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?

Abstract

We studied cytokeratin-positive (CK+) cells in the bone marrow (BM) and tumor 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 usefulness of immunomagnetic separation (IMS) for tumor cell enrichment in clinical 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) for 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 were 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 only by IC and in 6/28 patients only by IMS. At least one TM, including carcinoembryonic antigen, carbohydrate antigen 15-3 and tissue polypeptide antigen, 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 samples were within the normal range in every patient studied. After a 2-year 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 combination with TM determination is useful for identifying patients with a higher risk for relapse, however, tumor cell enrichment techniques will have to be improved for clinical use.