# Economic evaluation of personalised versus conventional risk assessment for women who have undergone testing for hereditary breast and ovarian cancer genes: a modelling study

## TL;DR

This study compares the economic impact of personalized versus conventional risk assessment for women with genetic risks for breast and ovarian cancer.

## Contribution

The study introduces a modeling approach to evaluate the cost-effectiveness of personalized risk assessment using genetic and non-genetic factors.

## Key findings

- Personalized risk assessment (PRA) was cost-effective for women with specific genetic variants and family history.
- Conventional risk assessment (CRA) was more cost-effective for BRCA1/BRCA2 carriers and those with unknown family history.
- PRA showed economic benefits in scenarios involving moderate-risk genetic variants like RAD51C/RAD51D/CHEK2/ATM.

## Abstract

The management of women with germline pathogenic variants (GPVs) in breast (BC) and ovarian cancer (OC) susceptibility genes is focused on surveillance and risk-reducing surgery/medication. Most women are assigned an average range of risk and treated accordingly, but it is possible to personalise this. Here, we explore the economic impact of risk personalisation.

We compared two strategies for risk stratification for female participants: conventional risk assessment (CRA), which only involves information from genetic testing and personalised risk assessment (PRA), using genetic and non-genetic risk modifiers. Three different versions of PRA were compared, which were combinations of polygenic risk score and questionnaire-based factors. A patient-level Markov model was designed to estimate the overall National Health Service cost and quality-adjusted life years (QALYs) after risk assessment. Results were given for 20 different groups of women based on their GPV status and family history.

Across the 20 scenarios, the results showed that PRA was cost-effective compared with CRA using a £20 000 per QALY threshold in women with a GPV in PALB2 who have OC or BC+OC family history, and women with a GPV in ATM, CHEK2, RAD51C or RAD51D. For women with a GPV in BRCA1 or BRCA2, women with no pathogenic variant and women with a GPV in PALB2 who have unknown family history or BC family history, CRA was more cost-effective. PRA was cost-effective compared with CRA in specific situations predominantly associated with moderate-risk BC GPVs (RAD51C/RAD51D/CHEK2/ATM), while CRA was cost-effective compared with PRA predominantly with high-risk BC GPVs (BRCA1/BRCA2/PALB2).

PRA was cost-effective in specific situations compared with CRA in the UK for assessment of women with or without GPVs in BC and OC susceptibility genes.