Discordance in HER2 gene amplification in circulating and disseminated tumor cells in patients with operable breast cancer. (6th March 2013)

• Record Type: Journal Article
• Authors: Krishnamurthy, Savitri; Bischoff, Farideh; Ann Mayer, Julie; Wong, Karina; Pham, Tam; Kuerer, Henry; Lodhi, Ashutosh; Bhattacharyya, Anirban; Hall, Carolyn; Lucci, Anthony
• Is Part Of: Cancer medicine. Volume 2:Number 2(2013:Apr.)
• Page Start: 226
• Page End: 233
• Publication Date: 2013-03-06
• Subjects: 616.994005
• DOI: 10.1002/cam4.70
• Languages: English
• ISSNs: 2045-7634

Abstract

<abstract abstract-type="main" xml:lang="en" id="cam470-abs-0001"> <title>Abstract</title> <p>Human epidermal growth factor receptor 2 (<italic>HER2</italic>) gene amplification in circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) might be useful for modifying Herceptin therapy in breast cancer. In the process of investigating the utility of a microfluidic platform for detecting <italic>HER2</italic> gene amplification in these cells, we observed novel results on discordance of <italic>HER2</italic> status. Peripheral blood (8.5 mL) and bone marrow (BM) (7.5–10 mL) were collected prospectively from patients with clinical stages I–IV breast cancer. Mononuclear cells were recovered, stained with cytokeratin (CK), CD45, and DAPI, and processed through microfluidic channels for fluorescence in situ hybridization (FISH). A ratio of HER2:CEP17 >2 in any CK+/CD45 or CK−/CD45 cell was regarded as positive for <italic>HER2</italic> gene amplification. Peripheral blood from 95 patients and BM from 78 patients were studied. We found CK+/CD45−/DAPI+ CTCs in 27.3% of patients. We evaluated HER2 gene amplification by FISH in 88 blood and 78 BM specimens and found <italic>HER2</italic>+ CTCs in 1 of 9 (11.1%) and <italic>HER2</italic>+ DTCs (27.2%) in 3 of 11 patients with <italic>HER2</italic>+ primary tumor. Among patients with a <italic>HER2</italic>− primary tumor, 5 of 79 had <italic>HER2</italic>+ CTCs (6.3%) and 14 of 67 had <italic>HER2</italic>+ DTCs (20.8%). The overall rate of discordance in <italic>HER2</italic> status was 15% between primary tumor and CTCs and 28.2% between primary tumor and DTCs. <italic>HER2</italic> was amplified in CTCs and DTCs in a portion of both <italic>HER2</italic>+ and <italic>HER2</italic>− primary tumors. <italic>HER2</italic> discordance was more frequent for DTCs. The clinical implications of evaluating <italic>HER2</italic> status in CTCs and DTCs in breast cancer needs to be established in prospective clinical trials. The cell enrichment and extraction microfluidic technology provides a sensitive platform for evaluation of <italic>HER2</italic> gene amplification in CTCs and DTCs.</p> </abstract>