International study on inter-reader variability for circulating tumor cells in breast cancer

Area of Science:

• Oncology
• Medical Diagnostics
• Biomarkers

Background:

• Circulating tumor cells (CTCs) are crucial biomarkers in breast cancer prognosis.
• The CellSearch® system is a standard method for CTC detection.
• Evaluating inter-reader agreement is vital, especially for non-metastatic breast cancer with low CTC counts.

Purpose of the Study:

• To assess the inter-reader agreement for CTC detection and HER2 expression analysis using the CellSearch® system.
• To identify factors influencing agreement, such as disease stage and CTC count.

Main Methods:

• 272 CellSearch® images from 131 breast cancer patients (109 M0, 22 M1) were reviewed by 22 academic readers and 8 Veridex readers.
• Readers classified images as No CTC, CTC HER2-, or CTC HER2+.
• Agreement was quantified using percentage agreement and kappa statistics, comparing academic readers to a Veridex Consensus (VC).

Main Results:

• High median agreement (92%, κ=0.83) was found for CTC definition (No CTC vs CTC).
• Agreement was significantly lower in non-metastatic (M0) patients, particularly those with fewer than 3 CTCs (median 87%, κ=0.74).
• Agreement for CTC HER2 expression analysis was also substantial (median 87%, κ=0.74).

Conclusions:

• The CellSearch® system demonstrates high inter-reader agreement for CTC detection.
• Lower agreement in M0 patients with low CTC counts necessitates standardized training and independent image review.
• Accurate CTC analysis is critical for guiding breast cancer treatment and monitoring.