Title: Genomic Risk Communication and Stakeholder Perspectives: Emerging Bioethics Issues in the WISDOM Pragmatic Trial Summary/Abstract This supplement request expands the work of our NCI-funded R01 [CA211999], titled ?Precision Genomics in the WISDOM Pragmatic Clinical Trial: An ?Embedded ELSI Study of Risk-based Breast Cancer Screening.? The R01 is an empirical bioethics study of the WISDOM (Women Informed to Screen Depending on Measures of Risk) trial. WISDOM was originally funded by PCORI (the Patient Centered Outcomes Research Institute), with additional support from NCI, to enroll 100,000 women in a preference-sensitive randomized controlled trial comparing ?personalized? risk-based screening (RBS) and annual mammography (PI Laura Esserman). WISDOM is one of the first precision medicine efforts to implement breast cancer screening according to individual genomic risk, as opposed to population characteristics. The WISDOM trial screens participants for germline mutations in 9 breast cancer genes and creates a polygenic risk score (PRS) based on >200 single nucleotide polymorphisms. The goal of WISDOM is to revolutionize breast cancer screening, moving the paradigm from a one-size-fits-all model of annual mammography to a risk-based model that screens high risk women more and low risk women less. Our embedded ELSI study of the WISDOM trial is a unique opportunity to follow the ELSI issues that accompany a pioneering trial of a risk-based, precision medicine approach to breast cancer screening. Our original aims were to: (1) Examine how ELSI concerns are addressed throughout the implementation of WISDOM. (2) Elucidate the experience of RBS for women and their primary care providers. (3) Explore the consequences of receiving a positive result for one of the nine cancer susceptibility genes. (4) Convene an Ethics Working Group that offers advice to WISDOM stakeholders. The overall goal of our study is to identify and analyze the ELSI challenges of RBS, with attention to the social, cultural, and political context of precision genomics screening. For this bioethics supplement, we propose two aims to expand upon this unique opportunity and to address critical emerging issues not included in our original study design. First, we will examine the development and implementation of an interactive Breast Health Decisions Tool. This novel tool streamlines all elements of breast cancer risk and prevention communication with WISDOM participants. Women will be told their PRS with the aid of this online tool. No previous studies have examined how precision genomics participants understand PRS, in interaction with other risk factors. Second, we propose to elucidate the experience and meanings of RBS for women diagnosed with breast cancer during their participation in the trial. Understanding this main WISDOM trial outcome from the stakeholder perspective is critical to establishing acceptability and guiding future implementation of both risk-based screening and pragmatic clinical trials. We will be guided by an overarching goal: understanding the intersection of precision genomics screening with known cancer health disparities, including the accuracy of PRS in women of diverse ancestral backgrounds.
This supplement application seeks additional funding to add two new specific aims to a currently funded project. The current project, funded by the National Cancer Institute, examines the ethical, legal, and social implications of the WISDOM clinical trial. We call this an ?embedded ethics? study. The WISDOM trial is one of the first efforts to tailor recommendations for population-based breast cancer screening according to a risk score that incorporates genomic data. It is an early example of precision medicine/precision population health. If the supplement request is funded, we will study an online ?breast health decisions tool,? a new way to communicate about risk and cancer prevention. We also will expand our interviews with key stakeholders to include women who develop breast cancer during the clinical trial. Attention to the ethical and social implications of risk-based screening for the women who are diagnosed also will have broad relevance for breast cancer screening policy. Our research will inform future policy directions related to precision population health and cancer screening.
