Genetic testing panels for breast cancer assess an individual’s inherited risk for the disease. These tests examine multiple genes associated with an increased likelihood of developing breast cancer and other related cancers. These panels identify pathogenic variants that elevate cancer risk. Understanding these genetic predispositions allows for informed decisions on cancer prevention, early detection, and personalized management.
Who Benefits from Testing
Genetic testing for breast cancer is recommended for individuals with a higher inherited risk. This includes a strong family history of breast cancer, particularly if diagnoses occurred at younger ages, or a family history of male breast cancer.
Individuals with a personal history of breast cancer diagnosed at age 50 or younger, or those with triple-negative breast cancer at any age, are also candidates. Cancer in both breasts, either simultaneously or at different times, especially if the first diagnosis was before age 50, is another indicator. Certain ethnic backgrounds, like Ashkenazi or Eastern European Jewish ancestry, are associated with an increased risk and may warrant testing.
Common Genes Included in Panels
The genes BRCA1 and BRCA2 are the most well-known and account for many hereditary breast cancers. These tumor suppressor genes normally help repair damaged DNA and regulate cell growth. Mutations can impair these functions, leading to uncontrolled cell division.
Panels also include other genes involved in DNA repair or cell regulation. PALB2 (Partner and Localizer of BRCA2) works closely with BRCA2 in DNA repair, and its mutations are associated with a high risk of breast cancer. CHEK2 (Checkpoint Kinase 2) is involved in DNA repair and cell cycle control, and mutations can increase breast cancer risk. ATM (Ataxia-Telangiectasia Mutated) also helps repair damaged DNA, and mutations are linked to an elevated breast cancer risk.
TP53 (Tumor Protein 53) is a tumor suppressor gene that, when mutated, can lead to Li-Fraumeni syndrome, causing a very high lifetime risk of various cancers, including breast cancer. CDH1 (Cadherin 1) is a tumor suppressor gene associated with hereditary diffuse gastric cancer and an increased risk of invasive lobular carcinoma. PTEN (Phosphatase and Tensin Homolog) is a tumor suppressor involved in cell survival and proliferation; mutations are linked to Cowden syndrome, increasing risks for breast, endometrial, thyroid, kidney, and colorectal cancers. STK11 (Serine/Threonine Protein Kinase 11) regulates the cell cycle and inhibits tumor growth; mutations are associated with Peutz-Jeghers syndrome, which also increases breast cancer risk.
Understanding Your Test Results
Genetic testing panels can yield different types of results. A “positive” result means a pathogenic or likely pathogenic variant was detected in one of the genes tested. This indicates an increased inherited risk for certain cancers, including breast cancer, but it does not predict if or when cancer will develop. For individuals already diagnosed with breast cancer, a positive result can influence treatment decisions and future risk management.
A “negative” result signifies that no known pathogenic variants were found in the genes included in the panel. It suggests the individual’s risk for hereditary breast cancer is not elevated, but it does not eliminate the general population risk for cancer. Remember that most breast cancers are not hereditary, and a negative test does not mean zero risk.
A “variant of uncertain significance” (VUS) result indicates a change in a gene where there is insufficient scientific data to determine if it increases cancer risk. VUS results are more common with multi-gene panel testing. Most VUS findings are eventually reclassified as benign, meaning they do not increase cancer risk, and do not impact current medical care decisions. However, ongoing research may lead to reclassification of a VUS over time, and individuals should discuss any updates with their healthcare provider.
Making Decisions Based on Results
Receiving genetic test results for breast cancer can lead to important discussions about future health management. For individuals with a positive result, increased surveillance is often recommended to detect cancer early. This may include more frequent mammograms, breast magnetic resonance imaging (MRI), or clinical breast exams, often starting at a younger age. These enhanced screenings aim to identify any cancerous changes at their most treatable stages.
Risk-reducing surgeries are another option for individuals with high-risk genetic variants. A prophylactic mastectomy, which involves the surgical removal of one or both breasts, can significantly reduce the risk of developing breast cancer. Similarly, a prophylactic oophorectomy, the removal of the ovaries and fallopian tubes, can reduce the risk of ovarian cancer and may also lower breast cancer risk, particularly for BRCA1 and BRCA2 carriers. Chemoprevention, using medications to reduce cancer risk, might also be considered.
Genetic testing results also have implications for family members, as certain genetic variants are inherited. Relatives may be encouraged to undergo testing to understand their own risks, allowing them to make informed decisions about their health management. Consulting with a genetic counselor is highly recommended after receiving test results. Genetic counselors provide detailed explanations of the results, discuss personalized risk assessments, and help individuals navigate the complex decisions regarding surveillance, preventive strategies, and the emotional impact of the findings.