DNA FLOW-CYTOMETRY AND PATHOLOGICAL GRADING AS PROGNOSTIC GUIDES IN AXILLARY LYMPH NODE-NEGATIVE BREAST-CANCER

Background. The recurrence or mortality rate of axillary lymph node-ne gative invasive breast cancer has been associated with the tumor S-pha se fraction, which is measured by DNA flow cytometry. Because many of the studies that established this association were performed using fro zen, pulverized tumor specimens, this association could not be tested for independence from the established prognostic factors of histologic and nuclear grading. Methods. Histologic, nuclear, and mitotic grades , DNA ploidy, and S-phase fraction (SPF) were determined from paraffin -embedded tumors obtained from 280 women with node-negative invasive d uctal carcinomas using standard grading schemes and flow cytometric te chniques. These variables were compared with disease-free and cancer-s pecific survival (CSS) in univariate and multivariate analyses of thes e patients. Results. Tumor diameter, SPF, histologic grade, and nuclea r grade were significant predictors of disease-free survival (DFS); di ameter and SPF had significant associations with CSS. Cox analysis sho wed histologic grade to be the only independent predictor of relapse, whereas diameter and SPF were independent predictors of mortality. The patients with low nuclear or histologic grade tumors had only a 5% ri sk of recurrence at 5 years. In contrast, 36% of patients in this seri es with medium-grade or high-grade high SPF tumors had a 30% risk of r ecurrence over the same interval. Conclusions. Histopathologic grading and flow cytometric determination of SPF appear to provide additive p rognostic information for patients with early invasive ductal carcinom as of the breast.