Hereditary Cancers and Genetic Testing

What Is Hereditary Cancer?

Hereditary cancer, also known as familial cancer, arises from inherited genetic changes (variants or mutations) passed down from a parent. Unlike most cancers that develop later in life due to environmental factors, hereditary cancers are rare, often manifest at a younger age, and can affect multiple blood relatives across generations.

Diagnosing Hereditary Cancer

Clinical Suspicion

Initial diagnosis typically begins with clinical suspicion. Certain features may raise this suspicion:

• Diagnosis of specific cancers at a younger age than usual
• Unusual tumor pathology
• Multiple primary cancers in one individual
• Family history of related cancers (e.g., breast and ovarian; bowel and uterine cancers)

If any of these features are present, an oncologist may refer the individual to a Familial Cancer Clinic for further risk assessment.

Risk Assessment

The assessment considers personal cancer and hormonal history, as well as family history, to determine the likelihood of a hereditary or familial cancer predisposition. If a reasonable chance exists, genetic testing is offered and organized, typically through a blood sample.

Genetic Testing: Process and Possible Results

Pre-Test Counseling

Genetic testing should only proceed after genetic counseling, which discusses the pros and cons of testing and the potential implications of the results for the individual and their family.

Testing Procedure

Testing usually begins with an affected family member who has a history of relevant cancers to increase the likelihood of identifying a causative variant.

Possible Results

1. Positive Result: Identification of a causative variant confirms a hereditary cancer diagnosis. This opens the option for predictive testing for other family members to determine if they have inherited the genetic predisposition, informing their risk management.
2. Negative Result: No causative variant is identified. However, this does not exclude an underlying genetic predisposition due to limitations in genetic testing. Close relatives may still be at increased risk and require ongoing cancer surveillance.
3. Variant of Uncertain Significance (VUS): Testing reveals a variant whose significance is not yet known. This result cannot be used for predictive testing or risk management until more evidence becomes available to reclassify it.

Purpose of Diagnosing Hereditary Cancer

Identifying a hereditary cancer syndrome guides ongoing management for the individual and risk management for their relatives.

• For the Individual: For example, a young woman diagnosed with breast cancer who has a positive gene variant and/or strong family history may consider a double mastectomy instead of breast-conserving surgery, as she is at risk of developing a second breast cancer. Additionally, there may be an increased risk of other cancers, such as ovarian cancer, associated with the gene variant, for which preventive surgery might be considered.
• For Relatives: Knowing the causative gene variant allows predictive genetic testing for biological relatives. Those who test positive for the family variant are at increased risk of developing certain cancers and can benefit from effective screening and risk management options. Those who test negative are not at heightened genetic risk and can follow standard population cancer screening guidelines.

Additional Resources

• Clinical Genomics and Genetics at St Vincent’s Clinic
• Insights: Adult Preventive Genomics

For more information or to schedule a consultation, please contact St Vincent’s Clinic.