What is the main purpose of the BRCA-P Study?
We aim to find out whether denosumab, compared to a placebo,  can decrease the risk of developing breast cancer in women with a BRCA1 gene mutation.

Why is the study important?
The BRCA-P Study is testing a possible new way to reduce the risk of breast cancer in women with BRCA1 mutations. Currently, removal of both breasts by surgery (mastectomy) is the only effective way to reduce the risk of breast cancer in women with a BRCA1 mutation. Such a surgery can have physical and emotional impacts. If successful, our study can give future generations a new option to reduce breast cancer risk without surgery.

How does the study work?
BRCA-P is a double-blind, randomized, two-arm study to evaluate the effects of denosumab on breast cancer.

  • Double-blind means neither you nor your doctor will know or decide in which group you will be placed.
  • Randomized, two-arm means that if you decide to take part in this study, you will be randomly assigned (like a flip of a coin) to one of two groups (“arms”): a denosumab group or a placebo group. You will have a 50/50 chance of receiving the study medication (denosumab).
    • Denosumab is approved by the FDA to treat bone loss in people who are at risk for bone fractures and for cancer patients whose cancer has spread to their bones.
    • A placebo is an inactive substance (saltwater solution) given in the same form (injection) as the study medication, denosumab.

Who is conducting the study?
The BRCA-P Study is conducted in the United States by the Alliance for Clinical Trials in Oncology, a national clinical research group supported by the National Cancer Institute (NCI). In the United States, the trial is co-led by a national breast cancer and cancer genetics expert, Dr. Judy Garber  from Dana Farber Cancer Institute and Dr. Judith Hopkins from the Alliance. The global coordinator of this study is the Austrian Breast & Colorectal Cancer Study Group (ABCSG). 

Who is funding the BRCA-P Study?
This study is funded by the Department of Defense and is supported by the National Cancer Institute. The medication that the study is researching is provided by the company that makes it, Amgen Global, which also provides the placebo for the study. The Breast Cancer Research Foundation and the Gray Foundation are supporting the trial monitoring in the US.

How can I participate in the BRCA-P Study?
You can participate in the following ways:

  • Join the study by contacting the study site nearest to you. You may be eligible to participate in the BRCA-P Study if you:
    • Have a confirmed BRCA1 gene mutation (variant)
    • Are 25 to 55 years old
    • Do NOT have a history of breast or ovarian cancer
    • Are not pregnant or breastfeeding
    • Have not had a mastectomy (removal of both breasts by surgery)

What is expected of me if I join the study?
If you are eligible and decide to join the BRCA-P Study, you will be asked to:

  • Have blood drawn annually for testing and research (up to 4 tablespoons)
  • Have a small injection of denosumab or a placebo (inactive substance) under the skin every 6 months for 5 years
  • Submit your mammogram when you enroll and after your first and second years in the study for the study team to evaluate your breast density
  • Have regular follow-ups with your study doctor/medical team to check on your overall health and talk about any symptoms or side effects
  • Have a dental exam to make sure you don’t have any infections in your mouth (denosumab can cause some dental side effects). If dental concerns are found, you may be asked to visit your dentist before enrolling in the study
  • Follow up with your study doctor yearly for up to 5 years after you finish the study
  • Take calcium and vitamin D supplements daily for 5 years

Note: We highly recommend undergoing a dental exam before you join the study and take Calcium and Vitamin D supplements while you are on the study. The study does not cover the costs of dental care and supplements. Please speak to your doctor if this presents an unusual hardship to you.

You may also be asked to consider:

  • Joining optional quality-of-life sub-studies to help researchers learn more about your symptoms and your physical, mental, and social well-being. These sub-studies are optional, but choosing to join 1 or more sub-studies, as well as the main study will help researchers to learn even more about what it’s like to take denosumab and to choose medication instead of surgery to reduce breast cancer risk.
  • Optional scans and tests that will help researchers for future studies

Where is the BRCA-P Study being conducted?
This is an international study being conducted at more than 30 sites across the United States. To find out if there is a site near you that is open for enrollment, visit our study sites page.

Are there any risks to participating in the BRCA-P Study?
There is a risk that denosumab may not be as good as the usual approach for preventing breast cancer (risk-reducing mastectomies). There is also a risk that you could have negative side effects from denosumab. Common side effects include muscle and bone pain, shortness of breath, and low levels of phosphate in the blood. If you decide to participate in our study, your study doctor will carefully evaluate if denosumab is right for you. Your study doctor will also follow the effects of denosumab on your health and will work with you to prevent and manage any side effects.

Please note that participation in this study is voluntary. You can choose to leave the study at any time.

Why can’t men participate?
Men with a BRCA1 mutation have a 4 to 6% lifetime risk of developing breast cancer compared to women with a BRCA1 mutation who have a 50 to 70% lifetime risk of developing breast cancer. To see any benefit of denosumab in men with a BRCA1 mutation, we would have to enroll thousands of men in this study, which is not feasible. Also, we have limited safety data for the impact of denosumab on men.

