Hereditary Breast Cancer Syndromes

A number of hereditary syndromes are associated with an increased risk of breast cancer. The most common involve mutations of the BRCA1 and BRCA2 genes.

The risk of breast cancer among women with BRCA1 mutations approaches 80%, with ovarian cancer risk as high as 45%.

BRCA2 carriers have slightly lower rates of both breast (up to 60%) and ovarian (up to 25%) cancers. Male breast cancers are more likely to be BRCA2 if the man is found to be a gene carrier.

Less than half of the hereditary cancers are secondary to non-BRCA genetic mutations.

Cowden Syndrome is associated with PTEN mutations and has an autosomal dominance inheritance pattern. Individuals have an increased lifetime risk of breast cancer (20% to 50%), with most diagnosed before age 50 years, as well as high rates of benign breast disease. Follicular thyroid and endometrial cancers are commonly seen in association with this syndrome as well. Screening includes surveillance of the kidneys and colon, as they are increased in risk for cancers of these organs as well.

Peutz-Jeghers syndrome is characterized by mutations in STK11 and also demonstrates autosomal dominant inheritance. Individuals have a breast cancer risk of 55%, along with elevated rates of both ovarian and uterine cancer. These individuals often have multiple hamartomatous polyps throughout the gastrointestinal tract, as well as multiple melanin deposits in the mouth, lips, fingers, and toes.

Li-Fraumeni syndrome is characterized by mutations of the TP53 a suppressor gene and is also inherited in an autosomal dominant pattern. These individuals have strikingly high rates of malignancy, with 50% of individuals diagnosed with cancer by age 30, and 90% diagnosed with cancer by age 70. Malignancies include breast, with the majority diagnosed by age 45 years, sarcomas, osteosarcomas, leukemias, brain tumors, and adrenocortical tumors. Radiation-induced tumors have been seen frequently among these patients, leading many radiation oncologists to advise against breast-conservation therapy in women with Li-Fraumeni diagnosed with breast cancers.


Economopoulou P, Dimitriadis G, Psyrri A. Beyond BRCA: New hereditary breast cancer susceptibility genes. Cancer Treat Rev. 2015;41:1-8.

Issacs C, Peshkin BN, Schwartz M. Genetic testing and management of patients with hereditary breast cancer diseases of the breast. In: Harris JR, Lippman ME, Morrow M, Osborne CK, eds. Diseases of the Breast. 4th ed. Philadelphia, PA: Wolters Kluwer/Lippincott Williams & Wilkins; 2010:224-247.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Genetic / Familial High-Risk Assessment: Breast and Ovarian. Available at

Ready K, Arun B. Breast cancer syndromes: counseling and management. In: Babiera GV, Skoracki RJ, Esteva FJ, eds. Advanced Therapy of Breast Disease. 3rd ed. Shelton, CT: People’s Medical Publishing House-USA; 2012:29-38.

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