Breakthrough for basal breast cancer

Australian researchers have used a novel technique for protein analysis to partly unravel the mystery of basal breast cancer.

Making up between 10 and 27 percent of all breast cancers, basal breast cancers have long puzzled doctors and researchers due to their unusual nature.

Because they lack oestrogen and progesterone receptors, basal breast cancers are resistant to hormone therapies such as tamoxifen, and are not affected by Herceptin, a monoclonal antibody effective in treating other breast cancer types.

One of the key reasons why treatment of certain cancers is so difficult to treat is due to the complex interaction of proteins at the sub-cellular level.

Cells house thousands of proteins. When they are healthy these proteins interact in predictable ways and in predictable numbers. However, in the case of cancerous cells the levels of proteins change as does the manner in which they interact.

Over the years researchers have begun to identify the protein ‘fingerprints’ corresponding to various types of cancer, but until now have not been able to pin down basal breast cancers.

Researchers at Sydney’s Garvan Institute have focussed on a process known as phosphorylation whereby proteins modify each other’s behaviour by exchanging phosphate molecules. What they found was that basal breast cancers display a characteristic ‘signature’ or ‘fingerprint’ of ‘tyrosine phosphorylation’, or phosphate molecules attaching to the tyrosine amino acids within proteins.

The researchers also found that these cancers display heightened activity of several different kinds of cell-signalling proteins known as ‘kinases’. Kinases are responsible for attaching the phosphate groups to proteins.

“We were able to outline the signalling network which is characteristic for basal breast cancers, and identify which kinases are present and active,” said Dr Falko Hochgräfe from the Garvan Institute of Medical Research, who worked on the study with the Professor Roger Daly, also from Garvan.

“Our findings suggest that it would be a good idea to stratify patients according to which signalling proteins, or kinases, were found in their cancers.”

It is hoped that the identification of multiple kinases will lead to the development of effective ‘combination’ therapies.

The researchers were also able to identify two novel marker proteins which could be used to more easily identify this patient subset in the future as well as guide the development of more tailored therapies.

The study appears in the current issue of Cancer Research.