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Osteoporosis drug touted as potential 'BRCA-blocker'

27 June 2016
Appeared in BioNews 857

A drug currently used to treat osteoporosis in old age may help prevent breast cancer in women with a genetic predisposition for the disease.

While still at a preliminary stage, the study found that the drug denosumab could 'switch off' the growth of cancer precursor cells in BRCA1-mutant breast tissue – a result that the researchers now hope to confirm in human clinical trials.

'This is potentially a very important discovery for women who carry a faulty BRCA1 gene,' said Professor Geoffrey Lindeman, whose lab at the Walter and Eliza Hall Institute in Melbourne carried out the research.

Women who carry BRCA1 mutations are at a high risk of developing breast and ovarian cancers. Carriers of the faulty gene can choose to undergo surgical removal of their breast tissue and ovaries to reduce the likelihood of developing the disease but, apart from regular screening, no other preventative approaches are currently available.

'We were interested in finding an alternative option, a non-surgical approach for these women,' said Emma Nolan, first author on the study, which was published in Nature Medicine.

In breast tissue samples provided by women with a mutated BRCA1 gene, the team identified cancer precursor cells that had properties that were very similar to aggressive breast cancer cells.

'These cells proliferated rapidly, and were susceptible to damage of their DNA – both factors that help them transition towards cancer,' said Nolan.

Importantly, the team also found that these cells could be identified by the presence of a marker protein called RANK on their surface.

The protein, which plays a role in cell growth, is inhibited by denosumab, a drug currently used to treat osteoporosis and breast cancer that has spread to the bone. By inhibiting RANK in BRCA1-mutated breast tissue, the researchers found that development of breast cancer was significantly curtailed.

Subsequent experiments in mice with BRCA1 mutations also slowed the development of breast cancer tumours.

'We are very excited by these findings because it means we've found a strategy that might be useful to prevent breast cancer in very high-risk women,' said Professor Lindeman.

It is hoped that these lab-based findings will translate to clinical trials. Further research is also needed to investigate implications of the long-term use of denosumab, which is already known to have side effects.

'[Nonetheless] when weighted against the potential for delaying cancer progression in high risk women, it is a worthy area for future work,' said Dr Jason Carroll, a Cancer Research UK scientist not involved in the study.

Breast cancer cell growth halted by osteoporosis drug, study shows
The Guardian |  20 June 2016
'Holy grail' for women with Angelina Jolie breast cancer gene: Drug that prevents tumours from developing now a step closer
MailOnline |  20 June 2016
‘Holy grail' of breast cancer prevention in high-risk women may be in sight
Walter and Eliza Hall Institute of Medical Research (press release) |  21 June 2016
Lab study ‘sheds new light’ on BRCA-linked breast cancer
Cancer Research UK |  21 June 2016
RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers
Nature Medicine |  20 June 2016
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