Hereditary Breast and Ovarian Cancer

Approved by the Cancer.Net Editorial Board, 05/2019

What is Hereditary Breast and Ovarian Cancer?

A diagnosis of Hereditary Breast and Ovarian Cancer Syndrome (HBOC) is considered when there are multiple cases of breast cancer and/or ovarian cancer on the same side of the family. The chance that a family has HBOC increases in any of these situations:

  • 1 or more women are diagnosed at age 45 or younger

  • 1 or more women are diagnosed with breast cancer before age 50 with an additional family history of cancer, such as prostate cancermelanoma, and pancreatic cancer

  • There are breast and/or ovarian cancers in multiple generations on the same side of the family, such as having both a grandmother and an aunt on the father’s side both diagnosed with these cancers

  • A woman is diagnosed with a second breast cancer in the same or the other breast or has both breast and ovarian cancer

  • male relative is diagnosed with breast cancer

  • There is a history of breast cancer, ovarian cancer, prostate cancer, and/or pancreatic cancer on the same side of the family

  • Having Ashkenazi Jewish ancestry

What causes HBOC?

HBOC is an inherited genetic condition. This means that the cancer risk is passed from generation to generation in a family. There are 2 primary genes linked with most families who have HBOC: BRCA1 and BRCA2. BRCA stands for BReast CAncer. A “mutation,” or harmful genetic change, in either BRCA1 or BRCA2 gives a woman an increased lifetime risk of developing breast and ovarian cancers. Men with these gene mutations also have an increased risk of breast cancer and prostate cancer. There is a slight increase in the risk of other cancers including pancreatic cancer and melanoma among people with BRCA1 or BRCA2 mutations.

Not all families with multiple cases of breast and ovarian cancer have mutations in BRCA1 or BRCA2. There are also other genes that have been linked with an increased risk of developing breast and other cancers, such as mutations in the TP53, PTEN, CDH1, ATM, CHEK2, or PALB2 tumor suppressor genes and others. Blood tests now include many of these genes, including BRCA1 or BRCA2, in a single, multiple-gene panel test. 

How is HBOC inherited?

Normally, each person has 2 copies of each gene in their body’s cells: 1 copy is inherited from a person’s mother and 1 copy is inherited from a person’s father. HBOC follows an autosomal dominant inheritance pattern. This means that a mutation needs to happen in only 1 copy of the gene for the person to have an increased risk of getting that disease. This means that a parent with a gene mutation may pass along a copy of their normal gene or a copy of the gene with the mutation. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother, sister, or parent of a person who has a mutation also has a 50% chance of having inherited the same mutation. However, if the parents test negative for the mutation (meaning each person’s test results found no mutation), the risk to the siblings significantly decreases but their risk may still be higher than an average risk. 

Can HBOC be avoided? 

There are options available for people with HBOC who are interested in having a child and reducing that child’s risk of this hereditary syndrome. Preimplantation genetic diagnosis (PGD) is a medical procedure done along with in-vitro fertilization (IVF). It allows people who carry a specific known genetic mutation to reduce the likelihood that their children will inherit the condition. For PGD, a woman’s eggs are removed and fertilized in a laboratory. When the embryos reach a certain size, 1 cell is removed and tested for the specific hereditary condition. The parents can then choose to transfer the embryos that do not have the mutation. PGD has been used for over 2 decades for several hereditary cancer syndromes. However, it is a complex procedure with financial, physical, and emotional factors to consider before starting. For more information, talk with an assisted reproduction specialist at a fertility clinic. 

How common is HBOC?

Most breast and ovarian cancers are sporadic, meaning they occur by chance with no known cause. Most women who have breast or ovarian cancer do not have HBOC.

Currently, it is estimated that less than 1% of the general population has a mutation in the BRCA1 or BRCA2 genes, and up to 10% of women and 20% of men diagnosed with breast cancer have a mutation in 1 of these genes. About 10% to 30% of women younger than 60 diagnosed with “triple-negative” breast cancer, which are cancers that do not have receptors for estrogen, progesterone, and HER2, have a BRCA1 or BRCA2 gene mutation, and others will have mutations in other breast cancer risk genes. Therefore, doctors recommend that women with triple-negative breast cancer receive genetic counseling and genetic testing (see below).

HBOC is most common in families who have had multiple cases of breast cancer and/or ovarian cancer on the same side of the family. In families with 4 or more cases of breast cancer diagnosed before age 60, the chance of HBOC is about 80%. To compare, the chance of finding HBOC when only 1 woman has had breast cancer diagnosed before age 50 is estimated to be 10% or less.

