Invitae Breast Cancer STAT Panel

• Cowden and Cowden-like syndrome
• hereditary breast and ovarian cancer syndrome (HBOC)
• hereditary diffuse gastric cancer syndrome (HDGC)
• Li-Fraumeni syndrome (LFS)
• Peutz-Jeghers syndrome (PJS)

The average woman’s lifetime risk of developing breast cancer is 12%. Most cases are sporadic and not inherited; however, approximately 5%-10% of breast cancer is hereditary and due to a pathogenic variant in a disease-causing gene. Pathogenic variants in BRCA1 or BRCA2 account for the majority of hereditary breast and ovarian cancer cases in individuals with a strong family history or an early-onset diagnosis.

The other genes on this panel are also associated with hereditary breast cancer, and their inclusion is expected to increase the clinical sensitivity of this test. Individuals with a pathogenic variant in one of these genes have a significantly increased risk of developing cancer, and many of these cancers may be difficult both to detect and to treat. Identifying those with an underlying hereditary cancer syndrome enables implementation of surgical and/or treatment decisions at the time of diagnosis. These efforts may also result in risk-reduction and early diagnosis of other cancers, increasing the chances of successful treatment and survival.

Individuals with a pathogenic variant in one of these genes have an increased risk of malignancy compared to the average person, but not everyone with such a variant will actually develop cancer. Further, the same variant can present differently, even among family members. Because we cannot predict which cancers may develop, additional medical management strategies focused on cancer prevention and early detection may benefit most patients who are found to have a pathogenic variant.

For gene-associated cancer risks, download our Cancer risk poster.

All of the genes on this panel have autosomal dominant inheritance for hereditary breast cancer. The BRCA2 and PALB2 genes are also associated with autosomal recessive Fanconi anemia. The ATM gene is associated with autosomal recessive ataxia-telangiectasia.

This panel comprises genes for which there are established medical management guidelines. It may be considered for individuals with a personal and/or family history of:

• breast, ovarian, uterine/endometrial, colon, pancreatic, melanoma, sarcoma, and/or prostate cancer, particularly if early onset (<50 years)
• male breast cancer
• breast or ovarian cancer and Ashkenazi Jewish ancestry

There are also some common, general features suggestive of a hereditary cancer syndrome family. These include:

• cancer diagnosed at an unusually young age
• different types of cancer that have occurred independently in the same person
• cancer that has developed in both organs of a set of paired organs (e.g., both kidneys, both breasts)
• several close blood relatives that have the same type of cancer
• unusual cases of a specific cancer type (e.g., male breast cancer)

For management recommendations, please refer to:

• Fitzgerald, RC, et al. Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J. Med. Genet. 2010; 47(7):436-44.
• National Comprehensive Cancer Network®, Clinical practice guidelines in oncology. Breast and Ovarian Management Based on Genetic Test Results.