Health

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

Summary:

Inherited mutations in the BRCA1 and BRCA2 genes are linked to a high lifetime risk of breast and other cancers. This study shows that women who know that they have a BRCA mutation before they are diagnosed with breast cancer have improved outcomes including diagnosis at earlier stages and improved overall survival. (10/26/20)

Relevance:

This article is most relevant for Young women with, or at high risk for an inherited BRCA mutation

Printer Friendly Page

Read the article that we reviewed

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

Contents

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

STUDY AT A GLANCE

This study is about:

Whether knowing that you have a BRCA 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 BRCA 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 BRCA 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 BRCA1 or BRCA2 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 bilateral mastectomy (RRBM). However, most people with BRCA mutations decline RRBM and risk-reducing medication.

Study findings:

  • 42 of 105 women (40%) were aware of their BRCA mutation before their breast cancer diagnosis (pre-diagnosis group).
  • 63 of 105 women (60%) were unaware of their BRCA 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 MRI.
    • 86% had early-stage cancer (stage 0-1: 86%, stage II-IV: 14%).
    • 64% chose to have bilateral 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 (stage 0-1: 39%, stage 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 BRCA status and declined risk-reducing bilateral mastectomy. This study supports the idea that early surveillance with MRI may be beneficial for women with inherited BRCA 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 BRCA 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 BRCA 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 BRCA 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 prostate cancer, you may want to consider genetic testing for an inherited mutation in BRCA 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 MRI testing in addition to mammography.

If you know that you have a mutation in a BRCA 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 BRCA status after your diagnosis.

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

Because this study looked at outcomes only in people with BRCA 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.

Expert Guidelines

The National Comprehensive Cancer Network is a consortium of experts in cancer and genetics. The group publishes consensus guidelines on genetic testing, risk management and treatment.

Genetic testing

NCCN guidelines recommend genetic testing for individuals who have any of the following:

  • breast cancer of any type (including ductal carcinoma in situ or DCIS) diagnosed before age 50  
  • breast cancer in both breasts or a second breast cancer in the same breast 
  • triple-negative (ER-/PR-/Her2-) breast cancer before age 60 
  • Ashkenazi (Eastern European) Jewish ethnicity 
  • relatives with breast, ovarian, pancreatic or prostate cancer or melanoma
  • men with breast cancer 

For people with HER2-negative, metastatic breast cancer, the NCCN recommends BRCA testing before starting chemotherapy to see if there may be benefit from treatment with a PARP inhibitor.

According to the NCCN, cancer risk assessment and genetic counseling is highly recommended before genetic testing is offered (pre-test counseling) and after results are disclosed (post-test counseling). A genetic counselor, medical geneticist, oncologist, surgeon, oncology nurse or other health professional with expertise and experience in cancer genetics should be involved early in the counseling of patients.

Breast-cancer screening and risk-reduction

For women with increased risk of breast cancer (a lifetime risk for breast cancer of 20 percent or more), NCCN guidelines recommend the following screening:

  • Have clinical exams every 6–12 months, starting when you are identified as being at increased risk, but not before age 21. 
  • Obtain a referral to genetic counselor or similarly trained health care provider, if you haven’t already done so. 
  • Start annual mammography screening 10 years earlier than the age of the youngest family member who has been diagnosed with breast cancer, but not prior to age 30. Consider getting a 3-D mammogram. 
  • Begin annual breast MRI 10 years earlier than the age of the youngest family member who has been diagnosed with breast cancer, but not prior to age 25. 
  • Consider recommended risk reduction strategies, such as preventive hormonal medications or risk-reducing surgeries that remove the breasts or ovaries. 
  • Develop breast awareness and report any changes to your healthcare providers. 

Additional recommendations

The NCCN also recommends that people keep a copy of all their test results. (Online patient portals are a great way to access test results.) This can come in handy during a second opinion, if necessary.

