What is Prosigna? The Prosigna Breast Cancer Prognostic Gene Signature Assay is currently the only FDA-cleared test that provides a risk category and numerical score to assess a patient's risk of distant recurrence of disease at 10 years in postmenopausal women with node-negative (Stage I or II) or node-positive (Stage II), hormone receptor-positive (HR+) breast cancer. The Prosigna Score ranges from 0 through 100 and correlates with the probability of distant recurrence in the tested population. Risk classification is provided to guide the interpretation of the Prosigna Score using cutoffs related to clinical outcome. http://prosigna.com/overview/ Indications for Use Per the FDA approval and package insert 2, the following are indications for use of Prosigna, in conjunction with other clinicopathological factors, in female breast cancer patients who have undergone surgery in conjunction with locoregional treatment consistent with standard of care: A prognostic indicator for distant recurrence-free survival (DRFS) at 10 years in post-menopausal women with hormone receptor-positive, lymph node-negative, Stage I/II breast cancer. A prognostic indicator for DRFS at 10 years in post-menopausal women with hormone receptorpositive, lymph node-positive (1-3 nodes), Stage II breast cancer, when used. The test is not intended for patients with 4 or more positive nodes.
Methodology The Prosigna assay is performed on RNA isolated from FFPE breast tumor tissue. It measures the expression levels of 50 genes used in the PAM50 5 classification algorithm, eight housekeeping genes used for signal normalization, six positive controls, and eight negative controls in a single hybridization reaction, using nucleic acid probes designed specifically to those genes. The Prosigna Score is derived from a proprietary algorithm that determines risk of distant relapse using molecular data from the PAM50 signature (subtype correlation and proliferation) as well as tumor size and node status. Specimen Requirements Specimen Attribute Tissue Input Minimum Tumor Size Sample Required Tissue Input Format Number of Slides Required Based on Measured Tumor Surface Area on H & E Slide (mm 2 ) Requirement Viable invasive breast carcinoma (ductal, lobular, mixed or NOS) 4 mm 2 tumor area Formalin-fixed paraffin-embedded (FFPE) tumor tissue samples with > 10% tumor Macro-dissected 10 µm thick slide-mounted sections 4 to 19 mm 2 = 6 slides 20 to 99 mm 2 = 3 slides 100 mm 2 = 1 slide Order Information: Test Name: Prosigna Breast Cancer Prognostic Gene Signature EPIC Number: LAB24158 PHS Lab SIM Code: 45250 CPT Codes: o Prosigna Assay: 81599 o Microdissection Manual: 88381 o Professional Fee Microdissection Manual: 88381-26 Turnaround Time: 7-14 days Please refer to your Providence Regional Laboratory Physician Sales & Service representative for additional information.
Understanding the Prosigna Patient Report Prosigna results are based on a large validation data set of postmenopausal women with early-stage breast cancer, including both node-negative and node-positive patients. The patient s tumor size and nodal status are required to determine her Prosigna Score and risk group. The Prosigna patient report is customized and includes only those results relevant to your patient s nodal status. Page 1 of the Prosigna Patient Report provides two customized outputs to determine your patient s probability of distant recurrence over 10 years: Prosigna Score: Derived from a proprietary algorithm based on the PAM50 gene signature. The Prosigna Score is a numerical value on a 0 to 100 scale that correlates with the probability of distant recurrence within 10 years when treated with endocrine therapy alone. Risk Group: Based on the Prosigna Score and nodal status, risk group is provided to allow interpretation of the Prosigna Score by using cutoffs related to clinical outcome in tested populations. EXAMPLE: Node-negative, Low Risk Patient
