Multi-Gene Panel Testing

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Five to ten percent of breast cancers are associated with an abnormality in a gene (called a genetic mutation) which was passed down from parent to child. These genes are called hereditary breast cancer syndrome genes, most well known to the general public as BRCA1 and BRCA2. The BRCA genetic mutations increase the risk of breast, ovarian, and other cancers. However, only one of four patients with hereditary predisposition to breast cancer have BRCA1 and BRCA2 genetic mutations. There are multiple other genes, which when abnormal, may elevate an individual’s susceptibility to breast cancer.

Multi-gene panel testing evaluates multiple genes at one time, searching for mutations that may increase an individual’s likelihood of breast cancer or other illnesses. Within the multi-gene panels, there is an array of genes whose harmful or “deleterious” mutations have varying degree of cancer risk. Genes included in these panels can be divided into the following subgroups:

  • High risk genes (for example, BRCA1, BRCA2, CDH1, PTEN, TP53);
    • These genes are well described in the literature.
    • Patients with these gene mutations have a high genetic predisposition, compared to the general population, of developing breast cancers or other cancers.
    • Standard management guidelines for screening, risk-reducing interventions and treatment have been devised for patients with harmful gene mutations.
  • Moderate risk genes (for example PALB2, CHEK, ATM)
    • These genes are also well described in the literature.
    • Patients with these gene mutations have a moderate genetic predisposition, compared to the general population, of developing breast cancers or other cancers.
    • Screening, risk reducing management, and treatment guidelines may not be well delineated.
  • More recently discovered genes (BARD1, BRIP1, FANCC, NBN, RAD51C, RAD51D, XRCC2)
    • Limited information about risk of breast cancer and management.

Some patients with breast cancer and/or a family history of cancer will be candidates for multi-gene panel testing.

  • Who may benefit from multi-gene panel testing?
    • Patients and/or their family members with a spectrum of cancers diagnosed at young age.
    • Patients with a personal history and/or family history of a cancer pattern that fits the diagnostic criteria of more than one genetic syndrome.
    • Patients with a personal history and/or family history of multiple cancers, but the cancer pattern does not follow any specific genetic syndrome.
    • Patients with negative single/limited gene test but personal or family history still fits the diagnostic criteria for other genes.
  • Who may benefit from single gene testing instead of multi-gene panel testing?
    • Patients with a family member with a known mutation corresponding to patient’s personal or family history.
    • Patients with a personal or family history strongly suggestive of one specific gene.

There are benefits and disadvantages of multi-panel testing rather than single gene testing.

  • Benefits
    • Testing more than one gene at a time allows for more information in a designated period of time.
    • Some insurance coverage allows only one genetic testing per lifetime.
  • Disadvantages
    • There is a chance of being diagnosed with a mutation with limited information known about the breast cancer risk and management.

    • There is a higher probability of finding one or more variant that can’t be confirmed or ruled out as causing disease. This is referred to as variant of unknown significance (VUS).
      • There is uncertainty whether these variants cause disease.
      • In general, treatment decisions should not be made based on VUS.
      • The majority of VUSs are reclassified at a later time as benign (not harmful), but may be upgraded to deleterious mutations.
      • Some companies will contact the physician automatically if a mutation is reclassified.
    • There is a low probability of finding an unexpected harmful mutation that does not correspond to a patient’s personal or family history, making it difficult to know how to intervene.

    • Multi-panel testing may take longer for results than single gene testing.

The turn-around time for genetic panel testing differs by company and is usually listed on the company’s website. A genetic counselor or certified physician will help you navigate through the options to determine if you qualify for a genetic testing panel and help you select which panel is best for you. Since interpreting your results may be difficult, it can be facilitated by a genetic counselor. Treatment for mutations of these genes may or may not be covered by insurance, depending on the insurance company’s guidelines.