Bone marrow micrometastasis in breast cancer: review of detection methods, prognostic impact and biological issues

Immunocytochemical detection of disseminated tumour cells in the bone marrow of patients with primary breast cancer at surgery has been shown to be an independent prognostic factor in single institutional studies and in a large pooled analysis. However, bone marrow sampling and assessment of disseminated tumour cells is not a routine procedure in the clinical management of patients with breast cancer, but will certainly play a role in the near future for risk stratification and monitoring of therapeutic efficacy. Accurate identification of disseminated tumour cells in bone marrow must be based on standardised methodologies and procedures. This review describes these methodologies and the standardised morphological criteria used for disseminated tumour cell detection. The prognostic value of circulating tumour cells detection in peripheral blood is demonstrated in patients with metastatic disease but remains to be substantiated at early stage. The significance of disseminated tumour cells in bone marrow and in the blood for the prediction of response to therapy is briefly summarised. Finally, this review addresses the main biological questions raised by disseminated tumour cells, in particular understanding tumour dormancy and identifying metastatic stem cells of DTC. In this review, we will summarise the methodologies most commonly used to detect DTC, discuss the clinical impact of DTC in bone marrow at initial diagnosis and during follow-up and treatment evaluation, and highlight the biological and clinical questions raised by DTC.