multi-institutional randomized clinical trial of adjuvanttherapy for patients with high-risk node-negative (n0) breast cancer hasbeen undertaken in Japan. The pathology panel was organized in order toestablish histological criteria to identify patient groups with higherrates of recurrence. METHODS: Initially, three pathologists independentlyjudged the nuclear grade, composed of nuclear atypia and mitotic counts, of100 n0 invasive ductal carcinomas, focusing on interobserver variation ofthe nuclear grade and its correlation with patient prognosis. Thesepathologists then gave consensus histological types and nuclear grades for130 other n0 breast carcinomas and examined the prognostic significance ofthe grade. RESULTS: In the first study, nuclear grade 2-3 significantlyidentified a patient group with a rate of recurrence of 17-20% by anypathologists and the degree of agreement for the grade was fair. In thesecond study, the consensus type and nuclear grade identified a group (n =66) with a 22% recurrence rate and another group (n = 64) with a 3.6%recurrence rate at 10 years. In 12 tumors, the resection-fixation intervalof the tumor did not generate any significant difference in mitotic counts.CONCLUSIONS: The histological type and the nuclear grade clearly identifieda higher-risk patient group with n0 breast carcinoma, and may be applied tothe multi-institutional protocol study when the criteria have been wellstandardized by the pathologists.