Circulating tumor cells: a useful predictor of treatment efficacy in metastatic breast cancer

Abstract

Purpose: Five or more circulating tumor cells (CTCs) per 7.5 mL of blood predicts for poorer progression-free survival (PFS) in patients with metastatic breast cancer (MBC). We conducted a prospective study to demonstrate that CTC results correlate strongly with radiographic disease progression at the time of and in advance of imaging.

Patients and methods: Serial CTC levels were obtained in patients starting a new treatment regimen for progressive, radiographically measurable MBC. Peripheral blood was collected for CTC enumeration at baseline and at 3- to 4-week intervals. Clinical outcomes were based on radiographic studies performed in 9- to 12-week intervals.

Results: Sixty-eight patients were evaluable for the CTC-imaging correlations, and 74 patients were evaluable for the PFS analysis. Median follow-up was 13.3 months. A statistically significant correlation was demonstrated between CTC levels and radiographic disease progression in patients receiving chemotherapy or endocrine therapy. This correlation applied to CTC results obtained at the time of imaging (odds ratio [OR], 6.3), 3 to 5 weeks before imaging (OR, 3.1), and 7 to 9 weeks before imaging (OR, 4.9). Results from analyses stratified by type of therapy remained statistically significant. Shorter PFS was observed for patients with five or more CTCs at 3 to 5 weeks and at 7 to 9 weeks after the start of treatment.

Conclusion: We provide, to our knowledge, the first evidence of a strong correlation between CTC results and radiographic disease progression in patients receiving chemotherapy or endocrine therapy for MBC. These findings support the role of CTC enumeration as an adjunct to standard methods of monitoring disease status in MBC.

Fig 1.

Study design. Eligible patients completed a baseline imaging evaluation and blood collection for circulating tumor cell (CTC) enumeration before starting a new line of systemic therapy (time = 0). Imaging studies and blood collection for CTCs were repeated at strictly defined intervals to perform the most rigorous analysis for correlation.

Fig 2.

Progression-free survival (PFS) for patients with less than five versus five or more circulating tumor cells (CTCs) at (A) baseline, (B) 3 to 5 weeks after initiating therapy, (C) 7 to 9 weeks after initiating therapy, and (D) the first blood draw after initiating therapy. PFS was measured as the time between the baseline CTC assessment and documentation of first radiographic evidence of disease progression or death.