Cancer Risks for Mutations in Breast Cancer Predisposition Genes

Women with breast cancer or ovarian cancer in their families are often advised to get genetic testing.

However, genetic testing for breast and ovarian cancer predisposition genes includes many genes whose involvement in these cancers is unclear. In addition, the risks of cancer associated with mutations in many of these genes are unknown.

As a result, women with mutations may be given improper recommendations for management of their cancer risks, which could lead to confusion and potentially to harm.

This research project in the Mayo Clinic Breast Cancer SPORE will establish the risks of breast cancer and other cancers associated with pathogenic mutations in cancer genetics testing panels by collecting information from cancer genetics testing companies and from Prospective Registry of Multiplex Testing (PROMPT), a registry for people who have had multigene panel genetic testing.

The project is enrolling participants who were tested for mutations in the study, along with their relatives.

Based on the information collected, the project will:

  • Determine which genes increase risks of breast cancer and ovarian cancer
  • Define the specific risks associated with mutations in each gene
  • Identify which variants of uncertain significance in these genes increase risks of cancer
  • Study tumors from participants with mutations to establish if certain tumors have the potential to be treated effectively with selected therapy

The most important clinical outcome of this project is that women found to have mutations in the cancer genetic panel genes will receive accurate information about their risks of cancer. This is expected to lead to improvements in the use of mammography screening, MRI screening and prophylactic surgeries for this group of people.

Project aims

This project has three aims:

  • Define the penetrance of breast cancer and ovarian cancer associated with inactivating mutations in panel-based predisposition genes
  • Determine the clinical relevance of variants of uncertain significance in panel-based, known predisposition genes
  • Assess clinical-pathological features of mutations in cancer predisposition genes