Suzanne C. O'Neill - US grants

DESCRIPTION (provided by applicant): BRCA1/2 mutation carriers have highly elevated odds of developing HBOC, as may their first- and second- degree relatives. Guidelines suggest that BRCA1/2 testing for these young relatives should not begin before age 18 due to limited medical benefit and potential psychosocial harm. In contrast, testing for women over age 25 is recommended as standard of care. Testing for women aged 18-25 presents a clinical dilemma. Testing at this young age could offer the advantage of providing definitive genetic risk information, allowing the opportunity to take a proactive stance to life planning. However, risk management strategies come with distinct disadvantages at this age. These include an increase of breast cancer risk associated with mammography in carriers prior to age 30. Young women face these advantages and disadvantages with limited decision making experience and decision processes that are more prone to affective biases than their older counterparts. Our ongoing qualitative work with providers suggests these emotional and developmental factors make counseling these women unique and challenging. The present application addresses the clinical dilemma that faces these young women and their providers. Guided by the Theory of Genetic Vulnerability, we will leverage our cancer genetic registry and clinical research program in a mixed-methods study of women age 18-25 with a first- or second-degree relative who is a BRCA1/2 carrier. Our resources contain well-characterized data about our large cohort of women and men with a known mutation (index carrier). These data include not only data regarding age of testing, affected status, and risk management decisions, but also psychosocial data such as distress. We will combine these secondary data with new primary data collected from young female relatives to assess variables associated with their likelihood to test. In Phase I, we will use these quantitative data to assess the relationship between a young woman's cancer family history and cancer-related emotions and cognitions on her likelihood to test. We also will assess the mediational effects of index carrier's psychosocial functioning and health behaviors on this relationship. In Phase II, we will follow our quantitative work with qualitative interviews of 20 tested women and their physicians. These interviews will allow us to determine how receipt of a genetic test result affects the psychosocial tasks of development and medical care of young female HBOC relatives from the perspective of tested young women and their providers. Our work would allow for targeted approaches to patient education and counseling in this population.

? DESCRIPTION (provided by applicant): Many of the over 232,000 women who developed invasive breast cancer last year were unaware of disease risk factors, their personal risk, and available risk management strategies. Along with better-known risk factors such as family history, having dense breasts (density) is one of the strongest breast cancer risk factors. Almost half of US states now require disclosure of density status following routine screening mammography. Disclosure provides an opportunity to capture women who are at clinically elevated risk due to density and additional risk factors, such as family history, and to inform them of risk management options available to them. Guidelines have long recommended risk counseling for women with clinically elevated breast cancer risk, including discussion of chemoprevention and additional breast imaging such as MRI. While uptake is an individual, preference-based decision, population use of these risk management options is low and efforts to improve uptake are limited. Our pilot data suggest that patients have strong interest in density-focused risk counseling and that our pilot intervention can shift risk management intentions. These data, together with the confluence of mandatory density reporting, expanded risk management guidelines, and coverage of services under the ACA provides an unprecedented opportunity to expand breast cancer risk management and to assess the economic impact. We propose the first randomized controlled trial to evaluate a method of density disclosure. Our goal is to encourage uptake of guideline-informed risk management without increasing distress. Guided by Protection Motivation Theory, we will implement and evaluate a web-based interactive intervention vs. usual care among members of Group Health (aged 40-69) whose high breast density and other risk factors place them at high 5-year (>1.66 percent) or lifetime (>20 percent) risk for breast cancer. We will assess the mechanisms of intervention effect and conduct an economic evaluation alongside the trial. Patients will complete assessments at pre-randomization baseline, as well as 6 weeks and 12 months post-randomization. We will integrate these self-report data with healthcare utilization and cost data to assess the potential public health impact of our intervention. Our aims are to 1) assess intervention effects on uptake and distress, 2) identify mediators/moderators of intervention impact on uptake, and 3) extend the time horizon of the trial to estimate the lifetime costs, benefits, and harms of the intervention from different perspectives using a Cancer Intervention and Surveillance Modeling Network (CISNET) model. Our trial will move the field forward by informing the sweeping national policy integration requiring density disclosure and estimating the cost-effectiveness of our approach.

