DIRECT COMPARISONS OF ADJUVANT ENDOCRINE THERAPY, CHEMOTHERAPY, AND CHEMOENDOCRINE THERAPY FOR OPERABLE BREAST-CANCER PATIENTS STRATIFIED BY ESTROGEN-RECEPTOR AND MENOPAUSAL STATUS

Based on estrogen receptor (ER) and menopausal status, operable breast cancer (UICC stage I, II, III-a) patients were randomized for adjuvan t endocrine therapy, chemotherapy, and chemoendocrine therapy, and the effects on the relapse-free survival (RFS) and overall survival(OS) w ere compared. Tamoxifen (TAM) 20 mg/day was administered orally for 2 years after mastectomy as an adjuvant endocrine therapy in postmenopau sal patients. In premenopausal patients, oophorectomy (OVEX) was perfo rmed before TAM administration. In the chemotherapy arm (CHEM), patien ts were given 0.06 mg/kg of body weight of mitomycin C (MMC) intraveno usly, followed by an oral administration of cyclophosphamide (CPA) 100 mg/day in an administration of a 3-month period and a 3-month intermi ssion. This 6-month schedule was repeated 4 times in 2 years. The chem oendocrine arm (CHEM + TAM) was composed of TAM with MMC + CPA chemoth erapy. The patients were randomized according to ER and menopausal sta tus. ER-positive patients were randomized to three arms: OVEX +/- TAM, CHEM, and CHEM + TAM. For ER-negative patients there were two arms: C HEM and CHEM + TAM. 1579 patients entered the trial between September 1978 and December 1991, with median follow-up of 8.2 years. In ER-posi tive, premenopausal patients, there were no significant differences in RFS or OS among OVEX + TAM, MMC + CPA, TAM + MMC + CPA arms. On the c ontrary, in ER-positive, postmenopausal patients, the chemoendocrine t herapy showed a significantly higher RFS (p = 0.0400) and OS (p = 0.01 87) as compared with TAM to chemotherapy alone. There were no signific ant differences in RFS or OS by addition of TAM on the chemotherapy, i n both pre- and post-menopausal ER-negative patients. It was concluded that in ER-positive premenopausal breast cancer, endocrine therapy al one may be equivalent in prolonging RFS and OS to chemotherapy or chem oendocrine therapy, and that ER-positive postmenopausal breast cancer may be better controlled with the combination of TAM and chemotherapy, as compared to TAM or chemotherapy alone. The importance of stratific ation of operable breast cancer by ER and menopausal status, as well a s the direct comparisons of different treatments, were stressed.