Occult Metastatic Cells in Breast Cancer Patients

Abstract

Blood-borne distant metastasis is the leading cause of cancer-related death in patients with breast cancer. The onset of this fundamental process can now be assessed in cancer patients using immunocytochemical and molecular assays able to detect even single metastatic cells. However, careful validation of technically confounding variables, including choice of detection antibody, preparation of cellular samples, and size of analyzed sample volumes, is mandatory for reproducible and comparable results. In studies with validated assays, analyses of bone marrow samples show that disseminated cells are present in 20–40% of primary breast cancer patients without any clinical or histopathological signs of metastasis. The common homing of circulating breast cancer cells in bone marrow is indicative of systemic tumor cell spread and growth of overt metastases in relevant organ sites such as bone, lung, or liver. Recent clinical studies involving more than 3000 breast cancer patients demonstrated that presence of tumor cells in bone marrow at primary diagnosis is an independent prognostic factor for unfavorable clinical outcome. To date, sampling of bone marrow, however, is not a routine procedure in clinical management of breast cancer patients. In this chapter, we review the existing tumor cell assays and discuss their current clinical relevance and perspectives for the clinical management of breast cancer patients.