Familial Cancer Testing – Specialist Pathway

Some families may have an increased risk of developing certain types of cancer through the inheritance of variants (mutations) in certain genes. Testing for these genetic variants can determine whether a patient might be at increased risk of developing cancer and suggest an appropriate prevention or surveillance strategy. This test is Medicare eligible for those patients satisfying testing criteria.

There are now Medicare rebates available for testing in women with breast and ovarian cancer who are at high (>10%) risk for detecting a genetic cause. Please refer to the HBOC Risk calculators section below for more information.

This panel is important for breast cancer patients with a family history that includes ovarian cancer and is also useful for families where there is a mixed cancer picture of breast +/- ovarian +/- colorectal cancer.

Hereditary cancers are those where altered genes contribute to an inherited predisposition to certain cancers. In breast cancer, 5-10% are due to inherited genetic alterations. These are most commonly identified in the breast cancer susceptibility genes, BRCA1 and BRCA2, but can also occur in other genes.

BRCA status can have significant implications for the therapeutic management of carriers. Cancer is complex, as one gene may be responsible for many different cancer types or many genes acting together may increase a woman’s risk of developing breast and ovarian cancer. Therefore, it is recommended these tests be ordered by, or in consultation with, specialists familiar with the implications for management.

Testing for genetic variants in BRCA1 and BRCA2 can also be used to determine eligibility for olaparib maintenance therapy in relapsed high grade serous ovarian cancer, metastatic castration-resistant prostate cancer, triple negative early breast cancer, or hormone receptor positive, HER2-ngative, early breast cancer with a high-risk characteristic.

Risk prediction models can be used to calculate the likelihood of carrying a variant in selected cancer risk genes. These are evidence-based tools that can assist in determining whether genomic testing should be performed.

The models available for HBOC are:

Manchester Score – from St Mary’s Hospital in Manchester.

BOADICEA – from Cambridge University – canrisk.org

Penn II Risk Model – from the University of Pennsylvania – pennmodel2.pmacs.upenn.edu/penn2

Colorectal cancer is the third most common type of newly diagnosed cancer in Australia. It is estimated that 30% of patients with colorectal cancer have a family history of the disease, and up to 10% have genomic variants associated with inherited cancer syndromes including Lynch syndrome (LS).

A diagnosis of LS is confirmed by the detection of a pathogenic germline variant in one of the MMR genes (MLH1, MSH2, MSH6 and PMS2) or the EPCAM gene.

Guidelines recommend testing to confirm the diagnosis of an inherited CRC syndrome in a patient with a personal history of disease in the following circumstances:

• • APC gene testing is indicated in patients with ≥10 colorectal adenomas before age 30, or ≥20 colorectal adenomas regardless of age.
  • MUTYH gene testing is indicated for patients with ≥20 colorectal adenomas at any age, but could also be considered in patients with fewer polyps following review by a familial cancer service, and patients with an FAP phenotype but no identifiable APC variant.