The drug denosumab, which blocks a bone gene, may also prevent breast cancer caused by a BRCA1 mutation. This already approved drug could be available quickly, and would be the first drug for breast cancer prevention.1
For women with a mutated BRCA1 gene, the lifetime risk for breast cancer is up to 87%, and the tumors usually develop early in life. Currently, prophylactic surgery is the only option to significantly reduce this risk, but it has postoperative complications.
In prior research, this team demonstrated that sex hormones can trigger breast cancer through the protein RANKL and its receptor RANK. In addition to being key factors in bone metabolism, RANKL and RANK link sex hormones to breast cells by providing signals that tell breast cells to grow, such as during pregnancy and the menstrual cycle. If deregulated, mammary cells start to divide and multiply and fail to die when they should, ultimately resulting in breast cancer.
The international research team, led by Austrian Institute of Molecular Biotechnology (IMBA), Vienna, Austria, and the University of Maryland School of Medicine, Baltimore, Maryland, made the discovery that RANKL is also the main driver of BRCA1 mutation-driven breast cancer. They demonstrated the ability to reduce growth and metastasis of breast tissue cells and in mice by inhibiting RANKL.
“Our finding is so exciting because there is already an approved drug against RANKL called denosumab. It is an antibody with very few side effects, which binds tightly to RANKL, thereby inhibiting its ability to act. Based on our discovery, the already approved drug denosumab or other future drugs that will block RANKL/RANK, could be used for breast cancer prevention in BRCA mutation carriers,” explained Verena Sigl, a graduate student at IMBA.
The next step is phase 3 clinical trials to confirm the efficacy of denosumab in humans. Then, if clinical trial data supports the risk reduction, any woman who carries the BRCA1 mutation could take RANKL blockade as a preventive measure to address her dramatically increased breast cancer risk.
1. Sigl V, Owusu-Boaitey K, Joshi PA, et al. RANKL/RANK control BRCA1 mutation-driven mammary tumors [published online May 31, 2016]. Cell Res. doi:10.1038/cr.2016.69.