From Reactive to Proactive: Tracing the Hereditary Cancer Risk

About one in 150 Singaporeans has an underlying risk of hereditary breast and ovarian cancer (HBOC) and one in 500 has an underlying risk of Lynch syndrome (LS) according to the recently published findings of SG10K_Health study by PRECISE^[1]. However, only the costs of cancer diagnosis and treatment are being subsidised currently while diagnostic testing for probands and their first-degree relatives (FDRs) are not. A clinical implementation pilot supported by Precision Health Research, Singapore (PRECISE) is seeking to address this gap.

Cost can be a barrier to the uptake of genetic testing and cascade screening. In addition, factors such as non-systematic referral of patients, and poor understanding of the need for genetic testing among patients and their family members also contribute to the current reactivity of hereditary cancer risk testing in Singapore.

Seeing the opportunity to address these gaps and implement a sustainable genetic testing programme for hereditary cancer risks, 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, and Associate Professor Ken Redekop, Erasmus School of Health Policy and Management, Erasmus University Rotterdam, embarked on a clinical implementation pilot (CIP) together—despite a geographical divide and a six-hour time difference.

Changing the Focus from Treatment to Prevention

“For most cancers, when patients go from pre-disease to disease, they increasingly have more symptoms. As a medical oncologist, it is not unusual that I only see them then. By the time their diagnosis is confirmed, I can only offer reactive care—and prescribe medicines—at best,” A/Prof Ngeow shared. “But what if we can find a way to identify these individuals before any actual pre-clinical symptoms present? It will be better for the individual, but also much better for our healthcare system.”

This CIP presents an opportunity to explore the viability and scalability of such an implementation. A/Prof Ngeow said, “We know from our past research that if we can improve cascade screening uptake to 30%, subsidising testing will be overall cost neutral to the healthcare system. But the question is, how can we sustainably increase the cascade testing rates from the current 10% to 15% to 30%^[2] —given our observation and understanding of current clinical practices? With this CIP, all hands are on deck to produce data that provides good, solid evidence on how we can do this in a safe and cost-efficient manner.”

Creating the Playbook for Hereditary Cancer Cascade Screening 

Agreeing, A/Prof Redekop said, “Exactly—this CIP is unique in that it doesn’t stop at research, data collection and analysis. It goes all the way to include implementation specifics. And if we think about it, that is really the most important link here—transforming insights into actual applications to help patients, their loved ones and the healthcare system.”

A/Prof Redekop continued, “Notably, Singapore’s size and availability of resources are advantageous towards this cause. They allow for deep understanding of issues, swift implementation of insights, evaluation of outcomes, and further adaptation as necessary. For example, through the pilot Resource Utilisation Study (RUS) funded by PRECISE, we were able to prove that offering virtual consults to individuals through a dedicated cascade testing clinic can reduce appointment waiting time for probands and their FDRs—and consequently, significantly improve uptake and compliance.”

“Concurrently, we are exploring the feasibility of a registry-aided outreach approach—because we found from one of our prior studies that relatives of probands tend to have a poor understanding of the significance and relevance of genetic testing to them. We recognise that this could be a result of probands being ill-equipped to explain benefits and implications of cascade screening,” explained A/Prof Ngeow. “With the registry-aided outreach approach, healthcare personnel will help reach out and discuss implications of germline cascade screening with at-risk relatives—reducing reliance on the proband to disseminate genetic test results while ensuring the accuracy of disseminated information.”

Going Beyond Genetic Testing for Hereditary Cancer

Four other CIPs are running concurrent to this one. Among which, cascade screening is a recurring theme not only for hereditary cancer, but also for familial hypercholesterolemia and primary glomerular diseases. A/Prof Ngeow commented, “Indeed, this is one of very few projects that brings together multiple institutions and disciplines to share resources and exchange expertise—in a systematic, coherent and cohesive manner—towards fostering a better healthcare system for everyone.” 

A/Prof Ngeow summed up, “It has been exciting and enriching thus far—we get to learn from one another’s experiences and find synergy in our proposed solutions. But at the end of the day, it only counts if we can take all these findings and implement them widely. And the way I see it, building a strong pipeline of genetics-trained talents and improving the general genetic literacy of all stakeholders are integral to the sustainability of the good efforts we’ve invested in so far.”

“That’s right. While our efforts for this CIP focus on hereditary cancer, there is definitely a huge potential for generalising the knowledge to other diseases—and even other countries and geographic regions. I am hopeful what we are doing now will benefit many people—and for many years ahead,” A/Prof Redekop smiled.  

Click here to read more about how A/Prof Ngeow and A/Prof Redekop are improving access for hereditary cancer genetic testing. 

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.

[1] Chan, S.H., Bylstra, Y., Teo, J.X. et al. Analysis of clinically relevant variants from ancestrally diverse Asian genomes. Nat Commun 13, 6694 (2022).

[2] 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.