The Who, What, Where, When and Sometimes, Why.

Inherited Gene Mutations

This section provides information on BRCA1, BRCA2 and other high-risk inherited gene mutations, and how these gene mutations impact breast cancer risk.

Genes and inherited gene mutations

Genes

Every cell in your body contains genes. Genes contain the blueprints (genetic code) for your body.

For example, genes contain the information that determines the color of your eyes. They also contain information that affects how the cells in your body grow, divide and die.

The information in your genes is passed on (inherited) from your mother and your father. And, you can pass this information on to your children (your daughters and your sons).

Inherited gene mutations

Some changes in the genetic code that affect the function of the gene are called mutations. Mutations are rare.

Just as with other information in genes, mutations can be passed on from a parent to a child.

You get half of your genes from your mother and half from your father. So, for example, if your mother has a BRCA1 gene mutation, there’s a 50 percent chance you will also have a BRCA1 mutation.

Inherited gene mutations may also be called germline mutations.

Inherited gene mutations and breast cancer risk

Inherited gene mutations known to increase the risk of breast cancer are rare in the general population.

In the U.S., 5-10 percent of breast cancers are related to an inherited gene mutation [4,28].

BRCA1 and BRCA2 (BReast CAncer genes 1 and 2) are the most well-known genes linked to breast cancer risk.

Everyone has these genes. But some people have an inherited mutation in one or both genes that increases the risk of breast cancer.

Inherited mutations in the following genes also increase the risk of breast cancer:

  • ATM
  • BARD1
  • BRIP1
  • CDH1
  • CHEK2
  • NBN
  • NF1
  • PALB2
  • PTEN
  • RAD51C
  • RAD51D
  • STK11
  • TP53

Other genes are under study and may also play a role in breast cancer.

BRCA1/2 and other inherited gene mutations can be passed to you from either parent and can affect the risk of cancers in both women and men.

Some inherited gene mutations slightly increase breast cancer risk, while others (such as BRCA1/2 mutations) greatly increase risk.

BRCA1 and BRCA2 inherited gene mutations

Like other inherited gene mutations, BRCA1 and BRCA2 gene mutations are rare in the general population. In the U.S., about 1 in 400 people have a BRCA1/2 mutation [28].

Prevalence varies by ethnic group. Among Ashkenazi Jewish men and women, about 1 in 40 have a BRCA1/2 mutation [28].

Learn more about BRCA1/2 mutations.

BRCA1/2 inherited gene mutations and cancer in women

Breast cancer

Women who have a BRCA1 or BRCA2 inherited gene mutation (BRCA1/2 carriers) have an increased risk of breast cancer [28-32].

Estimates of risk are different for BRCA1 carriers and BRCA2 carriers. By age 70, the chance of developing breast cancer is [3,28,30-34,155,189]:

  • 55-65 percent for BRCA1 carriers
  • 45-55 percent for BRCA2 carriers
  • 7 percent for women in the general population (Lifetime risk of breast cancer is 12 percent.)

This means by age 70:

  • In a group of 100 women with a BRCA1/2 mutation, 45-65 will get breast cancer
  • In a group of 100 women without a BRCA1/2 mutation, about 7 will get breast cancer

These numbers are averages, so the risk of breast cancer for any one woman with a BRCA1/2 mutation may fall outside this range.

BRCA1/2 mutations are thought to explain a large portion of hereditary breast cancers [28].

However, note these risks are not 100 percent. Many women with a BRCA1/2 mutation will never have breast cancer [29-31]. A combination of factors likely causes breast cancer.

Ovarian cancer and other cancers

BRCA1 and BRCA2 mutations increase a woman’s risk of ovarian cancer, pancreatic cancer and melanoma (BRCA2 mutations) [28,32,155].

BRCA1/2 mutations may also increase the risk of other cancers [28]. However, data are limited and these topics are still under study.

Learn more about BRCA1/2 mutations in women.

Learn about risk-reducing options for women at higher risk.

Learn about genetic testing

For a summary of research studies on BRCA1 and BRCA2 mutations and cancer, visit the Breast Cancer Research Studies section.

BRCA1/2 inherited gene mutations and cancer in men

Men can also have BRCA1 and BRCA2 inherited gene mutations and may pass them on to their children.

Men who have a BRCA2 mutation, and to a lesser degree, men who have a BRCA1 mutation, have an increased risk of breast cancer [28-29,31,36,155,190-191].

BRCA1/2 mutations also increase the risk of prostate cancer, pancreatic cancer and melanoma (BRCA2 mutations) [28,32,155,191].

Learn more about BRCA1/2 mutations in men.

Learn more about breast cancer in men.

Learn about cancer screening for men with a BRCA1/2 gene mutation.

Learn about genetic testing.

For a summary of research studies on BRCA1 and BRCA2 mutations and cancer, visit the Breast Cancer Research Studies section.

Other inherited gene mutations

In addition to BRCA1 and BRCA2 inherited gene mutations, other inherited gene mutations increase the risk of breast cancer. Some also increase the risk of other cancers.

These gene mutations are less common than BRCA1/2 mutations and there’s still much to learn about them.

Some of these mutations are linked to a high or moderate risk of breast cancer (similar to BRCA1/2 mutations). The lifetime risk of breast cancer is increased 20-49 percent for women with moderate-risk gene mutations and 50 percent or higher for women with high-risk gene mutations.

The table below provides a summary of high-risk and moderate-risk inherited gene mutations. Some of these gene mutations have only recently been shown to increase the risk of breast cancer. Data on these mutations and their related cancer risks are still emerging and will likely change over time.

In general, having a mutation in any of these genes leads to special breast cancer screening recommendations.

