Grant Details
Grant Number: |
3R01CA211999-04S1 Interpret this number |
Primary Investigator: |
Koenig, Barbara |
Organization: |
University Of California, San Francisco |
Project Title: |
Genomic Risk Communication and Stakeholder Perspectives: Emerging Bioethics Issues in the Wisdom Pragmatic Trial |
Fiscal Year: |
2020 |
Abstract
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.
Publications
None. See parent grant details.