The American College of Medical Genetics and Genomics (ACMG) highlighted the lack of evidence for universal testing of breast cancer patients for BRCA1/2 mutations -- specifically or as part of multigene panels -- in a statement published December 13 in its journal Genetics in Medicine.
There isn't enough evidence to support universal testing, according to the ACMG, which is a broad, national organization of professionals, including clinical geneticists, clinical laboratory geneticists, and genetic counselors. The statement was published during the annual San Antonio Breast Cancer Symposium (SABCS), being held December 10-14.
"A broad discussion about population-based screening of unaffected women for a subset of inherited breast cancer genes is needed prior to considering genetic testing for all," wrote lead author Dr. Tuya Pal, associate director of cancer health disparities at the Vanderbilt-Ingram Cancer Center, and colleagues.
Instead, the ACMG advised that women with breast cancer should be assessed for genetic testing based on a range of clinical factors, including the following:
- Age at diagnosis
- Family cancer history
- Expression of estrogen and progesterone receptors and human epidermal growth factor receptor 2 (HER2)
Furthermore, guidelines on genetic testing must be supported by evidence and resources to support screening, counseling, and medical care, according to the ACMG. Among other concerns about universal use, the authors cited the potential for detecting variants of unknown significance on multipanel tests and the risk that women will undergo prophylactic surgical procedures unnecessarily based on these unclear findings.
"There remain many genes on existing multigene cancer panels for which breast cancer risks are yet to be established or confirmed (e.g., RAD50, BRIP1, XRCC2, and MRE11A, among others)," the authors pointed out.
'Tremendous need' for testing
However, the authors also noted the importance of genetic testing and said that all breast cancer patients should be evaluated to see if they should undergo screening for germline mutations. They also recognized the underuse of testing, as fewer than 10% of those estimated to have BRCA1/2 mutations are actually identified. In particular, Pal et al noted a "tremendous unmet need to improve identification and testing" of racial and ethnic minority populations.
The ACMG statement includes a range of issues that should be considered regarding genetic testing.
"A critical analysis of the use of genetic testing to guide clinical care requires input from patients, [healthcare] providers, laboratory geneticists, [healthcare] systems, and public and private insurers," Pal and colleagues wrote. "This discussion should also include gene penetrance, the constitution of multigene panels, and the clinical management associated with [pathogenic/likely pathogenic] variants for genes included on multigene panels."
The authors also advised that genetic testing for inherited breast cancer should be done by laboratories that are CLIA-certified and/or accredited by the College of American Pathologists (CAP).
Genetic testing a hot potato
Genetic testing in breast cancer patients has become a hot and controversial topic. There is broad recognition that BRCA1/2 testing is underused, and some have pointed the finger at the complexity of guidelines determining eligibility.
In new recommendations published in August, the U.S. Preventive Services Task Force (USPSTF) expanded its advice on genetic testing to include all women with a personal or family history of breast or ovarian cancer. Previously, in February, the American Society of Breast Surgeons (ASBrS) issued new guidelines advising genetic testing for every patient with breast cancer, specifying that testing should include screening for BRCA1/2 and PALB2 mutations, as well as other genes deemed appropriate based on family history and clinical scenario.