Families with Ashkenazi Jewish ancestry have an increased chance of having HBOC. There are 3 specific gene mutations, known as “founder mutations,” that are common in these families:

  • 185delAG in BRCA1 (also reported as 187delAG)

  • 5382insC in BRCA1

  • 6174delT in BRCA2

It is estimated that about 1 person out of 40 people with Ashkenazi Jewish ancestry has 1 of these 3 mutations. Approximately 1 in 10 women with breast cancer and 1 in 3 women with ovarian cancer in Ashkenazi Jewish families have 1 of the BRCA1 or BRCA2 gene mutations.

If a person has a BRCA2 mutation, it is important for the other prospective parent to also be tested before pregnancy. This is particularly true for those of Ashkenazi Jewish ancestry in whom the risk of having the genetic mutation is higher. If both parents carry a BRCA2 gene mutation, there is a 25% risk of having a child with Fanconi anemia, which is an inherited disorder, associated with physical abnormalities, an increased risk of blood cancers, and other serious problems. Fanconi anemia is inherited in an autosomal recessive pattern, meaning that if a child inherits a copy of the BRCA2 gene with a mutation from each parent, he or she will be born with the disease.

Who should be tested for HBOC?

Most breast and ovarian cancers occur by chance with no known cause, so testing for BRCA1 or BRCA2 gene mutations may not be beneficial for the average woman. Genetic testing is recommended primarily for people who have a personal and/or family history that suggests HBOC. However, women younger than 60 with triple-negative breast cancer (see above), are at risk of having a BRCA mutation, regardless of family history.

For women with a previous diagnosis of breast cancer or ovarian cancer and/or a family history of breast or ovarian cancer, the National Comprehensive Cancer Network (NCCN) provides recommendations for when genetic counseling and testing may be needed. These recommendations are based on your family’s history of cancer and how closely related you are to the person(s) who developed cancer.

  • First-degree relatives include parents, siblings, and children.

  • Second-degree relatives include aunts/uncles, grandparents, grandchildren, and nieces/nephews.

  • Third-degree relatives include first-cousins, great-grandparents, or great-grandchildren.

Genetic testing should be considered if a person or family meets 1 or more of the criteria listed below:

  • A family member has a known mutation in the BRCA1 or BRCA2 genes or other related breast cancer risk genes

  • A personal history of breast cancer plus 1 or more of the following:

    • A diagnosis of breast cancer at age 45 or younger

    • A diagnosis of breast cancer between ages 46 and 50 with:

      • A diagnosis of a second breast cancer in the same or other breast

      • 1 or more first-, second-, or third-degree relatives on the same side of the family diagnosed with breast at any age

      • A diagnosis of high-grade prostate cancer in 1 or more first-, second-, or third-degree relatives on the same side of the family

      • An unknown or limited family history

      • A diagnosis at age 60 or younger with triple-negative breast cancer (see above)

    • A breast cancer diagnosis at any age with:

      • A personal history of ovarian cancer

      • 1 or more first-, second-, or third-degree relatives on the same side of the family diagnosed with breast cancer at age 50 or younger, ovarian cancer, pancreatic cancer, metastatic prostate cancer, or breast cancer in a male relative

      • 2 additional first-, second-, or third-degree relatives on the same side of the family diagnosed with breast cancer at any age

      • Being in a family of Ashkenazi Jewish ancestry

    • A personal history of male breast cancer

    • A personal history of metastatic prostate cancer

    • A personal history of high-grade prostate cancer at any age plus 1 or more of the following:Having 1 or more first- or second-degree relatives who meet any of the criteria above

      • 1 or more first-, second-, or third-degree relatives on the same side of the family with ovarian cancer, pancreatic cancer, or metastatic prostate cancer diagnosed at any age or breast cancer diagnosed younger than 50

      • 2 first-, second-, or third-degree relatives on the same side of the family with breast or prostate cancer diagnosed at any age.

      • Being in a family of Ashkenazi Jewish ancestry

How is HBOC identified?

Mutations in the BRCA1 or BRCA2 genes can be identified through a blood or saliva test. The usual method of testing, called standard gene sequencing, can find most BRCA mutations. There are other types of mutations called rearrangements, which include deletions or duplications in BRCA1 and BRCA2 that also may cause an increased risk for these cancers. Testing is also available for large rearrangements in BRCA1 and BRCA2.

