IMMUNOCYTOCHEMICAL DETECTION OF TUMOR-CELLS IN BONE-MARROW AS A PROGNOSTIC FACTOR IN BREAST-CARCINOMA

In a prospective study at the University of Erlangen, Dept. Gynaecol. and Obstet., 228 patients with breast cancer during their primary surgery and 20 patients during their metastatic surgery, underwent bone marrow punctions at six punction sides, which were twice at the sternum and twice at both iliac crest. The control group was 20 patients without an invasive carcinoma. Aim of the study was to detect or exclude tumour cells in the bone marrow via examination of the biopsies with monoclonal antibodies EMA and cytokeratin and consequently to find out the meaning of the results as prognostic criteria by statistical measurements. Tumour cells in the bone marrow were detected in 46.5% (106/228) of the patients, who underwent a bone marrow biopsy during primary surgery. 21% (23/106) of the patients who were bone marrow positive, but only 5.75% (7/122) of the patients, who were bone marrow negative, developed metastases during a median follow-up of 20 months. This difference is statistically significant. 17 of the 30 patients with recurrences developed bone metastases; 16 of them were EMA-positive. The median recurrence-free interval was 5 months in the bone marrow positive group and therefore noticeably shorter, than in the bone marrow negative patient group with 11 months. Of the nodal negative patients, 2 bone marrow positive patients developed distant metastases. With the knowledge of the nodal status and bone marrow biopsy result, it was possible to predict 28 of the 30 patients correctly in respect of their risk to metastasize. The result of the bone marrow puncture was proved in a multivariate analysis to be an independent prognostic factor. A second group of patients, in which bone marrow punkture was performed during surgery for recurrences, we found in 15 patients a positive tumour cell result in the bone marrow and all patients with additional distant metastases were positive with regard to their bone marrow biopsy. To prove the specificity of the method, bone marrow, samples on 20 patients without an invasive carcinoma were examined. In this group, no tumour cells were found in the bone marrow. The analysis showed, that the bone marrow sampled during primary surgery of a breast carcinoma and stained with a monoclonal antibody EMA in combination with cytokeratin is an independent prognostic factor. Patients with tumour cell detection in their bone marrow developed recurrences earlier and more frequently than bone marrow negative patients (p < 0.001).