Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Risk Assessment

“Multigene testing of women who tested negative for BRCA1 and BRCA2 found some of them harbored other harmful genetic mutations—most commonly, moderate-risk breast and ovarian cancer genes, as well as Lynch syndrome genes (which increase the risk of ovarian cancer)—according to an article by Desmond et al in JAMA Oncology.

“Multigene panel genetic tests are increasingly recommended for patients evaluated for a predisposition to hereditary breast/ovarian cancer. However, the rapid introduction of these tests has raised concerns, because many of the tested genes are low- to moderate-risk genes for which consensus management guidelines have not been introduced or were introduced only very recently, according to the study background.

“Leif W. Ellisen, MD, PhD, of Massachusetts General Hospital Cancer Center, and coauthors wanted to determine how often multigene panel testing would identify mutations that warranted some clinical action among women appropriately tested but lacking BRCA1 and BRCA2 mutations.”


Researchers Oppose Unvalidated Gene Panel Tests for Cancer Links

“A group of international researchers is making the case that genetic tests that look for multiple hereditary genes suspected of being linked to breast cancer should not be offered until they are proven to be valid and useful in clinical practice.

“Such tests, made by several companies including Myriad Genetics Inc, Ambry Genetics, Invitae and Illumina Inc, cover up to 100 inherited cancer genes, including more than 20 for breast cancer.

“They have become increasingly popular since June 2013, when the U.S. Supreme Court invalidated patents held by Myriad on BRCA1 and BRCA2, two well-characterized genes that put a woman at high risk for breast, ovarian and other cancers.

“What the researchers are concerned about are lesser-known genes included in the tests.

” ‘The reality is that we don’t have good risk estimates for mutations that occur in many of the genes on the panels,’ said Fergus Couch, a breast cancer expert at Mayo Clinic in Rochester, Minnesota.”


Penn Medicine Study Reveals Why Almost Half of At-Risk Patients Opt Out of Comprehensive Multiplex Cancer Screening

“Some at-risk patients opted out of comprehensive cancer gene screening when presented with the opportunity to be tested for the presence of genes linked to various cancers, according to a recent study led by researchers at the Perelman School of Medicine at the University of Pennsylvania and the Basser Center for BRCA in Penn’s Abramson Cancer Center. Concern for uncertainty and potential distress were cited among the most common reasons to refuse testing. The results, published in Genetics in Medicine, were released just weeks ahead of an announcement of the online availability of low-cost genetic testing for breast and ovarian cancer mutations. Authors say the results suggest that patients have varying interest in ‘gene panels’ when they are informed of the potential risks and benefits, reflecting the current need for pre-test counseling when genetic panel testing is considered for at-risk patient populations.

“The study found that of the 49 patient participants, all of whom have a family or personal history that puts them at-risk for development breast and other forms of cancer, more than one-third declined multiplex testing. Multiplex testing allows for the simultaneous analysis of alterations in multiple cancer-related genes, and is an alternative to targeted tests that screen for individual forms of cancer. A targeted test might look for inherited mutations in the BRCA1 and BRCA2 genes, for example, which increase the risk of breast, ovarian, and other types of cancer. Some patients also declined the study all together because they were concerned about the uncertainty or distress with testing.”


A Molecular Signature Predictive of Indolent Prostate Cancer

“Many newly diagnosed prostate cancers present as low Gleason score tumors that require no treatment intervention. Distinguishing the many indolent tumors from the minority of lethal ones remains a major clinical challenge. We now show that low Gleason score prostate tumors can be distinguished as indolent and aggressive subgroups on the basis of their expression of genes associated with aging and senescence. Using gene set enrichment analysis, we identified a 19-gene signature enriched in indolent prostate tumors. We then further classified this signature with a decision tree learning model to identify three genes—FGFR1PMP22, and CDKN1A—that together accurately predicted outcome of low Gleason score tumors. Validation of this three-gene panel on independent cohorts confirmed its independent prognostic value as well as its ability to improve prognosis with currently used clinical nomograms. Furthermore, protein expression of this three-gene panel in biopsy samples distinguished Gleason 6 patients who failed surveillance over a 10-year period. We propose that this signature may be incorporated into prognostic assays for monitoring patients on active surveillance to facilitate appropriate courses of treatment.”