Why is the BRCA-P Study only for women with a BRCA1 gene mutation?
We have excellent data from research studies done in the laboratory and some limited data in women with BRCA1 mutations that a medication blocking RANK Ligand reduces breast cancer risk. However, we need a large study, like BRCA-P Study, to prove that denosumab will help reduce the risk of breast cancer in women with a BRCA1 gene mutation. So far, in the laboratory, other genes, including BRCA2, do not show the same possible cancer risk-reducing effects from denosumab.

Why is there an age limit on this study?
The BRCA-P Study is enrolling younger women because laboratory research has shown that denosumab is most effective in younger women who have not yet gone through menopause.

What are my choices if I decide not to take part in this study?
You may choose to have the usual approach described below, under “What is the usual approach to reduce the risk or prevent breast or ovarian cancer in a woman with a BRCA1 mutation?” You may choose to take part in a different research study, if one is available.

Can I leave the study after I have joined?
Yes, participation is always optional. You can leave the BRCA-P Study at any time. Please contact us if you want to leave the study so we can make sure to address any concerns you may have. Also, sometimes women who have been taking the study medication denosumab will need to take an additional medication at the end of the study for extra bone protection.  

Where can I get more information?
You may visit the NCI website for more information about studies or general information about cancer. You may also call the NCI Cancer Information Service to get the same information at: 800-4-CANCER (800-422-6237).

A description of this clinical trial is available on www.ClinicalTrials.gov (NCT04711109), as required by U.S. law. You can search the website for more information or contact a site  near you. You can also contact our BRCA-P Study team at brcapstudy@dfci.harvard.edu.

What is genetic testing and how can I learn more about it?
Genetic testing is a process that looks for alterations (changes) in a person’s genes. Alterations in certain genes may lead to an increased risk of cancer. Therefore, genetic testing results may be helpful in tailoring cancer screening recommendations. Genetic testing involves sending a blood sample to a specialized lab for analysis. Results are returned to the ordering physician and genetic counselor, who then disclose them to the patient and arrange appropriate follow-up care. You can learn more about it by visiting the Dana-Farber website or the NCI website.

What is a BRCA1 gene, and what is its role?
Each cell in our body contains about 22,000 genes. Genes are made of DNA, are mostly in pairs (2 copies of each), and contain instructions that tell cells how to behave. One of these genes is called BRCA1, which is an important part of the system our cells use to fix errors in their DNA.  In women who are born with a change in 1 of their 2 copies of the BRCA1 gene, only 1 of the genes is working, but that is enough to keep breast, ovary, and pancreas (and in men, prostate) cells behaving normally. If something happens to the remaining copy, then the cell has no working BRCA1. The cell can then begin to collect errors in the DNA. Some cells will self-destruct, but others will become cancer cells. Because BRCA1 is so important in keeping normal cells healthy, it is called a tumor suppressor gene.

How did I get a BRCA1 mutation? And what about my children?
If one of your parents had a BRCA1 mutation, there is a 50% chance that you may inherit a non-working (mutated) BRCA1 gene from them. And, if you have a BRCA1 mutation, there is a 50% chance that you may pass this down to each of your children. Having a BRCA1 mutation significantly increases your chance of developing breast cancer compared to the general public.

What is the link between BRCA1 and tiple negative breast cancer?
Research shows that women with BRCA1 mutations have a much higher chance of developing triple negative breast cancer, an aggressive form of breast cancer that is difficult to treat and does not respond to many standard medications like tamoxifen. Triple negative breast cancer is most commonly found in young, Black, and Hispanic women.

What are the options to reduce breast cancer risk?
Currently, removal of both breasts by surgery (mastectomy) is the only effective way to reduce the risk of breast cancer in women with a BRCA1 mutation. Such a surgery can have physical and emotional impacts. If successful, our study can give future generations a new option to reduce breast cancer risk without surgery. We can only make this possible with the participation of eligible women. Learn more about study eligibility, and please consider joining us if you are eligible to do so.

What is the usual approach to reduce the risk or prevent breast or ovarian cancer in a woman with a BRCA1 mutation?
The usual approach for women who are not in a research study is to be followed closely by their doctor to watch for the development of breast cancer. Most recommendations include having a breast MRI annually and mammograms annually, about 6 months apart from the breast MRI. While this approach does not actually reduce the risk of occurrence, it can help doctors detect breast cancer in an early stage, so that it can be treated successfully.

If successful, the BRCA-P Study can give future generations a new option to reduce breast cancer risk without surgery.

What is a risk-reducing surgery?
A risk-reducing surgery lowers the chances of getting breast cancer. The most common such surgery is called bilateral risk-reducing mastectomy, which involves complete removal of both breasts. The other kind of risk-reducing surgery is bilateral prophylactic salpingo-oophorectomy, which involves removal of the ovaries and fallopian tubes. Such a surgery can have physical and emotional impacts. You can speak with a study doctor about the risks and benefits of these options. Learn more about these surgeries.

What organizations are available to support BRCA1 mutation carriers and their families?
You can find reliable information on BRCA1 genes and hereditary breast cancer on several websites, including:

Dana-Farber Cancer Institute

866-288-RISK (7475)