These guidelines were developed to ensure that appropriate consideration is given to germline testing in individuals with BRCA associated cancers who may undergo tumour testing to inform systemic treatment options.
Evidence from the literature and local experience was used to determine the following for each tumour stream:
- The probability of tumour BRCA1 and BRCA2 testing missing a germline pathogenic variant.
- The probability of an individual having a germline pathogenic variant in another cancer predisposition gene.
- The clinical utility of identifying a germline pathogenic variant in a cancer predisposition gene.
A lower than 10% probability of identifying a germline pathogenic variant in a cancer predisposition gene was accepted in cases where the clinical utility of identifying a variant is high.
The interface between tumour and germline testing is complex and there should be collaboration between local cancer genetics/familial cancer services and the relevant medical oncology, surgical oncology, anatomical pathology and molecular pathology services to determine the ideal local model of care.
This document does not cover cases with evidence of DNA mismatch repair (MMR) deficiency by immunohistochemical staining or microsatellite instability studies in the tumour tissue. The relevant panel testing document should be consulted for these cases.