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Several years ago, the actress and film director Angelina Jolie revealed that she had lost her mother to ovarian cancer and had learned, through genetic testing, that she carried a BRCA mutation. She decided to have elective double-mastectomy surgery and breast reconstruction. By writing and talking about her situation, the actress raised public awareness about BRCA genetic testing and an inherited disorder called Hereditary Breast and Ovarian Cancer (HBOC) syndrome. 

Of all the genes we are born with, every human has two called BRCA1 and BRCA2. We inherit copies of these genes from our parents, and they play important roles in fixing copying errors made within DNA. For most people, these genes function properly. But some individuals are born with mutations in these genes—that’s HBOC. Men and women with this condition face an increased lifetime risk of developing breast cancer, and, for women, ovarian cancer. Genetic mutations within those two genes are also associated with a higher risk of prostate, pancreatic, fallopian tube, peritoneal, and skin cancer, but the risks are not well-established. 

About 5 to 10 percent of breast cancers and 10 to 15 percent of ovarian cancers are linked to hereditary causes. 

The CDC lists HBOC syndrome as a “tier one” genomic health condition, which means that studies and research have shown that intervention options exist to decrease one’s chance of developing a disease—in this case, cancer—after receiving a positive genetic test for a particular mutation. 

“There’s value in BRCA genetic testing if you are a healthy person with a strong family history of BRCA-related cancers, or if you have been diagnosed with a cancer associated with BRCA,” says Yale Medicine medical oncologist Erin Hofstatter, MD. “For the healthy patient with a positive genetic result, there’s a lot that can be done with screening and prevention, starting as young as 25 years old. For those with cancer, certain drugs and treatments appear to be more effective in patients BRCA mutations. We are essentially providing more personalized medicine.” 

At Yale Medicine, we offer genetic testing and guidance on preventative actions that can be taken to decrease the chances of developing cancer after an HBOC syndrome diagnosis. 

What causes HBOC syndrome?

Mutations in the BRCA1 and BRCA2 genes are the primary cause of the syndrome. Genetic mutations in other genes are also associated with it, but those instance are rare. BRCA genes, a type of tumor suppressor gene, earned their name from the first two letters of the words ‘breast cancer.’ Their job is to act like the autocorrect function on text messaging, to correct genetic mistakes in DNA that have been copied into new cells. When these genes are not functioning properly, genetic mistakes can build up and cause a cell to become cancerous. 

Who is at risk of having BRCA1 and BRCA2 mutations?

A family medical history of cancer remains the most important tool when assessing the risk of inherited genetic mutations. Compared to the general population, BRCA mutations occur in 1 in 40 people of Ashkenazi Jewish descent. 

Who should receive genetic testing for BRCA1 and BRCA2 mutations?

Genetic testing for HBOC syndrome could be helpful in people with a family history (1st-, 2nd-, or 3rd-degree relative) of any of the following characteristics, according to the National Comprehensive Cancer Network (NCCN) guidelines: 

  • A previously identified BRCA1 or BRCA2 pathogenic mutation in the family
  • Two or more relatives with breast cancer, one under age 50
  • Breast cancer diagnosed at any age in an individual of Ashkenazi Jewish ancestry
  • Three or more relatives with breast cancer at any age
  • Multiple primary breast cancers either in one or both breasts
  • Triple-negative (estrogen receptor-negative, progesterone receptor-negative, and HER2/neu [human epidermal growth factor receptor 2]-negative) breast cancer, particularly when diagnosed before age 60
  • Breast cancer diagnosed at or before age 50
  • Ovarian cancer
  • Male breast cancer
  • The combination of pancreatic cancer and/or prostate cancer with breast cancer, and/or ovarian cancer

If someone is diagnosed with any of the cancers associated with HBOC syndrome, and meets any of the above criteria, genetic testing is also recommended so that a genetic mutation within a family can be established and family members can be tested. A positive or negative BRCA genetic mutation result can also inform a person’s individualized cancer treatment plan.

Which genetic tests are available to detect BRCA1 and BRCA2 mutations?

At Yale Medicine, our physicians offer multi-gene testing panels in order to determine whether HBOC mutations are present. This clinical genetic testing is very thorough, and a genetic counselor will go over the results of the test with you. Genetic test results can sometimes detect mutations of an unknown significance (VUS). That particular genetic mutation’s influence on the disease is uncertain. “In most cases, VUS are benign and we do not use them clinically,” Dr. Hofstatter says. This testing and counseling is generally covered by insurance.

Is it possible to do BRCA testing with at-home DNA test kits?

Some at-home DNA testing kits offer BRCA testing. However, these tests do not search for all possible mutations, and the results can be misleading. At Yale Medicine, our physicians gather clinical actionable data, which includes genetic testing and sequencing, together with genetic counselors and offer rigorous genetic testing methods. 

What preventative action can women take after an HBOC syndrome diagnosis?

Surgery, medication, and increased cancer screenings are all options that have been thoroughly studied and found to offer some benefit after an HBOC diagnosis. 

  • Risk-Reducing Surgery. It’s possible to have elective surgery to remove one or both breasts (mastectomy) and ovaries and fallopian tubes (salpingo-oophorectomy). However, it’s important to note that these surgeries have been found to reduce but not eliminate the risk of getting cancer in the future. All surgery comes with risks and benefits. Patients can carefully consider these when discussing surgical options with their medical team. Both of the above procedures can profoundly affect a woman’s physical and emotional health due, in part, to changes in hormones that could result when these organs are removed. Physicians usually recommend that pre-menopausal patients receive hormone-replacement therapy to help address these concerns.
  • Cancer Screening. Women can begin self-breast exams starting at age 18, depending on the age of the genetic diagnosis, and clinical breast exams with magnetic resonance imaging (MRI) scans twice a year beginning at age 25. Mammogram tests can usually begin around age 30. Screening for ovarian cancer can be done through transvaginal ultrasounds and CA-125 blood tests.
  • Medications. Medications can be taken to lower the chance of developing breast or ovarian cancer. Tamoxifen and raloxifene are two hormone therapies that can be prescribed to women with HBOC. 

Which preventative action steps can men take after an HBOC syndrome diagnosis?

Men with BRCA mutations should begin prostate cancer screening at age 40 and doctors can refer them to a dermatologist for melanoma screening.

What is unique about Yale Medicine’s approach to HBOC syndrome?

Our physicians are conducting research to better understand the complex relationship between BRCA mutations and cancer risks. “We aim to be a one-stop shop for patients who receive a positive genetic result. We have a team of physicians and nurse practitioners who are available for the planning and providing of longitudinal cancer screening and intervention care,” Dr. Hofstatter says.