After initial BRCA1 and BRCA2 genetic testing, additional testing may be recommended if:

  • The results were “negative,” meaning no genetic mutation was detected

  • A variant of uncertain significance was detected, which means that there is a genetic change, but it is not known how that change could affect cancer risk

Talk with your health care team and/or a genetic counselor for more information.

Most, but not all, insurance companies cover the cost of complete BRCA1 and BRCA2 testing, including Medicare and Medicaid. Many genetic specialists offer multigene panels, which may include 6, 20, 40, or more genes depending on your personal and family history. The multigene panel tests may often be done at the same time as BRCA1 and BRCA2 testing. Talk with your genetic counselor for more information on the type of testing you will have and your insurance coverage.

If a mutation is found in 1 of the other genes that increase risk for breast cancer, ovarian cancer, and other cancers, your health care team will create a screening plan for specifically for you. This plan will be based on the cancers associated with the gene changes found and your family history of cancer. A team of health care professionals who have expertise in clinical cancer genetics, such as genetic counselors, will create this plan.

What are the estimated cancer risks associated with HBOC

Cancer risks for women with HBOC

  • Lifetime risk of breast cancer                         50% to 85%

  • Risk of breast cancer before age 50              30% to 50%

  • Lifetime risk of ovarian cancer

    • BRCA1 gene mutation                              25% to 50%

    • BRCA2 gene mutation                              15% to 30%

  • Developing a second breast cancer               40% to 60% (the risk of breast cancer occurring in the other breast rises approximately 2% to 3% per year)

Cancer risks for men with HBOC

  • Lifetime risk of breast cancer

    • BRCA1 gene mutation                   1% to 2% (10-times increase over the general population)

    • BRCA2 gene mutation                   6%

  • Risk of prostate cancer

    • BRCA1 gene mutation                   some increased risk

    • BRCA2 gene mutation                   20%

  • Men with a BRCA2 gene mutation have a significantly increased risk of developing more aggressive prostate cancer before age 65 and therefore screening should begin at age 40. 

Breast cancer subtypes and inherited mutations

Cancers diagnosed in people with BRCA mutations often have specific characteristics:

  • 60% to 80% of the breast cancers in women with a BRCA1 mutation are triple negative, as discussed above,

  • 70% to 80% of the breast cancers in women with a BRCA2 mutation are estrogen receptor-positive, progesterone receptor-positive, and HER2-negative.

Other cancer risks for people with HBOC

Both men and women with mutations in the BRCA2 gene may be at an increased risk of other types of cancer, including melanoma and pancreatic, stomachesophageal, and bile duct cancers.

Mutations in other genes may be associated with an increased risk of developing breast and other cancers, including the Li-Fraumeni syndrome (TP53 gene), Cowden syndrome (PTEN gene), and others. The pattern of cancers in the family is often a clue to the specific gene that may explain the hereditary cancer for that family. Multigene panels are available for people with a strong personal and family history of cancer. Multigene panel tests include BRCA1 and BRCA2 and many other genes that increase the risk of breast, ovarian, and other cancers. If your BRCA1 and BRCA2 test was negative, then you may or may not have mutations in other genes. A newer type of testing, called “next generation sequencing,” “massively parallel sequencing,” or “deep sequencing,” has made testing for multiple genes at the same time faster and less expensive. If a genetic mutation is found, this could explain the cancers in a specific family and provide information about who is at risk and the appropriate types of monitoring and prevention/risk reduction methods. 

What can I do to reduce my risk of developing breast cancer or ovarian cancer if I have a BRCA gene mutation?

Risk-reducing surgery

A prophylactic, bilateral mastectomy, which is the preventive surgical removal of both breasts, can lower the risk of breast cancer by more than 90%. Only about 3% of breast cancers associated with BRCA mutations are diagnosed before age 30, so most women with a BRCA mutation could consider surgery after 30. However, bilateral mastectomy is an invasive and irreversible procedure.

A prophylactic salpingo-oophorectomy, which is the preventive surgical removal of the ovaries and fallopian tubes, can lower the risk of ovarian cancer by approximately 90%. It can also help lower the risk of breast cancer by 50% for women who have not been through menopause. A special procedure to look for microscopic cancer in the ovaries and fallopian tubes is recommended after this surgery.

