Mapping Mutations: The Future of Breast Cancer Screening and Treatment

Story and photos by Aaron Lam

An average of 78 Canadian women are diagnosed with breast cancer every day, and breast cancer is the leading cause of cancer-related death in women globally. In Canada, one in eight women will develop breast cancer during their lifetime. These stark figures underline the importance of breast cancer research at Women’s College Hospital (WCH), which is shedding light on how the disease works at a genetic level.  

By identifying gene mutations that significantly increase the chances of developing breast cancer, researchers are enhancing our ability to predict, detect and treat the disease. 

On March 27, 2023, The American Journal of Human Genetics published a landmark study that successfully identified a new breast cancer susceptibility gene called ATRIP, which appears to be less common than other genetic mutations. However, those with ATRIP mutations are at a significant risk of developing breast cancer.

Dr. Mohammad Reza Akbari, scientist at WCH, was the principal investigator of the study. To make this discovery, the team initially utilized genetic sequencing on the DNA of a small group of women with familial breast cancer in Poland. This group was selected as it is less genetically diverse than a large mixed population, making it easier to identify genetic variations.

Dr. Akbari sat down for an interview with Women’s College Hospital Foundation (WCHF) about his remarkable study and how the results will impact patients. The following excerpts from the interview have been edited for length and clarity. 

Q:  Could you please explain the medical significance of identifying the ATRIP gene? 

We estimate that five to 10 per cent of breast cancer cases are hereditary. It means that those patients inherit a mutation in their genome that make them prone to developing breast cancer. Several genes have been identified since 1994, such as BRCA1 as a breast cancer susceptibility gene.

However, there are still hereditary cases within families that, when we check them for previously known breast cancer susceptibility genes, we cannot find any mutation in those genes explaining multiple breast cancers in their families.

“Identifying new breast cancer susceptibility genes will help us solve the mystery in some of those families with hereditary cases of breast cancer.”

When we identify the gene mutation in family members, they can decide, depending on the risks associated, if they want to take preventative measures, such as surgery to remove a breast.

Q:  How will the identification of ATRIP impact breast cancer screening? 

A:  Ultimately, through our research, our goal is to provide evidence-based data to impact screening protocols. In our view, if individuals are able to know that they have the ATRIP gene, that knowledge is power. Intensive screening could then happen for those individuals to better detect breast cancer in early stages, and with more accurate screening tools.

For example, women who are known to have ATRIP would be recommended to start their breast cancer screening earlier. And instead of using mammography, they could use MRI, which is more accurate in detecting breast cancer in small sizes.

Q:  Will the discovery of ATRIP potentially result in more tailored treatment for individuals? 

Knowing if an individual carries a gene mutation associated with breast cancer will impact the treatment they will receive. For example, if somebody has been diagnosed with breast cancer but does not have the ATRIP gene, the choice of surgery might be a lumpectomy, which is removing just the tumour. But with someone who has ATRIP, that individual is at a higher risk of developing breast cancer again. So, that patient may want to do a total mastectomy.

For some specific breast cancer susceptibility genes, we know that they respond to a specific group of drugs, which is the case with ATRIP. The study showed that breast tissue of patients with the ATRIP mutation have specific characteristics which are called HRD (homologous recombination deficiency). Tumours with HRD respond very well to PARP (poly(ADP)-ribose polymerase) inhibitors, which is a targeted therapy.

Q:  It can take time for research findings to impact standards of care. Will the identification of ATRIP have immediate benefits for patients and families? 

A:  It won’t be immediate. Although we’ve confirmed the association of ATRIP mutations with breast cancer in populations in Poland and the UK, we need to further validate this information in other populations around the world through ongoing research.

To get the results we see today, we actually started our study back in 2016. Then, after identifying ATRIP, the research team leveraged a larger DNA data set of Polish women with breast cancer and healthy controls to validate the findings. The findings were further investigated using the DNA sequencing data of those with breast cancer registered in the UK-biobank population – confirming ATRIP as a breast cancer susceptibility gene, applicable to women outside of Polish descent.

Q:  What’s next for you in terms of research? What unknowns are you hoping to shed light on?   

A:  We need to elaborate on the role of ATRIP in breast cancer susceptibility. Also, we’ll continue our study of the characteristics of breast cancer tumours of ATRIP carriers. In parallel, we have a couple of other candidate genes that we’re still investigating. We’re hoping that one or more of them are also confirmed to be associated with breast cancer, but it’s too early to tell.

“I believe that the benefits of our research are not limited to hereditary breast cancer patients. Every single breast cancer susceptibility gene identified will improve our knowledge of the biology of breast cancer in general. And that could help us eventually develop better treatments for all breast cancer patients.” 

Q:  How important is donor support to research initiatives at WCH like your study on breast cancer? 

A:  When I started here as a scientist more than 10 years ago, the first money we received was for purchasing the first piece of equipment for our lab – a Sanger sequencer. It came from Women’s College Hospital Foundation. We’re still using that piece of equipment today. We couldn’t do the work we do without the generous support of donors. 

Learn more about this groundbreaking discovery:

Click here to read the full press release.

Canadian researchers find new gene mutation that could be linked to increased breast cancer risk – CBC News

Canadian breakthrough in breast cancer research – CTV Your Morning 

Human relationships, not high tech, sparked this breast cancer breakthrough – University of Toronto Dalla Lana School of Public Health

New gene mutation possibly linked to breast cancer susceptibility: researchers – CBC News: The National