Abstract
Circulating tumor cell (CTC) count has prognostic significance in metastatic breast cancer, but the predictive utility of CTCs is uncertain. Molecular studies on CTCs have often been limited by a low number of CTCs isolated from a high background of leukocytes. Improved enrichment techniques are now allowing molecular characterisation of single CTCs, whereby molecular markers on single CTCs may provide a real-time assessment of tumor biomarker status from a blood test or “liquid biopsy”, potentially negating the need for a more invasive tissue biopsy. The predictive ability of CTC biomarker analysis has predominantly been assessed in relation to HER2, with variable and inconclusive results. Limited data exist for other biomarkers, such as the estrogen receptor. In addition to the need to define and validate the most accurate and reproducible method for CTC molecular analysis, the clinical relevance of biomarkers, including gain of HER2 on CTC after HER2 negative primary breast cancer, remains uncertain. This review summarises the currently available data relating to biomarker evaluation on CTCs and its role in directing management in metastatic breast cancer, discusses limitations, and outlines measures that may enable future development of this approach.
Highlights
Breast cancer incidence in Western countries is estimated at around 125 per 100,000 women, of which 5% present with de novo metastatic disease [1,2], while a significant minority of women with early breast cancer develop recurrence after adjuvant or neoadjuvant systemic therapy [3]
While this is an adjuvant therapy trial, with ADCC potentially considered more relevant in the adjuvant than the advanced breast cancer setting, the rationale represents an alternate approach to Circulating tumor cell (CTC) eradication and results are anticipated with interest
metastatic breast cancer (MBC) patients, Cheng et al reported that detection of MUC-1 mRNA from CTCs after the first cycle of chemotherapy was significantly associated with poorer response rate compared with patients with undetectable MUC-1 mRNA, while there was a trend towards increased PFS in MUC-1 mRNA
Summary
Breast cancer incidence in Western countries is estimated at around 125 per 100,000 women, of which 5% present with de novo metastatic disease [1,2], while a significant minority of women with early breast cancer develop recurrence after adjuvant or neoadjuvant systemic therapy [3]. Lack of CTC response, even in the setting of a radiological response, portends a worse prognosis [16] Based on this concept, the predictive role of CTC count is currently being investigated in the SWOG 0500 randomised phase III trial (NCT00382018), which aims to enrol 651 patients with MBC, and is addressing the question of whether or not a treatment regimen should be altered early in its course based on lack of CTC. Rather than using CTC count alone, assessment of the molecular characteristics of CTCs might be useful This could enable improved treatment selection and better prediction of response to a specific therapy. Recent advances in isolation and enrichment techniques allow more detailed assessment of CTCs, including analysis of molecular characteristics or expression of biomarkers, with potential treatment implications
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