Aims: HER2 status can alter during the course of breast tumour development. While tissue sampling is invasive, liquid biopsy approach using circulating tumour cells (CTCs) provides accessible tumor material to phenotype the HER2 status of the patient to guide treatment decisions. In our study, we analyzed the HER2 status of 26 advanced stage breast cancer patient samples in the Asian population in the tumour tissue and CTCs.
Methods: The CTCs were isolated from peripheral blood samples using ClearCell FX ®, a label- free spiral microfluidics- based system. Fluorescence in situ hybridization (FISH) of circulating tumour cells was performed. Conventional immunohistochemistry (IHC) of tumour tissues was done to evaluate the HER2 status of the primary tumour.
Results: The number of CTCs range between 0- 30 per 7.5 ml of blood. Both HER2 amplification and chromosome 17 polysomy can be detected using FISH in the CTC samples. Concordance rate of HER2 positivity between CTCs and tumour tissue is 82.4% (14 out of 17 patients), while the concordance rate of HER2 negativity is 100% between CTCs and tumour tissues (9 out 9). Worse progression- free survival is observed in patients with 5 or more CTCs per 7.5 ml of blood, suggesting significant prognostic relevance of HER2 over-expression in CTCs. Interestingly, in time point cases, we observed changing HER2 profiles in the CTCs of patients as the tumour progresses during the course of treatment.
Conclusion: There is a strong concordance of HER2 status in CTCs and primary tumour. CTCs can provide real- time snapshots of HER2 status for tumor monitoring that may help informed treatment decisions.