Study: Is breast cancer risk increased in women who test negative for the BRCA mutation in their family?
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This study is about:
Whether women from mutation-positive families who test negative for their familial mutation are at higher risk of breast cancer than women in the general population.
Why is this study important?
If women who test negative for the mutation in their families are at higher risk than women in the general population, they may require different screening or prevention.
- Women who tested negative for their familial mutation were almost 5 times more likely to develop breast cancer than expected for an average-risk woman of the same age.
Women in this study who tested negative for may have been screened much more than women in the general population. Increased or could have resulted in more cancers being caught. Additionally, we have not identified and cannot always test for every gene that can affect cancer risk within families—abnormalities in other genes may influence risk in families with mutations. This study only looked at whether the women carried mutations; it did not consider whether they might have carried other genetic mutations that raise cancer risk. This is important, because if the BRCA-negative women who developed breast cancer carried mutations in other genes, their cancers could be attributed to those other mutations. Finally, this study was conducted through a cancer genetics clinic, a type of clinic that often sees families with very high cancer rates, which may have biased the results
What does this mean for me?
More research needs to be done to understand if women who do not carry the mutation found in their family are still at higher risk of breast cancer than women in the general population. Even if you don’t test positive for your family’s mutation, having a first-degree relative who has had breast cancer raises your risk for developing the disease compared to women in the general population. Patients from high-risk families should speak with a genetics expert before and after genetic testing to understand their risk for cancer and determine a screening program that is appropriate for them.
Evans GR, Ingham SL, Buchan I, et al. “Increased Rate of Phenocopies in All Age Groups in BRCA1/BRCA2 Mutation Kindred, but Increased Breast Cancer Risk Is Confined to Mutation Carriers.” Cancer Epidemiology, Biomarkers & Prevention. 2013 December; 22(12): 2269-2276.
Kurian AW, Gong GD, John EM, et al. “Breast cancer risk for noncarriers of family-specific and mutations: findings from the Breast Cancer Family Registry.” Journal of Clinical Oncology. 2011; 29:4505-4509.
IN DEPTH REVIEW OF RESEARCH
Researchers have noted the development of breast cancer in women who do not carry their family’s mutation. Researchers studied whether these women may have increased risk for breast cancer, even though they do not share their family’s abnormality.
In December 2013, Gareth Evans and his colleagues from the University of Manchester and other institutions published an article that examined whether women who tested negative for a familial mutation were at increased risk for breast cancer. Published over two years ago, the study raised a still controversial question regarding appropriate care for women who test negative for a mutation but are from a BRCA-positive family, as this is still an area of uncertainty.
Researchers of this study wanted to know:
Whether a woman with a negative test result may have increased risk of breast cancer if she is from a family that carries a mutation.
Population(s) looked at in the study:
This study included only first-degree relatives (parent or sibling) of mutation carriers in 809 families (428 families and 381 families).
- Women who tested negative for their familial mutation developed breast cancer about 4.5 times more than expected for women of their age. Within this population, 14 breast cancers developed at the follow-up time, rather than the 3 that were expected.
- This result was statistically significant, meaning that the result did not occur by chance, and was more likely to be a real finding.
- Women who tested negative for their familial mutation developed breast cancer about 1.8 times more than expected for women of their age. Within this population, 7 breast cancers developed at the follow-up time, rather than the 4 that were expected.
- This result was not statistically significant, meaning that it may have occurred by chance, and may not be a real finding.
Women in this study who tested negative for may have been screened much more than women in the general population. Increased or could have resulted in more cancers being caught. Additionally, we have not identified and cannot always test for every gene that can affect cancer risk within families—abnormalities in other genes may influence risk in families with mutations. This study only looked at whether the women carried mutations; it did not consider whether they might have carried other genetic mutations that raise cancer risk. This is important, because if the BRCA-negative women who developed breast cancer carried mutations in other genes, their cancers could be attributed to those other mutations. Finally, this study was conducted through a cancer genetics clinic, a type of clinic that often sees families with very high cancer rates, which may have biased the results.
