Prognostic significance of tumor grade in clinical trials of adjuvant therapy for breast cancer with axillary lymph node metastasis

The prognostic significance of histologic tumor grade has been evaluated in 1537 women entered into the Ludwig Trials I‐IV of adjuvant therapy for node‐positive breast cancer. Tumor grade was determined on histologic review of primary tumor sections by two central review pathologists using a modification of the Bloom and Richardson grading system. The 5‐year overall survival rates (±SE) were: Grade 1, 86% ± 2; Grade 2, 70% ± 2; and Grade 3, 57% ± 2 (P <0.0001). This survival difference was seen in both premenopausal (P <0.0001) and postmenopausal (P <0.0001) women. Significant differences in disease‐free survival (DPS) by tumor grade were also observed (P <0.0001). The tumor grade determined by the 75 contributing local clinic pathologists was also highly significant for predicting DPS and overall survival. Tumor grade remained a statistically significant prognostic factor for DPS (P <0.0001) and overall survival (P <0.0001) in multivariate analyses controlling for nodal status, tumor size, estrogen receptor status, menopausal status, age, peritumoral vessel invasion, and treatment assigned. In postmenopausal patients for whom adjuvant treatment was compared with no adjuvant therapy, the prognostic significance of tumor grade was modified by the effect of treatment. The presence of vessel invasion by primary tumor cells was a stronger predictor of early recurrence than was increasing tumor grade in postmenopausal patients who received no adjuvant therapy. The higher failure rates for patients with high‐grade tumors was due to a larger number of failures in regional and visceral sites. Tumor grade can be determined by any pathologist and allows for selection of a subpopulation of breast cancer patients at high risk for early mortality.