25-Gene Panel Offers More Thorough Screening


A 25-gene hereditary cancer panel can increase the identification of deleterious mutations by almost 70%, over testing for hereditary breast and ovarian cancer (HBOC) or Lynch syndrome alone.

Sami Diab, MD

Sami Diab, MD

A 25-gene hereditary cancer panel can increase the identification of deleterious mutations by almost 70%, over testing for hereditary breast and ovarian cancer (HBOC) or Lynch syndrome alone, according to US Oncology investigators who described the use of this panel in the community setting at the 2014 San Antonio Breast Cancer Symposium.

“Personal and family history are sometimes not sufficient to determine the presence or absence of a cancer syndrome,” said Sami Diab, MD, of Rocky Mountain Care Centers and Colorado Integrative Care in Aurora. The use of a hereditary cancer panel in community oncology practices may improve detection rates and offer an opportunity for enhanced cancer management, according to Diab et al.

Need for Profiling Is Increasing

“We found that almost 10% of high-risk patients had a mutation that could have been causing their cancer. If we limited our testing to theBRCAgenes or to Lynch syndrome genes, we would have identified only 60%. There are 40% of patients with other genes that could be identified,” Diab said in an interview at the meeting.In the era of effective preventative and therapeutic interventions for cancer, the identification of patients with an inherited cancer syndrome is becoming increasingly relevant. Testing with a panel of genes provides the opportunity to rapidly identify or rule out multiple deleterious mutations. The 25-gene panel, therefore, can streamline the genetic testing process toward greater efficiency and accuracy, Diab indicated.

Utility Evaluated in Almost 1000 Patients

The 25-gene panel, which is based on next-generation sequencing, targets 8 cancers: breast, ovarian, colorectal, endometrial, pancreas, melanoma, prostate, and stomach. The panel assay for the mutations inBRCA1,BRCA2,MLH1,MSH2,MSH6,PMS2,EPCAM,APC,MUTYH,CDKN2A,CDK4,PALB2,CHEK2,SMAD4,BMPR1A,STKII,TP53,CHD1,PTEN,ATM,NBN,BARD1,BRIP1,RAD51C, andRAD51D.US Oncology practices began offering the 25-gene panel to patients through a commercial early-access clinical program in September 2013. It is now commercially available and is covered by most insurance policies, according to Diab.

At the San Antonio meeting, Diab et al reported on the combined experience of 6 large community practices though October 2014.

US Oncology clinicians performed the test on 997 individuals (97% women), of whom 773 (77.5%) had a personal history of at least 1 of the 8 panel cancers. Almost all met the NCCN guidelines for testing for HBOC, Lynch syndrome or both; only 3.3% did not. Nearly half the patients were tested between the ages of 50 and 69 years.

“We found 83 mutations in 79 distinct patients,” Diab reported. Of the patients with a personal history of cancer, 72 (9.3%) had a pathogenic mutation. Seven patients harboring a mutation did not have a personal history of cancer. Four patients were identified with 2 mutations.

Significant Proportion of Genes Would Have Been Missed

Of the 79 patients (some of whom had multiple cancers), 55 (51.4%) had breast cancer, 19 (17.8%) had ovarian cancer, 12 (11.2%) had colon cancer, 3 (2.8%) had endometrial cancer, 1 (0.9%) had melanoma, 10 (9.3%) had another cancer type, and 7 (6.5%) had no cancer (but were identified as high risk).Mutations were identified in 15 different genes. Only 59% of these were among the 6 genes that are included in single-syndrome HBOC (BRCA1,BRCA2) and Lynch syndrome (MSH6,MLH1,MSH2,PMS2) testing, Diab reported.

The most frequent mutations wereBRCA2(27.7%) andBRCA1(19.3%), but the third most frequent,ATM(10.8%) would not have been included in single-syndrome testing, nor would the next 2 most common,CHEK2(8.4%) andPALB2(8.4%).

“A significant portion of mutations were found in genes not traditionally associated with HBOC or Lynch syndrome,” he said.

Diab emphasized in an interview, “If we limit our testing to specific genes, I think we are missing about 40% of high-risk patients who could otherwise be found. Clearly, we have an opportunity to identify more patients at high risk by using this 25-gene panel.”

Diab cautioned that this panel should be used in consort with genetic counseling. While the test result does contain information to be used in interpreting the test result, he said, “The danger is for a clinician to do this test, get a result, and not know what to do with it.”

Diab S, Rodriguez P, Leininger A et al. Experience in the community oncology practice with a 25-gene hereditary cancer panel. 2014 San Antonio Breast Cancer Symposium. Abstract P1-03-03.

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