The significance of circulating tumour cells in breast cancer: a review.

Haematogenous spread of circulating tumour cells (CTCs) is the principle mechanism for development of metastases. Research into the enumeration and characterisation of CTCs, particularly in the last decade, has allowed the introduction of semi-automated CTC assessment in the clinical setting. In breast cancer, CTC enumeration is being used as a prognostic biomarker, a predictive biomarker of treatment response and is being assessed to guide treatment in both the early and metastatic setting. CTC characterisation has the potential to direct targeted therapies, such as HER2 therapies in HER2 negative primary breast tumour patients. However, CTC assessment has considerable challenges. Capture and identification of these very rare cells is currently largely dependent on a presumed homogeneity of phenotype. In addition, high throughput assays are lacking. The clinical significance of CTCs is incompletely understood. A large proportion of CTC positive patients have no evidence of metastases, raising the issue of either inconsequential tumour dormancy or non-viable CTCs. CTCs may have additional clinical sequelae such as promoting venous thrombosis. However CTCs provide a real-time liquid biopsy of the tumour and represent an exciting, minimally invasive method of assessing disease status and also a novel therapeutic target for malignancy.