Abstract ES8-2: Circulating plasma tumor DNA as biomarkers for breast cancer therapy

Abstract

Abstract Currently, oncologists use prior clinical trials data to recommend therapies based upon features of the tumor and clinical stage of the patient. A limitation with this approach is that these data are averaged from large groups of patients that are then applied to each individual. This creates uncertainty as there is currently no reliable method to identify whether an individual patient truly is at risk for an unfavorable outcome and would benefit from a specific intervention. Recently, we and others have demonstrated the feasibility of detecting circulating plasma tumor DNA in metastatic breast cancer patients using digital PCR. We have now extended these studies to include early stage breast cancer patients using the second generation platform of droplet digital PCR (ddPCR). In this study the feasibility and accuracy of circulating plasma tumor DNA (ptDNA) detection was prospectively assessed by screening for the presence of tumor PIK3CA mutations in patients' plasma prior to and after breast surgery using ddPCR. We observed in early stage breast cancer patients that ddPCR could detect PIK3CA mutations preoperatively with 93.3% sensitivity (14 of 15 mutations detected) and 100% specificity (no false positives in 30 tumors). Moreover, 5 of 10 patients with PIK3CA mutation positive tumors continued to have mutant PIK3CA detected in their postoperative blood sample despite having no clinical evidence of disease. This work demonstrates that droplet digital PCR (ddPCR) can be used to accurately detect cancer DNA mutations in the blood of early stage breast cancer patients including those with minimal, clinically undetectable disease. Our results suggest that ddPCR provides an accurate and relatively non-invasive method for measuring residual disease and could be developed as a biomarker to identify early stage breast cancer patients at higher risk for recurrence to help make informed decisions regarding adjuvant therapies. Ongoing studies assessing mutational profiles from ptDNA from metastatic patients as well as patients undergoing neoadjuvant therapies will be discussed. Citation Format: Ben Ho Park. Circulating plasma tumor DNA as biomarkers for breast cancer therapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr ES8-2.