麻豆传媒

Next-generation sequencing and multigene panels have changed the landscape of germline mutation testing for patients with breast cancer, noted authors of a new ASCO guideline.

"However, the advent of expanded testing also presents challenges as the ease with which genes can be sequenced has outpaced the understanding of the clinical implications of the germline findings," Isabelle Bedrosian, MD, of the University of Texas MD Anderson Cancer Center in Houston, and other members of the expert panel wrote in the

In updating previous ASCO recommendations, the expert panel considered five key clinical questions:

• Should clinicians offer BRCA1/2 testing to all patients with newly diagnosed breast cancer?

• Should all people with recurrent disease, local or metastatic, or with second breast primary, be offered BRCA1/2 testing?

• Should people with a personal history of breast cancer (and no active disease) be offered BRCA1/2 testing?

• What is the value of testing patients with a diagnosis of breast cancer for breast cancer predisposition genes other than BRCA1/2?

• How should patients with breast cancer considering genetic testing be counseled?

Bedrosian discussed some of these issues and key new recommendations in the following interview.

Why was it time to update these guidelines?

Bedrosian: The field of germline testing has changed markedly in the last decade. The advent of widely available panel testing has created substantial complexity as to how to approach testing in breast cancer patients. It was important, therefore, to provide a framework for providers as to how they should approach the issue -- what factors should be considered in ordering a test? Who should be tested? What should the scope of testing look like?

What is one of the most important updates or changes from previous recommendations, and why was it made?

Bedrosian: The guidelines broadened the discussion to genes outside of BRCA1 and BRCA2, recognizing the ability to test for larger panels these days and recognizing the advances in genetics linking genes other than BRCA1/2 to risk of breast cancer. The criteria for testing were simplified to age-based selection instead of complex family history constellations.

What would you like to make sure clinicians understand about these guidelines?

Bedrosian: The rapidly evolving nature of genetics and germline testing means that for most clinicians, a close partnership with clinicians experienced in cancer genetics will be critical in order to provide appropriate guidance for testing and appropriate interpretation of test results.

What is one of the largest areas of uncertainty in this field?

Bedrosian: For many of the genes on panel tests, the clinical significance remains uncertain and/or the magnitude of associated risks have not been reliably estimated, especially for second primary cancers. This makes it challenging to know how to best counsel patients.

Additionally, the large number of variants of unknown significance (VUS) that are often identified remains problematic, a problem magnified in non-white populations as VUS results are more frequent in minority populations who have historically received less genetic testing and for whom the normal range of genetic variability is less well understood.

The guidelines noted that the traditional genetic counseling model is not sustainable, given the substantial number of patients who will qualify for testing and the shortage in genetic counselors nationally. What are the implications of this?

Bedrosian: New models of care are needed that will retain the key principles of testing -- informed consent and appropriate education on the implications of positive results -- but do not rely on the current practice of pre- and post-test counseling by genetics counselors.

Several models have been proposed and are being tested, including use of pre-test education videos, chatbot-enabled educational platforms, and telehealth. An important component of these efforts will be their ability to reach low-resource environments such as rural and underserved urban settings; these communities have historically had less access to genetic testing.

Read the guideline here and expert commentary about it here.