An update on genetic risk assessment and prevention: the role of genetic testing panels in breast cancer

ABSTRACT

Introduction: In the past 5 years, multi-gene panels have replaced the practice of BRCA1 and BRCA2 genetic testing in cases of suspected inherited breast cancer susceptibility. A variety of genes have been included on these panels without certainty of their clinical utility. Pertinent current and historical literature was reviewed to provide an up-to-date snapshot of the changing landscape of the use of gene panel tests in the context of breast cancer.

Areas covered: Following a recent review of the evidence, 10 genes have been found to have definitive evidence of increased breast cancer risk with variable penetrance. Here, we review the recent changes to the practice of multi-gene panel use in breast cancer diagnoses, including an update on next generation sequencing, alternative models of genetic testing, considerations when ordering these panel tests, and recommendations for management in identified carriers for a variety of genes. A comparison of screening recommendations and carrier frequencies from recent studies is also explored. Lastly, we consider what the future of hereditary oncologic genetic testing holds.

Expert opinion: The transition to multi-gene panels in breast cancer patients has improved the likelihood of capturing a rare variant in a well-established gene associated with hereditary breast cancer (e.g. BRCA1 and BRCA2, TP53). There is also an increase in the likelihood of uncovering an uncertain result. This could be in the form of a variant of uncertain significance, or a pathogenic variant in a gene with questionable breast cancer risk-association. Concurrently, a changing landscape of who orders genetic tests will improve access to genetic testing. This pervasiveness of genetic testing must be accompanied with increased genetic literacy in all health-care providers, and access to support from genetics professionals for management of patients and at-risk family members.

KEYWORDS:

• Gene panel testing
• hereditary breast cancer
• breast cancer
• next generation sequencing
• moderate risk genes
• germline testing
• tumor testing
• models of delivery in genetic testing

Article Highlights

• Gene panel tests are generally accepted of standard-of-care when ordering a germline genetic test in the context of familial breast cancer

• Many genes on breast panels have a definitive association with breast cancer and a clinical framework for their management, however, these are largely based on expert opinion and are continuously evolving

• It is unclear who should undergo panel testing as criteria have largely been based on BRCA1 and BRCA2

• These tests are increasingly becoming the purview of non-genetics providers to arrange, due to increased awareness and access

• Tumor testing is another emerging modality of genetic testing and may be another avenue to identify new carriers of germline mutations

• Medical interventions are available based on germline genetic test results for certain types of breast cancer, specifically, PARP inhibitors as a treatment for metastatic triple-negative breast cancer in BRCA carriers

• This article provides a summary of the current literature on 10 genes with definitive evidence of increased risk of breast cancer with a summary of overall carrier frequency, incidence in the breast cancer population, current screening recommendations, and associated autosomal-recessive conditions

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.