Gene
(in alphabetical order)

Lifetime risk of
breast cancer*

Other cancers at increased risk

ATM

20-40%

Pancreatic cancer and possibly, prostate cancer

BARD1

20-25%

None known

BRCA1

55-65%

Ovarian cancer, pancreatic cancer, prostate cancer

BRCA2

45-55%

Melanoma, ovarian cancer, pancreatic cancer, prostate cancer

BRIP1

Possible increase

Ovarian cancer

CDH1

40-60%

Diffuse stomach cancer

CHEK2

20-45%

Colorectal cancer, prostate cancer

NBN

20-30%

None known

NF1

40-60%

Brain and spinal tumors, gastrointestinal stromal tumors, neurofibroma, optic glioma, sarcomas

PALB2

35-60%

Ovarian cancer, pancreatic cancer

PTEN

80-85%

Colon cancer, endometrial cancer, thyroid cancer and possibly, kidney cancer

RAD51C

20%

Ovarian cancer

RAD51D

20%

Ovarian cancer

STK11

30-55%

Colorectal cancer, endometrial cancer, ovarian cancer, pancreatic cancer, stomach cancer

TP53

50-55%

Adrenocortical carcinoma, bone and soft tissue cancers (sarcomas), brain tumors, colon cancer, leukemia
* The age up to which lifetime risk was estimated varied among studies.

Adapted from selected sources [28,155,192-197]. 

Some gene mutations are related to certain breast cancers. For example, women who have a BRCA1 gene mutation tend to get breast cancers that are triple negative [28]. And, CDH1 gene mutations appear to be related more often to invasive lobular breast cancers rather than invasive ductal breast cancers [194].

Genetic testing

It’s now common for genetic testing to check for multiple high-risk and moderate-risk inherited gene mutations, including BRCA1/2 mutations. This is called expanded panel testing or multi-gene testing.

Because panel testing is still fairly new, the specific set of genes assessed for mutations can vary from test to test.

Panel testing is only recommended for some people.

As with any genetic testing, panel testing should only be done in a medical setting after a detailed discussion of the risks and benefits with a genetic counselor or a trained doctor or nurse [155]. These trained health care providers can also help determine the best test (and lab), given the pattern of cancer in your family.

Learn more about expanded panel (multi-gene) testing

Breast cancer screening

Guidelines for people with other high-risk gene mutations are less clear. As more is learned about these mutations, guidelines can become more personalized.

Learn more about special breast cancer guidelines for women with an inherited mutation in an ATM, BARD1, CDH1, CHEK2, NF1, PALB2, PTEN or TP53 gene.

Breast cancer risk reduction

There are special breast cancer risk reduction guidelines for women who have a BRCA1/2 gene mutation.

Guidelines for women with other high-risk or moderate-risk gene mutations are less clear. As more is learned about these mutations, guidelines can become more personalized.

Learn more about risk reduction options for women at higher risk of breast cancer

Talking about family health history with your health care provider

Your family history of breast cancer and other health conditions is important to discuss with your health care provider. This information helps them understand your risk of breast cancer.

Susan G. Komen®‘s My Family Health History Tool

My Family Health History tool is a web-based tool that makes it easy for you to record and organize your family health history. It can help you gather information that’s useful as you talk with your doctor or genetic counselor.

 

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KOMEN PERSPECTIVES

Read our perspective on genetic testing for breast cancer.*

 

Support for people with inherited gene mutations

Some support groups are tailored to people with BRCA1, BRCA2 or other high-risk gene mutations and those with breast cancers related to inherited gene mutations.

Our Support section offers a list of resources to help find local and online support groups. For example, FORCE is an organization that offers online support for people at higher risk of breast, ovarian or other cancers related to family history or inherited gene mutations.

Sharsheret offers online support for Jewish women affected by hereditary breast and/or ovarian cancer.

 SUSAN G. KOMEN® SUPPORT RESOURCES  

  • If you or a loved one needs more information about breast health or breast cancer, call the Komen Breast Care Helpline at 1-877 GO KOMEN (1-877-465-6636). All calls are answered by a trained specialist or oncology social worker in English and Spanish, Monday through Friday from 9:00 a.m. to 10:00 p.m. ET. You can also email the helpline at helpline@komen.org
  • Our online and telephone support groups provide a safe place for all to discuss the challenges of breast cancer, get information and exchange support. To learn more about upcoming group opportunities, call the helpline at 1-877 GO KOMEN (1-877-465-6636) or email helpline@komen.org.
  • We offer an online support community through our closed Facebook Group – Komen Breast Cancer group. The Facebook group provides a place where those with a connection to breast cancer can discuss each other’s experiences and build strong relationships to provide support to each other. Visit Facebook and search for “Komen Breast Cancer group” to request to join the closed group.
  • Komen Affiliates offer breast health education and some fund breast cancer programs through local community organizations. Your local Affiliate may also help you find breast cancer resources in your area. Find your local Affiliate.
  • Our fact sheets, booklets and other education materials offer additional information.

Finding clinical trials for people with inherited gene mutations

Susan G. Komen® Breast Cancer Clinical Trial Information Helpline

If you or a loved one needs information or resources about clinical trials, call our Clinical Trial Information Helpline at 1-877 GO KOMEN (1-877- 465- 6636) or email clinicaltrialinfo@komen.org.

BreastCancerTrials.org in collaboration with Komen offers a custom matching service to help find clinical trials on risk reduction.

You can also visit the National Institutes of Health’s website to find clinical trials.

Learn more about clinical trials.

*Please note, the information provided within Komen Perspectives articles is only current as of the date of posting. Therefore, some information may be out of date.

Updated 02/24/21