Testing an Intelligent Tutoring System to Enhance Genetic Risk Assessment

Specific Aims BRCA1/2 mutations are the most commonly identified Hereditary Breast and
Ovarian Cancer (HBOC) mutations. Women with these mutations have a 50-80% lifetime risk of
developing breast cancer. Breast cancer survivors with a BRCA1/2 mutation are at higher risk
of developing contralateral breast cancer than survivors without mutations. The National
Comprehensive Cancer Network (NCCN) recommends referral for HBOC genetic cancer risk
assessments (genetic counseling and consideration of genetic testing for a single gene or
panel testing; GCRA) for women at high risk for carrying a mutation. Obtaining a positive
test can inform treatment in newly diagnosed breast cancer patients and management in
survivors and unaffected women. Unfortunately, Latina and Black women have lower GCRA use
than non-Latina Whites. Reasons for lower GCRA use include access and psychosocial factors
(e.g. low knowledge, medical mistrust, low health literacy, anticipated negative emotions).
There have been few GCRA interventions in ethnic minorities; two recent efforts largely
focused on improving access, awareness, and knowledge with mixed success of impacting uptake.
Theoretically guided interventions that support GCRA uptake in underserved populations are
needed. Intervention development is particularly important given the growing complexity of
multiplex gene testing and the potential to identify founder mutations or large
rearrangements that are more prevalent in specific ethnic groups.

Our preliminary data with at-risk Black and Latina women suggests that improving access does
not necessarily translate into higher GCRA uptake and that providers face challenges in
communicating HBOC risk information. Patients have difficulty understanding HBOC numerical
risk information, especially populations with low health literacy. Additionally, many
existing educational tools were not theoretically derived, tend to prioritize quantitative
risk communication, and do not often consider emotional aspects, despite evidence that
emotions influence risk perceptions. Fuzzy Trace Theory posits that rather than relying on
factual knowledge and quantitative risk comprehension, people construct gist representations
that are anchored on culture and capture the essential bottom-line meaning of risk
information, including the emotional experience. Informed by Fuzzy Trace Theory, BRCA-gist is
an innovative Intelligent Tutoring System intervention that uses avatars to emulate tailored
one-to-one human tutoring and includes the bottom-line meaning of risk messages. The
preliminary efficacy of BRCA-gist was established in an experimental laboratory setting with
mostly non-Hispanic White college students. Adapting BRCA-gist for a clinical sample of
ethnically/racially diverse women at increased risk of carrying a mutation is important.
Thus, BRCA-gist constitutes a scalable, inexpensive intervention with promising translational
applications and potential to reduce disparities.

The goal of this mixed methods study is to adapt BRCA-gist and test the feasibility,
acceptability, and efficacy of this innovative intervention in a sample of Black and Latina
women at risk of HBOC (based on NCCN criteria using personal and family history of cancer).
Using the Learner Verification and Revision framework, in Aim 1 we will gather input from
site staff and community providers (n=10) about adaptations for implementation in clinical
settings and from at-risk Latina and Black women (n=20) about cultural adaptations. In Aim 2
we will test the feasibility, acceptability, and efficacy of the adapted BRCA-gist on uptake
of GCRA services. We will recruit 100 women from community/clinic sites. After completing a
brief baseline survey, we will randomize participants to BRCA-gist (n=50) or NCI Webpage arms
(n=50). We elected to use the NCI Webpage as a comparison as it includes current GCRA
recommendations for women at increased risk, the content overlaps with BRCA-gist, and the NCI
serves as a reputable source. Women will complete an immediate post-intervention assessment
and a research assistant (RA) will refer them to local free genetic counseling services. Our
primary outcome is GCRA uptake at 3 months. Knowledge, gist comprehension, and intentions
will be secondary outcomes. We aim to:

Aim 1: Adapt BRCA-gist. Providers and at-risk Black and Latina women will do the BRCA-gist
intervention and provide feedback and suggestions to make cultural adaptations to implement
BRCA-gist in community/clinic settings.

Aim 2: Test the feasibility, acceptability, and efficacy of BRCA-gist intervention in a
two-arm RCT. H.2.1. We expect high overall retention (≥75%). H.2.2. We expect high
satisfaction among women in the BRCA-gist arm (≥75%). H.2.3. Participants in the BRCA-gist
arm (vs. NCI Web) will have a higher uptake of GCRA services 3 months after the intervention.
H.2.4. Participants in the BRCA-gist arm (vs. NCI Webpage) will have a greater increase in
knowledge, gist comprehension, and intentions to use GCRA. We will explore differences by
ethnicity and health literacy and assess emotional reactions to risk information to inform
future affective-tailored interventions.

This project builds on our interdisciplinary teams' expertise in using innovative
technologies to improve risk communication, disparities, translational genomics, cancer
control interventions, and emotions. If successful, BRCA-gist can be tested in larger samples
and could easily be disseminated into clinical settings and community clinics that serve
underserved populations at increased risk for cancer.

Inclusion Criteria:

- Self-identify as Black and/or Latina

- English proficiency

- Be >21 years old

- Be able to provide informed consent

- Be at high risk of carrying HBOC mutation using personal/family cancer histories based
on the NCCN guidelines

Exclusion Criteria:

- Prior participation in genetic counseling