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Study: Knowing about an inherited BRCA mutation improves outcomes for women with breast cancer

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Contents

At a glance Clinical trials
Strengths and limitations Guidelines              
What does this mean for me? Questions for your doctor 
In-depth Resources and reference

 

STUDY AT A GLANCE

This study is about:

Whether knowing that you have a mutation affects your breast cancer diagnosis and survival.
 

Why is this study important?

Genetic testing for inherited mutations that affect cancer risk is more common than ever before. Knowing that you have a harmful mutation in a gene that increases your risk for breast cancer may affect decision-making about breast cancer screening and treatment for you and your doctor. This study shows that knowing about an inherited mutation before breast cancer occurs improves outcomes with diagnosis at earlier stages and improved overall survival.

Early detection of breast cancer is linked to better outcomes. Women who know that they have an inherited harmful mutation in or would be counseled about surveillance and prevention options. They can choose to increase surveillance for breast cancer, take medication to reduce their risk or consider risk-reducing mastectomy (RRBM). However, most people with mutations decline RRBM and risk-reducing medication.
 

Study findings: 

  • 42 of 105 women (40%) were aware of their mutation before their breast cancer diagnosis (pre-diagnosis group).
  • 63 of 105 women (60%) were unaware of their mutation until after their breast cancer diagnosis (post-diagnosis group).

The majority of women in the pre-diagnosis group were diagnosed at earlier stages and required less treatment compared to the women in the post-diagnosis group.

  • Among women in the pre-diagnosis group:
    • 64% had their breast cancer detected by .
    • 86% had cancer ( 0-1: 86%, II-IV: 14%).
    • 64% chose to have mastectomy at the time of their tumor surgery.
    • 85% had lymph node biopsy without further surgery, while only 7% needed more invasive lymph node surgery.
    • 55% did not require chemotherapy. None required chemotherapy before surgery.
       
  • Among women in the post-diagnosis group:
    • 63% detected their breast cancer by their own physical exam or clinical exam by a healthcare provider.
    • 61% were diagnosed with later stages of cancer ( 0-1: 39%, II-IV: 61%).
    • 78% chose to have unilateral mastectomy at the time of their tumor surgery.
    • 51% had lymph node biopsy without further surgery, while 35% needed more invasive lymph node surgery.
  • Only 5% did not require chemotherapy; 22% required chemotherapy before surgery.

Women in the pre-diagnosis group had better overall survival

  • 2 of 42 (5%) women in the pre-diagnosis group died.
  • 16 of 63 (25%) women in the post-diagnosis group died.
  • These results correspond to an estimated survival rate of 94% at 5 years after diagnosis for the pre-diagnosis group and 78% for the post-diagnosis group.

This is the first report of a survival advantage among women who knew their status and declined risk-reducing mastectomy. This study supports the idea that early surveillance with may be beneficial for women with inherited mutations.
 

Strengths and limitations

Strengths:

  • Women in the pre-diagnosis and post-diagnosis groups were well-matched for age at diagnosis and for the percentage with mutations in each of the genes.
  • All patients were seen at one healthcare institution, suggesting consistent care and guidance about breast cancer risk among participants.

Limitations:

  • This study used past medical records. Only women who were eventually diagnosed with breast cancer were included. It is possible that the women who did not develop breast cancer but who knew or did not know their status may have differed in other ways that were not accounted for.
  • The number of patients in this study was relatively small (105 women). Observed differences in small studies might not hold up in a larger study.
  • This study took place in Israel. Differences in Israeli and U.S. healthcare practices might alter these findings. Women who knew that they had an inherited mutation and declined RRBM may have declined for different reasons compared to women in the U.S.
     

What does this mean for me?

If you have a family history of breast, ovarian, pancreatic or cancer, you may want to consider genetic testing for an inherited mutation in or other breast cancer gene. Knowing that you have an inherited gene mutation may be helpful in determining the best plan for surveillance and prevention with your healthcare provider. You may want to consider screening for breast cancer with testing in addition to .

If you know that you have a mutation in a gene and are later diagnosed with breast cancer, your breast cancer is more likely to be diagnosed at earlier stages and linked to improved survival than if you learn your status after your diagnosis.

If you are diagnosed with breast cancer, knowing whether you have a mutation may also affect your treatment plan.

Because this study looked at outcomes only in people with mutations, more research is needed to learn if these results apply to people with other mutations that are linked to breast cancer.

Share your thoughts on this XRAYS article by taking our brief survey.

Posted 10/26/20


Reference

Hadar T, Mor P, Amit G, et al. Presymptomatic Awareness of Germline Pathogenic Variants and Associated Outcomes in Women with Breast Cancer. JAMA Oncology 2020;6(9):1460-1463. Published online July 9, 2020. 

 

Disclosure

FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board before publication to assure scientific integrity.

This article is relevant for:

Young women with, or at high risk for an inherited BRCA mutation

This article is also relevant for:

Women under 45

Women over 45

Previvors

People with a genetic mutation linked to cancer risk

People with a family history of cancer

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IN-DEPTH REVIEW OF RESEARCH

Study background:

Inherited mutations in and are linked to a high lifetime risk of breast, ovarian and related cancers. However, some women are not diagnosed with an inherited mutation until after their breast cancer diagnosis. This happens most often in people with no strong family history (perhaps due to small family size or few female relatives with the mutation). These women would have had general guidance about breast cancer surveillance and prevention.

In contrast, women who know that they have an inherited harmful mutation in or would be counseled about surveillance and prevention options. They can choose to increase surveillance for breast cancer or consider risk-reducing mastectomy (RRBM) to reduce their risk. However, the majority of people with mutations decline RRBM.
 