The study authors wrote: “In the context of a family mutation, especially when there are multiple close relatives affected with early-onset breast cancer, specialists should advise that breast cancer risks may still be increased compared with the general population.” However, this is the result of only one study. Other work involving this issue has resulted in the exact opposite conclusion: that a woman with a BRCA-negative test result for her family mutation is not at higher risk for breast cancer. Currently, the NCCN has no clear guidelines regarding care for women in this population, and more work is needed to understand the cancer risk for women who do not carry their familial mutation. This underscores the importance of genetic counseling by a genetics expert to determine what screening is appropriate for each individual woman.
NCCN guidelines recommend genetic counseling and testing for people without cancer who have the following family history:
- A relative who has tested positive for an in a gene that increases cancer risk.
- One or more first- or second-degree relatives with breast cancer and any of the following:
- diagnosed at age 45 or younger
- two separate breast cancers, with the first diagnosis at age 50 or younger
- male breast cancer
- One or more first- or second-degree relatives with:
- colorectal cancer before age 50
- endometrial cancer before age 50
- ovarian, , primary peritoneal cancer
- rare or childhood cancers
- One or more first-degree relatives with:
- or high-grade cancer
- pancreatic cancer
- Two or more relatives on the same side of the family diagnosed with any combination of the following at any age:
- breast cancer
- pancreatic cancer
- adrenal cancer
- brain tumors
- endometrial cancer
- thyroid cancer
- kidney cancer
- diffuse gastric cancer
- colon cancer
- I do not carry my family’s mutation. What type of cancer screening should I have?
- I developed breast cancer even though I do not carry my family’s mutation. What is my daughter’s risk?
- Should I have additional genetic testing?
- Can you refer me to a genetic counselor?
- What are risk factors for breast cancer?
- How can I reduce my breast cancer risk?
Below are clinical trials that include genetic counseling and testing.
- NCT02665195: Registry Of MultiPlex Testing (PROMPT). PROMPT is an online research registry. The goal of PROMPT is to help researchers to better understand the risks that are linked to mutations in less well-studied genes.
- NCT02620852: WISDOM Study: Women Informed to Screen Depending on Measures of Risk offers women age 40-74 the opportunity to undergo risk assessment and genetic testing in order to determine the best breast screening options based on their situation.
- NCT04476654: Improving Uptake of Genetic Cancer Risk Assessment in African American Women-Video. This study looks at the usefulness of intervention with a culturally-tailored video to improve uptake of genetic counseling in Black women who are at increased risk of .
- NCT05694559: Connecting Black Families in Houston, Texas to Genetic Counseling, Genetic Testing, and Cascade Testing by Using a Simple Genetic Risk Screening Tool and Telegenetics. This study will provide genetic testing to 150 Black individuals and families and provide genetic counseling and risk reduction resources to individuals with a mutation linked to increased cancer risk.
Other genetic counseling or testing studies 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.
The following resources can help you locate a genetics expert near you or via telehealth.
Finding genetics experts
- The National Society of Genetic Counselor website has a search tool for finding a genetic counselor by specialty and location or via telehealth.
- InformedDNA is a network of board-certified genetic counselors providing this service by telephone. They can also help you find a qualified expert in your area for face-to-face genetic counseling if that is your preference.
- Gene-Screen is a third party genetic counseling group that can help educate, support and order testing for patients and their families.
- JScreen is a national program based out of Emory University that provides low-cost at-home genetic counseling and testing with financial assistance available.
- Grey Genetics provides access to genetic counselors who offer genetic counseling by telephone.
- The Genetic Support Foundation offers genetic counseling with board-certified genetic counselors.
- The American College of Medical Genetics website has a tool to find genetics clinics by location and specialty.
Other ways to find experts
- Register for the FORCE Message Boards and post on the Find a Specialist board to connect with other people who share your situation.
- The National Cancer Institute (NCI)-designated comprehensive cancer centers have genetic counselors who specialize in cancer.
- FORCE's toll-free helpline at: 866-288-RISK, ext. 704 will connect you with a volunteer board-certified genetic counselor who can help you find a genetics expert near you.
Who covered this study?
Medical News Today
BRCA-negative results may not reduce cancer risk This article rates 3.5 out of 5 stars
Why women who test negative for BRCA mutation may still face a higher breast cancer risk This article rates 3.5 out of 5 stars
Negative BRCA gene test doesn’t always mean lower breast cancer risk This article rates 3.5 out of 5 stars