Also known as: Breast cancer risk of recurrence« Back to test list
In 2000, a genetic classification of breast cancer was developed which defines four distinct patterns of gene activity, or “intrinsic subtypes”, in breast cancer viz. luminal A, luminal B, HER2-enriched, and basal-like.
These subtypes can be reliably identified from a set of 50 genes (called “PAM50”). Various methods and analyses of the PAM50 gene set have been described, potentially compromising the reproducibility of the prognostic and predictive performance of the assay in different settings.
Prosigna is a validated and accredited implementation of the PAM50 assay that is robust in a wide variety of laboratory settings. The concordance of the Prosigna and PAM50 assays has been confirmed in women with post-menopausal, early-stage hormone-sensitive breast cancer. Prosigna has been validated using a broad range of patient samples, and it is anticipated that the Prosigna will have equivalent or better performance to PAM50 assays in other clinical settings.
The intrinsic subtype is the basis for providing information that is both prognostic i.e. risk of recurrence, and predictive i.e. probability of responding to therapy.
Prosigna goes a step further and utilises the activity of the 50 genes, together with the number of involved nodes and tumour size, to determine a score for the individual patient. In addition to providing information relating to the subtype to which the patient’s cancer belongs, the test also provides prognostic and predictive information for the individual patient.
The distinction between group-based versus individualised information is important as the evidence for the utility of Prosigna may be based on either cohort information e.g. outcomes for a subtype group, or on the individual information e.g. prognosis indicated by the score, or both. The prognosis or prediction for an individual may also be more precise than the probability cited for the group.
This is an assay for non-heritable mutations. It does not raise issues of ethics or consent that are different from most other investigations ordered in the routine care of a patient.
The accuracy and usefulness of the prognostic and predictive information provided by Prosigna has been documented in pre- and post-menopausal women, and in patients considering neoadjuvant, adjuvant, and post-relapse chemotherapy. The most detailed evidence deals with post-menopausal women with early-stage hormone-sensitive breast cancer who are receiving tamoxifen – and who need to decide whether adjuvant chemotherapy is warranted.
Prosigna has been demonstrated to provide information that is more detailed and more accurate than information from clinical factors, histology, and other gene expression assays.
The result of the Prosigna test is not the only factor that should be considered in deciding whether adjuvant chemotherapy is indicated in a specific patient.
This test involves analysis of the activity of 50 genes
RNA is extracted from a small section of formalin fixed tumour tissue, and RNA molecules from each of 50 genes are counted. These numbers, together with the tumour size and number of involved nodes, are combined to generate the intrinsic subtype and the Prosigna score.
This test should only be requested by the specialist responsible for managing a woman’s decision-making regarding chemotherapy. The sample required is formalin fixed, paraffin-embedded tissue (FFPE).
There are specific sample requirements; pathologists are requested to contact the laboratory for details.