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Prosigna Breast Cancer Prognostic Gene Signature Assay

Assess a patient's risk of distant recurrence of breast cancer

The Prosigna™ Breast Cancer Prognostic Gene Signature Assay (formerly called the PAM50 test) is an in vitro diagnostic assay performed 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.

Indications for testing:

The Prosigna Breast Cancer Prognostic Gene Signature Assay is indicated for use in postmenopausal women with hormone receptor–positive, node-negative or node-positive early-stage (stages I and II) breast cancer to be treated with adjuvant endocrine therapy

Test outputs for risk assessment:

1- 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

2- Risk group: Based on the Prosigna Score and nodal status, risk classification is provided to allow interpretation of the Prosigna Score by using cutoffs related to clinical outcome in tested patient populations

Distant recurrence-free survival (DRFS) rates are significantly different among risk groups:

In node-negative patients, the 10-year DRFS rates were >95% for the low-risk group, 90.4% for the intermediate-risk group, and <85% for the high-risk group

In node-positive patients, the 10-year DRFS rates were 94.2% for the low-risk group and 75.8% for the high-risk group.

clinical utility

 

The clinical utility of using the Prosigna assay has been demonstrated in multiple studies. Gnant et al examined whether the continuous ROR score adds prognostic value in predicting distant recurrence (DR) over and above standard clinical variables in a patient cohort of 1478 postmenopausal women with estrogen receptor (ER)+ early breast cancer (EBC) treated with tamoxifen or tamoxifen followed by anastrozole from the prospective randomized ABCSG-8 trial. Patients did not receive adjuvant chemotherapy. In all tested subgroups, ROR score significantly adds prognostic information to the clinical predictor (P<0.0001). The results constitute Level 1 evidence for clinical validity of the PAM50 test for predicting the risk of DR in postmenopausal women with ER+ EBC [1]. In a study that performed analysis on postmenopausal women with node-positive hormone receptor-positive early-stage breast cancer treated with endocrine therapy from both ABCSG-8 and ATAC trials, the prosigna test was able to identify node-positive patient subgroups with limited risk of metastasis after endocrine therapy, for whom adjuvant chemotherapy can be spared [2]. In a study that examined the ability of ROR score in predicting distant recurrence after 5 years of follow-up in a combined analysis of the Austrian breast and colorectal cancer study group 8 and arimidex, tamoxifen alone or in combination randomized trials, the ROR score added clinically meaningful prognostic information to the CTS in all patients and all subgroups in the late follow-up period [3]. The results suggest that the ROR score may be helpful for separating patients into risk groups who could be spared or potentially benefit from extended hormonal therapy beyond 5 years of treatment [3].

References:

1. Gnant M, Filipits M, Greil R, Stoeger H, Rudas M, Bago-Horvath Z, Mlineritsch B, Kwasny W, Knauer M, Singer C, Jakesz R, Dubsky P, Fitzal F, Bartsch R, Steger G, Balic M, Ressler S, Cowens JW, Storhoff J, Ferree S, Schaper C, Liu S, Fesl C, Nielsen TO; Austrian Breast and Colorectal Cancer Study Group. 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 Feb;25(2):339-45.

2. Gnant M, Sestak I, Filipits M, Dowsett M, Balic M, Lopez-Knowles E, Greil R, Dubsky P, Stoeger H, Rudas M, Jakesz R, Ferree S, Cowens JW, Nielsen T, Schaper C, Fesl C, Cuzick J. Identifying clinically relevant prognostic subgroups of postmenopausal women with node-positive hormone receptor-positive early-stage breast cancer treated with endocrine therapy: a combined analysis of ABCSG-8 and ATAC using the PAM50 risk of recurrence score and intrinsic subtype. Ann Oncol. 2015 Aug;26(8):1685-91.

3. Sestak I, Cuzick J, Dowsett M, Lopez-Knowles E, Filipits M, Dubsky P, Cowens JW, Ferree S, Schaper C, Fesl C, Gnant M. Prediction of late distant recurrence after 5 years of endocrine treatment: a combined analysis of patients from the Austrian breast and colorectal cancer study group 8 and arimidex, tamoxifen alone or in combination randomized trials using the PAM50 risk of recurrence score. J Clin Oncol. 2015 Mar 10;33(8):916-22.

Criteria for Patient Testing

In the U.S., the Prosigna Assay is indicated in female postmenopausal women with Hormone Receptor-Positive (HR+), lymph node-negative, Stage I or II breast cancer, or Stage II breast cancer with Hormone Receptor-Positive (HR+), lymph node-positive (one to three positive nodes),to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors.

Special Conditions for Use:

The Prosigna Assay is not intended for diagnosis, to predict or detect response to therapy, or to help select the optimal therapy for patients.

Specimen Requirements

Sample Type and Acceptable Specimen: 10-micron thick, unstained sections from FFPE tissue block of primary tumor, mounted on positively-charged slides

Quantity: Up to (6) total unstained slides, accompanied by one 5-micron thick H&E stained slide taken in series with the unstained slides.

Previously isolated RNA or tissue sections (curls) placed into micro-centrifuge tubes will NOT be accepted by UAGC-CS for processing in the Prosigna pipeline.

Prosigna Requisition: Each patient sample must be accompanied by a completed Prosigna Requisition Form, completed by the patient’s physician. Receipt of the requisition form signed by the doctor is considered consent. Incomplete requisition forms will result in the delay of sample processing while the additional information is obtained.

Turnaround Time

5−10 business days – Times begin from receipt of the tissue slides by UAGC-CS and are based on business hours of the laboratory: Monday through Friday, 9am-5pm Arizona Time

Additional Details

The Prosigna™ Breast Cancer Prognostic Gene Signature Assay is an in vitro diagnostic assay performed 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.

Prosigna translates tumor biology into an individualized risk assessment

Prosigna is indicated for use in postmenopausal women with hormone receptor–positive, node-negative or node-positive early-stage (stages I and II) breast cancer to be treated with adjuvant endocrine therapy
Prosigna provides two powerful outputs for risk assessment1:

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

Risk group: Based on the Prosigna Score and nodal status, risk classification is provided to allow interpretation of the Prosigna Score by using cutoffs related to clinical outcome in tested patient populations

Prosigna Breast Cancer Assay Named

TOP 10 Innovations of 2013 by The Scientist

Each patient sample must be accompanied by a completed Prosigna Requisition Form, completed by the patient’s physician. Receipt of the requisition form signed by the doctor is considered consent. Incomplete requisition forms will result in the delay of sample processing while the additional information is obtained.

Prosigna Requisition form ordering instructions