Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: Results from the Eastern Cooperative Oncology Group companion study, EST 4189

Purpose: The identification of a subset of patients with axillary lymph node-positive breast cancer with an improved prognosis would be clinically useful. We report the prognostic importance of histologic grading and proliferative activity in a cohort of patients with axillary lymph node-positive breast cancer and compare these parameters with other established prognostic factors. Patients and Methods: This Eastern Cooperative Oncology Group laboratory companion study (E4189) centered on 560 axillary lymph node-positive patients registered onto one of six eligible clinical protocols. Flow cytometric (ploidy and S-phase fraction [SPF]) and histopathologic analyses (Nottingham Combined Histologic Grade and mitotic index) were performed on paraffin-embedded tissue from 368 patients. Results: Disease recurred in 208 patients; in 161 (77%), within the first 5 years. Mitotic index and grade were associated with both ploidy and SPF (P less than or equal to.01). Within the first 5 years of follow-up, mitotic index (P =.004), grade (P =.004), ploidy (P =.006), and SPF (P =.05) were associated with time to recurrence; there was also a significant association with survival. The effect of mitotic index was largely a result of the difference between 0 to 2 mitoses/10 high-power fields (HPF; 5-year recurrence of 31%) and more than 2 mitoses/10 HPF (5-year recurrence of 52%). The 0 to 2 mitoses/10 HPF group was independently associated with improved prognosis at 5 years (P =.002) in regression models that included other standard prognostic factors. Conclusion: A subset of axillary lymph node-positive patients with improved prognosis may be identified using a lower (< 3 mitoses/10 HPF) mitotic count than is usually performed. J Clin Oncol 18:2059-2069. (C) 2000 by American Society of Clinical Oncology.