Study: Early research on a drug to prevent breast cancer

IN DEPTH REVIEW OF RESEARCH

Study background:

BRCA1 mutation carriers are predisposed to developing breast cancer that is more aggressive and occurs earlier than breast cancer in the general population. Women with BRCA1 mutations are counseled to undergo one or more risk management strategies, such increased screening, which does not prevent cancer but can catch it at an earlier stage; risk-reducing medication; and/or risk-reducing surgeries.  While these strategies have helped many women reduce their risk of cancer, there is still a need for better nonsurgical means of cancer prevention in BRCA mutation carriers.

Researchers of this current study explored the use of a type of drug known as a RANK ligand inhibitor for breast cancer prevention in BRCA1 mutation carriers. Emma Nolan and her colleagues at the Walter and Eliza Hall Institute of Medical Research and other institutions published research in Nature Medicine that explores what happens when RANK ligand is inhibited.   

Researchers of this study wanted to know:

Can inhibiting RANK ligand be used as a method for breast cancer prevention in BRCA1 mutation carriers?

Population(s) looked at in the study:

This research used a number of different laboratory models of breast cancer.

• For some of the experiments, the researchers used breast tissue from 33 premenopausal women undergoing breast reduction surgery (used as the ‘wild type’ control) and 24 BRCA1 mutation carriers undergoing prophylactic mastectomies (Study Findings #3 and #4).
• They also used human breast tumors from the Amgen Tissue Bank cohort in one of their experiments (Study Findings #1 and 2).
• For the remainder of the experiments (Study Finding #5), researchers used mice that were genetically engineered to have no BRCA1 genes in their breast tissue (these mice have been shown to develop breast cancers that are similar to human breast cancer).  Note that differs from humans, who have one defective and one healthy BRCA1 gene.

Study findings: 

1. RANK ligand, the target of the drug in this study, is found in much higher levels in BRCA1-mutated tumors compared to tumors with normal BRCA1.
2. RANK ligand was not found in significantly higher levels in BRCA2-mutated breast tumors.
3. Breast tissue cells from BRCA1 patients that had the RANK ligand formed tumors more easily in the laboratory than cells from the same BRCA1 patients that did not have the RANK ligand.
4. BRCA1-mutated cells that had the RANK ligand were more sensitive to DNA damage than BRCA1-mutated cells that did not have the RANK ligand.
5. Mice that were genetically engineered to have no BRCA1 genes and were given the RANK ligand inhibiting drug developed fewer breast tumors compared to the control mice, which were also BRCA1 mutated but were not given the inhibitor.
   • 11 of 17 mice given the RANK ligand inhibitor did not develop tumors by the researchers’ chosen end date for the experiment.

Limitations:

While the results are interesting, this is primarily a mouse study with some data in human cells to back it up. More work needs to be done to translate these findings to the clinic, particularly clinical trials to show that the drug is safe for long-term use and effective in preventing breast cancer. Additionally, the mice used in the experiment with the RANK ligand inhibitor were genetically engineered to have no BRCA1 genes. This is different than humans with BRCA1 mutations, who start off with one good copy of BRCA1 (out of the two that they inherited from their parents).  

Conclusions:

The results of this study suggest that inhibiting RANK ligand may help prevent breast cancer in mice with BRCA1 mutations. More work needs to be done before this can be used as a breast cancer prevention therapy in BRCA1 mutation carriers.  FORCE agrees with the Health News Review critique that media reports using the term “holy grail” to describe this early study were misleading. However, this is still an important first step towards developing a new option for BRCA1 mutations carriers who wish to delay or avoid risk-reducing surgery.  

For now, women who are interested in new risk-reducing measures that do not involve surgery should talk to their heath care provider about participating in clinical trials for breast cancer prevention in high-risk women or use our hereditary cancer research database to find clinical research studies that are enrolling people affected by hereditary cancer.

Posted 7/12/15

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