Detailed Map of Breast Cancer Reveals the Effects of Mutations on the Tumor Landscape

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An international team of scientists, spearheaded by a £20 million ($25.9 million) award from Cancer Research UK, has developed the most detailed maps of breast cancer available, which map breast tumor samples to a resolution smaller than a single cell.

The maps, published in Nature Cancer this week, detail the intricacies and complexity of the cancer landscape—comprising cancer cells, immune cells, and connective tissue—and how it varies both between, and within, tumors depending on their unique genetic makeup.

“At the moment, doctors only look for a few key markers to understand what type of breast cancer someone has,” said Dr. Raza Ali, junior group leader at the Cancer Research UK Cambridge Institute, and the study’s lead author. “But as we enter an era of personalized medicine, the more information we have about a patient’s tumor, the more targeted and effective we can make their treatment.”

In the future, the hope is that such a map could provide clinicians with a wealth of information specific to each patients tumor at the time of diagnosis, thus providing an opportunity to match patients with the most appropriate therapy. The information would also be used to analyze tumor during a patient’s treatment to more clearly see how a patient is responding to their therapy and to adjust the treatment regimen based this.

In the study, the international research teams from Cancer Research UK Cambridge Institute, University of Cambridge; the University of Zürich, Switzerland; and the British Columbia Cancer Research Centre, Canada, studied 483 different tumor samples collected during the Cancer Research UK funded METABRIC study, a project that has already significantly improved the understanding of the disease by revealing that there are at least 11 different subtypes of breast cancer.

The team looked within the samples for the presence of 37 key proteins, indicative of the characteristics and behavior of cancer cells. Using a technique called imaging mass cytometry, they produced detailed images, which revealed precisely how each of the 37 proteins were distributed across the tumour.

The researchers then combined this information with genetic data from each patient’s sample to further enhance the image resolution. This is the first time imaging mass cytometry has been paired with genomic data.

These tumor “blueprints” expose the distribution of different types of cells, their individual characteristics and the interactions between them.By matching these pictures of tumors to clinical information from each patient, the team also found the technique could be used to predict how someone’s cancer might progress and respond to different treatments.

Professor Carlos Caldas, from the Cancer Research UK Cambridge Institute and co-author of the study said: “We’ve shown that the effects of mutations in cancer are far more wide-ranging than first thought. They affect how cancer cells interact with their neighbours and other types of cell, influencing the entire structure of the tumour.”

The research was funded by Cancer Research UK’s Grand Challenge initiative. By providing international, multidisciplinary teams with £20 million grants, this initiative aims to solve the biggest challenges in cancer.

“This team is making incredible advances, helping us to peer into a future when breast cancer treatments are truly personalized,” said Dr. David Scott, director of Grand Challenge at Cancer Research UK. “There’s still a long way to go before this technology reaches patients, but with further research and clinical trials, we hope to unlock its powerful potential.”

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