Abstract SY11-01: Plasma tumor DNA: Changing the paradigm for administering systemic therapies.

Abstract

Abstract The ability to accurately detect somatic cancer DNA alterations from cell free circulating plasma tumor DNA (ptDNA) using next generation genomic technologies has many potential applications for clinical oncology. The initial use of this technology has been to detect point mutations in peripheral blood that could serve as predictors of response to various targeted therapies. Thus the development of a “liquid biopsy” that could easily match the mutational status of a given cancer with a specific therapy had great therapeutic implications. For example, the ability to assess certain epidermal growth factor receptor (EGFR) mutations via blood versus an invasive lung biopsy would allow for the rapid determination of whether a patient would be a candidate for small molecule EGFR inhibitors such as gefitinib or erlotinib. We initially sought to evaluate the feasibility of detecting PIK3CA mutations in circulating ptDNA from patients with metastatic breast cancer using a novel technique of digital polymerase chain reaction (PCR) called BEAMing (for Beads, Emulsions, Amplification, Magnetics). We demonstrated that BEAMing is both sensitive and specific for identifying PIK3CA mutations in metastatic breast cancer patients, though we also confirmed the work of other groups that PIK3CA mutation status can change with progression to metastatic disease. An overview of these data will be presented. While these studies demonstrated the feasibility of using ptDNA in metastatic patients as a liquid biopsy for detecting specific cancer mutations, we are now focusing efforts to exploit the quantitative nature of digital PCR technology. Specifically, by analyzing the amount of ptDNA before and after primary breast surgery in early stage breast cancer patients, we will identify which patients truly have residual microscopic disease post surgery and therefore would be the most appropriate candidates for additional systemic therapies. Thus, in contrast to the current paradigm of “over” treating breast cancer patients in the adjuvant setting, detection of ptDNA using next generation digital PCR technologies will enable us to make rational decisions regarding which patients truly have need for adjuvant systemic therapies. Preliminary data and ongoing studies will be discussed as well as the implementation of these technologies in future clinical trials. Citation Format: Julia A. Beaver, Patricia Valda, Danijela Jelovac, Michaela J. Higgins, Ben H. Park. Plasma tumor DNA: Changing the paradigm for administering systemic therapies. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr SY11-01. doi:10.1158/1538-7445.AM2013-SY11-01