407PPIK3CA MUTATIONS AND LOSS OF PTEN EXPRESSION IN CIRCULATING TUMOR CELLS (CTCS) IN PATIENTS WITH METASTATIC BREAST CANCER (MBC)

Abstract Aim: Currently, several methods are available to detect CTCs in peripheral blood; the enumeration of CTCs has emerged as a promising biomarker. CTCs shed from metastatic cancers may allow the non-invasive analysis of the evolution of tumor genomes during treatment and disease progression through “liquid biopsies” 1. PIK3CA mutations and loss of PTEN expression are being analyzed in many studies in breast cancer. Frequent deregulation and aberration of this pathway have been implicated not only in breast cancer development and progression, but also in breast cancer therapy resistance, and as a potential predictor of response to new treatments 2,3. The objective of this study is to analyze genomic alterations of the PTEN gene and PIK3CA (exon 20) in CTCs in patients with MBC. 1. Cristofanilli M, et al. N Engl J Med 2004;351:781-91. 2. Sarah-Jane Dawson, et al. N Engl J Med 2013;368:1199-1209. 3. Cancer Genome Atlas Network. Nature 2012;490:61-70. Methods: We carried out a descriptive study in patients with MBC currently undergoing treatment at Hospital Universitario de Salamanca (Spain). CTCs were quantified by means an automated fluorescence method (MetaFer-MetaCyte of MetaSystem), allowing selection of cells by size and genetic alterations. We analyzed genomic alterations in PTEN gene in CTCs by FISH and High Resolution Melting (HRM) was performed to measure PIK3CA mutations in circulating tumor DNA. Finally, we studied the association between PTEN deletion and PIK3CA mutations. Results: In this preliminary analysis, a total of 30 samples have been obtained. CTCs (size >7 µm) were detected in 27 of 30 women. Of 27 samples, there were 12 cases (44,4%) of PTEN loss detected by FISH, and there were 10 cases (37,1%) in which PIK3CA mutations were detected by HRM. In 5 samples, there were association between PTEN deletion and PIK3CA mutations. These 5 cases were Luminal (A and B) tumors. Conclusions: Monitoring and isolation of CTCs represents an opportunity to study specific genomic alterations. In this study, we carried out the analysis of two genes involved in the same signaling pathway: PTEN and PIK3CA; which may have additive or synergistic effects through non-canonical functional pathways. Disclosure: All authors have declared no conflicts of interest.