CASE REPORT Identification of E545k mutation in plasma from a PIK3CA wild-type metastatic breast cancer patient by array-based digital polymerase chain reaction Circulating-free DNA a powerful tool for biomarker testing in advance disease Q15 ATOCHA ROMERO, DANIEL ACOSTA-EYZAGUIRRE, JULI  AN SANZ, FERNANDO MORENO, GLORIA SERRANO, EDUARDO D  IAZ-RUBIO, TRINIDAD CALD  ES, and JOS  E  A. GARCIA-SAENZ MADRID, SPAIN Q1 PIK3CA gene is frequently mutated in patients with breast cancer and it has been the focus of intense research. Inhibitors of PI3K pathway are being evaluated in ongoing clinical trials but the impact of PIKC3A mutation status on tumor response is yet uncertain. In the metastatic setting, several studies are evaluating the predictive/ prognostic value of PIK3CA mutations Q2 . However, results could be biased by biopsy localization. Digital polymerase chain reaction is a new technology that enables detection and quantification of cancer DNA molecules from peripheral blood and can potentially overcome such situation. As a proof of the concept, we present the case of a metastatic patient with a PIK3CA wild-type primary tumor in which the PIK3CA E545K mutation was identified in both the circulating-free DNA obtained from a peripheral blood sample and in the FFPE liver metastasis Q3 . (Translational Research 2015;-:1–5) Abbreviations: cfDNA ¼ circulating-free DNA; dPCR ¼ digital polymerase chain reaction; ER ¼ estrogen receptor; PR ¼ progesterone receptor; wt ¼ wild-type Q4 INTRODUCTION T he PIK3CA gene, which encodes the p110a cata- lytic subunit of PI3K, is mutated in more than one-third of breast cancer cases, 1 making this gene an attractive candidate for the development of targeted therapies. The mutation spectrum displays a nonrandom distribution, existing hotspot positions within the helical domain (exon 9, commonly E542K and E545K), and the kinase domain (exon 20, commonly H1047R), which account for 70% of all PIK3CA mutations in breast tumors. 1-4 In recent years, the predictive/prognostic value of PIK3CA has been the focus of research interest. Howev- er, the clinical relevance of genetic events occurring at From the Medical Oncology Department, Hospital Cl  ınico San Carlos, Madrid, Spain; Medical Oncology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain; Medical Oncology Department, Centro Integral Oncol ogico Clara Campal, HM Hospitals, Madrid, Spain; Pathology Department, Hospital Cl  ınico San Carlos, Madrid, Spain. Submitted for publication February 20, 2015; revision submitted April 15, 2015; accepted for publication April 19, 2015. Reprint requests: Atocha Romero, Medical Oncology Department, Hospital Universitario Puerta de Hierro Madrid, C/Hospital Universi- tario Puerta de Hierro, Calle Manuel de Falla, no. 1, Majadahonda, Madrid 28222, Spain; e-mail: atocha10@hotmail.com. 1931-5244/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.trsl.2015.04.010 1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106