Ovarian Cancer Genetic Testing: Enhancing Treatment Decisions for Patients

Ovarian cancer is a serious and often elusive disease that primarily affects women and those assigned female at birth, typically originating in the ovaries or fallopian tubes. Known for its “silent” progression, ovarian cancer often goes unnoticed in its early stages, as symptoms are subtle and easily mistaken for common conditions like aging or irritable bowel syndrome.

Once diagnosed, genetic testing becomes a crucial tool, uncovering the underlying factors that may contribute to the cancer’s development, as well as shaping personalized treatment plans. In addition, it may also reveal hidden hereditary risks, illuminating implications for family members.

CancerVision, Inocras’s comprehensive target-enhanced whole genome test offers a detailed analysis of a patient’s genome to detect mutations that standard panel or whole exome tests might miss. This powerful tool is designed to guide treatment decisions, support oncologists in providing second opinions, and identify clinical trial opportunities based on unique genetic markers. Additionally, CancerVision provides personalized support from genetic counselors, helping patients gain a clear understanding of their results and the next steps in their treatment journey.

In this article, we’ll dive into the genetic connections of ovarian cancer, the importance of genetic tests, and essential information for those considering genetic testing.

Understanding ovarian cancer and its genetic links

BRCA genes

One of the most significant risk factors for developing ovarian cancer is an inherited variant in one of two specific genes: BRCA1 and BRCA2.

• Breast cancer gene 1 (BRCA1): The BRCA1 gene is a tumor suppressor that keeps cells from growing too rapidly and helps repair damaged DNA, helping to prevent cancer. A genetic variation in this gene can cause it to not work properly, which can increase the risk of developing breast cancer. BRCA1 is the most well-known breast cancer-related gene.
• Breast cancer gene 2 (BRCA2): Like BRCA1, the BRCA2 gene is also a tumor suppressor that can be disabled due to a genetic change. A variant in your BRCA2 gene is less likely to lead to ovarian cancers than a variant of the BRCA1 gene but still increases your risk over the general population.

A change in your BRCA1 gene increases your risk for ovarian cancer by 39-46% by the age of 70. The ovarian cancer risk caused by the BRCA2 gene is 10-27% by the age of 70. This is compared to an average risk of just 2% for the general population.

Other genes that increase risk

Additional genetic risk factors for ovarian cancer include:

• Lynch syndrome: For a person with a genetic variant in their Lynch Syndrome genes, which includes the MLH1, MSH2, and MSH6 genes, there is a 10-17% risk they’ll develop ovarian cancer in their lifetime.
• PALB2 variant: A variant in your PALB2 gene mostly increases your breast cancer risk, but it also slightly elevates your risk of ovarian cancer to 2-10%.
• RAD51C, RAD51D, and BRIP1 variants: These genetic variants can increase your ovarian cancer risk by at least 5% and up to 25%, respectively. However, variants in these genes are rare.
• STK11 variants: Variants in this gene affect risk in different ways. Genetic counseling can help you understand your personal risk following genetic testing.

Since these genetic variants impact cancer in unique ways, identifying them is crucial for tailoring your treatment plan. Knowing your genetic makeup may also reveal whether you’re at a heightened risk for other types of cancer, allowing you to follow a more precise and proactive screening schedule.

The role of germline and somatic variants in ovarian cancer

The lifetime risk of developing ovarian cancer is about 1 in 87 for the general population. It could occur due to either somatic or germline variants.

Germline variants

Germline variants are genetic variations that you inherit during conception. Also known as hereditary variants, these changes are incorporated into your DNA and can be inherited from either parent. They can put you at increased risk of developing cancer and impact how your ovarian tumors grow.

Up to a quarter of ovarian cancer cases are hereditary. National Cancer Institute Guidelines state that all people with ovarian cancer should be offered germline genetic testing, yet less than 7% of people diagnosed with cancer underwent germline testing in 2021.

People who have certain genetic variants are at higher risk of getting an ovarian cancer diagnosis.

Somatic variants

Somatic variants refer to gene changes that happen after conception and that alter your DNA. These changes can occur in any cells in your body except for your germ cells, which means they would not be passed on to your children.

Causes of somatic variants include:

• Errors in DNA repair mechanisms
• Environmental factors like exposure to certain chemicals or other environmental stressors, such as UV radiation
• Errors during cell replications

Somatic variants are changes in your genes. Some of them give cancer cells a survival advantage, helping tumors grow and spread. These changes tend to accumulate as you get older. The more somatic changes a tumor has, the more likely it is to behave aggressively. In some cases, these changes can increase your risk of developing cancer. Additionally, if you have certain inherited gene variants (germline variants), you may be more likely to develop these somatic changes, which can further raise your cancer risk.

