Quantification of the response of circulating epithelial cells to neodadjuvant treatment for breast cancer: a new tool for therapy monitoring

Abstract

Introduction: In adjuvant treatment for breast cancer there is no tool available with which to measure the efficacy of the therapy. In contrast, in neoadjuvant therapy reduction in tumour size is used as an indicator of the sensitivity of tumour cells to the agents applied. If circulating epithelial (tumour) cells can be shown to react to therapy in the same way as the primary tumour, then this response may be exploited to monitor the effect of therapy in the adjuvant setting.

Method: We used MAINTRAC analysis to monitor the reduction in circulating epithelial cells during the first three to four cycles of neoadjuvant therapy in 30 breast cancer patients.

Results: MAINTRAC analysis revealed a patient-specific response. Comparison of this response with the decline in size of the primary tumour showed that the reduction in number of circulating epithelial cells accurately predicted final tumour reduction at surgery if the entire neoadjuvant regimen consisted of chemotherapy. However, the response of the circulating tumour cells was unable to predict the response to additional antibody therapy.

Conclusion: The response of circulating epithelial cells faithfully reflects the response of the whole tumour to adjuvant therapy, indicating that these cells may be considered part of the tumour and can be used for therapy monitoring.

Figure 1

Fluorimetric analysis, relocalization and fluoromicrograph of individual circulating tumour cells. Shown are the procedure for quantification and visual control (1 hour for cell preparation and analysis) and three typical viable circulating tumour cells (green fluorescing cap). One cell is also stained for oestrogen receptor (orange fluorescence).

Figure 2

Changes in circulating tumour cell numbers. (a) Fourteen typical courses of changes in cell numbers in breast cancer patients monitored during neoadjuvant (primary) therapy. (b) Comparison of the response of circulating tumour cells during the first three (or four) therapy cycles versus tumour reduction in the therapy regimen without herceptin (thick lines) and the regimen including herceptin (thin line).