(246 days)
The Prosigna™ Breast Cancer Prognostic Gene Signature Assay is an in vitro diagnostic assay which is performed on the NanoString nCounter® Dx Analysis System using FFPE breast tumor tissue previously diagnosed as invasive breast carcinoma. This qualitative assay utilizes gene expression data, weighted together with clinical variables to generate a risk category and numerical score, to assess a patient's risk of distant recurrence of disease.
The Prosigna Breast Cancer Prognostic Gene Signature Assay is indicated in female breast cancer patients who have undergone surgery in conjunction with locoregional treatment consistent with standard of care, either as:
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A prognostic indicator for distant recurrence-free survival at 10 years in post-menopausal women with Hormone Receptor-Positive (HR+), lymph node-negative, Stage I or II breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors.
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A prognostic indicator for distant recurrence-free survival at 10 years in post-menopausal women with Hormone Receptor-Positive (HR+), lymph node-positive (1-3 positive nodes), Stage II breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors. The device is not intended for patients with 4 or more positive nodes.
Special Conditions for Use: Prosigna is not intended for diagnosis, to predict or detect response to therapy, or to help select the optimal therapy for patients.
Used together, the Prosigna™ Breast Cancer Prognostic Gene Signature Assay and nCounter Dx Analysis System are a nucleic acid hybridization and image analysis system based upon coded probes designed to detect the messenger RNA transcribed from 58 genes. The test input is purified RNA from FFPE breast tumor specimens which are acquired from surgical resection. The Prosigna assay uses gene-specific probe pairs that hybridize directly to the mRNA transcripts in solution. The nCounter Dx Analysis System delivers direct, multiplexed measurements of gene expression through digital readouts of the relative abundance of the mRNA transcripts. Specifications are included as part of the Prosigna Assay to control for sample quality, RNA quality, and process quality. Prosigna simultaneously measures the expression levels of 50 genes used in the PAM50 classification algorithm (Parker et al., 2009), 8 housekeeping genes used for signal normalization, 6 positive controls, and 8 negative controls in a single hybridization reaction, using nucleic acid probes designed specifically to those genes. The Prosigna assay utilizes prototypical expression profiles (centroids) which are associated with and define each of the four PAM50 molecular subtypes of breast cancer. The software algorithm produces a Prosigna Score (referred to as ROR Score or Risk of Recurrence Score in the literature (Dowsett et al., 2013)) based on the similarity of the expression profile to each PAM50 molecular subtype, as well as the gross pathological tumor size and a proliferation score computed from a subset of genes. Three risk categories (low, intermediate and high) were defined based on a study with over 1007 patient samples associating Prosigna score with longterm outcome.
The required components for the Prosigna Assay include the RNA Isolation kit (manufactured by Roche), Prosigna reagents (Reference Sample, CodeSet, Prep Pack, Cartridge(s) and Prep Plate) and the instruments that comprise the nCounter Dx Analysis System; the Prep Station and Digital Analyzer.
The test output is a patient specific report which includes a Prosigna score (0-100) and risk category (low/intermediate/high).
Let's break down the acceptance criteria and the study that proves the device meets those criteria for the Prosigna™ Breast Cancer Prognostic Gene Signature Assay, based on the provided FDA 510(k) summary.
1. Table of Acceptance Criteria and Reported Device Performance
The FDA 510(k) summary for the Prosigna assay demonstrates clinical performance relative to its intended use as a prognostic indicator for distant recurrence-free survival (DRFS) at 10 years. The acceptance criteria are implicit in the statistical significance and magnitude of the prognostic information provided by the Prosigna Score, both as a continuous variable and when categorized into risk groups.
| Acceptance Criteria (Implicit) | Reported Device Performance (ABCSG-8 Study) |
|---|---|
| Primary Clinical Performance: Prosigna Score must add "significant prognostic information" for DRFS over and above existing clinical and treatment variables (CTS). | For DRFS at 10 years: |
- Prosigna Score as a continuous variable: Added significant prognostic information (p 90%. |
| Clinical Utility (Small Score Changes): Small changes in Prosigna Score (5-10 units) should be statistically significant for time to distant recurrence. | C-index analysis showed statistically significant utility for small changes in Prosigna Score (P
§ 866.6040 Gene expression profiling test system for breast cancer prognosis.
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Identification. A gene expression profiling test system for breast cancer prognosis is a device that measures the ribonucleic acid (RNA) expression level of multiple genes and combines this information to yield a signature (pattern or classifier or index) to aid in prognosis of previously diagnosed breast cancer.(b)
Classification. Class II (special controls). The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Gene Expression Profiling Test System for Breast Cancer Prognosis.” See § 866.1(e) for the availability of this guidance document.