A randomized trial of adjuvant combination chemotherapy with or without prednisone in premenopausal breast cancer patients with metastases in one to three axillary lymph nodes.

The impact of adding "low-dose" continuous prednisone (7.5 mg daily) to an adjuvant cyclophosphamide-methotrexate-5-fluorouracil chemotherapy regimen was investigated in a randomized trial of 505 pre- and perimenopausal patients with operable breast cancer and one to three axillary lymph node metastases (Ludwig Breast Cancer Study I). As a consequence of lower hematological toxicity a significantly higher dose of cyclophosphamide-methotrexate-5-fluorouracil could be administered with added prednisone (P less than 0.0001). However, at a median followup of 48 months, no improvement in terms of disease-free survival (P = 0.35) or overall survival (P = 0.73) was observed. Induced amenorrhea was associated with a longer disease-free survival for younger patients, patients who received lower cyclophosphamide-methotrexate-5-fluorouracil doses and patients with estrogen receptor-positive tumors. It is suggested that the chemotherapy regimen with or without prednisone may also influence tumor growth by suppression of ovarian endocrine function.