Bone marrow and lymph node assessment for minimal residual disease in patients with breast cancer

Background. The immunocytological detection of disseminated epithelial cell s in bone marrow in patients with breast cancer has been performed at many hospitals and institutes since the early 1980s. Despite numerous publicatio ns in this field, it has not been possible to standardize the method and es tablish the ideal antibody, either nationally or internationally. Molecular biological methods using PCR technology could extend the diagnostic spectr um. However, one of the major problems in breast cancer is the lack of a di sease-specific marker gene. As a result, immunocytology is still the standa rd procedure for tumour cell detection. Methods. The detection of disseminated single cells in hone marrow in prima ry breast cancer (also known as minimal residual disease) is a new prognost ic factor for disease-free and overall survival. This has been demonstrated in three large (N>300) groups and several small to medium groups (N=50-300 ). As a marker of dissemination in a target organ for metastasis this progn ostic factor corresponds much more closely to the tendency of breast cancer to early haematogenic spread. Tumour cell detection may predict the course of the disease better than the axillary lymph node status. Bone marrow asp iration and detection of disseminated cells might replace lymph node dissec tion, at least in those patients with small tumours and no clinical signs o f lymph node involvement. This strategy will soon be investigated in approp riate studies. Another possible clinical use might be deciding on whether o r not to give adjuvant systemic therapy to node-negative patients. Patients with positive tumour cell detection are at a higher risk of subsequent met astasis, even if the axillary nodes are histologically normal. Application of methods. The immunohistological or molecular biological dete ction of tumour cells in axillary lymph nodes might also be very useful, no w that is has been shown that a considerable subset of patients determined to be node-negative by means of conventional methods,are positive according to these new techniques. These methods could be a useful supplement to sen tinel node biopsy. A further potential use of this method is in monitoring therapy with new treatment modalities such as gene therapy and immunotherap y. Repeated bone marrow aspiration can provide information on the success o f therapy in minimal residual disease (cytoreduction), Immunocytochemical i nvestigation of individual cells may he useful in studying the pathogenesis of metastasis, in particular in the skeleton. Phenotyping of cells might a llow statements to be made in the metastatic potential of cells and the que stion of cell dormancy. It remains to be hoped that this aspect of minimal residual disease will be granted more attention in future.