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PubMed This is a summary of 24 peer-reviewed journal articles Updated
Oncology · Hereditary Breast and Ovarian Cancer Syndrome

Genetic Testing and Understanding Your Results

At a Glance

Genetic testing for hereditary cancer uses multi-gene panels to find mutations that increase your risk. While a positive result can change your screening plan, a Variant of Uncertain Significance (VUS) is treated as a normal result and should not be used to make major medical decisions like surgery.

Genetic testing is no longer just about two genes. While BRCA1 and BRCA2 are the most well-known, we now know that several other genes can also increase the risk of breast, ovarian, and other cancers [1][2]. Testing is usually performed using a multi-gene panel, which is a single blood or saliva test that looks at many high-risk and moderate-risk genes simultaneously [3][1].

Who Should Consider Testing?

Doctors use specific “red flags” to determine who should be offered genetic testing. According to national guidelines (NCCN), you may be a candidate for testing if you or your family history includes:

  • Early Onset: Breast cancer diagnosed at age 50 or younger [4].
  • Specific Cancer Types: Any diagnosis of ovarian, pancreatic, or metastatic prostate cancer, regardless of age [5][6].
  • Triple-Negative Breast Cancer: Especially if diagnosed at age 60 or younger [4].
  • Family Clusters: Multiple relatives on the same side of the family with breast, ovarian, pancreatic, or prostate cancers [4][5].
  • Ashkenazi Jewish Heritage: Due to a higher frequency of specific “founder” mutations in this population [5][7].

The Genes Beyond BRCA

Modern panels often look for other “drivers” of cancer risk. These include:

  • PALB2: A high-risk gene that carries a lifetime breast cancer risk similar to BRCA2 [8][9].
  • ATM and CHEK2: These are “moderate-penetrance” genes, meaning they increase risk, but often not as significantly as BRCA or PALB2 [9][10].
  • TP53, CDH1, and PTEN: Mutations in these genes are rarer and are often associated with specific syndromes that may involve other organs, such as the stomach or thyroid [11][12].

Understanding Your Results

Genetic test results typically fall into one of three categories:

1. Pathogenic or Likely Pathogenic

This is often called a “positive” result. It means a mutation was found that is known to increase cancer risk [2]. This result is actionable, meaning it will likely change your medical management, such as starting screenings earlier or considering preventive surgery [13][14].

2. Benign or Likely Benign

This is a “negative” result. It means the laboratory found no mutations or only found common genetic variations that do not affect your health [15].

3. Variant of Uncertain Significance (VUS)

A Variant of Uncertain Significance (VUS) is a common but often confusing result. It means the lab found a change in a gene, but they do not yet have enough data to know if it is harmful or harmless [16][15].

  • The Golden Rule for VUS: A VUS should not be used to make major medical decisions, such as choosing to have a double mastectomy [16][17].
  • Management: Clinically, a VUS is treated as a “negative” or “normal” result. You should follow the screening guidelines based on your personal and family history, not the VUS itself [16][18]. Over time, most VUS results are eventually reclassified as benign [19][20].

Cascade Testing: Protecting Your Family

If you test positive for a pathogenic mutation, your biological relatives (parents, siblings, and children) have a 50% chance of carrying the same mutation [21].

Cascade testing is the process of testing these relatives for that specific mutation [21][22]. This is a powerful preventive tool because it allows your family members to learn their risk and start life-saving screenings before cancer ever develops [23][24]. Your genetic counselor can often provide a “family letter” to help you share this information with your loved ones [22].

Common questions in this guide

Who should consider genetic testing for breast and ovarian cancer?
You may be a candidate for testing if you have an early-onset breast cancer diagnosis, triple-negative breast cancer, or certain cancers like ovarian or pancreatic. A strong family history of these cancers or Ashkenazi Jewish heritage are also important indicators.
Does genetic testing only look for BRCA mutations?
No, modern genetic testing uses multi-gene panels to look at many high-risk and moderate-risk genes simultaneously. While BRCA1 and BRCA2 are the most well-known, panels also test for other important genes like PALB2, ATM, CHEK2, and TP53.
What does a pathogenic or positive result mean on my genetic test?
A pathogenic or likely pathogenic result means a mutation was found that is known to increase your risk for cancer. This actionable result will likely change your medical care, such as starting cancer screenings earlier or considering preventive surgery.
What is a Variant of Uncertain Significance (VUS)?
A VUS means a change was found in a gene, but there is not enough medical data to know if it increases your cancer risk or is harmless. Most VUS results are eventually reclassified as benign, so they should not be used to make major medical decisions like choosing to have a double mastectomy.
What is cascade testing for cancer genes?
Cascade testing is the process of testing biological relatives for a specific genetic mutation after a family member tests positive. Since first-degree relatives have a 50% chance of carrying the same mutation, cascade testing helps them learn their risk and start life-saving screenings early.

Questions for Your Doctor

5 questions

  • •Which specific genes were included in my testing panel, and why were those chosen?
  • •If my result is a VUS, how often does your office check to see if that variant has been reclassified?
  • •Do my test results change the age at which I should start cancer screenings?
  • •Can you provide a 'family letter' that I can share with my relatives to help explain why they might need testing?
  • •Does my insurance typically cover the cost of testing for my family members (cascade testing)?

Questions for You

3 questions

  • •Which family members on both my mother's and father's sides have had cancer, and what types were they?
  • •How do I feel about sharing my genetic test results with my siblings, children, or extended family?
  • •If my result is a VUS, am I comfortable following the standard screening guidelines rather than seeking more aggressive surgery?

References

References (24)
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    Clinical Validity of Next-Generation Sequencing Multi-Gene Panel Testing for Detecting Pathogenic Variants in Patients With Hereditary Breast-Ovarian Cancer Syndrome.

    Yoo J, Lee GD, Kim JH, et al.

    Annals of laboratory medicine 2020; (40(2)):148-154 doi:10.3343/alm.2020.40.2.148.

    PMID: 31650731
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    A dominant RAD51C pathogenic splicing variant predisposes to breast and ovarian cancer in the Newfoundland population due to founder effect.

    Dawson LM, Smith KN, Werdyani S, et al.

    Molecular genetics & genomic medicine 2020; (8(2)):e1070 doi:10.1002/mgg3.1070.

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    Clinical Actionability of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Risk Assessment.

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    JAMA oncology 2015; (1(7)):943-51 doi:10.1001/jamaoncol.2015.2690.

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    Population prevalence of individuals meeting criteria for hereditary breast and ovarian cancer testing.

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    NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 1.2020.

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    Prevalence of Suspected Hereditary Cancer Syndromes and Germline Mutations Among a Diverse Cohort of Probands Reporting a Family History of Prostate Cancer: Toward Informing Cascade Testing for Men.

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This page provides educational information about cancer genetic testing and interpreting results. Always consult your genetic counselor or oncologist for medical advice regarding your specific test results and screening plan.

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