The measurement and therapeutic implications of circulating tumour cells in breast cancer

Abstract

Circulating tumours cells (CTCs) represent an important biologic link in the spread of breast cancer from primary to metastatic disease. CTCs are strong predictors of prognosis in patients with metastatic breast cancer. Research to date has focused on development of methods with adequate sensitivity and specificity to reproducibly identify these rare events. Future research will focus on the biologic phenotypes of these cells with goals to understand mechanisms of metastasis, to identify novel therapeutic targets, and to monitor response to therapy.

Figure 1

Kaplan–Meier curves demonstrating differences in PFS (A and C) and OS (B and D) based upon high and low risk CTC classifications. Patients with elevated CTCs at baseline (A and B) and at first follow-up after one cycle of therapy (C and D) have significantly worse median PFS and OS compared to the corresponding patients with low CTCs. Adapted with permission from (Cristofanilli et al, 2004).

Figure 2

Quantification of HER-2 density on cell lines and on CECs of three breast cancer patients by flow cytometry. (A) HER-2 expression of leukocytes, PC3 cells and SKBR-3 cells immunomagnetically selected from 5 ml of blood and gated on size, CD45 expression, and cytokeratin expression. The expression levels of HER-2 were subdivided into four categories (−, +, ++, +++), based on the quantitative assessment of HER-2 expression on PC3 and SKBR-3 cells. (−) designates no expression or less than 5000 receptors (WBC); (+) designates expression between 5000 and 50 000 receptors (PC-3); (++) designates expression between 50 000 and 500 000 receptors; and (+++) designates expression of more than 500 000 receptors (SKBR-3). (B–D) show the expression of cytokeratin and HER-2 on CECs from three patients with breast cancer. Only the CECs are shown in the panels. Reproduced with permission from (Hayes et al, 2002).