'Molecular wiring of tumour' predicts breast cancer relapse

Author: Mark Gould

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A new study* shows that breast cancer is made up of 11 separate diseases with each contributing a different risk of the disease as a whole recurring or remitting.

Scientists writing in the journal Nature say the findings could help identify people in need of closer monitoring and reassure others at low risk of recurrence.

Professor Karen Vousden, Cancer Research UK's chief scientist, said the findings demonstrate "incredibly encouraging progress".

"We're still a way off being able to offer this type of detailed molecular testing to all women and we need more research to understand how we can tailor treatments to a patient's individual tumour biology," he added.

Scientists at the University of Cambridge and Stanford University looked in detail at nearly 2,000 women's breast cancers. They went beyond considering all breast cancers as a single disease and beyond modern medicine's way of classifying the tumours - based on whether they respond to the hormone oestrogen or targeted therapies like Herceptin.

Instead the team analysed the genetic mutations inside the tumour to create a new way of classifying them. Previous work by the group has shown breast cancer is 11 separate diseases, each with a different cause and needing different treatment. By following women for 20 years, they are now able to show which types of breast cancer are more likely to come back. It showed that triple negative breast cancers - one of the hardest types to treat - were not all one class of cancer, but two.

Lead researcher Professor Carlos Caldas told the BBC: "This is really biology-driven, it's the molecular wiring of your tumour.

"Once and for all we need to stop talking about breast cancer as one disease, it's a constellation of 11 diseases.

"This is a very significant step to more precision-type medicine."

Professor Caldas said there may be a sub-group of women that have not relapsed by five years who may be probably cured, but a second subgroup may still be at significant risk of later relapse. The research could help inform women of their future risk, but may also change the way their cancers are treated.

There were four subgroups of breast cancer that were both driven by oestrogen and had a "markedly increased" risk of recurrence. These women may benefit from a longer course of hormone therapy drugs like tamoxifen.

However, the way the scientists analysed and sorted the cancers is still too expensive and time consuming for the NHS. It will need refining into a form that could be used as a routine way of analysing a woman's cancer. Much larger studies involving up to 12,000 women are also planned, so that researchers can be certain of their results.

Professor Caldas said: "I would not recommend it clinically yet, but we really are committed to making this available.

"We are totally committed to having an NHS test, we haven't patented any of this."


*Rueda MO, Sammut S-J, Seoane JA, et al. Dynamics of breast-cancer relapse reveal late-recurring ER-positive genomic subgroups. Nature (2019). DOI: 10.1038/s41586-019-1007-8

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