Randomized controlled trial of ovarian function suppression plus tamoxifen versus the same endocrine therapy plus chemotherapy: Is chemotherapy necessary for premenopausal women with node-positive, endocrine-responsive breast cancer? First results of International Breast Cancer Study Group Trial 11-93

Adjuvant systemic treatment with ovarian function suppression/ablation (OFS), tamoxifen (Tam) and polychemotherapy are effective in reducing recurrence and mortality in early breast cancer. However, little is known of the value of chemotherapy added to the combination of OFS and Tam in premenopausal women. In a randomized trial we evaluated the role of four cycles of adjuvant chemotherapy (AC = doxorubicin 60 mg/m² or epirubicin 90 mg/m², plus cyclophosphamide 600 mg/m², each 21 days) in addition to OFS and 5 years of Tam (20 mg day) in premenopausal patients with node-positive, oestrogen-receptor-positive and/or progesterone-receptor-positive breast cancer who underwent either mastectomy or breast-conserving surgery with axillary dissection. 174 patients were randomized from May 1993 to Nov 1998. The trial was closed before the target accrual was reached due to low accrual rate. The method of OFS was selected by the participating centre, either surgical (26%), radiation (11%) or chemical (GnRH analogue 63%). Although all patients with node-positive, receptor-positive tumours were eligible, patients randomized tended to be at lower risk, (95% 1-3 nodes involved, 53% only 1 node; 76% grade 1-2; and 58% with tumour size 2 cm or smaller). The median age was 45 years. After a median follow-up of 4.4 years, 13 of the 89 patients randomized to OFS plus AC plus Tam had relapsed and seven had died. Of 85 patients randomized to OFS plus Tam without AC, 10 had relapsed and four had died. The 4-year DFS for the group that received AC was 87% ± 4; for the endocrine alone group it was 88% ± 4 (relative risk for addition of AC = 1.22, 95% CI = 0.53-2.81, P = 0.63). The 4-year OS for the group that received AC was 92% ± 3; for the endocrine alone group it was 96% ± 2 (relative risk = 1.77, 95% CI = 0.52-6.05; P = 0.36). Patient self-assessment of quality of life (QL) indicated the expected adverse short-term effects of chemotherapy. These results should stimulate international collaboration on a larger study to determine whether chemotherapy is useful for premenopausal patients classified as having an endocrine-responsive breast cancer who receive adequate adjuvant endocrine therapy, and whether ovarian function suppression is an essential component of an adjuvant treatment program for these patients.