Skip to main content
Premium Trial:

Request an Annual Quote

Relaunched Canadian BRCA1/2 Screening Project Aims to ID High-Risk Carriers, Intervene Early


NEW YORK – A newly relaunched population screening project in Canada is attempting to improve identification of germline BRCA1/2 mutation carriers, and in particular, flag high-risk patients with early-stage breast or prostate cancer so doctors can given them the necessary screening and treatment that allows them to live better and longer. 

The Screen Project, which is led by investigators at Women's College Hospital (WCH), is making germline BRCA1 and BRCA2 testing available to adult Canadians for just a few hundred dollars, and in doing so, providing access to those who may not meet the narrow criteria for free testing through provincial healthcare plans.

Patients who inherit mutations in BRCA1 and BRCA2 genes are at heightened risk for breast, ovarian, pancreatic, and other cancers. Canadian provincial governments generally cover testing for those who meet certain criteria based on a person's own and family cancer history. However, studies suggest mutation carriers may not have the family disease history required for coverage, and the criteria do not necessarily encompass early-stage cancers and related conditions.

Steven Narod, an oncologist at the Women's College Research Institute who specializes in breast and ovarian cancer, sees the Screen Project as a way to increase awareness of and access to genetic testing and counseling for cancer risk.

Members of his team are on track to test around 1,000 individuals this year, according to Narod, though they ultimately hope to evaluate 10,000 patients per year through the open-ended project. To achieve that, they have teamed up with the San Francisco-based medical testing company Invitae, which will offer its commercial BRCA1/2 test to participants for US$250 (around C$326).

As the cost of genetic cancer risk assessments has dropped from several thousand to a few hundred dollars in the past decade, Allison Kurian, an oncologist and an epidemiology and population health researcher at Stanford University Medical Center, has been tracking the impact of broader genetic testing access on cancer patients and the broader population. Kurian, who is not involved with the Screen Project, noted that the debate over whether BRCA1/2 testing should be done only within specific, high-risk patient groups or across the general population has raged for years and warrants further study.

The Screen Project is taking a decidedly population-based approach by allowing individuals over 18 years old to access testing for a relatively small fee. Narod and his colleagues believe there is no good reason to deny testing to anyone who wants it.

"We call it population testing but that, in our world, means anybody who wants to be tested can be tested," Narod explained, though participants so far often do have a clinical motivation when they sign up.

Although researchers took a broad testing approach in the earlier version of the study and in the new Screen Project, Narod is particularly interested in identifying BRCA1/2 mutations in women with early-stage breast cancer, such as ductal carcinoma in situ (DCIS), and men with prostate cancer, in the hopes that this knowledge will change their treatment trajectory long term and help avoid future, more aggressive cancers later on.

For example, although prostate cancer patients with non-aggressive disease often don't meet BRCA1/2 testing criteria, knowing their mutation status may be important for how their disease is managed. Studies have shown that men with risky BRCA alterations tend to be diagnosed with prostate cancer that has already metastasized and is far more difficult to treat.

"If a man gets identified as having prostate cancer, there is currently the option of active surveillance or watchful waiting, [where] you just wait and see before you intervene with treatment, which for many men is really a good idea," he explained. "But it would be a very bad idea to do that for a person with a BRCA1/2 mutation because we know they're going to progress."

For this reason, Narod would advise any man with prostate cancer considering an active surveillance protocol to first make sure he is not a BRCA2 mutation carrier. "Our goal is to get everybody with prostate cancer tested so that we can intervene early," he said.

Likewise, the knowledge that a woman with DCIS is a BRCA1/2 mutation carrier could impact her management considerably. It may cause clinicians to recommend a bilateral mastectomy, tamoxifen treatment, and more frequent screening.

"DCIS is not a standard criterion for genetic testing … [but] it should be," Narod said. "It should really be incumbent upon all of the women with DCIS in Canada to come for the Screen Project to make sure they don't have a BRCA1 or BRCA2 mutation before they make any decisions about treatment."

