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A team from Lawson Health Research Institute has shown that triple-negative breast cancer cells can facilitate changes to the lung that both attract cancerous cells and allow them to grow, leading to lung metastasis. 

Metastasis is the spread of cancer cells from a primary tumour to different organs. Lung metastasis is responsible for approximately 60 to 70 per cent of deaths related to breast cancer. 

“The best way to explain lung metastasis is the seed and soil analogy,” says Dr. Alison Allan, Lawson Scientist. “The seeds are the breast cancer cells from a primary tumour and the soil is the lung’s microenvironment. Seeds can break away, but they only grow if the soil is fertile.”

The majority of studies on metastatic cancer have focused on the characteristics of tumour cells and not on the organs to which they spread. Dr. Allan’s team is studying how the lung microenvironment itself is contributing to lung metastasis.

In the new study, the team examined the lung microenvironment in preclinical models. They compared models with two different subtypes of breast cancer. The luminal A subtype is the least aggressive form of breast cancer and does not often metastasize to the lung. Triple-negative breast cancer, meanwhile, is the most aggressive form with a higher likelihood of metastasis and no targeted therapies available. 

The team found that models with triple-negative breast cancer had a drastically different lung microenvironment that was much more hospitable to the growth of cancer. They also found that triple-negative breast cancer cells might be sending ‘signals’ to the lung to help it attract cancerous cells that enter the bloodstream.

“We suspect that triple-negative breast cancer cells release tiny particles called exosomes which are delivered to the lung,” explains Dr. Allan, who is also Chair of the Department of Anatomy and Cell Biology at Western University’s Schulich School of Medicine & Dentistry. “Once delivered, the exosomes signal the lung to start changing into a hospitable environment for tumour cells.”

With support from Lawson’s Internal Research Fund, the team is continuing to research this process. They are also studying ways to make the lungs less receptive to cancerous cells.

Their findings could help in the development of targeted therapies to prevent breast cancer from metastasizing. For example, in collaboration with investigators at the University of Alberta, they are developing an inhalable spray that is aimed at preventing cancer from spreading to and growing in healthy lungs.

“The ultimate goal is to eliminate the metastasis-promoting exosomes as a therapeutic strategy to prevent triple-negative breast cancer from spreading to the lungs,” says Dr. Allan.

The study “Triple-Negative Primary Breast Tumours Induce Supportive Premetastatic Changes in the Extracellular Matrix and Soluble Components of the Lung Microenvironment,” is published in Cancers. It was funded by the Cancer Research Society, the Canadian Cancer Society Research Institute, a London Regional Cancer Program Catalyst Grant, London Health Sciences Foundation, the Breast Cancer Society of Canada and an Ontario Graduate Scholarship awarded to Braeden Medeiros – the paper’s first author.

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Above: Visual representation of the research findings

Ashmeet Gill had her first PET/CT scan shortly after being diagnosed with Hodgkin’s lymphoma, a cancer of the body’s germ-fighting immune system. She was nervous. Claustrophobia is an issue for the young Stratford resident and the scan, necessary to determine if the cancer had spread beyond the lymph nodes in her neck, would take 34 to 45 minutes, she was told.

Wrapped in a sheet and tucked inside the tube of the PET/CT at St. Joseph’s Health Care London (St. Joseph’s), Ashmeet, then 24, steeled herself to remain calm. But near the end of the scan, a sense of panic set in.

“It was not pleasant but I endured it. I made it through.”

Ashmeet’s next PET/CT scan would be six months later, after six cycles of chemotherapy, to determine if the treatment had worked. She was terrified of another panic episode. By then, however, St. Joseph’s had a brand-new PET/CT – Canada’s first, next generation, state-of-the-art Omni Legend PET/CT from GE HealthCare.

This time, Ashmeet’s scan took “barely 15 minutes or so,” she recalled.

“I thought, seriously? I couldn’t believe I was done. I was so happy.”

With the very first patients scanned with St. Joseph’s new PET/CT machine, it was obvious the breakthrough technology was living up to high expectations.

The machine is fast – decreasing the time it took for a scan from about 45 minutes on the older system to less than 14 – head to toe. Patients are exposed to less radiation, and the ability to precisely detect disease and tiny abnormalities is outstanding.

“This is what we have been waiting for,” says Ting-Yim Lee, a pioneer in the use of machines like PET/CT to gather new, vital information about diseases. “St. Joseph’s new Omni Legend by GE HealthCare is answering the call for patients, clinicians and researchers alike.”

PET/CT is the medical ace in imaging for the assessment and treatment monitoring of cancer, neurodegenerative disorders, and metabolic and cardiovascular diseases. At St. Joseph’s, the possibilities of this technology took a giant leap forward in August 2023, thanks in part to the generosity of donors and a $1 million contribution from St. Joseph’s Health Care Foundation. With the arrival of the new system, St. Joseph’s is set to become Canada’s first national GE HealthCare centre of excellence in molecular imaging and theranostics. This two-pronged approach to diagnosing and treating cancers and other diseases merges molecular imaging with the use of radiopharmaceuticals to identify the location and extent of diseased tissues and selectively destroy the abnormal cells.

“The speed at which we can now do exams means significantly improved comfort for patients while the exceptional image quality changes the game in the hunt for cancerous lesions,” explains Ting, Director of PET/CT Research at Lawson Health Research Institute (Lawson) and medical physicist at St. Joseph’s Hospital.

“For young adults undergoing repeat PET/CT exams due to their medical conditions, managing the radiation dose is critical,” explains Dr. Narinder Paul, Lawson scientist and Chief, Medical Imaging, at St. Joseph’s. “These individuals already face an elevated life-time risk of developing cancer from radiation, and this risk further increases with additional exposures.”

For older adults, the time it takes for the examination is also of great concern. Lying still for long periods can be a hardship due to pain from bone metastases or other conditions, and is a challenge for those who have dementia, are claustrophobic or experiencing other issues, adds Dr. Paul.

“Reducing the exam time is a huge improvement in the patient experience for these individuals.”

While patients hail the new PET/CT experience, clinicians and scientists are raving about the machine’s imaging prowess. The advanced AI-driven image formation technology now empowers the precise detection of cancer within lymph nodes and other anatomical structures, “achieving remarkable accuracy even for very small lesions,” says Dr. Paul.

“The advantages we have seen so far are already impressive but what’s on the horizon in research and care – what we will be able to study and do – is even more exciting,” says Ting.

In particular, the new PET/CT is expected to be the catalyst for ground-breaking clinical research for patients facing breast cancer, Alzheimer’s disease, prostate cancer, epilepsy and obesity. Scientific exploration in these areas is currently being planned at St. Joseph’s that will pave the way for novel treatments, new, non-invasive ways to identify a patient’s risk of disease, the potential to clearly and painlessly view how treatment is working, and the ability to uncover the tiniest abnormalities at play when it comes to diseases and conditions.