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Study: Is breast cancer risk increased in women who test negative for the BRCA mutation in their family?

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Contents

At a glance In-depth
Findings     Limitations               
Questions for your doctor Resources


STUDY AT A GLANCE

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.  

Study findings: 

  1. 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.

Limitations:

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.

Posted 4/19/16

References

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.

This article is relevant for:

Women from a family with a known BRCA mutation who tested negative for the mutation in the family

This article is also relevant for:

Women under 45

Women over 45

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IN DEPTH REVIEW OF RESEARCH

Study background:

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).

Study findings: 

  1. 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.
  2. 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. 

Limitations:

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.

Conclusions:

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.

Expert Guidelines
Expert Guidelines

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 inherited mutation 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
    • cancer
    • melanoma
    • sarcoma
    • adrenal cancer
    • brain tumors
    • leukemia
    • endometrial cancer
    • thyroid cancer
    • kidney cancer
    • diffuse gastric cancer
    • colon cancer

Updated: 12/04/2021

Questions To Ask Your Doctor
Questions To Ask Your Doctor

  • 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?

Open Clinical Trials
Open Clinical Trials

Below are clinical trials that include genetic counseling and testing.

Other genetic counseling or testing studies may be found here.

 

Updated: 12/05/2021

Peer Support
Peer Support

FORCE offers many peer support programs for people with inherited mutations. 

Updated: 08/06/2022

Find Experts
Find Experts

Health care providers who are specially trained in genetics can help you more clearly understand your risk for . The following resources can help you locate a genetics expert in your area.

  • The National Society of Genetic Counselor website offers a searchable directory for finding a genetic counselor by state and specialty. To find a genetic counselor who specializes in cancer genetics, choose "cancer" under the options "Area of Practice/Specialization." 
  • 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. 
  • 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. 
  • FORCE's toll-free helpline at: 866-288-RISK, ext. 704 will connect you with a volunteer board-certified genetic counselor who can answer general questions about genetic testing and cancer and help you find a genetics expert near you. 
  • FORCE Peer Navigator Program will match you with a volunteer who has undergone genetic counseling and can help you navigate resources to find a genetic counselor near you.
  • Ask your doctor for a referral to a genetics expert. 

Updated: 03/16/2022

Who covered this study?

Medical News Today

BRCA-negative results may not reduce cancer risk This article rates 3.5 out of 5 stars

Fox News

Negative BRCA gene test doesn’t always mean lower breast cancer risk This article rates 3.5 out of 5 stars

EmaxHealth

Negative BRCA test not reliable for lower chance of breast cancer This article rates 2.5 out of 5 stars

How we rated the media

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