Mapping the tumour landscape in breast cancer

An international team of scientists has created what they claim is one of the most detailed maps of breast cancer ever achieved, revealing how genetic changes shape the physical tumour landscape.

Brought together by a £20 million Grand Challenge award from Cancer Research UK, the team developed intricate maps of breast tumour samples, with a resolution smaller than a single cell. These maps show how the complex cancer landscape, made up of cancer cells, immune cells and connective tissue, varies between and within tumours, depending on their genetic makeup. The work has been described in the journal Nature Cancer.

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

The researchers studied 483 different tumour samples, collected as part of the Cancer Research UK-funded METABRIC study, and looked within them for the presence of 37 key proteins that are indicative of the characteristics and behaviour of cancer cells. Using a technique called imaging mass cytometry, they produced detailed images that revealed precisely how each of the 37 proteins were distributed across the tumour.

The researchers combined this information with vast amounts of genetic data from each patient’s sample to further enhance the image resolution, in what is said to be the first time imaging mass cytometry has been paired with genomic data. These tumour ‘blueprints’ expose the distribution of different types of cells, their individual characteristics and the interactions between them. By matching these pictures of tumours to clinical information from each patient, the team also found that the technique could be used to predict how someone’s cancer might progress and respond to different treatments.

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

The technique could one day provide doctors with an unparalleled wealth of information about each patient’s tumour upon diagnosis, allowing them to match each patient with the best course of treatment for them. It could also be used to analyse tumours during treatment, allowing doctors to see in unprecedented detail how tumours are responding to drugs or radiotherapy. They could then modify treatments accordingly, to give each patient the best chance of beating the disease.

Dr David Scott, Director of Grand Challenge at Cancer Research UK, said, “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.”

Image caption: Molecular map of a breast tumour. Image ©University of Cambridge/H Raza Ali.

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