THE IMPORTANCE OF THE HISTOLOGIC GRADE OF INVASIVE BREAST-CARCINOMA AND RESPONSE TO CHEMOTHERAPY

BACKGROUND. Histologic grade is well recognized for its prognostic sig nificance in cases of primary operable invasive breast carcinoma; howe ver, the majority of studies in which grade has been assessed have bee n based on single-center trials. In addition, the role of grade in pre dicting response to chemotherapy has not been examined in many previou s studies. METHODS. The authors assessed the value of Nottingham histo logic grade (NHG) in a group of 465 patients enrolled in a multicenter , randomized International Breast Cancer Study Group clinical trial of adjuvant chemotherapy for patients with lymph node (LN) positive and LN negative primary breast carcinoma (formerly named Ludwig Trial V). RESULTS. NHG was a predictor of overall survival for both LN negative and LN positive patients (P = 0.045 and P < 0.001, respectively). NHG was associated with a poorer prognosis for both LN positive and LN neg ative patients, with hazard ratios of 1.651 (P < 0.001) and 1.437 (P = 0.045), respectively, for an increase of one grade. Among LN negative patients, this survival disadvantage was observed only for those who received perioperative chemotherapy. For LN positive patients, an incr ease of one grade resulted in a significant overall survival disadvant age regardless of whether prolonged or perioperative chemotherapy was given. For LN negative patients grouped by grade, there was no observe d difference in overall or disease free survival according to whether perioperative chemotherapy or no adjuvant therapy was given. However, LN positive patients with Grade 3 tumors had a significantly greater o verall and disease free survival benefit from prolonged chemotherapy t han from perioperative chemotherapy (P = 0.016 and P = 0.013, respecti vely); LN positive patients with Grade 1 or 2 disease in both treatmen t arms had comparable overall and disease free survival. A strong corr elation between the previously utilized Bloom-Richardson grading syste m (BRG) and NHG was observed (P < 0.001 and kappa = 82%) and no appare nt differences in overall and disease free survival were observed betw een the two systems. NHG did, however, identify a greater proportion o f tumors as Grade 1, and BRG identified a greater proportion of breast carcinomas as Grade 3. CONCLUSIONS. This multicenter clinical study c onfirms the value of histologic grade, and the authors propose that th is technique be used to identify Grade 3, LN positive patients who wil l benefit from prolonged rather than perioperative chemotherapy. Cance r 1998;83:1529-39. (C) 1998 American Cancer Society.