Hereditary breast cancer is not limited to BRCA mutations; there are many other pathogenic gene variants that have been identified.
Genetic testing for hereditary breast cancer should be based on national guidelines, family history, and guidance from genetic counselors.
Deep dives
Understanding Hereditary Breast Cancer
Hereditary breast cancer is not limited to BRCA or BRACO mutations; there are now more pathogenic genes to be aware of. Pathogenic variants refer to gene mutations that render a gene unreadable or lead to a non-functional protein, increasing the risk for breast cancer. On the other hand, variants of uncertain significance (VUS) are alterations in genes that are not necessarily associated with higher cancer risk. As more genetic testing data is collected, VUS will be reclassified, with the majority being found to be normal variations. It is important for individuals with VUS to have routine follow-up to ensure their variant has not been reclassified as a pathogenic mutation.
Genetic Testing Modalities for Hereditary Breast Cancer
Genetic testing for hereditary breast cancer can involve panel testing, where a panel of genes is analyzed for mutations. The size of the panel can vary, ranging from 8 genes to 250 genes. The cost of these gene panels has decreased over the years, making testing more accessible. Referring patients for genetic testing depends on various factors, including national guidelines and family history. It is recommended that all patients with a new breast cancer diagnosis undergo testing, although specific criteria based on age, type of cancer, and family history should also be considered. Guidance from genetic counselors is crucial to ensure appropriate testing and follow-up.
High Penetrance Genes and Breast Cancer Susceptibility
In addition to BRCA1 and BRCA2, other high penetrance breast cancer susceptibility genes include PALB2, CHECK2, P53, and PTEN. These genes are associated with increased risk of breast cancer, and patients with specific gene mutations should undergo genetic testing. Family history plays a crucial role in identifying individuals who may benefit from testing, especially those with close blood relatives who have had breast, ovarian, pancreatic, or metastatic prostate cancer. Genetic testing helps identify individuals at high risk and informs management decisions, such as preventive surgeries or intensified screening protocols.
Surgical Management and Risk Reduction for Hereditary Breast Cancer
For individuals with known pathogenic mutations and breast cancer, treatment recommendations depend on various factors. For individuals without a diagnosis, options include intensified screening or prophylactic surgeries. Risk-reducing surgeries like bilateral mastectomy are common choices, but breast-conserving surgery is also possible with high-risk surveillance. Patients with known genetic mutations should be referred to gynecology for ovarian cancer risk assessment. The choice of surgery for breast cancer patients with pathogenic mutations is influenced by the gene involved and other factors like tumor biology. Risk-reducing endocrine therapy may be considered for certain gene mutations, but the benefits and side effects should be carefully evaluated.
While you are likely aware of BRCA mutations as a significant risk factor for development of breast cancer (60-80% lifetime risk), there are many other pathogenic gene variants that have been identified in recent years. The surgical treatment of women with hereditary breast cancer differs from that of women with sporadic breast cancer, and women with hereditary breast cancer are also eligible for prophylactic mastectomy or intensive surveillance protocols. In this episode of BTK, we examine current national consensus guidelines for management of hereditary breast cancer, discuss a recent population-based study that establishes risk associated with various genes, and address both surgical and surveillance strategy for patients without breast cancer but with known pathogenic gene variants.
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