Value of estrogenic recruitment before chemotherapy: First randomized trial in primary breast cancer

Purpose: Several preclinical studies showed that short-term pretreatment of breast cancer cells with estrogens can increase the antitumor efficacy of different cytotoxic drugs. Some early clinical studies in patients with adv anced breast cancer did seem to support these findings. Therefore, the effi cacy of estrogenic recruitment followed by chemotherapy was compared with t hat of chemotherapy alone in a randomized phase III study in women with lym ph node-positive primary breast cancer. Patients and Methods: Three hundred twenty-eight patients with stage II/III A breast cancer who were younger than 66 years of age were randomly allocat ed to chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide (FA C) or FAC plus pretreatment with ethinyl estradiol (EE2). FAC (500, 50, and 500 mg/m(2), respectively) was administered intravenously once every 4 wee ks for four cycles. EE2 (0.5 mg) was administered orally, both 24 hours and immediately preceding FAC chemotherapy. Results: Patient and tumor characteristics and chemotherapy dosages were co mparable in both treatment groups. Of 318 assessable patients, with a media n follow-vp of 6.8 years, 177 patients had a relapse and 127 died. No signi ficant differences were observed between the two treatment groups with resp ect to relapse-free, local recurrence-free, and overall survival according to univariate and multivariate analyses adjusted for age, menopausal status , tumor size, grade, number of positive nodes, and steroid-receptor status. The power for the detection of an increase of 50% in the median relapse fr ee survival was 80%. Conclusion: Estrogenic recruitment of breast cancer cells before FAC chemot herapy did not influence the efficacy of adjuvant chemotherapy in stage II/ IIIA breast cancer patients after a follow-up of 6.8 years. (C) 2000 by Ame rican Society of Clinical Oncology.