Increased Identification of Candidates for High-Risk Breast Cancer Screening Through Expanded Genetic Testing

Area of Science:

• Oncology
• Genetics
• Medical Screening

Background:

• Breast MRI screening is recommended for women with over 20% lifetime breast cancer risk.
• Risk is often estimated using family history, but genetic testing for BRCA1/2 and other genes is an alternative.
• Identifying at-risk individuals is crucial for early detection and risk reduction.

Purpose of the Study:

• To evaluate the impact of genetic testing for genes beyond BRCA1/2 on identifying candidates for enhanced breast cancer screening.
• To determine the proportion of pathogenic variant carriers in non-BRCA1/2 genes who would have met the >20% lifetime risk threshold based on family history alone.

Main Methods:

• A 25-gene hereditary cancer panel, including BRCA1/2 and 7 other high-risk genes, was used for testing.
• Women with pathogenic variants (PVs) were assessed using the Claus model for lifetime breast cancer risk based on family history.

Main Results:

• 9,641 women had 9,751 PVs across the tested breast cancer risk genes.
• BRCA1/2 accounted for 59.1% of PVs; ATM, CHEK2, or PALB2 comprised 38.8%.
• Only 24.7% of all PV carriers met the >20% lifetime risk threshold via the Claus model.

Conclusions:

• Genetic testing beyond BRCA1/2 significantly expands the pool of women eligible for breast MRI screening.
• A majority of women identified through expanded genetic testing would not have been flagged by family history assessment alone.
• This highlights the importance of comprehensive genetic panels for identifying high-risk individuals for breast cancer surveillance.