This news release covers new published research around the use of a drug — denosumab — as a preventative treatment for those women who might have a genetic disposition to a certain type of breast cancer, those who carry the BRCA1 or BRCA2 mutations. While this multinational research news release presents the discovery as hopeful and exciting, the leap from rodent studies to humans is likely long, tenuous and far from certain. The news release treats the benefits and evidence found in the research somewhat vaguely, but over-reaches in describing the potential application of denosumab in preventing breast cancer. The release also claims that denosumab would be the first drug for preventing breast cancer, but Tamoxifen and raloxifene have already been approved for reducing breast cancer risk.
The main contribution of this research is the role of a previously approved drug, denosumab in treating patients with a gene mutation that increases the likelihood of breast cancer. The research advances our knowledge of the breast cancer proteins RANKL and its receptor RANK, yet it bears to be seen how this mice-related research is going to apply to humans down the road. It is a little irresponsible to title a news release that “prevention of breast cancer is within reach” when the genetic anomaly that increases a woman’s risk of breast cancer is so rare in the population. The risk of a news release like this is that many women, fearful of breast cancer, may seek genetic testing and be subject to all its downstream consequences (dealing with false positives, the psychological impact and the stress and anxiety caused by the tests themselves).
It needs to be emphasized that mutations in the genes BRCA1 and BRCA2 are rare and are linked to a very small fraction of all breast cancer. In the U.S., between one in 400 and one in 800 people in the general population have a BRCA1/2 mutation.
The cost of the treatment in question, denosumab, (trade name: Prolia) is not mentioned.
While the release states that the cell cultures receiving the RANKL blockade treatment had “significant reduction of growth and spreading of breast tissue cells” and “virtually no malignant changes in breast tissue” compared to those in the control group that developed multiple early breast cancer lesions. But no hard numbers or percentages are provided to quantify what a “significant reduction” is or what “virtually” means in this case.
We also want to underscore that the results were only seen in cell cultures and in mice, not in humans.
Denosumab — as well as carrying out genetic testing — comes with harms, none of which are mentioned in the release. Denosumab is described as “an antibody with very few side effects,” but this does not accord with the results of a online drug database which shows a lengthy side effects list, some of which are serious.
Denosumab was approved by the FDA for osteoporosis in postmenopausal women in 2010 and for giant cell tumor of the bone in 2013. It carries an increased risk of osteonecrosis (a painful condition caused by reduced blood flow to the bone which causes it to die) of the jaw and femoral hip fractures, increased infection susceptibility, and low calcium levels in the blood, among others. Women at risk might be expected to take such a drug for decades.
We’re not provided the parameters of the study, with the exception that it was a phase 2 and that there was a treatment group and a control group. There were useful disclaimers around the research presented here such as “careful phase III clinical trials are now needed to confirm the efficacy in humans.” However, the next sentence asserts: “thereafter, any woman who has been tested positive for a BRCA1 mutation could take RANKL blockade as prevention measure to reduce her dramatically increased breast cancer risk.” People reading this release may jump to the conclusion that it will dramatically reduce their chance of breast cancer, when that is simply extremely tentative at this moment.
The release doesn’t exaggerate (or sugar coat) the risk of breast cancer. And yet it does seem to “drug monger” a bit by pressing the idea that denosumab could be a preventive “for everyone” even though the research is clearly limited to mice and cell cultures with the BRAC1 or BRAC2 gene.
The release states that the research received funding from the U.S. Department of Defense but it doesn’t provide other important information that adds transparency. According to the published study, the Institute of Molecular Bioltechnology has applied for a patent on using RANKL inhibition to block breast cancer and that Amgen, Inc. (the maker of denosumab) provided RANK-Fc and financial support for the study.
The release mentions prophylactic surgery as the only current method for reducing breast cancer risk. It doesn’t compare denosumab to mastectomy nor to bisphosphonates, which are other drugs that interfere with RANKL proteins and RANK receptors.
Denosumab has been on the U.S. market as an approved treatment for certain types of osteoporosis since 2010 and tumors since 2013 but it is not approved as a preventative breast cancer treatment. The release may be misleading readers by suggesting it is “already approved.” The completion of safety and efficacy trials in humans are years down the road. The release doesn’t even say that advanced trials are planned, only that they’re “needed.”
The release claims that the research led to the discovery that RANKL is the main driver BRCA1 mutation-driven breast cancer. A second claim is that an already approved drug could be “the first breast cancer prevention drug.” However, that’s misleading since Tamoxifen and raloxifene are FDA-approved drugs for reducing the risk of breast cancer.
The release appears overly optimistic throughout considering the research has not yet been performed in humans. Statements like those below may give false hopes to women or encourage them to undergo additional genetic screening when the drug isn’t even tested or approved for use in breast cancer prevention.
In addition, the mention of the actress Angelina Jolie seemed inappropriate, considering that this celebrity had a very rare genetic condition that led her to take drastic measures in undergoing prophylactic mastectomies. This reference is more likely to confused than inform the reader.