Questions To Ask Your Doctor

  • Should I consider genetic testing for inherited mutations in BRCA 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 BRCA mutation, what would you recommend regarding surveillance and preventive options?
  • Would you recommend screening with MRI instead of or in combination with mammography?
  • If I know that I have an inherited BRCA mutation, what would you recommend for treatment of my breast cancer?

Open Clinical Trials

IN-DEPTH REVIEW OF RESEARCH

Study background:

Inherited mutations in BRCA1 and BRCA2 are linked to a high lifetime risk of breast, ovarian and related cancers. However, some women are not diagnosed with an inherited BRCA 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 BRCA1 or BRCA2 would be counseled about surveillance and prevention options. They can choose to increase surveillance for breast cancer or consider risk-reducing bilateral mastectomy (RRBM) to reduce their risk. However, the majority of people with BRCA mutations decline RRBM.

Researchers of this study wanted to know:

Whether women who knew that they inherited a harmful BRCA1 or BRCA2 mutation and declined RRBM had improved outcomes compared to women who were unaware that they had inherited a harmful BRCA1 or BRCA2 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 BRCA mutation seen at the Sha’are Zedek Medical Center in Israel from 2005 to 2016. In this study, 83% of women were of Ashkenazi Jewish 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 staging, 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 BRCA mutations, including the option of risk-reducing bilateral mastectomy (breast removal) and risk-reducing salpingo-oophorectomy (ovary and fallopian tube removal).

Study findings:

  • 42 of 105  women (40%) were aware of their BRCA mutation before their breast cancer diagnosis (pre-diagnosis group).
  • 63 of 105  women (60%) were unaware of their BRCA 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 MRI.
    • 86% had early-stage cancer (stage 0-1: 86%, stage II-IV: 14%).
    • 64% chose to have bilateral 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 (stage 0-1: 39%, stage 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 BRCA1 mutation and 36% had a BRCA2 mutation.
  • The two groups of women had a similar number of tumors with different grades, hormone-receptor status and HER2 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 BRCA 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 retrospective 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 BRCA 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 bilateral salpingo-oophorectomy (ovary and fallopian tube 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 BRCA 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 BRCA mutation and declined RRBM may have declined for reasons that are different than women in the U.S.

Context:

Women with BRCA mutations who chose to have risk-reducing bilateral mastectomy had improved outcomes. It was not known whether knowing about an inherited BRCA 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 BRCA status and declined risk-reducing bilateral 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 BRCA1 or BRCA2 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 BRCA mutation had better outcomes, it does suggest that increased surveillance with MRI may be beneficial for women with BRCA mutations.

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

Rating Details:

Relevance: Medium-High

  • This study is relevant for young women with a breast cancer or a high risk of breast cancer. It is particularly relevant for women with a BRCA mutation or family history of breast cancer.
  • Becasuse this study is focused on women with BRCA mutations, it is not generalizable to women without BRCA mutations including those with other inherited breast cancer gene mutations.
  • The results of this work need to be verified in a larger population in the U.S. However, once verified this inforamtion can be used in the clinic for counseling women about the utility of genetic testing for BRCA mutations and the benefit that information may provide.

Scientific Strength:Medium-High

  • This study is the first to look at the impact of knowing BRCA status before breast cancer diagnosis on outcomes for women with BRCA mutations.
  • This study is carefully analyzed statistically. The results were statistically significant for the key findings.
  •  This is a retrospective study of medical records for patients with breast cancer and BRCA mutations. As such, there are possible biases. A prospective study that followed patients forward in time would be a more rigorous way to test this idea. However, a large number of breast cancer patients would be required for a prospective study since most will not have a BRCA mutation.
  • The number of patients in this study is relatively small. It is unknown whether these findings would be similar or different in a larger sample of patients.
  • It is not known how generalizable this information is. There may be differences in healthcare specifically in breast cancer treatment between patients in Israel and in the United States.

Research Timeline: Post-approval