Study: Early research on a drug to prevent breast cancer
|At a glance||Questions to ask your doctor|
This study is about:
Whether inhibiting a potential new target (RANK ligand) can help prevent breast cancer in mutation carriers.
Why is this study important?
Women who carry a mutation have an approximately 65% risk of developing breast cancer by the time they are 70 years old, and they often develop more aggressive tumors at an earlier age than women who do not have mutations. To lower their breast cancer risk, carriers can opt to undergo prophylactic mastectomy or take risk-reducing medications such as tamoxifen or raloxifene. However, no current medication reduces breast cancer risk as much as surgery.
- Mice that were genetically engineered to have no genes and were given a drug known as a RANK ligand inhibitor developed fewer breast tumors compared to mice that were not given the drug.
What does this mean for me?
This interesting early work suggests drugs that inhibit RANK ligand might prevent breast cancer in carriers. However, more work needs to be done before inhibiting RANK ligand becomes an established method of prevention—drugs that work well in mice don’t necessarily work well for humans. Mice can be used to model a human disease, but differences between the species means that drugs that work in one do not always work in the other.
Some media outlets called the RANK ligand inhibitor drug the ‘holy grail’ of breast cancer prevention for mutation carriers. But these headlines are misleading and inaccurate because this study was only done in mice and cells grown in the lab. Clinical trials need to determine whether this drug works for humans. mutation carriers should talk to their health care providers to determine which method of breast cancer risk reduction they are most comfortable with.
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Nolan E, Vaillant F, Branstetter D, et al. “RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers.” Nature Medicine. Published online first on June 20, 2016.
Health News Review. “It’s never OK to use ‘holy grail of breast cancer prevention’ when talking about pre-clinical animal study.”
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This article is relevant for:
Women with a BRCA1 mutation
This article is also relevant for:
people with a genetic mutation linked to cancer risk
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IN DEPTH REVIEW OF RESEARCH
mutation carriers are predisposed to developing breast cancer that is more aggressive and occurs earlier than breast cancer in the general population. Women with 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 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 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 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 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 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 gene.
- 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 .
- RANK ligand was not found in significantly higher levels in BRCA2-mutated breast tumors.
- Breast tissue cells from patients that had the RANK ligand formed tumors more easily in the laboratory than cells from the same patients that did not have the RANK ligand.
- BRCA1-mutated cells that had the RANK ligand were more sensitive to damage than BRCA1-mutated cells that did not have the RANK ligand.
- Mice that were genetically engineered to have no genes and were given the RANK ligand inhibiting drug developed fewer breast tumors compared to the control mice, which were also 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.
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 genes. This is different than humans with mutations, who start off with one good copy of (out of the two that they inherited from their parents).
The results of this study suggest that inhibiting RANK ligand may help prevent breast cancer in mice with mutations. More work needs to be done before this can be used as a breast cancer prevention therapy in 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 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 research database to find clinical research studies that are enrolling people affected by .
Share your thoughts on this XRAY review by taking our brief survey.
The National Comprehensive Cancer Network (NCCN) provides breast cancer risk management guidelines for people with and mutations. We recommend that you speak with a genetics expert who can look at your personal and family history of cancer and can help you to determine the best risk management plan. Note that when we use "men" and "women" we are referring to the sex you were assigned at birth.
Screening for women:
- Beginning at age 18, be aware of how your breasts normally look and feel. Tell your doctor about any breast changes.
- Beginning at age 25, have a doctor examine your breasts every 6-12 months.
- Beginning at age 25, have an annual breast with contrast (or if is unavailable).
- Beginning at age 30 until age 75, have an annual and an annual breast with contrast.
- After age 75, speak with your doctor about the benefits and risks of screening.
Risk reduction for women:
- Speak with your doctor about of the advantages and disadvantages of risk-reducing mastectomy.
- Research has shown that risk-reducing mastectomy can lower the risk for breast cancer in high risk women by about 90%. Despite this, mastectomy has not been shown to help high risk women live longer.
- Even after mastectomies, some breast tissue-and therefore some breast cancer risk remains.
- Speak with your doctor about the benefits and risks of tamoxifen or other estrogen-blocking drugs to reduce breast cancer risk. The benefits and risks may be different for women with vs. mutations. Research on the benefit of these drugs to reduce breast cancer risk in women with mutations has been mixed.
Risk management in men:
- Beginning at age 35, learn how to do breast self-exams to check for breast changes.
- Beginning at age 35, have a doctor examine your breasts every 12 months.
- Beginning at age 50, consider annual (especially for men with mutations).
- I am a mutation carrier. What can I do to lower my breast cancer risk?
- I am a mutation carrier who has not had cancer. Are there clinical trials looking at new ways to prevent cancer, and do I qualify for them?
- Are there currently drugs available to lower the risk of breast cancer in mutation carriers?
The following are breast cancer screening or prevention studies enrolling people at high risk for breast cancer.
- NCT04711109: Denosumab for Preventing Breast Cancer in Women with a Inherited Mutation (BRCA-P). This study will test the effectiveness of a drug (denosumab) on preventing the development of breast cancer in women with an inherited mutation.
- NCT04067726: Denosumab and Mammographic Density in Premenopausal Women With Dense Breasts (TRIDENT). This study is looking at the drug denosumab to learn if it can reduce breast density in high-risk premenopausal women who have dense breasts.
- The Risk Factor Analysis of Hereditary Breast and Ovarian Cancer In Women with , or Mutations. This study seeks to improve researchers’ understanding of how hormonal, reproductive and lifestyle factors may be associated with cancer in high-risk people.
- NCT02620852: Women Informed to Screen Depending on Measures of Risk (WISDOM) study. The goal of this study is to determine if breast cancer screening can be made better by personalizing each woman’s schedule, compared to the current one-size-fits-all, annual approach.
Additional risk-management clinical trials for people at high risk for breast cancer may be found here.
FORCE offers many peer support programs for people with inherited mutations.
- Our Message Boards allow people to connect with others who share their situation. Once registered, you can post on the Diagnosed With Cancer board to connect with other people who have been diagnosed.
- Our Peer Navigation Program will match you with a volunteer who shares your mutation and situation.
- Our moderated, private Facebook group allows you to connect with other community members 24/7.
- Check out our virtual and in-person support meeting calendar.
- Join one of our Zoom community group meetings.
Who covered this study?
Cancer Research UK
Lab study ‘sheds new light’ on BRCA-linked breast cancer This article rates 4.0 out of 5 stars
Medical News Today
Breast cancer: Existing drug shows promise for prevention in high-risk women This article rates 3.5 out of 5 stars
Unlikely drug may block breast cancer in high-risk women This article rates 3.5 out of 5 stars
Breast cancer treatment 'holy grail' within reach after breakthrough, scientists claim This article rates 2.5 out of 5 stars