Kurian agreed that there is much to be learned about how greater access to genetic testing is impacting patients who currently fall outside of current guidelines-based testing criteria. Studies she and others have published suggest that the US healthcare system is not doing a good job testing all those who do meet BRCA1/2 testing criteria. In particular, a study published in the Journal of Clinical Oncology last year indicated that fewer than one-third of women with serous high-grade ovarian cancer may be receiving BRCA1/2 test results, despite recommendations that have been in place for more than a decade.

"Our biggest problem in the US, based on our own research and that of others, is people who are widely known to benefit are not getting tested," Kurian said.

For an earlier iteration of the population-based Screen Project, launched in 2017, participants had access to a US$165 USD BRCA1/2 test from Veritas, along with follow up clinical guidance for those with pathogenic BRCA1 or BRCA2 mutations.

"They all got counselled by us or their local counselor, and we followed them for satisfaction. Many of them had preventative surgery and most of them had screening," Narod said, noting that the results will be discussed in more detail in an upcoming paper. "The clinical care for women who had a new mutation identified through the Screen Project seemed to be adequate and comparable to that seen through our own genetic counselors."

More than 1,000 individuals signed up for that earlier service, and the investigators saw actionable BRCA1/2 mutations in around 2 percent of the participants. Veritas, which has restructured its business, is no longer the test provider for the study.

Instead, Invitae is now providing BRCA1/2 testing at a slightly higher price point, which should make testing available to thousands of Canadians, while maintaining a financial incentive for the company, Narod said.

After the clinical team puts in the test order, participants submit a spit sample through a kit mailed to their homes and return it for genetic analysis to the California company. "We're informed of the results, and we take a certain responsibility for patient care, but that's sort of shared with [the patient's] own doctor, their own genetic counselor, and the Invitae staff," said Narod.

While some individuals may find their way to the Screen Project through referrals from their doctors, individuals can also reach out to the project directly if they are interested in genetic testing or belong to a group that may benefit from testing but do not fit provincial criteria for BRCA1/2 test coverage.

In Ontario, where WCH is located, patients qualify for government-covered genetic testing if they have a personal or family history of breast or ovarian cancer, for example. But individuals who fall outside of the fairly tightly defined eligibility criteria may not be eligible for testing in Ontario or other Canadian provinces.

Based on experiences in the first iteration of the Screen Project, Narod suspects that some participants may be drawn in by the at-home, saliva-based sample collection method, which facilitates testing without having to travel to a hospital or clinic for a blood draw, similar to the Veritas test used previously.

Within the project, participants also have the option of getting broader panel tests, though Narod cautioned that variants in non-BRCA1/2 genes may not change a person's clinical management.

"Originally, our interest was in BRCA1 and BRCA2 because I felt we could give an unequivocal clinical recommendation based on that information," Narod said. "Then, there was an overwhelming feeling among patients, doctors, and laboratories that we should include [around] 20 genes. We made an agreement that we would do that [and] the patients could opt for the information on many genes."

Kurian pointed out that the chance of getting a variant of uncertain significance (VUS) is currently far lower in BRCA1 and BRCA2 than in genes that have not been as well characterized, though there are almost certainly additional genes beyond BRCA1/2 that may offer insights into hereditary cancer risk, including genes linked to Lynch syndrome.

As in the earlier version of the project, participants who are positive for pathogenic BRCA1/2 alterations will get counseling from the Screen Project's in-house genetic counselor and be referred to appropriate clinics to manage or screen their conditions. Those with negative test results are typically offered post-test counseling as well, though the team has seen very low uptake of counseling among those individuals so far.

The team is also getting ready to do another study focused on hundreds of BRCA1/2 mutation-positive men with prostate cancer in the hopes of identifying the most effective treatment protocol based on outcomes following chemotherapy, radiotherapy, surgery, chemotherapy, or other targeted therapies. It remains to be seen whether a significant proportion of those prostate cancer cases will be uncovered with the help of the Screen Project.

Ultimately, Narod hopes that such efforts will make it possible to treat cancers earlier and more effectively, rather than relying on treatments to modestly extend life in individuals with cancers that have already progressed to advanced stages. "The goal of the scientists doing the Screen Project is to prevent [cancer-related] death in the first place, and we think genetic testing has a really important role to play there," he said.