The management of locally advanced breast cancer: a combined modality approach

The prognosis for patients who have locally advanced breast cancer and are treated with conventional locoregional therapy is poor. Between 1974 and 1981, 93 evaluable patients with stages III (nine patients) and IV (84 patients) disease who had received no prior therapy were placed on a combined regimen of 5-fluorouracil, 500 mg/m² on days 1 and 8, doxorubicin (adriamycin), 50 mg/m², and cyclophosphamide, 500 mg/m² on day 1 (FAC) every 3 weeks for three cycles or until maximum tumor reduction occurred. This treatment was followed by mastectomy, local irradiation or both. FAC chemotherapy was then resumed until a total of 450 mg/m² of adriamycin had been given. At this time adriamycin was discontinued and replaced with methotrexate, 30 mg/m² on days 1 and 8 (CMF), in 3-week cycles until the patient had received therapy for a total of 24 months. The complete and partial response rate to initial FAC chemotherapy was 86%, allowing 89 of 93 patients who had tumors considered to be technically unresectable to become free of clinically detectable disease with subsequent local therapy. After a median follow-up of 53 months disease recurred in 47 patients, six of whom had attained a second disease-free status following local therapy. The estimated median length of survival for the whole group was 66 months, and the median disease-free interval (DFI) was 30 months. Age, race, menopausal status and the presence of supraclavicular lymphadenopathy had no effect on prognosis. In patients with stage III disease DFI and survival duration were increased, as was true also for patients with residual tumors of ≤1 cm in their mastectomy specimens. Patients in whom the tumors were estrogen receptor (ER)-positive also had longer DFI than those with ER-negative tumors. In spite of the encouraging results obtained with the combined modality approach to treating locally advanced breast cancer, future improvement should be pursued through additional hormonal therapy, optimal local radiation therapy timing and early resumption of intensive chemotherapy following locoregional treatment.