Genomics in Clinical Practice, Part 3: Expanding Access to Genetic Services

Kate M. O'Rourke


August 02, 2016

Editor's Note:
This is the third part of a three-part series on Medscape Oncology designed to update and familiarize practicing oncologists with the most important issues in multiplex and genomic testing.

It's hard to overstate the current growth of genetic testing in cancer: The number and variety of tests are increasing constantly; the demand for genetic counselors outpaces their availability; oncologists in practice need education and guidance on using clinically relevant tests; and, all the while, basic and translational scientists continue to pour forth a steady stream of potentially important mutations. These themes flowed through several presentations on practical issues in genetic testing at the recent annual meeting of the American Society of Clinical Oncology (ASCO).

Rapid Rise in Genetic Testing

The explosion in genetic testing has been driven by a number of factors, including the rapid growth of genetic knowledge, a ruling by the Supreme Court that you cannot patent a gene, and the rise of multiplex gene panels.[1] The development of strategies for managing patients has further spurred uptake. For example, clinicians now know that risk-reducing salpingo-oophorectomy prevents breast and ovarian cancer in BRCA-positive women and that frequent colonoscopy reduces mortality in individuals with Lynch syndrome.[2,3] Demand for BRCA1/2 testing almost doubled after high-profile celebrity Angelina Jolie announced her plans to have a double mastectomy for a BRCA1-positive breast cancer.[4]

Jeffrey Weitzel, MD, director of the Clinical Cancer Genetics program and a professor of medical oncology at City of Hope in Duarte, California, said that determining the cancer risk associated with various genes, and explaining this risk to patients, is complex. Many multiplex gene tests include genes of moderate to low penetrance and ones for which the risks for cancer are unclear.

And genetic risks that were thought to be well understood are still evolving. For example, researchers are learning that BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. A recent study showed that the lifetime risk for breast cancer for the 5% of BRCA1 carriers at lowest risk was 28%-50%, compared with 81%-100% among the 5% at highest risk.[5] Cancer risk-modifying loci were also used to refine ovarian cancer risk for BRCA-positive carriers (lowest risk 28% vs 63% for highest).

Elizabeth Swisher, MD, professor of gynecology and adjunct professor of medical genetics at University of Washington School of Medicine, and medical director of the Breast and Ovarian Cancer Prevention Program for the Seattle Cancer Care Alliance, pointed out that the rise of targeted agents has increased tumor sequencing, which can lead to genetic counseling.

at the minimum, patients undergoing tumor sequencing should be informed about the possibility of identifying a germline mutation

"When we do tumor sequencing, we are picking up both germline and somatic mutations. A germline mutation is usually present in tumor, while a somatic mutation is never present in the germline," said Dr Swisher. "One of the questions that has come up is whether patients should undergo some kind of genetic counseling before they undergo tumor sequencing. The major cancer organizations have come to an agreement that, at the minimum, patients undergoing tumor sequencing should be informed about the possibility of identifying a germline mutation." Clinicians may not have to give patients formal counseling for tumor testing, but patients should at least be aware that the tests may find something that has implications for family members.[6]

Studies show that while clinicians have significant concerns about the utility of next-generation sequencing panels and their ability to interpret and counsel patients about test results, there has been a rapid increase in the use of these tests.[7] In a survey of US community-based clinicians, respondents ordering panel tests rose from 29% (27/94) at the initial survey to 43% (46/107) within 8 months.


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