The role of polygenic risk scores in breast cancer risk perception and decision-making.

Polygenic risk scores (PRS) have the potential to improve the accuracy of clinical risk assessments, yet questions about their clinical validity and readiness for clinical implementation persist. Understanding how individuals integrate and act on the information provided by PRS is critical for their effective integration into routine clinical care, yet few studies have examined how individuals respond to the receipt of polygenic risk information. We conducted an embedded Ethical, Legal, and Social Implications (ELSI) study to examine if and how unaffected participants in a US population breast cancer screening trial understood and utilized PRS, as part of a multifactorial risk score combining traditional risk factors with a genetic risk assessment, to make screening and risk-reduction decisions.

A qualitative study of unaffected ATM and CHEK2 carriers: How participants make meaning of 'moderate risk' genetic results in a population breast cancer screening trial.

Relatively little is known about experiences of individuals with a pathogenic variant in a moderately penetrant breast cancer gene, particularly those without a personal history of cancer. The WISDOM trial is testing a model of risk-based breast cancer screening that integrates genomic (nine genes and polygenic risk) and other risk factors. In the context of an embedded Ethical, Legal, and Social Implications (ELSI) study of WISDOM, we conducted qualitative interviews at two timepoints post-result disclosure with 22 ATM and CHEK2 carriers.

The limits of personalization in precision medicine: Polygenic risk scores and racial categorization in a precision breast cancer screening trial.

Population-based genomic screening is at the forefront of a new approach to disease prevention. Yet the lack of diversity in genome wide association studies and ongoing debates about the appropriate use of racial and ethnic categories in genomics raise key questions about the translation of genomic knowledge into clinical practice. This article reports on an ethnographic study of a large pragmatic clinical trial of breast cancer screening called WISDOM (Women Informed to Screen Depending On Measures of Risk).