PROMPT to Detail Breast Cancer Risk

When women undergo genetic testing to see if they have an increased risk for breast cancer, many learn that they have changes in genes other than BRCA1 and BRCA2.

Although mutations in p53, PALB2, RAD51C, CDH1, and other genes have been associated with an increased risk of breast cancer, doctors don't know much about them—they don't know to what degree the mutations heighten risk, how those mutations might interact with others, or at what age the risk starts to climb.

Four major cancer institutions—Dana-Farber Cancer Institute (Boston, MA), Mayo Clinic (Rochester, MN), Memorial Sloan Kettering Cancer Center (MSKCC; New York, NY), and Penn Medicine (Philadelphia, PA)—are now teaming up to address these types of questions. By combining their expertise and partnering with commercial laboratories—Ambry Genetics, Gene Dx, Myriad Genetics, Pathway Genomics, and Quest Diagnostics have all agreed to participate—they hope to enroll enough patients in an online registry to better understand the effects of these genetic mutations. Although they are starting with breast cancer, the registry, called Prospective Registry Of Multi-Plex Testing, or PROMPT, will also gather information on other cancer-associated genes.

“We have had 20 years to get really great evidence for what to recommend for individuals with BRCA1 and BRCA2 mutations, and we want to quickly obtain such evidence for these other high, moderate, and unknown penetrant genes,” says PROMPT co-founder Susan Domchek, MD, director of the Basser Research Center for BRCA in the University of Pennsylvania's Abramson Cancer Center in Philadelphia.

When doctors order multigene panel tests, several of the labs that conduct those tests will send information about the registry to patients and providers and invite them to participate, says Domchek. If patients choose to join, they can contribute their gene test results and family history to the registry. Over time, they will be informed of any relevant findings the consortium might make.

Findings will be made publicly available, and participants may volunteer for other studies as well. “We want to build a resource that many different investigators will use to try to [answer] questions as quickly as possible,” says Mark Robson, MD, PROMPT co-founder and clinic director of the Clinical Genetics Service at MSKCC.

Each of these gene mutations is likely to be uncommon, which is why the group needs to enroll a large number of patients. However, that can take a long time. In a recent paper, for instance, researchers reported that it took them several years to enroll the 150 families needed to analyze, with sufficient statistical power, links between PALB2 and breast cancer (N Engl J Med 2014; 371:497–506).

“To try to get the answers in a meaningful timeframe, we have to throw a much, much wider net and make [studies] available to a much, much broader group of people,” Robson says.

For more news on cancer research, visit Cancer Discovery online at http://CDnews.aacrjournals.org.