Deciding whether to have preventive surgery to lower your risk of developing breast or ovarian cancer is a very personal decision. Your health care team and genetic counselor can help you understand the risks and benefits, based on your health, type of BRCA mutation, and family history of cancer.

Chemoprevention

Cancer chemoprevention is the use of drugs to stop or keep cancer from developing. Tamoxifen (available as a generic drug) taken for 5 years by women with a high risk of breast cancer lowers this risk by 50%. Some research suggests that tamoxifen can help lower breast cancer risk for women with BRCA1 and BRCA2 mutations. However, because women with BRCA1 mutations are more likely to develop hormone receptor-negative cancers, it may not be as effective for these women. Risk-reducing tamoxifen is a reasonable option for women with BRCA1 or BRCA2 mutations to consider in addition to screening (see below). Raloxifene (Evista) and aromatase inhibitors (AIs) can also help lower breast cancer risk for women with higher risk of the disease. However, there is not much research on how well they work for women with BRCA1 or BRCA2 mutations. 

Taking oral contraceptives, or birth control pills, for 5 years may lower the risk of ovarian cancer for women with BRCA1 or BRCA2 mutations by 50%. However, this must be balanced by a potential slight increase in the risk of breast cancer. 

What are the screening options for HBOC?

Screening is the use of different tests to find specific types of cancer before signs and symptoms appear. It is important to talk with your health care team about the following screening options, as each person is different: 

Screening for women with a BRCA1 or BRCA2 gene mutation

  • Monthly breast self-examinations, beginning at age 18

  • Clinical breast examinations performed twice a year by a health care team or nurse, beginning at age 25

  • Yearly magnetic resonance imaging (MRI) scans of both breasts, between ages 25 and 29.

  • Yearly mammogram and breast MRI, between ages 30 and 75.

  • Pelvic examination, trans-vaginal ultrasound, and CA-125 blood test every 6 months, beginning at age 30 to 35. It should be noted, however, that screening for ovarian cancer is not yet able to find most early cancers.

  • Consideration of prophylactic salpingo-oophorectomy, between ages 35 and 40, and once a woman is done giving birth to children

Screening for men with a BRCA1 or BRCA2 gene mutation

  • Monthly breast self-examinations, beginning at age 35

  • Yearly clinical breast examinations, beginning at age 35

  • Consider a baseline mammogram at age 35 for men with a BRCA2 gene mutation, if there is gynecomastia, meaning swelling of the breast tissue in boys or men, or if enough breast tissue is present for mammogram

  • Yearly prostate cancer screening with digital rectal exam and PSA blood test, beginning at age 45. Current U.S. Preventive Services Task Force (USPSTF) guidelines for men that recommend reducing the use of PSA screening do not apply to men with a BRCA1 or BRCA2 gene mutation.

Screening options may change over time as new methods are developed and more is learned about HBOC. Talk with your health care team about appropriate screening tests for you.

Learn more about what to expect when having common tests, procedures, and scans. 

Questions to ask the health care team

If you are concerned about your risk of cancer, talk with your health care team. It can be helpful to bring someone along to your appointments to take notes. Consider asking your health care team the following questions:

  • What is my risk of developing breast cancer and ovarian cancer?

  • What can I do to reduce my risk of cancer?

  • What are my options for cancer screening?

If you are concerned about your family history and think your family may have HBOC, consider asking the following questions:

  • Does my family history increase my risk of breast cancer or ovarian cancer?

  • Should I meet with a genetic counselor?

  • Should I consider genetic testing?

Related Resources

The Genetics of Cancer

Genetic Testing

What to Expect When You Meet With a Genetic Counselor

Collecting Your Family Cancer History

Sharing Genetic Test Results with Your Family

Family Genetic Testing Q&A 

More Information 

National Comprehensive Cancer Network - Guidelines for Patients (registration required)
https://www.nccn.org/professionals/physician_gls/PDF/genetics_screening.pdf

Facing Our Risk of Cancer Empowered (FORCE) 
www.facingourrisk.org

Young Survival Coalition
www.youngsurvival.org

National Ovarian Cancer Coalition 
www.ovarian.org

Foundation for Women’s Cancers
www.foundationforwomenscancer.org

John W. Nick Foundation for Male Breast Cancer Awareness
www.malebreastcancer.org

To find a genetic counselor in your area, ask your health care team or visit the following websites:

National Society of Genetic Counselors
www.nsgc.org

National Cancer Institute: Cancer Genetics Services Directory
www.cancer.gov/about-cancer/causes-prevention/genetics/directory