Researchers of this study wanted to know:

Whether women who knew that they inherited a harmful or mutation and declined RRBM had improved outcomes compared to women who were unaware that they had inherited a harmful or mutation (and therefore did not consider RRBM or other risk-reducing choices).


Populations looked at in this study:

This study looked at medical information for 105 women diagnosed with an inherited mutation seen at the Sha'are Zedek Medical Center in Israel from 2005 to 2016. In this study, 83% of women were of heritage. The average age at time of breast cancer diagnosis was 50 years.

Study design:

Researchers collected previous medical information from records in the Israeli Cancer Registry,  including information about cancer , tumor type and characteristics, family history, method of cancer detection, type of treatment and survival.

All patients had counseling for surveillance and prevention based on standard guidelines for those with known mutations, including the option of risk-reducing mastectomy (breast removal) and risk-reducing salpingo-oophorectomy (ovary and removal).


Study findings:  

  • 42 of 105  women (40%) were aware of their mutation before their breast cancer diagnosis (pre-diagnosis group).
  • 63 of 105  women (60%) were unaware of their mutation until after their breast cancer diagnosis (post-diagnosis group).

The majority of women in the pre-diagnosis group were diagnosed at earlier stages and required less treatment compared to women in the post-diagnosis group.

  • Among women in the pre-diagnosis group:
    • 64% had their breast cancer detected by .
    • 86% had cancer ( 0-1: 86%, II-IV: 14%).
    • 64% chose to have mastectomy at the time of their tumor surgery.
    • 85% had lymph node biopsy without further surgery, while only 7% needed more invasive lymph node surgery.
    • 55% did not require chemotherapy after surgery. None required chemotherapy before surgery.
       
  • Among women in the post-diagnosis group:
    • 63% had their breast cancer detected by their own physical exam or clinical exam by a healthcare provider.
    • 61% were diagnosed with later stages of cancer ( 0-1: 39%, II-IV: 61%).
    • 78% chose to have unilateral mastectomy at the time of their tumor surgery.
    • 51% had lymph node biopsy without further surgery, while 35% needed more invasive lymph node surgery.
    • Only 5% did not require chemotherapy after surgery. 22% required chemotherapy before surgery.

Women in the pre-diagnosis group had better overall survival.

    • 2 of 42 (5%) women in the pre-diagnosis group died.
    • 16 of 63 (25%) women in the post-diagnosis group died.
    • This corresponds to an estimated survival rate at 5 years after diagnosis of 94% for the pre-diagnosis group and 78% for the post-diagnosis group.
       
  • Women in the pre-diagnosis group had a stronger family history of cancer and were better off socio-economically than women in the post-diagnosis group.


Some features did not differ between women in the pre-diagnosis group and the post-diagnosis group.

  • Among both groups, about 64% of the women had a mutation and 36% had a mutation.
  • The two groups of women had a similar number of tumors with different grades, hormone-receptor status and status.
     

Strengths and limitations:

Strengths:

  • Women in the pre-diagnosis and post-diagnosis groups were well-matched for age at diagnosis and for the percentage of women with mutations in each gene. This suggests that the women in each group had similar general features. This is a goal of most scientific studies, that groups are similar apart from the features being tested. Statistical analysis was done to determine what other factors might be similar or different between these two groups of breast cancer patients. The statistical analysis was appropriate for this type of study.
  • Also, because all patients were seen at one healthcare institution, the care and guidance about breast cancer risk would be consistent.

Limitations:

  • A limitation of this study was that it was based on past medical records. This type of study depends on the medical records containing relevant information. Only women who eventually were diagnosed with breast cancer were included. It is possible that other women who did not develop breast cancer but who knew or did not know their status may have differed in other ways that were not tested.
  • Another limitation of this study was the relatively small sample size of patients (105 women). In such a small study, it is possible that the differences observed might not hold up in a larger study. The study’s statistical analysis suggests that it is reliable, but repeating it with larger numbers would help validate the results. The small size of the study prevented researchers from making any conclusions about the effect of risk-reducing salpingo-oophorectomy (ovary and removal) on outcomes.
  • This study took place in Israel. There may be differences in healthcare, genetic counseling and guidance for people in the U.S. with mutations. It is unknown whether such differences might alter these findings. Given the differences in insurance and medical coverage in Israel and the United States, the women who knew that they had an inherited mutation and declined RRBM may have declined for reasons that are different than women in the U.S.


Context:

Women with mutations who chose to have risk-reducing mastectomy had improved outcomes. It was not known whether knowing about an inherited mutation among women who had not yet had a breast cancer diagnosis would be helpful. This is the first report of a survival advantage among women who knew their status and declined risk-reducing mastectomy.


Conclusions:

The researchers state:

"These results provide further support for BRCA1/BRCA2 screening in unaffected women, particularly in populations such as Ashkenazi Jews with high BRCA1/BRCA2 carrier rates."

Knowing about an inherited or mutation before a breast cancer diagnosis is linked to earlier diagnosis, less aggressive treatment and better overall survival. While this study did not directly test why women who knew about their mutation had better outcomes, it does suggest that increased surveillance with may be beneficial for women with mutations.

Share your thoughts on this XRAYS article by taking our brief survey.

Posted 10/26/20

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

  • Should I consider genetic testing for inherited mutations in or other breast cancer genes?
  • How do I get a referral for genetic counseling and genetic testing?
  • If I know that I have an inherited mutation, what would you recommend regarding surveillance and preventive options?
  • Would you recommend screening with instead of or in combination with ?
  • If I know that I have an inherited mutation, what would you recommend for treatment of my breast cancer?

Open Clinical Trials
Open Clinical Trials

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?

Medscape

'Knowledge is power': Knowing BRCA1/2 status tied to survival This article rates 2.5 out of 5 stars

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