NEOADJUVANT VERSUS ADJUVANT CHEMOTHERAPY IN PREMENOPAUSAL PATIENTS WITH TUMORS CONSIDERED TOO LARGE FOR BREAST-CONSERVING SURGERY - PRELIMINARY-RESULTS OF A RANDOMIZED TRIAL - S6

The aim of this study was to assess a potential advantage in survival by neoadjuvant as compared to adjuvant chemotherapy. 414 premenopausal patients with T2-T3 N0-N1 M0 breast cancer were randomised to receive either four cycles of neoadjuvant chemotherapy (cyclophosphamide, dox orubicin, 5-fluorouracil), followed by local-regional treatment (group I) or four cycles of adjuvant chemotherapy after primary irradiation +/- surgery (group II). Surgery was limited to those patients with a p ersisting mass after irradiation, and aimed to be as conservative as p ossible. 390 patients were evaluable. With a median follow-up of 54 mo nths, we observed a statistically significant difference (P = 0.039) i n survival in favour of the neoadjuvant chemotherapy group, A similar trend was seen when the time to metastatic recurrence was evaluated (P = 0.09). At this stage, no difference in disease-free interval or loc al recurrence between these two groups could be observed. The mean tot al dose of chemotherapy administered was similar in both groups. On av erage, group I had more intensive chemotherapy regimes (doxorubicin P = 0.02) but fewer treatment courses (P = 0.008) as compared to the tre ated patients in group II. Haematological tolerance was reduced when c hemotherapy succeeded to exclusive irradiation. Breast conservation wa s identical for both groups at the end of primary treatment (82 and 77 % for groups I and II, respectively). Of the 191 evaluable patients in the neoadjuvant treatment arm, 65% had an objective response (>50% re gression) following four cycles of chemotherapy. The objective respons e rate to primary irradiation (55 Gy) was 85%. Improved survival figur es in the neoadjuvant treatment arm could be the result of the early i nitiation of chemotherapy, but we cannot exclude that this difference might be attributable to a slightly more aggressive treatment. So far, the trend in favour of decreased metastases was not statistically sig nificant. The local control appeared similar in both subgroups.