Approximately half of all newly-diagnosed patients with breast cancer are affected with estrogen-receptor positive, early-stage disease. Clinical guidelines for these women integrate genomic tumor profiling tests such as the Oncotype DX Recurrence Score to refine recurrence estimates and systemic therapy selection when combined with existing markers. Guidelines suggest that the 25% with a high Score benefit from chemotherapy and the 50% with a low Score can safely avoid chemotherapy. While the NCI-funded TAILORx trial has provided prospective validation of the utility of low-risk test results, the primary trial objective is to determine the appropriate use of chemotherapy for the >25% of women who receive intermediate recurrence Scores (for whom the benefits of chemotherapy are unclear). Many challenges remain to maximize the benefits of testing as we await these trial results in the next year. For example, many women have a poor understanding of their Recurrence Score and its impact of treatment selection. Further, our data suggest that, along with distress, patient's pretesting preferences for chemotherapy are a powerful driver of treatment utilization, predicting treatment received over and above the effect of the Score. This suggests that preferences remain stable, even following disclosure and discussion of test results that should guide treatment selection. Finally, tested patients who do not take an active role in their care and report poorer communication by their oncologist are at risk for higher distress and poorer quality of life. Strong clinical communication can impact proximal outcomes of patient comprehension, treatment preferences and satisfaction, involvement in care decisions as well as longer-term outcomes of treatment adherence and QOL. These proximal outcomes can be influenced by patient activation interventions utilizing a question prompt list (QPL). In the context of patients receiving Oncotype DX testing, our QPL could allow them to better understand the rationale for their oncologist's treatment recommendation, what it means for managing their disease, and encourage alignment of treatment preferences and selection with the Recurrence Score. Guided by Street et al.'s model of communication, we propose research in two phases to test the feasibility and impact of our QPL. In Phase 1, we will further refine our draft QPL based on in-depth interviews with patients (N=20) and medical oncologists (N=10). In Phase 2, we will conduct a single-arm trial (N=75) to demonstrate feasibility and preliminarily assess the impact of the QPL on key outcomes. Our aims are to examine intervention feasibility, evaluate intervention effects on comprehension and treatment preferences, and assess potential intervention mechanisms on comprehension, preferences and satisfaction. We will explore variation in our outcomes across Aims 1-3 based on patient and provider sociodemographics, patient-provider concordance, and patient's language preference. We will achieve our aims by incorporating patient self-report data with observational coding of audiorecordings of clinical encounters in which the Score is integrated with treatment plans. Our intervention and mixed-method approach to assessment will directly inform how test results influence care received by thousands of women.

BRCA1/2 mutation carriers have highly elevated odds of developing hereditary breast and ovarian cancer, as may their first- and second-degree relatives. The National Academies of Sciences Engineering and Medicine?s Genomics and Population Health Action Collaborative highlights the testing of carriers? relatives and their uptake of screening and risk-reducing surgeries as a primary way that genetics can contribute to the reduction of population cancer burden. Patterns of testing over the past decade have shifted to include more younger and cancer-unaffected women to capitalize on this cancer prevention opportunity. However, interventions have not kept pace with this changing landscape, as there are currently no funded trials that meet the unique clinical, developmental and psychological needs of young adult relatives (YARs) of mutation carriers. Our pilot data suggests that YARs report high levels of distress and desire to seek HBOC risk information and emotional support beyond their healthcare providers and families?especially support from knowledgeable peers who can relate to their experiences and offer neutral grounding and objective guidance about coping strategies. Peer support is a promising psychosocial cancer care approach that could fill this void. However, few evidence-based standards inform its practice. In response to this cancer control challenge, we developed a new, fully manualized/scripted intervention for YARs called ?Peers and Cancer Empowerment? (PeACE). PeACE is grounded in evidence-based psychosocial telephone counseling protocols for HBOC distress reduction. We adapted those protocols for our target population through a systematic approach without contradicting their core features. PeACE includes streamlined telephone counseling delivered by well-trained community peer coaches. Session content incorporates coping training for HBOC stress reduction, and decision making and problem solving training about confronting and managing cancer risk. We will rigorously test PeACE?s efficacy in an RCT to improve HBOC-related outcomes for YARs. Trial participants are randomized to an intervention or equated control condition, and followed for up to 12 months. We hypothesize that PeACE better reduces cancer-specific and general distress, uncertainty, and decision conflict, as well as increased uptake of genetic counseling. This innovative project expands capacity to address psychological distress management and related outcomes in persons living with HBOC risk.

This application seeks funding for a new Cancer Population Science (CaPS) Postdoctoral Training Program at Georgetown University and Georgetown Lombardi Comprehensive Cancer Center. The overall goal of the CaPS Program is to train future leaders in cancer population science who will translate basic and clinical advances into the clinic, communities and policy. This postdoctoral program provides dual-mentored transdisciplinary training centered around core competencies?integrating novel technologies and methods, applying multilevel approaches, using knowledge integration to inform policies and care, and addressing health disparities?using a team science approach and integrating cancer biology and domain-specific expertise. The 21 Primary Faculty lead active research programs supported by substantial peer-reviewed funds, with extensive mentoring experience at the postdoctoral level that apply these core competencies. The faculty represent nine departments/institutes across Georgetown University, underscoring the emphasis on translational cancer population science. Aims are to: 1) leverage our successful infrastructure to recruit and retain a diverse group of promising population scientists; 2) implement complementary co-mentorship and individualized development plans that cut across at least two phases of the translational continuum, with formal and informal didactics to facilitate the acquisition of core competencies to transition successfully to the next career stage; and 3) evaluate training efforts at the trainee and program level to ensure a sustainable cancer population science training program in the Nation?s capital. We are motivated to create this new program by unprecedented growth in our understanding of molecular events in cancer development and progression and the multilevel influences of the host and environment on these processes. This new and growing knowledge base has evolved against the backdrop of an increasingly diverse US population, disparities in cancer risk and receipt of evidence-based screening and treatment, societal aging patterns, and evolving models of healthcare delivery. Moving the field of cancer population science forward will require enhancing our ability to translate basic and clinical advances into populations, communities and policy. The next generation of scientists must be trained to meet this challenge with specific expertise to embark on translational research.