Expanded genetic testing points more women to screening breast MRI

Testing for gene mutations beyond just BRCA1 and BRCA2 would indicate screening breast MRI and other proactive measures for many women who would not have been considered candidates for such measures going by family history alone, according to a large-sample study published online Dec. 21 in the Journal of the American College of Radiology.

In introducing their findings, Eric Rosenthal, PhD, ScM, of Myriad Genetic Laboratories in Salt Lake City, and colleagues note that breast MRI screening is recommended for women whose family history points to a lifetime risk for breast cancer of greater than 20 percent.

Meanwhile, BRCA1 and BRCA2 mutations account for about 20 to 25 percent of hereditary breast cancers and about 5 to 10 percent of all breast cancers, according to the National Cancer Institute.

Rosenthal and colleagues designed their study to quantify the impact of testing for genes other than BRCA1/2 and to gauge the extent to which mutation carriers in these genes would have been identified as candidates for enhanced screening on the basis of family history alone.

They derived their data from tests ordered for 194,107 women using a 25-gene hereditary cancer panel between September 2013 and February 2016 at Myriad Laboratories.

Along with BRCA1/2, the panel included seven additional genes known to be associated with a lifetime risk of greater than 20 percent for breast cancer. The additional genes were ATM, CHEK2, PALB2, TP53, PTEN, CDH1, and STK11.

Women found to carry pathogenic variants (PVs) were evaluated to assess whether they would have been found to be at greater than 20 percent lifetime risk on the basis of family history.

The team found that, in total, 9,751 PVs in the selected breast cancer risk genes were identified in 9,641 women.

BRCA1/2 accounted for 59.1 percent of the PVs, and some 38.8 percent were in ATM, CHEK2 or PALB2.

Only 24.7 percent of all women with PVs found in any gene reached the greater than 20 percent lifetime risk threshold (using the Claus model).

“This study showed that genetic testing for multiple genes found more women at an increased risk for breast cancer than testing only for BRCA1 and BRCA2 or from relying only on family history analysis,” the authors write in their conclusions.

“If genetic testing finds mutations in any of the breast cancer risk genes,” they add, “women can consider undergoing breast MRI or advanced digital mammography for improved detection of breast cancer, as well as other steps to reduce the risk for breast cancer.”

JACR has posted the study online in full for free.