Abstract 4568: Estrogen receptor and progesterone receptor immunocytochemistry staining in circulating tumor cells as compared to primary tumor or metastatic biopsy

Abstract

Introduction: Hormone receptor (estrogen receptor (ER) and progesterone receptor (PR)) status in all breast cancer patients is recommended by immunohistochemistry (IHC) and is considered standard practice for selection of treatment options. However, the analytical sensitivity of IHC in detecting low levels of ER/PR is often poor and likely due to methodological variation. Because biopsy is not often feasible in all patients presenting with recurrent and/or metastatic breast disease, circulating tumor cells (CTCs) offer an attractive alternative source of tumor tissue for determining ER/PR status and can be monitored more readily to enable a more effective course of treatment. Experimental Design: Twenty ml of peripheral blood was collected prospectively from 14 patients diagnosed with late stage metastatic/recurrent breast cancer. CTCs were isolated using the microfluidic OncoCEETM platform. A cocktail of antibodies was utilized for CTC capture and detection with an expanded anti-cytokeratin (CK) cocktail mixture and anti-CD45. ER/PR protein expression was assessed by immunocytochemistry (ICC) on the cells captured within the microchannels and compared to IHC performed on the primary tumor or metastatic biopsy. Results: CK+/CD45-/DAPI+ cells were located and assessed for ER/PR immunocytochemistry. Among the 14 cases a high concordance (12/14; 86%) in ER/PR status between primary tumor/metastatic biopsy and CTCs was observed. Two cases were found to be discordant where one was positive by IHC and negative on the CTCs and the other was negative on by IHC on the primary tumor/metastatic biopsy and positive on the CTCs. However, both cases that were discordant had low numbers of CTCs detected. Conclusions: There is significant heterogeneity between ER/PR protein expression in CTCs and primary tumor/metastatic biopsy and this status may change over time due to therapy. ER/PR ICC on CTCs from peripheral blood using the OncoCEETM platform is shown to be feasible with high concordance (86%) in ER/PR status between primary tumor/metastatic biopsy (by IHC) and CTCs (by ICC). The significance of heterogeneity at the ER/PR protein level in CTCs ascertaining to the prognosis and predictive response to anti-estrogen therapy needs further evaluation in larger prospective clinical trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4568. doi:1538-7445.AM2012-4568