Why comprehensive genetic testing matters for ovarian cancer patients

Comprehensive understanding on both somatic and germline mutations is critical for the following reasons:

Personalized treatment

Comprehensive testing provides insights that allow for more personalized treatment. Predicting how your tumor may grow and develop can help your doctors and care team make informed decisions about which treatments could be more effective for you. This can help prevent unnecessary treatments that might not work and may also cause harsh side effects, as well as over-treatment.

Clinical trials

Data shows that 55% of all clinical oncology trials involve the use of biomarkers, which is in an increasing trend. Knowing driver mutations behind your ovarian cancer and if the driver mutations are from somatic or germline would be critical to access to the novel treatments.

Implications on family health considerations

If the test identifies hereditary variants related to your cancer, family members may want to consider genetic testing to better understand their own health risks. This information empowers them to take proactive steps in managing their health.

Comprehensive genetic testing with CancerVision: What patients need to know

Inocras believes every cancer patient should be empowered with as much information as possible about their genes and their cancer so they can pursue the best treatment and health outcomes possible. Our CancerVision test is comprehensive in two ways:

1. It looks at more than 99% of your genetic make-up, capturing more mutations that other genetic tests often miss.
2. It provides both somatic and germline findings all at once. Sometimes, we see recurring cancer patients who went through a treatment based on somatic test results (tumor-only test), but are missing critical information about germline mutations that can be the cause of the recurrence of the cancer.

The testing process

You can get started with CancerVision in two ways:

1. Consult with your oncologist to discuss CancerVision, a whole genome cancer profiling test (somatic-matched germline)

2. Request an order on our website

• You request the test online and your request will be approved by an external physician.
• You will get a link to make an appointment for a phlebotomist to visit your home and draw your blood sample.
• Based on the information you provide, we will work with your care team/pathologist’s office to collect it. No action is required from you.
• Once your results are ready, you will meet with a genetic counselor who will interpret your test results and discuss them with you in detail, and also answer your questions. We recommend you bring back the results to your treating oncologist or care team.

The CancerVision test also comes with in-depth clinical trial matching services that will inform you of your potential eligibility in current ovarian cancer clinical trials. If a match is found, it could widen your treatment options to treatments that aren’t yet available to everyone.

Taking control: empowering ovarian cancer patients with genetic insights

When it comes to managing ovarian cancer, having a complete understanding of your genetic profile can open doors to better treatment options. By providing both germline and somatic insights, CancerVision equips you with the detailed information needed to make more informed decisions about your care.

Take charge of your treatment journey with clarity and confidence. Start with CancerVision today to explore all your options.

References

• BRCA1 and BRCA2 mutations. (n.d.). ACOG. https://www.acog.org/womens-health/faqs/brca1-and-brca2-mutations
• Cancer of the ovary – Cancer Stat Facts. (n.d.). SEER. https://seer.cancer.gov/statfacts/html/ovary.html
• Few People with Cancer Undergo Germline Testing. (2023, August 1). Cancer.gov. https://www.cancer.gov/news-events/cancer-currents-blog/2023/germline-testing-for-cancer-underused
• Genetics, Somatic mutation. (2024, January 1). PubMed. https://pubmed.ncbi.nlm.nih.gov/32491819/
• Kurian, A. W., Abrahamse, P., Furgal, A., Ward, K. C., Hamilton, A. S., Hodan, R., Tocco, R., Liu, L., Berek, J. S., Hoang, L., Yussuf, A., Susswein, L., Esplin, E. D., Slavin, T. P., Gomez, S. L., Hofer, T. P., & Katz, S. J. (2023). Germline genetic testing after cancer diagnosis. JAMA, 330(1), 43. https://doi.org/10.1001/jama.2023.9526
• NCI Dictionary of Cancer Terms. (n.d.). Cancer.gov. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/somatic-mutation
• Ovarian cancer. (2024, June 13). Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/4447-ovarian-cancer
• Ovarian cancer – Symptoms and causes – Mayo Clinic. (2023, May 9). Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/ovarian-cancer/symptoms-causes/syc-20375941
• Ovarian Cancer Risk Factors and Prevention | OCRA. (n.d.). OCRA. https://ocrahope.org/get-the-facts/causes-risk-factors/
• Ovarian Cancer Statistics | How Common is Ovarian Cancer. (n.d.). American Cancer Society. https://www.cancer.org/cancer/types/ovarian-cancer/about/key-statistics.html
• Target Ovarian Cancer. (n.d.). Gene variants. https://targetovariancancer.org.uk/about-ovarian-cancer/genetic-genomic-testing/hereditary-ovarian-cancer/gene-variants