NEW YORK (GenomeWeb) – Huntsville, Ala.-based HudsonAlpha Institute for Biotechnology has taken up breast cancer research pioneer Mary-Claire King's challenge and will be offering free genetic cancer screening to all 30-year-old women in the community for one year.
Founded in 2008, the non-profit institute located in the Cummings Research Park biotech campus operates a sequencing center specializing in plant genomics research and a CLIA-certified lab that analyzes human samples for cancer and other diseases. For this project, however, testing for BRCA1/2 genes and 17 others associated with heightened risk of breast and ovarian cancer will be provided by Kailos Genetics, located on the same research campus as the institute.
The institute will begin offering free testing to 30-year-old women in Madison County starting Oct. 28 through the "Information is Power" campaign. HudsonAlpha serves a fairly young community and expects several thousand women may be eligible for testing. The institute will pay out of pocket for this program, and is hoping to raise some funds through donors and local municipalities.
Kailos will perform testing at cost, estimated to run around $100. Men or women in Madison, Morgan, Limestone, Marshall, or Jackson County not 30 years old but over 17 years of age will be eligible to purchase testing at a discounted rate, according to Kailos' website.
The "Information is Power" campaign was inspired by King, who in 1990 discovered that a single gene on chromosome 17 — which would be later known as BRCA1 — was responsible for the breast and ovarian cancers seen frequently in certain families. Based on more recent research, King has been advocating BRCA mutation screening for women 30 years or older regardless of their family history.
King elaborated on this at the San Antonio Breast Cancer Symposium: "My proposal is that we offer population screening for unambiguously damaging mutations in these [BRCA1/2] genes to all women at about age 30. In other words, we move beyond testing only women in severely affected families to testing women regardless of family history of breast or ovarian cancer — who can then undertake preventive action if they learn they carry a mutation."
King visited the HudsonAlpha Institute last year and challenged Huntsville to become the first place in the country to implement this type of screening. The institute took up the challenge and, according to President Richard Myers, the institute has expended significant energy and resources to figuring out how to pilot such a program. "This is a complicated problem," said Myers, who has known King since his graduate school days. "If you get this DNA sequencing done, you're getting information that has big implications."
Last year, King led a research team that conducted a study of 8,000 healthy Ashkenazi men for three cancer-associated BRCA mutations and found that half of the tested men with BRCA mutations came from families without a strong history of breast and ovarian cancers. The research team, led by Ephrat Levy-Lahad of Shaare Zedek Medical Center in Israel, concluded based on the results that the country should implement a screening program for these markers for all Ashekanzi Jewish women from age 30.
BRCA1/2 mutations are linked to around 25 percent of hereditary breast cancers but account for only between 5 percent to 10 percent of allbreast cancers and 15 percent of ovarian cancers. Experts estimate that in the general US population these mutations show up in between 1 in 300 people to 1 in 500 people. Comparatively, BRCA-mutation related cancers are much more prevalent among Ashkenazi Jews, in whom these mutations are associated with 11 percent of breast cancers and 40 percent of ovarian cancers. Government-supported population screening programs are being explored within Israel's single payor healthcare system, but are not yet a reality.
When King began recommending that the US implement a BRCA mutation screening strategy for women 30 years or older, it raised some eyebrows, since policymakers are increasingly concerned about reining in unnecessary healthcare spending. The most recent recommendations from the US Preventive Services Task Force (USPSTF) says that a woman begin receiving mammograms at age 50, instead of age 40, and continue to get screened every two years instead of annually. While some groups disagree with this recommendation, the guidelines seem rooted in concerns that diagnostic advances are identifying early-stage, precancerous tumors that aren't life threatening, but for which women are receiving unnecessary treatment.
When it comes to BRCA mutation testing, guidelines in the US recommend it for women with a family history of breast and ovarian cancer. The Centers for Medicare & Medicaid Services recently released a draft local coverage determination that also lays out when it will pay for testing based on detailed medical and family history criteria. But such a strategy would certainly miss a proportion of women who don't have a family history, as King's study in the Ashkenazi population showed. And testing for mutations after a woman already has cancer has failed if the aim is prevention.
"It makes perfect sense, because women who have BRCA1/2 mutations, as well as mutations in some other genes that predispose them to breast and ovarian cancer, may be missed because the only testing that's done broadly right now is if you have a family history," said Myers. "My wife is a perfect example, because she comes from a family with very few women and there may have been mutations generations back."
There aren't precise estimates for how many women without family history have pathogenic BRCA mutations, but this is something that HudsonAlpha hopes to gather information on through this campaign. The institute is approaching the initial testing phase as a research project, although women will not have to partake in the research component in order to receive free testing.
The research portion of the effort will collect demographic information on the women who get tested. For example, Myers hopes the program will shed light on the prevalence of BRCA mutations in women of different ethnicities, since Alabama has a fairly large population of African Americans and other minority groups.
The institute will also assess the best way to communicate test results, track how women react to finding out their mutation status, and follow them to see if that knowledge impacts healthcare utilization. "A big part of this in the initial phase is to learn how this goes," Myers said. "At the least, it starts families talking about it rather than brush it under the rug or have misconceptions."
The National Cancer Institute estimates that approximately 12 percent of women in the general population will develop breast cancer during their lives. That risk can be as high as 65 percent for women who have a pathogenic BRCA1 mutation and 45 percent for those with a BRCA2 mutation. These mutations also increase a woman's risk of ovarian cancer up to 39 percent and 17 percent for BRCA1 and BRCA2 mutation carriers, respectively. In comparison, the lifetime risk of ovarian cancer in the general population is around 1.3 percent.
If test results reveal that a woman has a pathogenic mutation, she may have to make some difficult decisions about preventive, risk-reducing surgery. On the other hand, not finding such a mutation doesn't mean that a woman is free from cancer risk. Recognizing that mutation status must be accompanied with careful interpretation and counseling, Kailos will report test results through women's physicians.
For women who don't have insurance or a healthcare provider, the institute will partner with clinics to provide pro bono interpretation and counseling. The institute also offers genomics educational programs for physicians who have questions about how to interpret test results.
Another concern with a broad genetic screening program is the risk of identifying variants of unknown significance (VUS) — markers that are so infrequently seen in the population that their associated risk for cancer is unknown. VUS are particularly problematic when testing BRCA genes, which happen to be highly variable.
In the testing provided through HudsonAlpha, VUS will not be reported. "A VUS should be treated as a negative result, and should not warrant changes in medical management recommendations," genetic counselors at the institute told GenomeWeb in a statement. "As we continue to learn more about genetic contribution to disease, these VUS results will continue to be reclassified into their proper categories."
Ultimately, based on the information collected through this initial project, the HudsonAlpha Institute hopes to expand genetic risk screening for breast and ovarian cancer throughout Alabama. Given the complex considerations involved, Myers acknowledged that such a proposition may be disruptive to the way healthcare is currently delivered and paid for. "Most of the actuaries think of today's cost and not next year's cost or the year after," he said. "We recognize there's a difficulty here."
But ultimately, he believes that not figuring out how to best implement preventive strategies incurs a higher toll on patients and the community. For them, "this is something this country has to figure out," Myers said.