Management of Hereditary Breast Cancer

Last updated March 17, 2022

Key Points

Key Points

  • The integration of genomics into the care of oncology patients has led to an increasing population of breast cancer patients identified with germline (i.e., inherited) mutations in breast cancer susceptibility genes, requiring physicians to integrate this information into treatment decision-making.
  • Pathogenic or likely pathogenic variants (commonly referred to as mutations) in high-penetrance breast cancer susceptibility genes increase the risk of breast cancer more than 4-fold.
    • Germline mutations in BRCA1 or BRCA2 (BRCA1/2) are found in 3–4% of all women with breast cancer, including 10–20% of those with triple negative breast cancer and 10–15% of Jewish women with breast cancer.
    • The lifetime risk of breast cancer for a BRCA mutation carrier varies from 50–90% based on populations studied, gene, study design and method of analysis.
    • Other high-penetrance breast cancer susceptibility genes include PTEN (Cowden's Syndrome), TP53 (Li-Fraumeni Syndrome), STK11 (Peutz-Jeghers Syndrome), and CDH1 (Hereditary Invasive Lobular Breast-Diffuse Gastric Cancer).
    • Mutations in more moderate-penetrance genes such as PALB2CHEK2, and ATM occur in 4–6% of breast cancer patients with lifetime risk of 35%–60% (PALB2) and 25%–30% (ATM and CHEK2).
  • Providers caring for breast cancer patients with germline BRCA1/2 mutations should discuss treatment options related to the index cancer and the increased risk of contralateral breast and new ipsilateral breast cancer.

Management

Recommendation 1.1Germline BRCA status...


...on 1.2Surgical management of the index m...


...endation 1.3The following factors should be c...


...ion 1.4BRCA1/2 mutation carriers who do not h...


...2.1For women with newly diagnosed b...


...2.2In breast cancer patients with a mutation i...


...ion 2.3The evidence regarding contralater...


...dation 2.4Patients with mutations...


...ion 3.1For women with newly diagnosed...


...mendation 3.2For women with newly diag...


...ion 4.1For women with breast cancer...


...n 4.2For women with breast cancer w...


...5.1For breast cancer patients with a deleteriou...


...commendation 5.2For breast cancer pati...


...endation 6.1For women with breast cancer who ar...


...ation 6.2For women with breast cancer who ar...


...6.3For women with breast cancer who are carri...


...When offering chemotherapy for germline BRC...


...mendation 8For germline BRCA mutation carr...


...ommendation 9.1For BRCA1/2 mutati...


...ecommendation 9.2For breast cancer p...


...tion 10For germline BRCA mutation carriers, there...


...ment of Hereditary Breast Cancer in BRCA1/...