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Genetic Testing for HBOC Syndrome

Different types of genetic testing are available to test for hereditary breast and ovarian cancer (HBOC), depending on whether a mutation has been identified already in the family. For individuals of Ashkenazi Jewish ancestry, specific testing may be done to look at the three founder mutations most commonly found in those with this ancestry.

Comprehensive testing is performed when the mutation in the family has not been identified. If possible, this testing should be done on an individual in the family who has had breast or ovarian cancer. The testing involves both sequencing and deletion/duplication studies. It is the most sensitive, costly, and time-consuming test, and it is likely to identify variants of uncertain significance.

Multisite testing looks for the presence of the three founder mutations that are common in those with Ashkenazi Jewish ancestry. For those with this ancestry, this is where genetic testing would typically start.

Single-site testing is done when the mutation in the family has been identified; this test looks only for the presence of that specific mutation. Targeted testing can save money and time.

HBOC Genetic Results Interpretation and Risk Management

To learn what to do for people at varying risk levels, start with the National Coalition for Health Professional Education in Genetics’ risk stratification screening guidelines, and then review their cancer risk and screening guidelines.

Genetic test results are best given to patients by a genetic counselor or other health professional with special training in genetics. The following table, adapted from the Hereditary Breast and Ovarian Cancer Program’s Result Interpretation Table, can help you better understand your patients’ genetic testing results.

HBOC Result Interpretation Table
Family Mutation Status HBOC Test Result Patient’s Clinical Status Interpretation Management At-Risk Relatives
Family Mutation Known Positive With or without cancer Patient is at high risk for breast, ovarian, and other HBOC-related cancers. Follow National Comprehensive Cancer Network (NCCN) guidelines for high-risk surveillance and risk reduction. Offer counseling and single-site testing to first-degree relatives. If testing is declined, treat as high-risk for surveillance.
Negative Never had cancer The patient is a “true negative”; he or she did not inherit the gene mutation. His or her cancer risk is the same as the general population. General population guidelines apply. Offspring are at general population risk for breast cancer.
Personal history of cancer The patient did not inherit the gene mutation; his or her cancer is coincidental. Future cancer risk is based on personal history of cancer. Use surveillance and risk reduction interventions based on personal history of cancer. Offspring are not at risk for the genetic mutation. Cancer risk is increased above background.
Unknown Family Mutation Positive With or without cancer Patient is at high risk for breast, ovarian, and other HBOC-related cancers. Follow NCCN guidelines for high-risk surveillance and risk reduction. Offer counseling and single-site testing to first-degree relatives. If testing is declined, treat as high-risk for surveillance.
Negative Never had cancer “Uninformative negative” testing: results do not indicate whether the patient has a mutation causing cancer in the family. Risk assessment is based on family history. Use surveillance and risk reduction interventions based on family history of cancer. Tests for at-risk relatives are not available.
Personal history of cancer “Uninformative negative” testing: results do not indicate whether the patient has a mutation causing cancer in the family. Risk assessment is based on family history. Use surveillance and risk reduction interventions based on personal and family history of cancer. Tests for at-risk relatives are not available. Treat close relatives as high-risk for surveillance.
Variants of uncertain significance (VUS) With or without cancer “Uninformative” testing: results do not indicate whether the patient has a known mutation that increases risk for cancer. Risk assessment is based on family and personal history. This category is subject to change given new data. Updates in this category are common. Use surveillance and risk reduction interventions based on personal and family history of cancer. Tests for at-risk relatives are not available. Treat close relatives as high-risk for surveillance.

Identification of a deleterious mutation in BRCA1/2 by genetic testing is sufficient for the diagnosis of HBOC. Management can include—

  • Increased surveillance (mammogram and breast MRI).
  • Chemoprevention with selective estrogen receptor modulators (SERM).
  • Preventive mastectomy and/or salpingectomy/oophorectomy.

Knowledge Check

Answer the question on your own and check your answer.

Based on family history, you send a healthy patient for genetic counseling. The patient ultimately undergoes genetic testing for HBOC and the results come back positive. What are some possible interventions? Check Answer

Answer: Increased surveillance, chemoprevention, and a preventive mastectomy and/or salpingectomy/oophorectomy. Encourage her to share these results with other family members so they can speak with their providers about genetic testing and their risk of developing cancer.

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