Cost effectiveness analysis of a polygenic risk tailored breast cancer screening programme in Singapore

Abstract

Background: This study aimed to evaluate the cost-effectiveness of a breast cancer screening programme that incorporates genetic testing using breast cancer associated single nucleotide polymorphisms (SNPs), against the current biennial mammogram-only screening programme to aid in its implementation into the current programme in Singapore.

Methods: A Markov model was used to compare the costs and health outcomes of the current screening programme, against a polygenic risk-tailored screening programme, which can advise a long-term screening strategy depending on the individual's polygenic risk. The model took the perspective of the healthcare system, with a time horizon of 40 years, following women from the age of 35 to 74. Epidemiological and cost data were taken from Asian studies, and an annual discount rate of 3% was used. The model outcome was the incremental cost-effectiveness ratio (ICER), calculated from the difference in costs per quality-adjusted life year (QALY). Scenarios with varying risk thresholds for each polygenic risk group were examined. One-way and probabilistic sensitivity analyses were performed to assess parameter uncertainty.

Results: The ICER for a polygenic risk-tailored breast cancer screening programme, compared with the current biennial mammogram-only screening programme, was - 3713.80 SGD/QALY, with incremental costs < 0 and incremental effects > 0. The scenario analysis of different polygenic risk cutoffs showed that the ICERs remain negative, with all ICERs falling within the south-east quadrant of the cost-effectiveness plane, indicating that tailored screening is more cost effective than mammogram-only screening, with lower costs and higher QALYs to be gained. This suggests that a polygenic risk-tailored breast cancer screening programme is cost effective, entailing lower cost than the current mammogram-only programme, while causing no additional harm to women.

Conclusion: Results from this cost-effectiveness analysis show that polygenic risk-tailored screening is cost effective with an ICER of - 3713.80 SGD/QALY. Tailored screening remains cost effective even across varying percentile cutoffs for each risk group. While the results look promising for incorporating polygenic risk into the current breast cancer screening programme, further studies should be conducted to address various limitations.

Keywords: Breast cancer screening; Cost effectiveness analysis; Economic evaluation; Polygenic risk scores; Risk stratification.

Fig. 1

Markov Model of breast cancer progression. Patients diagnosed with breast cancer will transition into the stage-specific diseased states and remain there, as remission and treatment were not modeled. Patients who are healthy remain in a healthy state until diagnosis or death

Fig. 2

Summary of proposed polygenic risk tailored screening programme

Fig. 3

Tornado diagram of one-way sensitivity analysis

Fig. 4

Cost effectiveness planes for probabilistic sensitivity analysis for all four scenarios in scenario analysis. Legend: In the 40 L-50I-10H scenario (d), approximately 57% of the ICERs for tailored screening will be cost effective when WTP is at 1SGD /QALY, compared to the mammogram arm. All ICER points for the three other scenarios ((a), (b), (c)) remain in the south-east quadrant, indicating that tailored screening is more cost effective than mammogram-only screening, entailing lower costs and higher QALY gain in these scenarios

Fig. 5

Cost effectiveness acceptability curve for the 40 L-50I-10H scenario