Evaluation of different methods for the detection of minimal residual disease in blood and bone marrow of patients with primary breast cancer: importance for clinical use ?

We studied cytokeratin-positive (CK+) cells in the bone marrow (BM) and tum or markers (TM) in the blood of 128 patients with primary breast cancer in order to obtain an early diagnosis of residual disease. CK+ cells of two BM aspirations were detected by immunocytochemistry (IC). To evaluate the use fulness of immunomagnetic separation (IMS) for tumor cell enrichment in cli nical samples, IMS was performed prior to IC and compared with the results for IC alone. The overall CK+ rate was 34% (44/128 patients), 29% (15/51) f or patients with T1 tumors, 33% (28/84) for N0 patients and 31% (26/82) for patients with G1-2 breast carcinoma. Interestingly, 67% of CK+ patients we re only positive in one of the two aspirates studied. A comparison between IC alone and IMS/IC could be performed in 70/128 patients (28/70 CK+). In 6 /28 patients, CK+ cells were detected by both methods, in 16/28 patients on ly by IC and in 6/28 patients only by IMS. At least one TM, including carci noembryonic antigen, carbohydrate antigen 15-3 and tissue polypeptide antig en, was increased in 58/128 (45%) patients [21/58 (36%) were CK+ in the BM] . Surprisingly, levels for the extracellular domain of Her-2/neu in serum s amples were within the normal range in every patient studied. After a 2-yea r follow-up, 7/128 patients relapsed (3/7 CK+/TM-; 2/7 CK-/TM+; 2/7 CK-/TM- ). We conclude that studying two BM aspirates for CK+ cells by IC in combin ation with TM determination is useful for identifying patients with a highe r risk for relapse, however, tumor cell enrichment techniques will have to be improved for clinical use.