RANDOMIZED TRIAL OF CHEMOENDOCRINE THERAPY STARTED BEFORE OR AFTER SURGERY FOR TREATMENT OF PRIMARY BREAST-CANCER

Purpose: To evaluate in a randomized clinical trial systemic chemoendo crine therapy used as primary (neoadjuvant) treatment before surgery i n women with primary operable breast cancer. Patients and Methods: Pat ients aged less than 70 years with clinically palpable, primary operab le breast cancer diagnostically confirmed by fine-needle aspiration cy tology (FNAC) and suitable for treatment with surgery, radiotherapy, c ytotoxic chemotherapy, and tamoxifen were considered eligible. Patient s randomized to neoadjuvant treatment received four cycles of chemothe rapy for 3 months before surgery followed by another four cycles after surgery, and were compared with patients randomized to adjuvant thera py who received eight cycles of chemotherapy over 6 months after surge ry. Results: Of 212 patients who were randomized to receive either adj uvant (n = 107) or neoadjuvant (n = 105) chemoendocrine therapy, 200 a re now assessable for response. The two groups are comparable for age, menopausal status, disease stage, and surgical requirements. The over all clinical response rate was 85%, with a complete histologic respons e rate of 10%. There was a significant reduction in the requirement fo r mastectomy in patients who received neoadjuvant treatment (13%) as c ompared with those who received adjuvant therapy (28%) (P < .005). Sym ptomatic and hematologic acute toxicity was low and similar for adjuva nt and neoadjuvant therapy. The median follow-vp period for patients i n this trial is 28 months, during which time four patients have relaps ed locally and 20, including one of the local relapses, have developed metastatic disease, 19 of whom have died. The follow-up period is too brief to evaluate relapse rate or survival duration. Conclusion: This trial confirms previous reports of a high rate of response to neoadju vant therapy, but is the first to include small primary cancers and to show, in the concert of a randomized trial, a reduction in the requir ement for mastectomy. Until disease-free and overall survival data are available from the larger National Surgical Adjuvant Breast and Bowel Project (NSABP)-18 trial, such neoadjuvant treatment cannot be recomm ended outside of a clinical trial. (C) 1995 by American Society of Cli nical Oncology.