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Study: New cancer risk estimates for BRCA1/2 mutation carriers

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This study is about:

Estimating age-specific risk of breast, ovarian and (breast cancer in the other breast of patients who are already diagnosed with breast cancer) for mutation carriers.

Why is this study important?

Accurate cancer risk estimates are especially important for mutation carriers, because they impact patient medical decision-making. With more accurate cancer risk estimates, health care providers can better advise mutation carriers on when to begin cancer screening or consider risk reduction options.

Previously, most studies that estimated cancer risk for mutation carriers were —they developed estimates by looking back at patients who already had cancer. This new study is important because it included a large number of women and is , meaning that it followed mutation carriers who did not have cancer forward over time. While studies take a very long time, they can provide better risk estimates for use in patient decision-making.

Study findings:

  • Among the 9,856 women who had a mutation:
    • The lifetime breast cancer risk to age 80 was 72% for and 69% for .
    • The lifetime ovarian cancer risk to age 80 was 44% for and 17% for .
    • The lifetime risk of 20 years after a breast cancer diagnosis was 40% for and 26% for .
    • Cancer risks were different depending on family history and where a mutation was located in the or gene.

What does this mean for me?

This study may provide more accurate risk estimates for breast, ovarian and for BRCA1/2 mutation carriers than previous studies. Because cancer risk estimates are used to help guide the timing of important decisions, these new estimates may change when mutation carriers consider screening and risk reduction options.  This study suggests that cancer risk estimates should be more personalized, and that they can be more precise with consideration of an individual’s unique family cancer history and where the mutation is located in the gene. Together, these results emphasize the importance of genetic counseling for mutation carriers.

Posted 7/28/17

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Kuchenbaecker KB, Hopper JL, Barnes DL, et al. “Risks of Breast, Ovarian, and for  and  Mutation Carriers.” Journal of the American Medical Association. 2017;317(23):2402-16. doi:10.1001/jama.2017.7112.


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This article is relevant for:

Women with an inherited mutation in BRCA1 or BRCA2

This article is also relevant for:


people with triple negative breast cancer

people with ER/PR + cancer

people with Her2-positive cancer

people with a genetic mutation linked to cancer risk

people with breast cancer

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Study background:

For mutation carriers, accurate, age-specific cancer risk estimates are important because they affect medical decisions and their timing. Virtually all previous cancer risk estimates for mutation carriers have been based on studies. These studies reported breast cancer risk estimates ranging from 40% to 87% for mutation carriers and from 27% to 84% for mutation carriers.

Previous ovarian cancer risk estimates ranged from 16% to 68% for mutation carriers and from 11% to 30% for mutation carriers. The wide range of estimates was likely due to the way the different studies were designed: how families were selected, different characteristics of individual families, how the data were analyzed, and other genetic and lifestyle factors. 

studies are less likely to produce accurate cancer risk estimates, particularly if an analysis is not adjusted for these factors. On the other hand, studies in which participants are recruited based on their mutation status and are followed over a long period of time can avoid the limitations associated with studies. Thus, studies are thought to provide more accurate cancer risk estimates.

For studies, the accuracy of cancer risk estimates depends on both the number of people followed and length of follow-up. The more people followed for substantial periods of time, the more accurate the cancer risk estimates. This study was conducted by Karoline Kuchenbaecker, PhD, of the Centre for Cancer Genetic Epidemiology at the University of Cambridge, England and colleagues.

Researchers of this study wanted to:

  • Use data from a large study to estimate age-specific risks of breast, ovarian, and .
  • Determine how a family’s cancer history and location of the or 2 mutation in the gene modified an individual’s cancer risk.

Population(s) looked at in the study:

This study only included women with a known mutations. Women were recruited to participate in this study through several registries: the International BRCA1/2 Carrier Cohort Study (IBCCS), the Breast Cancer Family Registry (BCRF), and the Kathleen Cunningham Foundation Consortium for Research into Familial Breast Cancer (kConFab). The 9,856 study participants were from Europe, Australia, New Zealand, Canada, and the United States. Follow up for all participants was approximately 15 years.

