Is Population-Based BRCA Testing Cost-Effective?

Providing genetic testing for BRCA1 and BRCA2 mutations in all women aged 30 years or older would be cost-effective and prevent more breast and ovarian cancers than current screening, which is based on family history, Canadian researchers said.

In Canada, only women with a family history of breast and ovarian cancer are offered genetic testing for BRCA1 and BRCA2. Making all women eligible for genetic testing could potentially prevent more than 2000 breast cancers and 485 ovarian cancers in the Canadian population, the authors wrote.

“We have identified a better strategy to identify people in the population who are high risk, and once we identify them, we can offer them better life-saving prevention and screening,” study author Lesa Dawson, MD, clinical associate professor of gynecology at the University of British Columbia in Vancouver, British Columbia, Canada, told Medscape Medical News.

Their research was published on September 12 in JAMA NetworkOpen.

Apparent Cost-Efficacy

The BRCA1 and BRCA2 gene mutations were first identified in the mid-1990s. Historically, the cost for testing was high, and healthcare systems had to be selective about who they offered the tests to, said Dawson.

“Those strategies were designed to select people who would have the highest risk for having those mutations, so the testing would be offered to women who either had a personal history or a substantial family history of cancer,” she said.

Unfortunately, family history is a poor surrogate for cancer risk, senior author Ranjit Manchanda, MD, PhD, professor of gynecological oncology at Queen Mary University of London in London, England, told Medscape Medical News.

“More than 95% of people who have BRCA genes don’t know about it, and 50%-80% of the people who die of BRCA mutation cancers cannot give a strong family history. The health system is not set up to identify and maximize our ability to prevent cancer. We need to change our screening paradigm and look at alternative options. If you were looking to test someone for diabetes, and the blood test for blood sugar you use for diagnosis would miss 50%-80% of diabetics, would you use it? Changing from a family history-based strategy to a population-based strategy will allow us to pick up more people at risk and therefore prevent more cancers in the general population. This is paradigm-changing for me, applying genomics to healthcare to maximize early diagnosis and prevention of cancer,” said Manchanda.

In the current study, the investigators developed a Markov model to compare the lifetime costs and outcomes of BRCA1 and BRCA2 testing for all women in the general population aged 30 years vs family history-based testing.

The model simulated 1,000,000 Canadian women aged 30 years at model entry, among whom BRCA carriers were offered risk-reducing salpingo-oophorectomy to reduce their ovarian cancer risk and MRI and mammography screening, medical prevention, and risk-reducing mastectomy to reduce their breast cancer risk.

The study was conducted from October 1, 2022, to February 20, 2024.

An analysis of the model showed that the cost of population-based BRCA testing was CAD $32,276 (US $23,403) per quality-adjusted life year (QALY) from the payer perspective or CAD $16,416 (US $11,903) per QALY from the societal perspective, compared with family history-based testing. This cost is well below the conventional CAD $50,000-CAD $100,000 per QALY willingness-to-pay threshold in Canada.

Population-based BRCA testing could prevent 2555 breast cancers and 485 ovarian cancers per 1,000,000 Canadian women, which corresponds to averting 196 breast cancer deaths and 163 ovarian cancer deaths per 1,000,000 women, the authors concluded.

Questionable Assumptions

The authors assumed that all eligible women would choose to get genetically tested. This assumption is unreasonable, said Dean A. Regier, PhD, senior scientist at the BC Cancer Research Institute and associate professor of population and public health at the University of British Columbia in Vancouver.

“While there are too few well-conducted studies examining genetic testing uptake for BRCA1 and BRCA2, the literature suggests that the uptake of currently available genetic testing for eligible and at-risk women is between 20% and 30%. For screening mammography in Canada, participation uptake is just over 60%,” said Regier, who did not participate in the current study.

“At uptake levels of genetic testing between 20% and 60%, the incremental cost-effectiveness ratio would be significantly higher than that which was reported, thus reducing the probability that population-based testing would be cost-effective. Given that existing testing rates are worse among racial and ethnic minority groups, realistic cost assumptions required for achieving 100% uptake of genetic testing by all women further reduce the probability that population-based screening would be cost-effective,” he said.

Regier also noted that the study failed to address the “real-world challenge” of establishing additional testing infrastructure that would be needed to provide population-based genetic testing.

“Each year, there would be an estimated 150,000-350,000 women eligible for testing. While the model rightly suggests that these patients would require genetic counseling alongside their genetic testing, it fails to consider the fact that provinces would need to add testing capacity, infrastructure, and genetic counselors. It’s established that Canada does not have sufficient capacity to address the current demand for genetic counseling under the current guidelines. We would need a significant policy shift to train new healthcare professionals and augment testing infrastructure in Canada,” he said.

“Meeting the demands for population testing would be difficult, with extended wait times creating frustrations among eligible members of the population. Population-based genetic testing and screening can significantly enhance lives, improve health outcomes, and be cost-effective, but only if we thoughtfully change our healthcare system. This includes training more genetic counselors and engaging women in meaningful discussions about the risks and benefits of such testing. Simply offering widespread access to genetic testing, without a strategic approach, falls short of realizing its full potential for improving the health of Canadians,” said Regier. “The problem of investing our resources in training and attracting genetic counselors should be addressed first, before creating new expanded programs.”

The Screen Project

Canada’s current program for genetic testing requires patients who wish to be tested to pay out of pocket.

The Screen Project was developed by Steven Narod, MD, professor of medicine at the University of Toronto’s Dalla Lana School of Public Health, and his colleagues at Women’s College Hospital in Toronto, Ontario, Canada.

“Anybody in Canada can have a good-quality genetic test through an online service. It’s unique in the world. We test for 19 genes in The Screen Project. The problem is that people have to pay for it, and the cost is about CAD $400. I set that up about 5 years ago to address some of the problems set out in this paper. Genetic testing should be accessible to all people who want it and should not be denied because it is not available,” Narod told Medscape Medical News.

Before The Screen Project was established, anyone who wanted a genetic test had to see a genetic counselor first, and this process could take a year or more.

“We set up The Screen Project specifically to get access for people who were denied testing by the government. Before we set it up, the only way to be tested was if you qualified for testing through provincial guidelines,” said Narod, who codiscovered the BRCA1 and BRCA2 gene mutations in 1995.

“When we started The Screen Project, we were optimistic and had hoped that eventually, the government might pick up the tab, but we weren’t prepared to wait around for that to happen. Those things aren’t going to happen overnight. If we tested everybody in Canada, we would save more lives. I agree with the authors that there’s a real potential for saving lives. The issue is cost. But it would be an investment in Canadian women.”

The study was supported by the BC Cancer Foundation, the Rosetrees Trust, and Yorkshire Cancer Research. Dawson, Regier, and Narod reported having no relevant financial relationships. Manchanda reported receiving grants from GSK, Barts Charity, Eve Appeal, MSD, AstraZeneca, and EGL.