Breast Cancer Risk and Multigene Panel Testing

Multigene Panel Testing Provides Broader Information About Breast Cancer Risk

By The ASCO Post
Posted: 5/4/2015 2:50:15 PM
Last Updated: 5/4/2015 2:50:15 PM



Key Points:
•No statistical difference was found for positive deleterious BRCA mutations between the full multigene panel and limited BRCA testing groups.
•In the panel group, 3.9% of patients were found to have non-BRCA mutations, and 13.4% had non-BRCA variants of uncertain significance.
For women with a family history of breast cancer, new multigene panel testing yields greater information about cancer risk while assessing deleterious BRCA1/2 mutations as accurately as BRCA testing alone, according to a study presented at the American Society of Breast Surgeons Annual Meeting. Lead researcher Nimmi Kapoor, MD, of Breastlink, noted that until recently, genetic testing involved an initial evaluation for deleterious BRCA mutations only, followed as needed by testing for other breast cancer–related genetic abnormalities—with greater cost and time delays.

“BRCA testing can now be incorporated in single broader genetic tests offered by a wide range of vendors, as a result of recent patent law rulings,“ explained Dr. Kapoor. “But some concern exists about the precision of these newer panel tests in detecting all deleterious BRCA mutations. Additionally both patients and physicians face a rapidly changing landscape of testing that may find mutations whose significance is not understood. Through our study, we hoped to address some of this confusion.”

Study Details

Researchers retrospectively analyzed data for 966 patients who underwent genetic testing at three sites at a single institution. All met National Comprehensive Cancer Network guidelines testing criteria and had no history of BRCA1/2 testing. Full panel testing was performed on 337 patients, while 629 received limited BRCA testing. In addition to BRCA1/2 mutations, panel tests focused on PTEN, TP53, CDH1, and up to 28 additional cancer-related genes.

No statistical difference (3.6% vs 4.0%, respectively) was found for positive deleterious BRCA mutations between the panel and limited BRCA testing groups. Similarly, no statistical differences were found between the two groups for variants of uncertain significance in BRCA genes (3.3% vs 4.0%, respectively).

For the panel group, 3.9% were found to have non-BRCA mutations, whereas 13.4% had non-BRCA variants of uncertain significance. Mutations in PALB2, CHEK2, MUTYH, and ATM were the most common non-BRCA mutations identified. The most frequent non-BRCA variants of uncertain significance were in the ATM gene.

“The door has been opened. With today’s new panel tests, women at risk for hereditary breast cancers will benefit from more timely and efficient multigene testing, without compromising BRCA accuracy,” said Dr. Kapoor. “Test results may help women with other known breast cancer–related genetic abnormalities take preventive measures. Newer tests are also increasingly being covered by insurance. Both panel and BRCA limited tests are as simple as sampling saliva with a swab.”

More Data May Pose New Questions

Dr. Kapoor notes, however, that women should be aware that recently discovered genetic variants may pose unanswered questions about cancer risk. “Scientists do not yet understand the significance of many of these mutations, and protocols for dealing with them do not exist,” she said. “Further, negative findings for known mutations do not necessarily reduce a woman’s cancer risk based on factors such as family history. Cancer genetics are complex. But tests can certainly rule out certain genetic problems and add to the picture of a woman’s overall chance of being diagnosed with breast cancer.”

Dr. Kapoor also noted that patients undergoing genetic testing will be contributing vital information to enhance the understanding of breast cancer development for future generations of scientists and women. “We are not only gaining useful clinical information, but also enhancing our understanding of breast cancer biology with multigene panel testing. This is an essential step towards developing and utilizing better, targeted therapy.”