RELATIONSHIP OF VARIATIONS IN TUMOR-CELL KINETICS INDUCED BY PRIMARY CHEMOTHERAPY TO TUMOR-REGRESSION AND PROGNOSIS IN LOCALLY ADVANCED BREAST-CANCER

The relationship of changes in H-3-thymidine labelling index (TLI) ind uced by primary chemotherapy to tumor response and relapse rate in 36 patients with previously untreated locally advanced breast cancer (LAB C) was analyzed. All patients received primary chemotherapy (3 cycles FAC), followed by mastectomy and subsequent adjuvant chemotherapy (3 F AC alternated with 3 CMF). Tumor TLI was evaluated immediately prior t o primary chemotherapy and at the time of mastectomy. Median pretreatm ent TLI was used to discriminate between tumors with a high or low pro liferative rate. Clinical objective response to primary chemotherapy w as 83% in patients with high TLI and 56% for those with low pretreatme nt TLI (p = 0.06). Primary chemotherapy induced a greater than or equa l to 50% reduction of the proliferative rate in 83% and 39% of the tum ors with high and low pretreatment TLI, respectively (p = 0.006). Pati ents were classified into 4 groups according to TLI values both before and after primary chemotherapy: patients who remained in the high TLI group after primary FAC had the highest response rate (100%) and the lowest 2-year relapse rate (20%). These data suggest that: a) improved response to aggressive cytotoxic treatment occurs in tumors with high TLI at diagnosis; b) there is a significant correlation between TLI c hanges induced by primary chemotherapy and pretreatment proliferative activity; c) patients who remain in the high TLI group after primary c hemotherapy are more likely to benefit from subsequent adjuvant system ic therapy.