CTC characterization in metastatic breast cancer

Background: Breast cancer is the second most common cause of cancer related death among women in the developed world. Around 30% of patients diagnosed with primary breast cancer will develop metastatic breast cancer. It is believed that the tumor cells found in the blood, termed Circulating tumor cells (CTCs), could serve as a prognostic marker for this disease as it progresses. Objectives: To study CTCs potential as a biomarker predictive of the expression of ER and HER2 in the metastases and primary tumor. The objective is to do this using immunocytochemistry on blood samples collected before the start of therapy in patients with MBC. Patients and methods: The CellSearch system was used to capture and enumerate CTCs from blood samples collected from patients suffering from metastatic breast cancer. Immunocytochemistry was used to characterize and enumerated the CellSearch enriched samples to study the ER and HER2 expression of the CTCs. Results: 5 or more CTCs per 7.5ml of whole blood at baseline is predictive of a shorter PFS and OS. The presence of ER-positive CTCs was not significantly predictive of a shorter or longer PFS or OS. There is a significant discordance of ER expression between the CTCs, the primary tumor and the metastases. No HER2-positive CTCs were found in any samples. ER-positive CTCs were found in 17 out of 50 samples which were from patients with ER-positive primary tumors. Conclusions: 5 or more CTCs per 7.5ml of whole blood is at baseline predictive of a shorter PFS and OS. The expression of ER and HER2 on the CTCs are not predictive for the expression of either the PT or the metastases. This discordance could be explained by plasticity. One process which might cause this is EMT, which is a process closely connected to the loss of the ER. Keywords: Estrogen receptor, Human Epidermal Growth Receptor 2, breast cancer, plasticity