Background: Oncotype DX™ is a clinically validated, high-complexity, multianalyte reverse transcription-PCR genomic test that predicts the likelihood of breast cancer recurrence in early-stage, node-negative, estrogen receptor-positive breast cancer. The Recurrence Score™ (RS) provides a more accurate, reproducible measure of breast cancer aggressiveness and therapeutic responsiveness than standard measures. Individualized patient management requires strict performance criteria for clinical laboratory tests. We therefore investigated the analytical performance of the assay. Methods: Assays used a pooled RNA sample from fixed paraffin-embedded tissues to evaluate the analytical performance of a 21-gene panel with respect to amplification efficiency, precision, linearity, and dynamic range, as well as limits of detection and quantification. Performance variables were estimated from assays carried out with sample dilutions. In addition, individual patient samples were used to test the optimized assay for reproducibility and sources of imprecision. Results: Assay results defined acceptable operational performance ranges, including an estimated maximum deviation from linearity of <1 cycle threshold (C T ) units over a >2000-fold range of RNA concentrations, with a mean quantification bias of 0.3% and CVs of 3.2%-5.7%. An analysis of study design showed that assay imprecision

Background-MitraClip has been shown to reduce mitral regurgitation (MR) severity safely but to a lesser degree than surgery. No data exist on the magnitude of MR reduction necessary to reverse left ventricular (LV) and left atrial (LA) dilation in patients with severe MR. Therefore, an analysis was performed to evaluate the relationship between MR reduction and LV and LA volumes after MitraClip therapy. Methods and Results-A total of 801 patients treated with MitraClip and 80 patients treated surgically were included. All patients had severe (3-4+) MR. MR severity, LV volumes at end-diastole and end-systole, and LA volumes were measured at baseline, discharge, 30 days, 6 months, and 1 year by an independent echocardiographic core laboratory. A linear repeated measures model was developed to determine the relationship between MR severity and time of measurement postindex procedure on longitudinal LV and LA volumes. Separate models were fit for functional MR and degenerative MR. In both degenerative and functional MR, reduction in LV volumes at end-diastole was associated with degree of residual MR at 12 months (P<0.0001). LV volumes at end-systole was significantly reduced in functional MR but not degenerative MR. LA volumes were significantly related to reduction of MR severity in both groups. Conclusions-Reduction of LV volumes at end-diastole and LA volumes, but not LV volumes at end-systole in degenerative MR, is consistent with correction of volume overload from primary MR. Reduction of all 3 measurements in functional MR demonstrates reverse remodeling when MR severity is reduced to either 1+ or 2+ by MitraClip therapy. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00209274.