Search

One-step nucleic acid amplification (OSNA) is a molecular procedure used intraoperatively for the detection of sentinel lymph node (SLN) metastases. The aim of the present study was to define a cut-off of cytokeratin (CK)19 mRNA copy number predictive of positive completion axillary lymph node dissection (ALND). The OSNA procedure was employed for SLN analysis in 812 patients with T1-T2 N0 breast cancer. A total of 197 patients with SLN metastases were retrospectively analyzed. A total of 40 patients (20%) had non-SLN metastases. Receiver operating characteristics curve analysis established a cut-off of 5,000 CK19 mRNA copy number with 75% sensitivity and 72% specificity. The positive and negative predictive values were 40.5 and 92%, respectively. Multivariate analysis showed that this cut-off and tumor localization in the outer or lower-outer quadrant of the breast were significantly associated with non-SNL involvement (P

International audience; This book is a comprehensive guide to the techniques, clinical applications, and benefits of the different forms of liquid biopsy employed in patients with a variety of tumor types, including lung, breast and colorectal cancer. Offering detailed explanations, it discusses the how changes in tumors can be tracked using these cutting-edge technologies, which enable the detection and analysis of diverse circulating biomarkers: tumor cells, tumor DNA, tumor RNA (free or in exosomes), and fluid biomarkers identifiable by means of targeted proteomics. The use of such advanced technologies is enabling us to tackle questions and problems in a way that was not possible just a few years ago. We now have at our disposal an effective means of overcoming the problem of intratumor heterogeneity, which has limited the value of conventional biopsy approaches. As a consequence, oncology practice is about to change radically, toward truly personalized precision medicine. This book provides both clinicians and researchers with a thorough and up-to-date overview of progress in the field.

published in Cancer Research,79(4 Suppl):OT1-03-02, February 2019; International audience; Activating ESR1 mutations have recently been reported as a key mechanism leading to Aromatase Inhibitor (AI) resistance. ESR1 mutations occur rarely in primary breast cancers. However, in large retrospective studies, ESR1 mutations occurred in up to 39% of Estrogen-Receptor(ER)-positive metastatic breast cancer resistant to AI. Numerous hotspot mutations have been identified, most of them affecting the ligand-binding domain (LBD) and leading to ligand-independent activation of the ER and to resistance to AI.Phosphatidylinositol 3-kinase (PI3K)/AKT pathway is involved in key Cellular Mechanisms and mutations in PIK3CA and AKT1 are frequently reported in breast cancer.In this study, we propose to use a capture-based Next Generation Sequencing (NGS) assay and to use the barcoding and polishing features in our analysis pipeline. This assay will be able to detect all mutations on AKT1, PIK3CA, ESR1 and other genes on circulating tumor DNA (ctDNA) extracted from blood samples of patients with breast cancer. We consider that this exon-screening strategy is relevant according to the recent knowledge.We plan to prospectively include women with advanced breast cancer about to begin standard-of-care first line endocrine therapy (ET). Patients will be required to have histologically confirmed ER-positive, HER2-negative breast cancer and documented loco-regionally advanced or metastatic disease, not amenable to surgery or radiation with curative intent. Patients with endocrine sensitive disease (no prior ET or relapse more than 12 months after completing adjuvant ET) as well as patients with endocrine resistant disease (relapse while on adjuvant ET or within 12 months of completing adjuvant ET) will be enrolled.ET can be prescribed alone or in combination with a targeted therapy. Nevertheless, we will recruit at least 25% of patients with exclusive ET in the endocrine sensitive group.Peripheral-blood samples, for analysis of ctDNA, will be obtained from participating patients at pre-specified time points: at start of ET to determine the baseline mutational status of ESR1, PIK3CA, AKT1 and other genes included in a panel of genes of interest in solid tumors, and then, at evaluation of response to therapy until disease progression or end of study.Patients will be followed for 36 months or until disease progression. Determination of progression will be done per local investigator.The primary objective is to describe the prevalence of activating ESR1 mutations affecting the LBD, using NGS, from the start of ET to progression or end of study. Secondary objectives include to describe the prevalence of ESR1 mutations affecting other domains, the prevalence of ESR1 mutations in patients with and without endocrine resistance at enrolment and the prevalence of PIK3CA and AKT1 mutations, to demonstrate that ESR1, PIK3CA and AKT1 mutations whatever their times of onset are predictors of progression free survival.As of June 2018, 8 sites were opened to recruitment and 18 pts were included; the target enrollment is 146. The trial is supported by AstraZeneca.