SCIENCE: New potential breast cancer prevention drug for BRCA1 mutation carriers

Published 29 Jun 2016

Research has recently been published that points the way to a new therapy for use in the prevention of breast cancer amongst women who carry a faulty BRAC1 gene. These women have a particularly high risk of developing breast cancer. The faulty gene is rare - it is present in less than 0.1% of the UK female population (1).

Published in Nature Medicine last week (2), a paper by Australian scientists from the Walter and Eliza Hall Institute of Medical Research and the University of Melbourne shows that it is possible to identify pre-cancerous cells in BRAC1 mutation carriers, due to the presence of a characteristic protein on the cell surface. The protein is known as RANK. RANK is a regulator of cell growth in breast tissue and it has recently been shown that the RANK pathway plays a significant role in primary breast cancer development, especially in triple negative breast cancers (3). Triple negative cancers are often aggressive and difficult to treat. They are common in BRAC1 mutation carriers, but less common in the general population.

Laboratory tests demonstrated that the drug denosumab, currently approved for use in the treatment of osteoporosis and bone cancer, was successful in slowing, and even preventing mammary tumour growth.

A small pilot study involving three pre-menopausal women who are BRAC1 mutation carriers has shown that breast cell proliferation was reduced following treatment with denosumab.

If results are confirmed in human trials, this treatment offers women who carry the BRAC1 gene a strategy for dealing with the possible consequences of their genetic makeup, and an alternative to radical surgery, which can have profound psychological effects, as well as effects on future child-bearing. Any therapy that could reliably delay the onset of the disease would at the very least allow planning for the future.

However, the risk of getting breast cancer by age 50 for women carrying a BRCA mutation is estimated to be around 3 times higher for those women born after the 1940’s, compared to those born earlier (4, 5). Therefore, whilst this research offers hope to women who are at particular risk, we should not shy away from the need to find out why more women with this genetic mutation go on to develop the disease than they did previously. The hike in incidence rates amongst this specific cohort suggests that there is something in our modern environments or lifestyles that may be triggering the disease.

Breast Cancer UK has called for more research funding into all types of cancer prevention (see here).

1. Anglia Breast Study Group (2002). Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases. British Journal of Cancer 83(10): 1301–1308. http://www.ncbi.nlm.nih.gov/pubmed/11044354
2. Emma N. et al. (2016). RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers. Nature Medicine 2016. doi:10.1038/nm.4118. http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.4118.htm
3. Kiesel L. and Kohl A. (2016). Role of the RANK/RANKL pathway in breast cancer. Maturitas 86: 10–16. http://www.maturitas.org/article/S0378-5122(16)30001-9/abstract
4. King et al. (2003). Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 302(5645):643-646. http://www.ncbi.nlm.nih.gov/pubmed/14576434
5. Antoniou A. et al. (2003). Average Risks of Breast and Ovarian Cancer Associated with BRCA1 or BRCA2 Mutations Detected in Case Series Unselected for Family History: A Combined Analysis of 22 Studies. American Journal of Human Genetics 72: 1117–1130. http://www.ncbi.nlm.nih.gov/pubmed/12677558

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