  • The breast cancer risk analysis included 3,886 participants (39% of participants). Women were excluded if they were previously diagnosed with breast, ovarian, or other cancer before joining the study; had a risk-reducing mastectomy; or did not participate in scheduled follow-ups. 
  • The ovarian cancer risk analysis included 5,066 participants (51%). Women were excluded if they were previously diagnosed with ovarian or other cancer, had a risk-reducing salpingo-oophorectomy, or did not participate in scheduled follow-ups. 
  • The contralateral cancer risk analysis included 2,213 participants (22%) Women were excluded if they were previously diagnosed with , ovarian cancer, or other cancer; or did not have a first breast cancer diagnosis at the end of the follow-up period. They were also excluded if they had risk-reducing mastectomy or did not participate in scheduled follow-ups.

Study findings: 

  • Of the 3,886 women eligible for the breast cancer risk analysis, 426 were diagnosed with breast cancer during follow-up.
    • Lifetime breast cancer risk estimates to age 80 were:
      • 72% for  mutation carriers
      • 69% for mutation carriers
    • Breast cancer diagnoses increased rapidly in early adulthood until ages 30-40 for mutation carriers and until ages 40-50 for mutation carriers. The number of breast cancer diagnoses then remained constant.
  • Of the 5,066 women eligible for the ovarian cancer risk analysis, 109 were diagnosed with ovarian cancer during follow-up.
    • Lifetime ovarian cancer risk estimates to age 80 were:
      • 44% for mutation carriers
      • 17% for mutation carriers
  • Of the 2,213 women eligible for risk analysis, 245 were diagnosed with during follow-up.
    • Lifetime risk estimates of 20 years after a breast cancer diagnosis were:
      • 40% for  mutation carriers
      • 26% for mutation carriers
  • Breast cancer risks estimates differed depending on family history.
    • Risk was higher with increasing number of first- and second-degree relatives diagnosed with breast cancer for both and mutation carriers.
    • For women with a mutation and 2 or more first- or second-degree relatives diagnosed with breast cancer, the risk was 73% to age 70 compared to 53% for women with no family history.
    • For women with a mutation and 2 or more first- or second-degree relatives diagnosed with breast cancer, the risk was 65% to age 70 compared to 39% for women with no family history.
  • Cancer risks were different depending on the location of a mutation in the gene. ( and mutations were grouped by location: in the beginning, middle, or end of the gene.)
    • BRCA1: Breast cancer risks were higher for mutations located in the beginning (68%) and end (71%) of the gene compared to those in the middle (56%).
    • BRCA2: Breast cancer risks were higher for mutations located in the beginning (69%) and end (67%) compared to those in the middle (51%).
    • The large middle region of the gene was previously described as the “ovarian cancer cluster region"; however, this study found no significant difference in ovarian cancer risk for mutations located in this region.


This study had several limitations.  Although this study found that cancer risk varied by family history, participants were identified through clinical genetic centers and were more likely to have a family history of cancer. Therefore, the overall cancer risk estimates may not be directly relevant for women who have a or mutation with no family history of cancer. The results of this study suggest that cancer risks are likely lower for mutation carriers with no family history; however, carriers who have small families, limited knowledge of their families cancer history, few female relatives or female relatives who died young of other causes, or had prophylactic removal of breasts or ovaries should not use these data to assume lower risks. Additionally, because no data (, hormone receptor status, etc.) were available on breast and ovarian cancers that developed in study participants, the results represent averages across all tumor types. Furthermore, life time risk estimates were based on a follow-up of 15 years. Actual life time risk may vary for younger participants (i.e. a participant who entered the study at age 30 and was followed to age 45 versus a participant who entered the study at age 60 and was followed to age 75). Finally, this study did not take into consideration the use of strategies (tamoxifen, aromatase inhibitors, etc.) to reduce breast cancer risk or the use of oral contraceptives to reduce ovarian cancer risk. 


For women with a mutation, the results of this study may provide less biased age-related cancer risk estimates than previous studies. These results should be used in conjunction with careful genetic counseling and family cancer assessment to guide mutation carriers and their health care providers in clinical decision making. This study demonstrates the importance of knowing your family history and the location of your mutation because this information may impact individual cancer risk.    

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Posted 7/28/17

Expert Guidelines
Expert Guidelines

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 review your personal and family history of cancer and help you to determine the best risk management plan. Note that our use of "men" and "women" refers to the sex you were assigned at birth.

