Women born with a mutation of the BRCA gene have as much as an 87% lifetime risk of breast cancer. Unfortunately, they also have a significantly increased risk of ovarian and colorectal cancer. At the present time, there are only a few preventive strategies available to women afflicted with a BRCA mutation: remove both breasts and both ovaries as soon as possible, consider long-term anti-hormonal therapy, or undergo a mammogram and breast MRI every year beginning in young adulthood in the hope of finding the seemingly inevitable breast cancer at an early enough stage to render the patient curable – a chance not many women care to take. Nothing on that menu looks appealing, does it?
Scientists may have found a breathtakingly easier, less punitive remedy: A drug that has already been approved by the FDA, “Denosumab”, blocks RANKL, a protein that has been found to drive the BRCA-mutated cells toward cancer. Blocking RANKL – which uses the patient’s own estrogen to light a fire on the mutated logs of the BRCA mutation – sets up an effective barricade against BRCA mutation-driven breast cancer. It’s as if denosumab commands the cells that carry the BRCA mutation, “Don’t cross this line!”
Denosumab has already been approved by the FDA for use in other patients, and it has been used safely and effectively for several years. Happily, it does not appear to be associated with a preponderance of undesirable side effects.
Tests of denosumab in mice programmed with the BRCA mutation have already been carried out at the University of Maryland, The results were astonishing! None of the mice that received the RANKL-blocking denosumab developed breast tumors, even after a long period of followup. On the other hand, the mice that were not given denosumab developed multiple early breast cancers – just as we see occur in women who carry the BRCA mutations.
Clinical studies of denosumab in women with BRCA mutations are obviously the next step. But this ought to proceed quickly because denosumab has already been approved by the FDA for use in humans.
The door has been opened. Let’s make sure it stays wide open. And let’s insist that sufficient money and attention be given to this potentially life-saving, breast-saving, breakthrough.
Reference: S Owusu-Boaitey, “RANKL/RANK control Brca1 mutation-driven mammary tumors”, Cell Research, May 2016