Improving Access to Hereditary Cancer Genetic Testing

Overall, approximately 5% to 30% of all cancers may have an inherited genetic basis^[4]. Associate Professor Joanne Ngeow, Head and Senior Consultant, Cancer Genetics Service, National Cancer Centre Singapore, and Associate Professor, Genomic Medicine, Lee Kong Chian School of Medicine said, “Unlike many other genetic conditions, hereditary cancer has strong evidence for early detection and risk reduction strategies. Cost effectiveness studies for hereditary breast and ovarian cancer syndrome (HBOC) and Lynch syndrome (LS) as well as other high-penetrant hereditary cancer syndromes have repeatedly shown that hereditary cancer germline testing is a cost-effective public health intervention.”

Like other genetic disorders such as familial hypercholesterolemia and primary glomerular diseases, cascade screening offers an efficient and cost-effective method for identifying high risk individuals. Besides the need for fewer tests, timely intervention and management of at-risk but unaffected individuals also reduces healthcare burden for the economy further down the road. However, despite evidence supporting cascade testing for hereditary cancers, cascade testing rates stand at only 10% to 15%^[5].

A/Prof Ngeow said, “In a study conducted in 2018, our modelling showed that if we can improve cascade screening uptake to 36%, we may reduce costs through early detection and prevention of cancers in Singapore^[6]. With this clinical implementation pilot (CIP), we are looking to build upon this knowledge and answer the question: what strategies will allow us to overcome barriers for cascade screening and improve adoption rates for a financially sustainable implementation in Singapore?”

Enabling More Seamless Cascade Screening Processes

Under optimal circumstances, systematic cascade testing should be activated following the identification of a germline pathogenic variant or likely pathogenic variant (PV/LPV) in a proband. This enables the determination of disease risk in unaffected relatives. It also allows better targeting of risk-reducing strategies towards relatives in whom the familial PV/LPV is detected while avoiding unnecessary interventions for those without.

“At the moment, an at-risk family member must present themselves to a general practitioner for a cascade screening referral which can be inconvenient for them. Add to that, some healthcare providers may lack genetic literacy and knowledge, which can lead to non-uniform advice and confusion among the probands and their first-degree relatives (FDRs),” explained A/Prof Ngeow. “Then there’s also the problem of limited healthcare resources which can negatively impact genetic testing uptake.”

Sharing initial findings from a recent Resource Utilisation Study (RUS) funded by the Precision Health Research, Singapore (PRECISE), A/Prof Ngeow said, “When we offered virtual consults to individuals through a dedicated cascade testing clinic, we saw significant improvements in uptake and compliance. We were also able to provide FDRs with more timely testing. This goes to show that—with the right implementation, there is potential for cascade screening adoption to increase sufficiently to offset the cost of health risks to the healthcare system.”

Making it Harder for At-Risk Individuals to Reject Cascade Screening 

In Singapore, the government subsidises the costs of diagnosis and treatment of cancers, but not the cost of diagnostic testing for probands and their FDRs^[7]. “We expect the healthcare system to save lives—even to save lives and money at the same time. But that is tricky because we might also need to spend more to save lives. If we can pick up early-stage cancers or intervene before cancer develops, maybe we can achieve the ideal or at least try to save more lives without spending more,” said Associate Professor Ken Redekop, Erasmus School of Health Policy and Management, Erasmus University Rotterdam.

“Studies have shown that provision of subsidies has a positive impact on genetic testing uptake. We think it would make sense for health systems to contribute to testing costs and we aim to demonstrate that in our CIP,” A/Prof Ngeow explained. “Another focus of our CIP is also to explore the feasibility of a registry-aided outreach to family members of probands. This solution reduces reliance on the proband to disseminate genetic test results and ensures that accurate information is relayed by trained genetic professionals to at-risk relatives.”

