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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 PALB2, CHEK2, 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.
