Understanding How Familial Genetics Impact Breast Cancer Risk: Bridging the Gap Between DNA Mutations and Triple-Negative Breast Cancer
Assessing individual cancer risk can be a critical first step in the prevention and early detection of hereditary breast cancer. Recently, the importance of cancer risk assessment was brought to light by actress Olivia Munn who credits her own early-stage breast cancer diagnosis to her breast cancer risk assessment score.
A key factor in determining cancer risk is evaluating family history, which can be uncovered through genetic screening. Approximately 10% of breast cancer cases are caused by inherited genetic changes, called variants or mutations, which can be passed down from parents to children. Importantly, many genetic mutations found in sporadic cancers are also present in families with a history of breast cancer.
The types of genes most intimately associated with hereditary breast cancer, particularly triple-negative breast cancers, are involved in repairing cellular DNA damage. The most frequently mutated genes are BRCA1 and BRCA2. In normal cells, BRCA1 and BRCA2 work in tandem with additional genes, including RAD51C, to preserve our DNA and repair any harmful lesions that might form. In the case of cancer, these genes are inactivated, causing damaged DNA to be unstable, and ultimately leading to cancer development.
The focus of our work is to understand how mutations that inactivate the RAD51C gene impact triple negative breast cancer risk, and to identify therapeutic strategies to prevent cancer relapse.
To better understand the consequences genetic mutations have on RAD51C function, we are leveraging a new mutational scanning technology to analyze RAD51C variants. This technology can simultaneously screen hundreds of RAD51C variants for response to cancer drugs, helping to find any inherited mutations that are potentially cancer-causing. Further, this approach will aid in identifying combination therapies to prevent chemotherapy resistance. Overall, our goal is to help doctors develop a personalized treatment regimen based on a patient’s unique genetics to prevent cancer relapse and cure the disease.
