Multigene testing offers cost-effective, broader approach to breast cancer prevention

Blood sample for BRCA test | Image credit: jarun011 – stock.adobe.com

Regardless of family history, population-based testing was a more cost-effective way to prevent breast and ovarian cancer compared to current family history-based testing strategies.¹ Until 1994 when BRCA1 and 1995 when BRCA2 mutations were discovered, allowing for more targeted and individualized cancer prevention care for women who show susceptibility to breast or ovarian cancer.² Both gene mutations are highly responsible for the hereditary breast and ovarian cancer syndrome, experiencing a lifetime risk of between 60% and 80%.

Patients carrying pathogenic variants of one of BRCA genes are offered early diagnostic options such as MRI, including mammography screenings for breast cancer.¹ However, multigene tests can be combined BRCA mutation testing of other genes with high penetrance to detect different forms of cancer-causing genes.

Currently, family history is the main form of BRCA gene mutation testing, which presents a problem because it often fails to identify more than 50% of carriers of the pathogenic variant in patients. The US Centers for Disease Control and Prevention have also emphasized the importance of understanding that not all patients who inherit a BRCA the mutation will develop breast or ovarian cancer.³ Furthermore, it does not mean that all inherited forms of each cancer are caused by genetic mutations in BRCA genes.

Between September 1, 2020 and December 15, 2023, a health economic analysis study was conducted to evaluate the cost-effectiveness of multigene testing for women aged 30 to 35 years compared with current family history-based testing.¹ The economic evaluation focused on BRCA1, BRCA2AND PALB2 genes as they are associated with high penetrance genes associated with breast cancer susceptibility.

Participants were offered genetic counseling after the test, even for noncarriers, because research shows that noncarriers tend to decline mammogram screenings, potentially missing any early detection. Non-carriers receiving counseling will have further guidance on appropriate screening methods.

An individual-level simulation model was used to track health care decisions, clinical events, and health care costs over a woman’s lifetime. The main outcomes measured were quality-adjusted life year (QALY) and incremental cost-effectiveness ratio (ICER). The simulation study included 1 million female participants aged 30 to 35 from the US.

Results revealed that population-based multigene testing was more cost-effective compared to family history-based testing, resulting in an additional cost of $469 per woman, an incremental QALY of 0.0085 per woman, and an ICER of $55,548 per QALY. Population-based multigene testing showed prevention of 1,338 cases of breast cancer and 663 cases of ovarian cancer compared with family history-based testing. However, population-based testing resulted in 69 excess coronary heart disease cases and 10 excess coronary heart disease deaths per million women.

In a probabilistic sensitivity analysis, the probability of cost-effectiveness for population-based multigene testing was 100% for all simulations when applying the willingness-to-pay threshold of $100,000 QALY. During a separate scenario analysis, the cost of the test exceeded $825 and population-based multigene testing was no longer considered cost-effective. Regardless of the scenario, population-based testing was a cost-effective option even under extreme conditions compared to other model parameters.

The population consisting primarily of white women from the US limits the generalizability of the results, especially since genetic variations and disease risks differ between racial and ethnic groups. The study also used a fairly low cost of $300 for the multigene panel test. Studies have neglected to include cascade testing of the proband’s family members in the revised manuscript or family history when modeling cancer risk for carrier variants. This exclusion hinders the study results because the risk of cancer is increased for variant carriers who have a previous family history of breast or ovarian cancer.

Economic evaluation of population-based multigene testing demonstrated cost-effectiveness for the prevention of hereditary breast and ovarian cancer, but the results highlight a necessary shift toward comprehensive genetic testing strategies to identify carriers of pathogenic variants and enable decision-making informed personalized risk management.

References:

1. Guo F, Adekanmbi V, Hsu CD, Berenson AB, Kuo Y, See YT. Cost-effectiveness of population-based multigene testing for breast and ovarian cancer prevention. JAMA Netw Open. 2024; 7 (2): e2356078. doi:10.1001/jamanetworkopen.2023.56078

2. Somasundaram K. BRCA1 and BRCA1 genes and hereditary breast and/or ovarian cancer: benefits of genetic testing. Indian J Surg Oncol. 2010; 1 (3): 245-249. doi: 10.1007/s13193-011-0049-7

3. Family health history and BRCA1 and BRCA2 genes. US Centers for Disease Control and Prevention. May 15, 2024. Accessed May 31, 2024. https://www.cdc.gov/breast-ovarian-cancer-hereditary/risk-factors/family-health-history-and-the-brca1-and-brca2-genes . html