Purpose Detecting circulating plasma tumor DNA (ptDNA) in early stage cancer patients has the potential to change how oncologists recommend systemic therapies for solid tumors after surgery. Droplet digital polymerase chain reaction (ddPCR) is a novel sensitive and specific platform for mutation detection. Experimental Design In this prospective study, primary breast tumors and matched pre- and post-surgery blood samples were collected from early stage breast cancer patients (n=29). Tumors (n=30) were analyzed by Sanger sequencing for common PIK3CA mutations, and DNA from these tumors and matched plasma were then analyzed for PIK3CA mutations using ddPCR. Results Sequencing of tumors identified seven PIK3CA exon 20 mutations (H1047R) and three exon 9 mutations (E545K). Analysis of tumors by ddPCR confirmed these mutations and identified five additional mutations. Pre-surgery plasma samples (n=29) were then analyzed for PIK3CA mutations using ddPCR. Of the fifteen PIK3CA mutations detected in tumors by ddPCR, fourteen of the corresponding mutations were detected in pre-surgical ptDNA, while no mutations were found in plasma from patients with PIK3CA wild type tumors (sensitivity 93.3%, specificity 100%). Ten patients with mutation positive ptDNA pre-surgery had ddPCR analysis of post-surgery plasma, with five patients having detectable ptDNA post-surgery. Conclusions This prospective study demonstrates accurate mutation detection in tumor tissues using ddPCR, and that ptDNA can be detected in blood before and after surgery in early stage breast cancer patients. Future studies can now address whether ptDNA detected after surgery identifies patients at risk for recurrence, which could guide chemotherapy decisions for individual patients.
Digital PCR is a new technology that enables detection and quantification of cancer DNA molecules from peripheral blood. Using this technique, we identified mutant PIK3CA DNA in circulating plasma tumor DNA (ptDNA) from a patient with concurrent early stage breast cancer and non-small cell lung cancer. The patient underwent successful resection of both her breast and lung cancers, and using standard Sanger sequencing the breast cancer was shown to harbor the identical PIK3CA mutation identified in peripheral blood. This case report highlights potential applications and concerns that can arise with the use of ptDNA in clinical oncology practice.
Preoperative sentinel node localization (SNL) using a subareolar injection of radiotracer technetium-99m-sulfur colloid (Tc99mSC) is associated with significant pain. Lidocaine use during SNL is not widely adopted partly due to a concern that it can obscure sentinel node identification and reduce its diagnostic accuracy. We prospectively identified women with a biopsy-proven infiltrating breast cancer who were awaiting a SNL. The women completed the McGill pain questionnaire, Visual Analog Scale, and Wong–Baker FACES Pain Rating Scale prior to and following SNL. We identified a retrospective cohort of women with similar demographic and tumor characteristics who did not receive lidocaine before SNL. We compared sentinel lymph node identification rates in the two cohorts. We used Wilcoxon rank sum tests to compare continuous measures and Fisher's exact test for categorical measures. Between January 2011 to July 2012, 110 women consented, and 105 were eligible for and received lidocaine prior to Tc99mSC injection. The post-lidocaine identification rate of SNL was 95 % with Tc99mSC, and 100 % with the addition of intraoperative methylene blue dye/saline. Pain range prior to and following the SNL was unchanged (P = 0.703). We identified 187 women from 2005 to 2009 who did not receive lidocaine during preoperative SNL. There was no significant difference in the success rate of SNL, with or without lidocaine (P = 0.194). The administration of lidocaine during SNL prevents pain related to isotope injection while maintaining the success rate. We have changed our practice at our center to incorporate the use of lidocaine during all SNL.
How do eligible jurors perceive trial consultants? A survey was administered to 1251 participants from 50 states. Results indicated that individuals who thought the legal system was fair, those who earned higher incomes, and Anglo Americans rated trial consultants most favorable. Survey respondents estimated that 43% of court cases use trial consultants, and 18% of participants indicated that if they knew one side was using a trial consultant, they would be biased against the side that hired the consultant. Trial consultants need to consider the potential impact their presence makes during the course of legal proceedings and make the necessary adjustments to improve their services.
<div>Abstract<p><b>Purpose:</b> Detecting circulating plasma tumor DNA (ptDNA) in patients with early-stage cancer has the potential to change how oncologists recommend systemic therapies for solid tumors after surgery. Droplet digital polymerase chain reaction (ddPCR) is a novel sensitive and specific platform for mutation detection.</p><p><b>Experimental Design:</b> In this prospective study, primary breast tumors and matched pre- and postsurgery blood samples were collected from patients with early-stage breast cancer (<i>n</i> = 29). Tumors (<i>n</i> = 30) were analyzed by Sanger sequencing for common <i>PIK3CA</i> mutations, and DNA from these tumors and matched plasma were then analyzed for <i>PIK3CA</i> mutations using ddPCR.</p><p><b>Results:</b> Sequencing of tumors identified seven <i>PIK3CA</i> exon 20 mutations (H1047R) and three exon 9 mutations (E545K). Analysis of tumors by ddPCR confirmed these mutations and identified five additional mutations. Presurgery plasma samples (<i>n</i> = 29) were then analyzed for <i>PIK3CA</i> mutations using ddPCR. Of the 15 <i>PIK3CA</i> mutations detected in tumors by ddPCR, 14 of the corresponding mutations were detected in presurgical ptDNA, whereas no mutations were found in plasma from patients with <i>PIK3CA</i> wild-type tumors (sensitivity 93.3%, specificity 100%). Ten patients with mutation-positive ptDNA presurgery had ddPCR analysis of postsurgery plasma, with five patients having detectable ptDNA postsurgery.</p><p><b>Conclusions:</b> This prospective study demonstrates accurate mutation detection in tumor tissues using ddPCR, and that ptDNA can be detected in blood before and after surgery in patients with early-stage breast cancer. Future studies can now address whether ptDNA detected after surgery identifies patients at risk for recurrence, which could guide chemotherapy decisions for individual patients. <i>Clin Cancer Res; 20(10); 2643–50. ©2014 AACR</i>.</p></div>
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