Page 2 of the Prosigna Patient Report provides context for your patient s reported risk group based on the results of a large clinical validation study, ABCSG-8. Both the Prosigna Score and risk group add statistically significant prognostic information beyond other clinical variables for node-negative and node=-positive patients (P<0.0001). Node-negative patients: 10 year distant recurrence-free survival (DRFS) rates were >95% for the lowrisk group, 90.4% for the intermediate-risk group and <85% for the high-risk group. Node-positive patients: 10 year DRFS rates were 94.2% for the low-risk group and 75.8% for the highrisk group. Nodal Status is used to determine Risk Classification for the Prosigna Breast Cancer Gene Signature Assay. Nodal Status Node-Negative Node-Positive (1-3 nodes) Prosigna Score Range Risk Classification 0-40 Low 41-60 Intermediate 61-100 High 0-40 Low 41-100 High Kaplan-Meier curves and data tables showing the percent of patients without distant recurrence by risk group through 10 years and by node status. 2 DRFS by Risk Group for Node-Negative Patients DRFS by Risk Group for Node-Positive (1-3) Patients
Prosigna Clinically Validated in Two Studies: TransATAC and ABCSG-8 Trial TransATACStudy: 1 ABCSG8 Study: 4
Patients in Risk Group Comparison of Prosigna to Oncotype Dx A retrospective analysis of more than 1,000 patient samples from the TransATAC study evaluated the relationship between clinical variables, immunohistochemistry markers (IHC4), Oncotype Dx Recurrence Score (RS) and Prosigna Score (ROR) for distant recurrence in post-menopausal women with hormone receptor-positive breast cancer. The study concluded that the Prosigna ROR provides more prognostic information in endocrine-treated patients with ER-positive, Node-negative disease than Oncotype DX RS, with better differentiation of intermediate and high risk groups. 1 Fewer Patients Categorized as Intermediate Risk and more as High Risk Using FDA Cleared Prosigna Assay Kaplan-Meier plot shows distant recurrence over 10 years for node-negative populations predicted to be at low, intermediate, or high risk by risk of recurrence (Prosigna ROR; solid lines) or recurrence score (Oncotype Dx RS; dashed lines) in the absence of clinical treatment score. 1 500 400 428434 Patient Distribution 300 200 100 243 192 119 62 Prosigna Oncotype Dx 0 Low Intermediate High Risk Category Description Population Report Oncotype DX Breast Cancer Assay Analysis of a 21 gene expression signature used to generate a Recurrence Score. Recurrence Score is used to predict chemotherapy benefit and indicates the 10-year risk of distant recurrence in ER-positive, HER2-negative breast cancer. HR+, Stage 1 & 2, Node negative and Node positive (1-3 Nodes) in Pre- and Post-menopausal women Excludes HER2 DCIS Recurrence Score, 3 risk groups (Low, Intermediate, High) Prosigna Breast Cancer Prognostic Gene Signature Assay Analysis of 50 genes associated with intrinsic biology of the tumor. PAM50 based algorithm used to calculate Prosigna Score associated with risk of recurrence (ROR) at 10 years in HR+ breast cancer given endocrine therapy alone. HR+, Stage 1 & 2, Node negative and Node positive (1-3 Nodes) in Post-menopausal women Prosigna Score, 3 risk groups (Low, Intermediate, High) Service Model Testing performed by single reference laboratory Testing provided by Providence Regional Laboratory Turn Around Time Reported within 14 days 90% of the time FDA Approval No Yes Reported within 7-14 days
References: 1. Dowsett, M et al., Comparison of PAM50 Risk of Recurrence Score With Oncotype DX and IHC4 for Predicting Risk of Distant Recurrence After Endocrine Therapy, J Clin Oncol 2013; 31:2783-90. 2. Prosigna Package Insert: Prosigna Breast Cancer Prognostic Gene Signature Assay; Version 03; created 2013-11; REF LBL-C0223-03. 3. Gnant M et al., Predicting Risk for Late Metastasis: The PAM50 Risk of Recurrence (ROR) Score After 5 Years of Endocrine Therapy in Postmenopausal Women with HR+ Early Breast Cancer. A Study on 1,478 Patients for the ABCSG-8 Trial. Ann Oncol 2013; 24 (Supplement 3):iii29-iii37. 4. Gnant M et al., Predicting distant recurrence in receptor-positive breast cancer patients with limited clinicopathological risk: using the PAM50 Risk of Recurrence score in 1478 postmenopausal patients of the ABCSG-8 trial treated with adjuvant endocrine therapy alone. Ann Oncol 2014; 25: 339-345.