A/Prof Ngeow added, “Sometimes individuals do not come for testing not because they didn’t want to, but because they’ve forgotten about it. So if we can understand the causes, we can do something—as we’ve seen from success in similar alternative cascade screening approaches. In US, an online email approach from a centralised centre saw 47.5% of invited FDRs undergoing testing and 12% of the FDRs continuing the cascade by inviting additional second-degree relatives^[8]. In Australia, letters were sent and phone calls were made to FDRs who did not present to the genetics centre after a six-month interval. The uptake rates approached 50%, an increase of 20% over the usual cascade testing rates^[9]. These results tally with the RUS conducted.”

Building Capabilities for Sustainable Implementation

Currently, cascade testing appointments compete with new proband diagnostic testing appointments. “This problem is not going away anytime soon, and it will only become more severe if we don’t do something about it. As a strong advocate for matching talent to jobs, I see a certain urgency in building a pipeline of genetic counsellors who can deliver care and ensure that genetic testing is ably done. And let’s not forget the need to retain them with an attractive career growth track,” A/Prof Ngeow said.

Agreeing, A/Prof Redekop said, “Manpower shortage is a prevalent issue not just in Singapore—and we are unlikely to completely resolve it in the short run. Hence, we’ll do well to explore other non-human interventions, including artificial intelligence, that are readily accessible with regular and updated advice. They can complement human genetic counsellors’ efforts to bring about better impact.”

“However, that does not replace the genetic literacy that the public, patients, physicians and policymakers should possess. While the depth and breadth of knowledge would vary—and rightly so—patients should minimally know what they can do to protect their health, and healthcare personnel should know when they need to reach out to perhaps genetic counsellors for more advice.” A/Prof Ngeow concluded.

Click here to read more about how A/Prof Ngeow and A/Prof Redekop are changing the approach towards tracing hereditary cancer risk. 

This project is supported by the National Research Foundation, Singapore, through the Singapore Ministry of Health’s National Medical Research Council and the Precision Health Research, Singapore (PRECISE), under PRECISE’s Clinical Implementation Pilot grant scheme.

References:

1. Principal Causes of Death. Ministry of Health. https://www.moh.gov.sg/resources-statistics/singapore-health-facts/principal-causes-of-death

2. Singapore Cancer Registry Annual Report 2018. National Registry of Diseases Office. https://www.nrdo.gov.sg/docs/librariesprovider3/default-document-library/scr-annual-report-2018.pdf

3. https://www.moh.gov.sg/docs/librariesprovider5/medishield-life-documents/recommendations-of-the-medishield-life-council-on-medishield-life-coverage-for-cancer-drug-treatments.pdf

4. Huang K-L, Mashl RJ, Wu Y, et al: Pathogenic Germline Variants in 10,389 Adult Cancers. Cell 173:355-370.e14, 2018 

5. Li S-T, Yuen J, Zhou K, et al: Impact of subsidies on cancer genetic testing uptake in Singapore. J Med Genet 54:254–259, 2017.

6. Li, Shao-Tzu & Yuen, Jeanette & Zhou, Ke & Ngeow, Joanne. (2017). Abstract 4285: Impact of subsidies on cancer genetic testing uptake in Singapore. Cancer Research. 77. 4285-4285. 10.1158/1538-7445.AM2017-4285.

7. Courtney, E., Chok, A.KL., Ting Ang, Z.L. et al. Impact of free cancer predisposition cascade genetic testing on uptake in Singapore. npj Genom. Med. 4, 22 (2019). https://doi.org/10.1038/s41525-019-0096-5

8. Caswell-Jin JL, Zimmer AD, Stedden W, et al: Cascade Genetic Testing of Relatives for Hereditary Cancer Risk: Results of an Online Initiative. JNCI J Natl Cancer Inst 111:95–98, 2019

9. Suthers GK, Armstrong J, McCormack J, et al: Letting the family know: balancing ethics and effectiveness when notifying relatives about genetic testing for a familial disorder. J Med Genet 43:665–670, 2006