heralds short survival, regardless of the primary site or the status of extracranial metasta~es.~,~*'** Without therapeutic intervention, the median survival is only 1 or 2 month^.^ Central nervous system involvement occurs in approximately 10% of stage I V breast cancer patients. It has been suggested that, as the survival of cancer patients with disseminated disease is extended and as adjuvant therapy becomes more effective, brain metastases will present a problem of greater magnitude. T o determine the natural history of breast cancer patients with brain metastases and to identify factors that influence occurrence and prognosis, we have reviewed our recent experience with the problem. MATERIALS AND METHODSThe records of all patients with the histologic diagnosis of carcinoma of the breast who were suspected of having brain metastases from December 1972 through December 1976 were reviewed. Patients with meningeal carcinomatosis were excluded. All patients initially presented with localized breast cancer (stage I,
Twenty-five breast cancer patients with meningeal carcinomatosis seen over a period of 16 months were reviewed. In all cases, the clinical diagnosis was made in the presence of diverse neurological manifestations by the demonstration of malignant cells in the cerebrospinal fluid. In ten patients, the clinical diagnosis was documented at autopsy. All patients were receiving systemic chemotherapy at the time the diagnosis of meningeal carcinomatosis was made. In 9 of the 25 patients, meningeal involvement was associated with progression of systemic metastases, while 5 exhibited stable or partial remission from systemic metastases and 7 were in complete remission at the time of their CNS relapse. CNS involvement was the first manifestation of recurrent disease from breast cancer in 4 of 25 patients. Meningeal involvement can, therefore, occur at any time during the course of breast cancer. With increasing diagnostic awareness and the employment of several therapeutic strategies, the prognosis of these patients, though poor, was significantly improved over that of historical control patients.
Sixty-two patients with breast cancer treated with Adriamycin-containing adjuvant chemotherapy developed recurrent disease. Four patients refused to take any form of systemic therapy at the time of relapse. Fifty-eight patients were managed with various treatment modalities, and of these 33 (57%) achieved on objective remission, 11 (19%) had stable disease and 14 patients (24%) did not respond to any form of therapy. Twenty-four patients received more than one treatment modality. Thirty-eight patients were treated with chemotherapy and 35 received endocrine therapy. Eight of 20 patients (40%) achieved objective remission upon retreatment with higher dose of 5-fluorouracil, Adriamycin, and cyclophosphamide at time of relapse, and seven of 18 patients (38%) treated with other chemotherapeutic agents showed objective remission. Fourteen of 35 patients (40%) achieved objective remission with hormonal therapies. The median survival from first relapse was 15 months for all patients, and was 25.7 months for responding patients. Survival was significantly longer in asymptomatic patients compared with those who were symptomatic from recurrent disease.
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