Mission BREATHE: Reshaping the Age Based Paradigm for Breast Cancer Screening

“As far as breast cancer treatment is concerned, we have gone through transformational progress over the years. It used to be that a large proportion of women diagnosed with the condition will die. Now, when you find it early, it is pretty much a curable disease with only a small proportion of women not surviving. But the key is we need to find better ways to discover it early because traditionally only women above 50 years old are encouraged to do mammographic screening,” says Associate Professor Mikael Hartman, Department of Surgery, National University Hospital.

Many Hands make Light Work

Dr Li Jingmei, Group Leader, A*STAR’s Genome Institute of Singapore (GIS) elaborates, “That is what we are trying to do with the BREATHE clinical implementation project. With Mikael’s vast experiences as a breast cancer specialist surgeon, my training in genomics and Wang Yi’s economic modelling capabilities, we are working together to assess how we can change the current breast screening practices from age-based to risk-based.”

“Indeed, unlike Jingmei and Mikael who have been researching and practising in this area for a long time, I am just learning about breast cancer screening, like current barriers causing low adherence, and what it means by genetic cancer polygenic risk score. But more importantly, my role is to examine the use case of the possible technology, challenges for its application in the clinical context and how can we include them in our modelling for scaling,” says Dr Wang Yi, Assistant Professor, Saw Swee Hock School of Public Health, National University of Singapore.

A/Prof Hartman laughs, “I have to add that Wang Yi is a rare Pokémon who is very essential for our study. Because we may land on a brilliant technology, but without a clear understanding of its affordability for our healthcare system—it’s useless. Hence his evaluation is important to determine whether what we are proposing makes sense for the country to foot the bill.”

He continues, “What is special about our team is that we are on an exciting journey to potentially prevent breast cancer, which kills women all around the world, by transforming breast cancer screening. And this is happening at a time when significant breakthroughs are happening in genomics—the field that Jingmei is in. Imagine asking every woman and using their genetic information for a good cause, the opportunity to make a difference is exponential.”

Dr Li adds, “That’s true. I always remember a conversation with Per Hall, who is Mikael and my common supervisor. I was curious about why he switched from a medical doctor to a full-time researcher—and he said ‘As a doctor, I treat one patient at a time, but as a scientist, my findings can potentially benefit millions’. That is exactly what Mikael, Wang Yi and I are trying to achieve with BREATHE!”

The Team who Works Together, Wins Together

Dr Li goes on, “With BREATHE, we are hoping to answer some important questions about breast cancer screening. There is a gap between awareness of breast cancer screening and actually doing it—we want to know how we can bridge that.”

A/Prof Hartman says, “Similarly, we are also investigating how we can enhance the current national breast cancer screening guidelines by leveraging data models and analytical methods such as the Gail model, information from most recent mammography screening, polygenic risk score, or Breast and Ovarian Analysis Disease Incidence and Carrier Estimation Algorithm (BOADICEA).”

Dr Li says, “Incidentally, the last two play a critical role in informing one about their risks. While breast cancer predisposition genes like BRCA1/BRCA2 provide certainty to one’s risk, the polygenic risk score offer insights into the combination of variants that heightens risk. The science is ready to offer these information. But there is also the part about how women would want to receive these information. We have come to realise that it can be less straightforward than it seems—what is too much information for some could be insufficient for others. So we are trying to determine what breast cancer risk reports should look like to be meaningful to recipients so that they would go get their screening done.”

Dr Wang injects, “That’s the first step. After the screening, we need to start thinking about how to categorise these women into different risk groups. We can classify more people into high risk to prevent more cancers, but that will also mean that the cost for implementing the programme could be high. However, there is also the probability that we can save more money in the long run. So we need to find this balance in the trade-off. We are working closely to find the answers.”

“Yes, at the same time we are also exploring how to make this scalable—maybe in the community with the general practitioners and at the polyclinics. Or can we enable women to assess their own risk using electronic means, and doing buccal swabs and sending in DNA samples by themselves for analysis. We are piloting these processes before scaling them,” shares A/Prof Hartman.

BREATHE(ing) On

A/Prof Hartman continues, “With this clinical implementation pilot, there are many moving parts—recruitment, testing, profiling, communication, follow-up, etc. With each, we are progressing and adjusting along the way. But there are a number of important solutions that we are still trying to land on. And with breast cancer screening, a two-year period is not quite enough. Hence we are going to run BREATHE beyond the end of the clinical implementation pilot, which is slated for completion in 2024. Ultimately, the hope is to transition Singapore from an age-based to risk-based screening in five years’ time.”

Dr Wang agrees, “Yes, my goal is to show the value of a risk-based screening approach while ensuring that it is affordable for our healthcare system. With good numbers, I am optimistic that we will convince the government to implement and subsidise risk-based breast cancer screening.”

Dr Li rounds up, “With Healthier SG and the growing emphasis on customised health plans, I believe this is the right timing for BREATHE to encourage customised screening.”

Read more about the research behind BREATHE here.

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] Breast Cancer Foundation, Take Charge of Your Breast Health – Journeys of Young Women with Breast Cancer in Singapore. https://www.bcf.org.sg/take-charge-of-your-breast-health/