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 insert2, 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 PAM505 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 (mm2)
Requirement
Viable invasive breast carcinoma
(ductal, lobular, mixed or NOS)
4 mm2 tumor area
Formalin-fixed paraffin-embedded (FFPE)
tumor tissue samples with > 10% tumor
Macro-dissected 10 µm thick slide-mounted sections
4 to 19 mm2 = 6 slides
20 to 99 mm2 = 3 slides
≥ 100 mm2 = 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
Prosigna Score
Range
Risk Classification
0-40
Low
41-60
Intermediate
61-100
High
0-40
Low
41-100
High
Node-Negative
Node-Positive
(1-3 nodes)
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
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
Patient Distribution
Patients in Risk Group
500
428 434
400
300
243
192
200
Prosigna
119
62
100
Oncotype Dx
0
Low
Intermediate
High
Risk Category
Oncotype DX® Breast Cancer Assay
Description
Population
Report
Prosigna™ Breast Cancer Prognostic Gene
Signature Assay
Analysis of a 21 gene expression signature used to
generate a Recurrence Score®.
Analysis of 50 genes associated with intrinsic biology
of the tumor.
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
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
Recurrence Score,
3 risk groups (Low, Intermediate, High)
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
Reported within 7-14 days
FDA Approval
No
Yes
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.