Polygenic Risk Scores for Breast Cancer Among African American Women With High Risk

Area of Science:

• Genetics
• Oncology
• Epidemiology

Background:

• Validating polygenic risk scores (PRSs) is crucial for breast cancer (BC) risk stratification in high-risk populations.
• African-ancestry PRSs require evaluation in diverse cohorts for clinical utility.

Purpose of the Study:

• To assess the performance of African-ancestry PRSs for overall BC and triple-negative BC (TNBC) risk.
• To evaluate PRSs in an independent cohort of African American women with a high familial risk of BC.

Main Methods:

• A case-control study included 31,522 women of African ancestry undergoing genetic testing.
• Six African-ancestry PRSs and one European-ancestry PRS were evaluated.
• Performance was measured using area under the receiver operating characteristic curve (AUC) and odds ratios (OR).

Main Results:

• African-ancestry PRSs showed improved performance over European-ancestry PRS for overall BC.
• A 162-variant PRS demonstrated superior performance for TNBC, with an AUC of 0.609 and OR of 1.47.
• PRSs performed well in women with a strong family history of BC.

Conclusions:

• PRSs demonstrated good performance in African American women, particularly those with a strong family history of BC.
• The 162-variant TNBC PRS shows potential as a cost-effective tool for risk assessment.
• These findings support the use of PRSs to promote equitable breast cancer care.