Genetic risk testing for breast cancer more cost-effective than mammogram alone

Incorporating genetic testing for single nucleotide polymorphisms is a cost-effective surveillance method for breast cancer, according to a recent Singapore study. Compared to a biennial mammogram-only approach, the polygenic risk (PRS)-tailored programme is not only cheaper but also poses no additional harm to patients.

“Overall, a polygenic risk-tailored screening programme proved to be more cost-effective compared with the current age-based mammogram-only strategy, offering both health and monetary advantages,” the researchers said.

A Markov model was used to carry out the comparison, looking at Singaporean women aged 35–74 years over a 40-year time horizon. The PRS-tailored strategy entailed genotyping through buccal swabs, followed by a questionnaire on breast cancer risk factors. Depending on the resulting risk, as well as age, patients will then be required to undergo a subsequent test: self-examination, ultrasound, or mammogram. The resulting holistic genetic score will be the basis for long-term screening strategy.

The cost-effectiveness model yielded an estimate of 25.5 breast cancer cases per 1,000 women in the PRS-tailored screening programme, as opposed to 31.2 cases in the mammogram-alone approach. [BMC Health Serv Res 2021;21:379]

In turn, the tailored programme led to life year and quality-adjusted life year (QALY) gains per woman were 0.9720 and 0.9884, respectively. At the same time, the genetic testing programme was cheaper by SGD 3,670.83 than the existing surveillance system, resulting in an incremental cost-effectiveness ratio (ICER) of –3,713.80 SGD/QALY.

Even when adjusting PRS cutoffs using different standards, the ICERs remained negative and in the southeast quadrant of the cost-effectiveness plane, suggesting that across various scenarios, the tailored approach led to gains in QALYs with negative incremental costs.

Monte-Carlo simulations further confirmed these findings, with incremental costs remaining negative and QALYs remaining positive even after 10,000 runs.

Using the minimum willingness-to-pay (WTP) threshold of 1 SGD/QALY, around 57 percent of the ICERs of the PRS screening programme would be cost-effective. At a maximum WTP of 1,820 SGD/QALY, the tailored approach would be 100-percent cost-effective.

Sensitivity analyses was then conducted to find variables that could strongly affect ICER. These parameters include direct medical costs for stage II breast cancer, sensitivity of mammogram and ultrasound tests, and low- and high-risk multipliers. Nevertheless, ICERs still mostly remained negative.

“These results are crucial for policymakers in demonstrating the feasibility of a risk-based approach in Singapore,” the researchers said. “However, while the results may serve as important foundations for a risk-based approach to be implemented, further studies should be conducted to address the limitations related to data availability and modelling.”

“Successful implementation requires the buy-in of relevant stakeholders which include decision makers, primary care and specialist physicians and screen-eligible women, appropriate funding mechanism, tried-and-tested workflow for the return of results, tracking of follow-ups and outcomes, infrastructure for doing genetic testing at scale, and many other considerations. The translation from concept to reality is not trivial,” they added.