Recommended screening for women with mutations:

  • 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 and continuing 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 the advantages and disadvantages of risk-reducing mastectomy.
    • Research shows that risk-reducing mastectomy can lower the chance of developing breast cancer in high-risk women by about 90 percent. Mastectomy has not been shown to help high-risk women live longer.
    • Because some breast tissue remains after mastectomy, some breast cancer risk also remains. 
  • Speak with your doctor about the benefits and risks of tamoxifen or other estrogen-blocking drugs to reduce your breast cancer risk. The benefits and risks may be different for women with or  mutations. Research on the benefit of these drugs to reduce breast cancer risk in women with  mutations has been mixed.

Risk management for 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 chest every 12 months.
  • Beginning at age 50, consider an annual  (especially for men with mutations). 

Updated: 06/21/2024

Expert Guidelines
Expert Guidelines

The National Comprehensive Cancer Network (NCCN) provides guidelines for management of gynecologic cancer risk in people with and mutations. 


  • Risk-reducing removal of ovaries and , (known as salpingo-oophorectomy) is recommended between ages 35-40 for and 40-45 for and upon completion of childbearing.
    • Research studies show that removing the ovaries can increase survival for women with  mutations. 
    • Women should talk with their doctors about the effects of early menopause and options for managing them.
  • Women should talk with their doctors about the risks and benefits of keeping or removing their uterus (hysterectomy), including:
    • Women with a  mutation have an increased risk for a rare form of aggressive uterine cancer; hysterectomy removes this risk. 
    • For women considering hormone replacement after surgery, the presence or absence of a uterus can affect the choice of hormones used.
      • Estrogen-only hormone replacement is less likely to increase the risk for breast cancer, although it increases the risk for uterine cancer. Women who still have their uterus are typically given hormone replacement with both  and progesterone.
      • Adding progesterone to hormone replacement can protect against uterine cancer. However, the combination of these hormones may increase the risk for breast cancer more than alone. 
    • A medical history of fibroids or other uterine or cervical issues may justify a hysterectomy. 
  • Oral contraceptives (birth control pills) have been shown to lower the risk for ovarian cancer in women with  mutations. Research on the effect of oral contraceptives on breast cancer risk has been mixed. Women should discuss the benefits and risks of oral contraceptives for lowering ovarian cancer risk with their doctors. 
  • Removal of the  only () is being studied as an option for lowering risk in high-risk women who are not ready to remove their ovaries. Studies on the effects of are ongoing. At this time whether  lowers the risk for ovarian cancer in high-risk women remains unknown. 
    • Consider enrolling in a research study looking at this procedure to lower cancer risk.


  • There are no proven benefits to routine ovarian cancer screening using transvaginal  and a  blood test. However, some doctors still recommend this screening, starting at ages 30-35.
  • Women should be aware of the symptoms of gynecologic cancer and report abnormalities to their doctors. 

Updated: 05/08/2024

Questions To Ask Your Doctor
Questions To Ask Your Doctor

  • What is my risk for developing breast, ovarian, contralateral breast or other cancers?
  • What are my options for managing my risk for these cancers?
  • Was my particular family history of cancer included in estimating my cancer risk?
  • Does the type of mutation or the location of the mutation on the gene affect my cancer risk?

Open Clinical Trials
Open Clinical Trials

The following clinical trials include genetic counseling and testing. 

Other genetic counseling or testing studies may be found here.


Updated: 02/29/2024

Peer Support
Peer Support

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

Updated: 08/06/2022

Find Experts
Find Experts

The following resources can help you locate a genetics expert near you or via telehealth.

Finding genetics experts

  • The National Society of Genetic Counselors 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 from 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. 

Related experts

Genetics clinics

Other ways to find experts

Updated: 07/21/2023

Who covered this study?

Medical News Today

Breast and ovarian cancers: Large study improves estimates of genetic risk This article rates 4.0 out of 5 stars

Cancer Research UK

Study estimates breast and ovarian cancer risk linked to faulty BRCA genes This article rates 3.5 out of 5 stars


Researchers define cancer risk in BRCA1/BRCA2 carriers This article rates 3.0 out of 5 stars

Medpage Today

Study details BRCA carriers' breast ca risk by age This article rates 3.0 out of 5 stars


Most precise estimates ever of cancer risks with BRCA This article rates 3.0 out of 5 stars


When Is risk highest for women with BRCA gene? This article rates 3.0 out of 5 stars

How we rated the media

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