Breast Cancer (BC)

Hereditary forms of breast cancer

Up to 10% of breast cancer cases are hereditary.

The most common cause of hereditary breast cancer is a mutation in the BRCA1 or BRCA2 genes. If there is a pathogenic variant in these genes:

• lifetime risk of breast cancer is on average 70%,
• breast cancer is more likely to be diagnosed at a younger age,
• cancer of both mammary glands is more likely to be diagnosed,
• a higher risk of developing ovarian cancer and some other types of cancer, including in men.

Other genes / syndromes associated with an increased risk of BC:

PALB2

CHEK2

ATM: Inheritance of 2 abnormal copies of this gene causes disease called ataxia-telangiectasia. Inheritance of one abnormal copy of this gene is associated with a high risk of breast cancer. The 7271T>G missense mutation increases the lifetime risk of developing breast cancer to 60% by the age of 80 (which is higher than with nonsense mutations, the risk for which is 30-40%). Autosomal recessive forms in offspring are possible.

TP53: Mutations in this gene cause Li-Fraumeni syndrome. People with this syndrome have an increased risk of developing breast cancer, as well as some other cancers such as leukemia, brain tumors, and sarcomas (cancer of the bones or connective tissue).

PTEN: Cowden syndrome is a rare disease that puts people at increased risk of developing both cancer and benign (non-cancerous) breast tumors, as well as neoplasms in the digestive tract, thyroid, uterus, and ovaries.

CDH1: Mutations in this gene cause hereditary diffuse gastric cancer, a syndrome in which people develop a rare type of stomach cancer. Women with mutations in this gene also have an increased risk of invasive lobular breast cancer.

STK11: Defects in this gene can lead to Peutz-Jeghers syndrome. People suffering from this disorder have polyps in the urinary and digestive tract, as well as a higher risk of developing cancers in various parts of the gastrointestinal tract, endometrium, and breast cancer.

If you are at increased risk for breast cancer (for example, because you have a family history of a known genetic mutation, there are a few things you can consider that may help lower your risks of developing breast cancer (or help detect it on the early stage):

Genetic counseling and testing for breast cancer risk (if not already done)

Medications to reduce the risk of breast cancer

The drugs tamoxifen and raloxifene block the action of estrogen in breast tissue. Tamoxifen may be an option even before menopause, while raloxifene is only used for women who are in menopause.

Aromatase inhibitors may also be used in women after menopause.

All of these drugs have side effects, so it is important to understand the possible benefits and risks of taking them.

Preventive (prophylactic) surgery

For a small proportion of women with a very high risk of breast cancer, such as a BRCA gene mutation, surgery to remove the breast (prophylactic mastectomy) may be an option.

One more option may be to remove the ovaries, which are the main source of estrogen in the body. While surgery may reduce the risk of breast cancer, it cannot completely eliminate it and may have its side effects.

Careful surveillance for early signs of breast cancer

For women at increased risk of breast cancer, doctors may recommend careful monitoring:

• More frequent visits to the doctor (for example, every 6-12 months) for breast examination and ongoing risk assessment.
• To start breast cancer screening with an annual mammogram at a younger age.
• Another screening test, such as an MRI, may be added.