Integrated genomics and spatial heterogeneity to enhance personalized therapies for rare metaplastic breast carcinomas

Sharing data and expertise to accelerate research into rare and aggressive breast cancers 

Metaplastic breast cancer (MpBC) is an aggressive but rare disease that affects less than 1 per cent of all patients diagnosed with breast cancer in Canada. Because it is so rare, it has historically been difficult to study. This means that very little is understood about it, which in turn means that there are very few options to treat it.  

To shed new light on this aggressive disease, the Marathon of Hope Cancer Centres Network is funding a multi-disciplinary team of experts who will come together for the first time ever to study the genomic and clinical underpinnings of these cancers, with the goal of finding better ways to treat them. 

Funded through the MOHCCN’s Pan-Canadian Project Program, the team unites experts from institutions in Quebec, British Columbia, Alberta and Ontario, who will come together to collect, share and analyze data from patients diagnosed with MpBC. The team will also be contributing this data to the MOHCCN Gold Cohort, ensuring that the entire MOHCCN Network, and future patients treated at its centres, can benefit from it. 

We spoke to the project lead, Dr. Morag Park, Director of the Rosalind and Morris Goodman Cancer Institute in Montreal, to better understand this pan-Canadian collaboration and its potential for impact on the lives of patients diagnosed with MpBC. 

MOHCCN: Congratulations on being named one of the recipients of the pan-Canadian Project Program. How would you describe your project? Why is it important?  

Morag Park: Thank you! We are very excited about this initiative!  

I think it’s important to start by saying that rare cancers disproportionally contribute to death from cancer because they are so poorly understood. This is also the case with metaplastic breast cancers (MpBC). That is why we are joining forces with researchers and clinicians from institutions across Canada to work together to understand these cancers, which are not only rare, but also one of the most aggressive types of breast cancer. Our goal is to study these cancers so we can improve outcomes for patients diagnosed with it.  

MOHCCN: What do you hope to achieve by the end of the project?  

MP: As part of this project, we started a collaborative network of hospitals and biobanks to gather the maximum number of MpBC samples. This is really important for rare cancers, because a single centre may not get enough samples to actually study a disease, but when we come together our sample size grows.  

Once we have these samples and sequence them, we will use new computational approaches to predict therapeutic strategies to treat MpBC and validate our predictions using pre-clinical models in vitro and in vivo. Results from this pipeline may be applied to MpBC patients in the future to improve their quality of life and outcomes with more effective therapies.  

MOHCCN: Why is this project important? What potential impact could it have on cancer therapies? 

MP: One challenge in identifying new therapeutic options for MpBC is that it is composed of several cancer cell populations. These cells are very different and respond differently to therapeutic drugs. This means that a drug may kill some cancer cells but not the entire tumour. 

Our project aims to provide an in-depth understanding of all MpBC cells, which we call heterogeneity, to improve choice of therapies in the future. 

MOHCCN: Why is it important for the Marathon of Hope Cancer Centres Network to fund this type of work?  

MP: Our pan-Canadian effort will gather MpBC samples across Canada. By identifying the MpBC molecular landscape, we will contribute to understanding the cancer biology of a rare and understudied cancer subtype. Only a multi-center collaborative effort, as proposed in this project, can gather enough samples to provide meaningful biological results. Access to cutting-edge technologies and platforms across our collaborative network will enable research that was not feasible before the establishment of our team. With the support of MOHCCN, we are starting the first pan-Canadian metaplastic network to collect samples and start analyzing them. This cohort will represent one of the most extensive single compendiums of MpBC with linked patient and clinical outcome data worldwide.