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by Lisa Rezende, PhD
Panel testing for mutations in multiple genes associated with increased cancer risk has become widely available over the past few years. Panel test are available from many different laboratories, with some focusing primarily on a single hereditary cancer syndrome, such as HBOC, while others look for genes associated with a number of different hereditary cancers. Some panels include only gene mutations that have national guidelines recommending the course of care for mutation carriers, while other panels also include genes for which less is known about the extent of cancer risk or how to best manage it. There were many reports on the use of panel testing in the clinic at the 2015 ASCO meeting.
Mutations in Women With High-grade ER+ Breast Cancer
National guidelines recommend BRCA mutation testing in women who have breast cancer before age 45 or who have triple negative breast cancer before age 60. However, BRCA mutations are also associated with estrogen receptor positive (ER+) breast cancer. Dr. Judy Garber of the Dana Farber Cancer Institute presented genetic testing data for 106 women under age 50 diagnosed with high grade (3 or higher) ER+ invasive breast cancer. Mutations in known genes associated with increased cancer risk were found in 10.6% of patients including:
Although many of these women had undergone genetic testing prior to the study, four of the mutations (including the ATM mutation found in the patient with a BRCA2 mutation) had not been identified before the study. Dr. Garber noted that these data reinforce the need to offer genetic testing to women under age 50 who have ER+ high-grade breast cancer to assure they receive treatment appropriate for mutation carriers.
Use of Panel Tests With Genes Associated With Multiple Cancer Types
Dr. Eric Rosenthal and colleagues at Myriad Genetics reported the results of more than 76,000 tests using a 25-gene panel that includes genes associated with hereditary breast, ovarian, colon, uterine, gastric, and prostate cancers, as well as melanoma. Patients were tested using this panel regardless of the type of cancer(s) in their personal or family histories. About half of the women tested (49%) had a personal history of cancer; the other half were believed to be high risk but had not had cancer. A smaller number of men tested, the majority of whom (73%) had a personal history of cancer. Looking at all tests performed, the researchers found that about 10% of people had a mutation associated with increased cancer risk in one or more gene(s) on the panel. Mutations were more common in people with a personal history of cancer than those without it. The most common mutations were in BRCA2 (1,311 patients) and BRCA1 (1,228 patients), followed by CHEK2 (641 patients), ATM (503 patients), and PALB2 (392 patients).
Mutations in More Than One Gene Associated With Increased Cancer Risk
As expanded panels have become available, many people who have BRCA mutations wonder if they should pursue further testing. Does having a mutation in more than one gene affect cancer risk? Dr. Jeffrey Weitzel and colleagues at City of Hope looked at data from more than 80,000 patients who were tested using a panel that included 25 different genes associated with a variety of hereditary cancers. They found just over 5,700 patients who had a mutation in a single gene, and only 154 patients who had mutations in more than one gene associated with increased cancer risk.
Of those patients with multiple mutations:
When they looked at the reported cancer history for these patients, the researchers found patients with mutations in multiple genes associated with increased cancer risk were more likely to have been diagnosed with cancer than those with mutations in only one gene associated with increased cancer risk. They found no significant difference in age at diagnosis between the two patient groups. More research will be needed to determine which combinations of gene mutations are associated with increased cancer risk.
National Comprehensive Cancer Network (NCCN) guidelines recommend genetic testing for mutations in BRCA 1/2 to assess cancer risk in people based on their personal and/or family history of cancer. However, not everyone who meets testing criteria undergoes testing. Dr. Brooke White and colleagues at the Carolinas HealthCare System presented a study that asked why people who qualified for BRCA testing declined to have it. Researchers looked at the medical records of 1,082 people who met NCCN guidelines for BRCA testing. Of those, 267 decided not to undergo testing. Approximately 41% declined testing after being referred to genetic counseling, while 27% refused testing. Notably, 100 patients (38%) declined BRCA testing for financial reasons. Of those 100 patients, a majority (67%) had a Medicare or Medicaid policy, underscoring the need to align Medicare reimbursement policies with NCCN guidelines.
posted September 29, 2015