At some point in their life, 1 in 8 women will develop breast cancer. Approximately 20% of breast cancer cases are familial, affecting two or more women in the same family, usually at a later age. An estimated 5% to 10% of breast cancers are caused by a genetic mutation, called hereditary breast cancer.

Red flags for hereditary breast cancer include breast cancer at age 50 or under, breast cancer among multiple women on one side of a family, or when a patient has more than one primary breast cancer or breast cancer with another cancer.

A family history of male breast cancer, a personal or family history of ovarian cancer or pancreatic cancer, and triple-negative breast cancer are other red flags. Triple-negative breast cancer refers to the characteristics of the cancer cells: They don’t have estrogen or progesterone receptors or the human epidermal growth factor receptor 2 (HER2) protein.

“Genetic testing for hereditary breast/ovarian cancer syndrome is indicated if one or more of these red flags is present,” said Kara M. Goodin, M.D., a cancer geneticist with Norton Cancer Institute. Dr. Goodin presented on “Hereditary Breast Cancer” in a 2021 continuing medical education opportunity.

Genetic testing for breast cancer risk is different from genetic testing of the tumor cells themselves. Historically, genetic testing of the tumor cells has focused on looking for a mutation in either the BRCA1 or BRCA2 gene.

Someone whose genetic testing is positive for a mutation in one of the breast cancer predisposition genes is considered to have a hereditary breast cancer syndrome. Currently, there are about 20 genes associated with an increased breast cancer risk. The cancer risk varies by gene, and recommendations for screening and management depend on the gene.

When a diagnosis of breast cancer is made, testing is performed on the tumor, looking at hormone receptor status, determining if it is estrogen- or progesterone- receptor-positive, and at the HER2 gene to see if the cancer cells are making too many copies. When a test result is positive, additional treatment options are available to block the hormones or HER2 overexpression.

Most cancers diagnosed in people with the BRCA1 gene mutation are triple-negative, which is a more aggressive type of tumor with a higher risk of metastasis and recurrence.

Counseling whether the genetic test is positive or negative

Genetic counseling provides information and support to people who have, or may have, a genetic condition. It is conducted by a genetic provider, either a genetic counselor or geneticist, who has specialized training in the field. The purpose of cancer genetic counseling is to assess risk for familial or hereditary cancer syndrome, and provide information in an unbiased way so the individual can decide whether or not to have genetic testing.

Genetic providers obtain a family history that covers at least three generations, collecting information on at least first-, second- and third-degree relatives, including types of cancer and ages of onset, as well as ages of death.

“Not all negatives are the same. It may decrease the chance to have a hereditary cancer syndrome, but doesn’t eliminate it. … During post-test genetic counseling, we review residual risks, which may include breast cancer risk models. These models combine personal risk factors, such as height, weight and hormone exposure, along with family history of breast and ovarian cancer to determine a woman’s lifetime risk for breast cancer. If the risk is 20% or greater, they qualify for annual breast cancer screening MRIs even if genetic testing was negative,” Dr. Goodin said.

Overall, a woman has approximately a 13% chance of developing breast cancer, with the median age 63 at diagnosis.

Genetic testing as a risk assessment

Genetic testing impacts recommendations for cancer screening, management and prevention options. For patients with breast cancer, it can affect the medical decision, including whether to use platinum-based therapies or PARP inhibitors, and surgical decisions such as whether to perform a lumpectomy or mastectomy and whether the mastectomy should be one side or both.

Possible prevention options for patients whose genetic test result is positive but do not have breast cancer include chemoprevention with anti-estrogen treatment. This reduces the risk of breast cancer but can lead to symptoms of menopause. Prophylactic mastectomy provides the most significant risk reduction. This surgery reduces the risk for breast cancer by at least 95% in women with a BRCA1 or BCRA2 gene mutation and up to 90% in women with a strong family history of breast cancer.

“The National Comprehensive Cancer Network recommends discussing risk-reducing mastectomy as an option for several other genes as well, while for some genes it recommends managing based on family history,” Dr. Goodin said.

The main option for decreasing ovarian cancer risk is salpingo-oophorectomy. This surgery decreases the risk for ovarian cancer by about 90%. When performed prior to menopause, it can decrease the breast cancer risk as well by approximately 50% in high-risk patients.

“While providing genetic counseling, we also discuss recommendations regarding other cancers when indicated. For all patients, whether positive or negative, we provide a summary letter which reviews their history, genetic testing, risk assessment and recommendations for them and their family members,” she said.