Multigene Testing for Breast Cancer May Be Beneficial

Rosemary Frei, MSc

May 2014, Vol 5, No 4 - Personalized Medicine


Las Vegas, NV—Researchers are making a compelling case for screening women at high risk for breast cancer for more than BRCA mutations. In fact, 4 genetic mutations are well recognized in genetic-based breast cancer, including CDH1, PTEN, STK11, and TP53.

At the 2014 National Consortium of Breast Centers meeting, a team from Ambry Genetics presented their study results, showing that among 4323 women with inherited breast cancer who were tested for gene mutations, more than 50% of those with non-BRCA mutations had no indication they were carrying these mutations. Testing positive for these women can have a direct impact on the medical management.

Overall, 202 (4.7%) women had gene mutations; of these women, 27 (13.4%) had non-BRCA mutations. Although the majority of the women had BRCA1 mutation (44.5%) or BRCA2 (42%), the others were TP53 (9.4%), PTEN (2.5%), CDH1 (1%), and STK11 (0.5%). Of those with non-BRCA mutations, 56% did not meet the clinical criteria that are used to suggest the presence of these mutations.

“A lot of physicians are only ordering BRCA testing, because they only know 1 lab that tests for breast cancer mutations, and that lab only tests for BRCA, or they think the other mutations are so rare they’re not worth testing for,” said Steven Keiles, MS, Director of Clinical Affairs, Ambry Genetics Corporation, Aliso Viejo, CA, who led the study. “But in fact, in many cases it’s beneficial to test for all these genes at once.”

Mr Keiles also pointed out that the testing criteria have been broadened recently—for example, in 2013, the National Comprehensive Cancer Network (NCCN) increased the range of women who are appropriate for TP53 testing to a maximum of 35 years from the previous 30-year upper age limit.

CDH1 is associated with hereditary diffuse gastric cancer. PTEN is associated with Cowden syndrome, TP53 with Li-Fraumeni syndrome, and STK11 with Peutz-Jeghers syndrome. All of these conditions also confer an elevated risk for breast cancer.

Mr Keiles and his colleagues reviewed the results from 4323 women who underwent genetic testing with the 6-gene panel between June 17, 2013, and January 17, 2014. The investigators also examined the proportion of patients who were found to have a mutation and who did or did not meet the syndrome-based testing criteria defined by the NCCN.

Furthermore, 44% of women who tested positive did not meet clinical criteria for one of the diseases that the mutations are classically associated with. These included women who would not normally routinely be tested for the non-BRCA gene mutations, according to Mr Keiles. “But for these women, it was worth doing the testing, because more than 13% of the women who ended up testing positive were positive for genes other than BRCA1 and BRCA2,” he said, adding that the team has now reviewed the results of approximately 5000 women, and the numbers are similar for this larger group.

Mr Keiles noted that Myriad charges $4000 for BRCA1 and BRCA2 testing, whereas his company’s price is $2200, and $3300 for the 6-gene panel. The BRCAplus panel uses next-generation and Sanger sequencing.