The importance of treatment sequence in advanced and metastatic carcinoma of the breast

From 1965 to the present, 287 patients with advanced and metastatic carcinoma of the breast have been treated according to a uniform philosophy of sequential therapy. Surgical castration was the initial procedure for premenopausal women and for postmenopausal women with clinical or laboratory evidence of endocrine responsive tumors. Tumor progression following castration was treated with major endocrine ablation, either adrenalectomy or hypophysectomy. Patients who relapsed following major ablation were treated with antiestrogen therapy as it became available. Nonresponders to major ablation and patients relapsing after antiestrogen therapy were treated with combination chemotherapy including cytoxan, methotrexate, 5-fluorouracil, and vincristine followed by adriamycin alone or in combination. Progression following chemotherapy was treated with additive hormonal therapy. Radiation therapy was used throughout for the control of localized disease, usually following complete hormonal ablation, except in cases of brain and spinal metastatic disease. The median survival for the entire group was 40.5 months from the onset of metastatic disease. Patients who responded to both oophorectomy and major ablation had a median survival of 61 months, which compares favorably to survival of 14 to 22 months reported in major combination chemotherapy trials. Survival following this method of sequential therapy is superior to other plans of management.