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. Semi-structured qualitative interviews were conducted with 24 trial participants who were designated at elevated risk for breast cancer due to their combined risk score. Interviews were analyzed using a grounded theory approach. Participants understood PRS conceptually and accepted it as one of many risk factors to consider, yet the value and meaning they ascribed to this risk estimate varied. Most participants reported financial and insurance barriers to enhanced screening with MRI and were not interested in taking risk-reducing medications. These findings contribute to our understanding of how PRS may be best translated from research to clinical care. Furthermore, they illuminate ethical concerns about identifying risk and making recommendations based on polygenic risk in a population screening context where many may have trouble accessing appropriate care

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. Results disclosure and interview recordings were transcribed and analyzed using a grounded theory analysis framework. We found that participants minimized the significance of their results in comparison to BRCA; were surprised but not alarmed by the results in the absence of family history; did not fundamentally change their perception of their breast cancer risk despite the new genomic information; exhibited variable responses to WISDOM's screening and risk reduction recommendations; and shared test results with family but did not strongly encourage cascade testing. Participants viewed the results as having limited utility and responded accordingly. Our study offers important insights into how genetic test results for moderate-risk genes are received, understood, and acted upon in population screening context

Development and early implementation of an Accessible, Relational, Inclusive and Actionable approach to genetic counseling: The ARIA model

ObjectiveTo describe the training and early implementation of the ARIA model of genetic counseling (Accessible, Relational, Inclusive, Actionable).MethodsAs part of the Cancer Health Assessments Reaching Many (CHARM) study, an interdisciplinary workgroup developed the ARIA curriculum and trained genetic counselors to return exome sequencing results using the ARIA model.CurriculumThe ARIA curriculum includes didactic elements, discussion, readings, role plays, and observations of usual care genetic counseling sessions. The ARIA model provides the skills and strategies needed for genetic counseling to be accessible to all patients, regardless of prior knowledge or literacy level; involves appropriate psychological and social counseling without overwhelming the patient with information; and leaves the patient with clear and actionable next steps.ConclusionWith sufficient training and practice, the ARIA model appears to be feasible, with promise for ensuring that genetic counselors' communication is accessible, relational, inclusive and actionable for the diverse patients participating in genomic medicine.Practice implicationsARIA offers a coherent set of principles and strategies for effective communication with patients of all literacy levels and outlines specific techniques to practice and incorporate these skills into routine practice. The ARIA model could be integrated into genetic counseling training programs and practice, making genetic counseling more accessible and meaningful for all patients