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Scientists discover new breast cancer origin

Scientists searching for the source of aggressive and deadly breast cancers may have been looking in the wrong place, new research suggests.

The findings, which shed light on how the most dangerous breast cancers grow, could lead to new treatments and prevention strategies.

Tumours arise in two types of glandular tissue in the breast, the outer "basal" cells and inner "luminal" cells.

Previously it was thought that more aggressive cancers sprung from basal stem cells. Milder forms of cancer were believed to arise from "intermediate" luminal cells.

The vast majority of inherited breast tumours with defective BRCA1 genes - one of the most aggressive types - have basal-like characteristics.

But scientists who conducted studies on mice to confirm the origin of BRCA1 cancer tumours found that looks can be deceptive.

The researchers deleted the BRCA1 gene in both mouse basal stem cells and luminal intermediate cells.

Tumours formed in both kinds of cell, but only luminal cells had features identical to human BRCA1 cancers. They also matched the majority of human basal-like "triple negative" cancers not associated with BRCA1 mutations.

Study leader Dr Matt Smalley, from the charity Breakthrough Breast Cancer, said: "These results represent a major advance in our understanding of breast cancer. It means we can now look very closely at where the disease forms and which genes are involved in that process.

"This knowledge will greatly improve the chance of finding effective new targeted treatments for breast cancer patients in the future."

The work, carried out at Breakthrough's laboratories at the Institute of Cancer Research in London, is reported today in the journal Cell Stem Cell.

BRCA and triple negative breast cancers are two of the most aggressive forms of the disease.

They represent about 8,000 of the nearly 46,000 cases of breast cancer diagnosed each year in the UK.

Currently there are no targeted treatments for triple negative breast cancer, which is more common in younger and black women.

A targeted therapy for inherited breast cancer, called a PARP inhibitor, is now showing promise in clinical trials.

Professor Alan Ashworth, director of the Breakthrough Breast Cancer Research Centre, said: "Understanding the biology of breast cancer is essential for the future development of new ways to treat and prevent the disease. Our research gives a considerable new insight into how the

disease forms and grows."


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