Hereditary breast–ovarian cancer syndrome

Overview

Hereditary Breast–Ovarian Cancer Syndrome (HBOC) is a genetic condition that significantly increases an individual's risk of developing breast cancer, ovarian cancer, and other related cancers. It is most commonly associated with mutations in the BRCA1 and BRCA2 genes. Individuals with HBOC typically have a family history of breast or ovarian cancer, often at younger ages than seen in the general population. Early identification and management through genetic testing and preventive strategies are crucial to reducing cancer risk and improving outcomes.

Causes

HBOC is caused by inherited mutations in tumor suppressor genes, primarily:

• BRCA1 (Breast Cancer gene 1): Located on chromosome 17

• BRCA2 (Breast Cancer gene 2): Located on chromosome 13

These genes normally help repair damaged DNA and prevent uncontrolled cell growth. When mutated, they lose their protective function, leading to increased cancer susceptibility. The condition follows an autosomal dominant inheritance pattern, meaning a person only needs one copy of the altered gene from either parent to be at risk.

Symptoms

HBOC syndrome itself does not cause symptoms, but individuals are at a higher risk of developing specific cancers, including:

• Breast cancer: Often early-onset, may be bilateral or triple-negative

• Ovarian cancer: Including fallopian tube and primary peritoneal cancers

• Male breast cancer: Particularly associated with BRCA2 mutations

• Prostate cancer: More aggressive and earlier onset

• Pancreatic cancer: Increased risk in both BRCA1 and BRCA2 carriers

Family history may reveal multiple relatives with breast or ovarian cancer, often diagnosed before age 50, or individuals with multiple primary cancers.

Diagnosis

Diagnosis of HBOC involves a combination of personal and family cancer history and genetic testing. Key diagnostic steps include:

• Risk assessment: Evaluation of family history of breast, ovarian, and related cancers

• Genetic counseling: Provided before and after testing to discuss risks and implications

• Genetic testing: Blood or saliva test to detect mutations in BRCA1, BRCA2, and potentially other genes (e.g., PALB2, CHEK2, ATM)

• Tumor testing: Sometimes used to guide germline testing decisions

Testing is typically recommended for individuals with strong family histories or personal history of early or multiple cancers.

Treatment

Management of HBOC involves cancer surveillance, risk-reducing strategies, and treatment if cancer develops. Options include:

• Enhanced screening: Annual breast MRI and mammography starting at an earlier age

• Risk-reducing surgery:

  • Bilateral mastectomy to lower breast cancer risk

  • Salpingo-oophorectomy (removal of ovaries and fallopian tubes) to reduce ovarian cancer risk

• Medications: Chemoprevention with tamoxifen or raloxifene may be considered

• Targeted therapies: For individuals with cancer, PARP inhibitors (e.g., olaparib) are effective in BRCA-mutated cancers

• Lifestyle modifications: Maintaining a healthy weight, avoiding smoking, and regular physical activity

Management should be personalized based on the individual's mutation status, family history, and preferences.

Prognosis

Individuals with HBOC who do not develop cancer can lead healthy lives with appropriate preventive care. For those who develop cancer, early detection through screening and access to targeted treatments significantly improves survival. The lifetime risk of breast cancer in BRCA1/2 mutation carriers can range from 45% to 85%, and the risk of ovarian cancer ranges from 10% to 45%, depending on the gene involved. With proactive monitoring and intervention, many risks can be effectively managed.