The evolution of primary multimodality treatment in resectable breast cancer

Based on both laboratory and clinical data, two major prospective randomized clinical trials were initiated in 1972 and 1973 by the NSABP and the Instituto Nazionale Tumori, of Milano, Italy, under the sponsorship of the National Cancer Institute, to test the value of administering chemotherapy to patients with Stage II breast cancer in the postoperative period. With a follow-up time of nearly five years, both studies continue to demonstrate a significantly prolonged disease-free interval for treated premenopausal women. The Milano trial also indicates an increase in survival from 74% to 90% in the treated group of premenopausal women. A recent analysis of the postmenopausal women treated in the Milano study show that those treated patients who received 75% of the calculated drug dose have significantly prolonged disease-free intervals. These positive results from these trials and byproducts of other basic and clinical research, particularly the value of the estrogen receptor as a prognostic factor of disease-free interval survival and possible treatment selector, have stimulated the scientific community to undertake additional adjuvant therapy studies. The design and rationale for these subsequent studies are discussed. Preliminary indications exist that these trials will lead to a reduction in the national mortality and the overall economic impact from this disease will be lessened within the next five years. Based on the positive results of these studies, rationale currently exists for designing clinical trials that have the potential to extend similar benefit to the 60,000 patients with Stage I disease.