Rachel L. Yung’s research while affiliated with Fred Hutch Cancer Center and other places

Purpose Assess the feasibility, acceptability, and preliminary efficacy of lay health educators to enhance Hispanic/Latino survivors’ knowledge of their cancer history, screening needs, and health-related self-efficacy. Methods Hispanic/Latino survivors diagnosed within 5 years were recruited from three clinics and a regional cancer registry. Survivors were randomized to receive a personalized survivorship care plan (SCP; control) or SCP plus telephone session with a bilingual-bicultural lay health educator (intervention). Survivors were reassessed after 3 months. Primary outcomes were feasibility (meeting accrual, n = 60–100) and acceptability of the SCP and education session. Secondary outcomes were changes in survivors’ knowledge of their cancer history, screening needs, and health-related self-efficacy. Results Ninety-fine survivors (median age 55 years, 78% female, 56% low/marginal health literacy) were randomized (n = 48 intervention). Seventy-nine completed the study; most found the SCP useful (82% intervention; 68% control); 84% of the intervention group rated the education session useful. Over time, both groups had improved knowledge of their cancer history (accuracy increased from 71.5 ± 16.4% to 73.8 ± 15.0%; p = 0.19) although differences over time and between groups were not statistically significant. At follow-up compared with baseline, participants were more likely to report plans for future screening: cervical (57% versus 31%, p = 0.002); colorectal (39% versus 26%, p = 0.10). Although the change in self-efficacy did not differ between study groups, self-efficacy significantly improved within the control group over time (0.3; 95% CI 0.1, 0.5). Conclusions Hispanic/Latino survivors found the SCP and education session acceptable. SCPs alone may improve knowledge and adherence to cancer screening. Implications for Cancer Survivors Provision of a SCP may benefit Hispanic/Latino survivors. Clinical trial registration clinicaltrials.gov NCT04081779.

We tested the feasibility and preliminary efficacy of an online diet and physical activity program for women with early-stage breast cancer who had completed surgery, chemotherapy, and radiation therapy (ongoing endocrine therapy allowed). Participants with low fruit and vegetable (F/V) consumption and/or low moderate-to-vigorous physical activity (MVPA) levels were randomized to one of two doses - low (one Zoom group session) or high (12 Zoom group sessions) - of an online lifestyle program with the goal of improving F/V intake and MVPA. All participants received eHealth communications (text messages, study website access), a Fitbit, and a WiFi-enabled scale. Primary objectives evaluated feasibility. Secondary objectives compared the 6-month change in F/V intake and MVPA between the two dose groups. Seventy-four women (mean age = 58.4 years; 87% non-Hispanic White; mean time since diagnosis = 4.6 years) were accrued. Among women in the low dose group, 94% attended the single session; among women in the high dose group, 84% attended at least 8 of the 12 sessions. Retention at 6 months was 93%. High relative to low dose participants consumed 1.5 more servings/day of F/V at 6 months ( P = 0.007) but MVPA levels did not differ between groups. We successfully implemented an online lifestyle program for early-stage breast cancer survivors. The high dose intervention demonstrated preliminary efficacy in improving F/V consumption in early-stage breast cancer survivors. Future trials can test the intervention in a larger and more diverse population of breast cancer survivors.

BACKGROUND Sleep disturbance is one of the most common health concerns reported by breast cancer (BC) survivors and is associated with poor quality of life (QoL) and greater mortality after treatment. Cognitive behavior therapy for insomnia (CBTi) has shown efficacy for improving sleep and quality of life for BC survivors. Considered the gold standard insomnia treatment, CBTi can be delivered remotely, including via digital intervention. Despite the potential for wider dissemination of CBTi via digital means, these modalities have unique challenges, including technology barriers and poor adherence. We developed a conversational agent (CA) to deliver CBTi via short message service (SMS), supported by mobile-ready web content. Named “Cecebot”, this CA delivers sleep education, implements sleep compression, provides just-in-time intervention on sleep-disrupting behaviors, and includes enhanced support for physical activity (PA) beyond what is typically included in CBTi. This represents a novel modality for a CBTi and PA intervention in BC survivors. OBJECTIVE We aim to examine the safety and acceptability of the Cecebot intervention for BC survivors with symptoms of insomnia and explore intervention efficacy. METHODS This trial will recruit 60 BC survivors who are experiencing moderate to severe sleep disturbance. Participants will be assigned to the Cecebot intervention or waitlist control group at a 1:1 ratio. The treatment group will receive Cecebot intervention during weeks 1-6 of the study, while the waitlist control condition will receive the Cecebot intervention during weeks 6-12. The Cecebot intervention utilizes SMS technology paired with Fitbit. Participants will be assessed at baseline, week 6, and week 12. Measurements will include feasibility and acceptability, and explore the effect of a Cecebot intervention. RESULTS Recruitment of participants began in Spring 2024. The completion of data collection is anticipated to be by Winter 2025. CONCLUSIONS The study results will give insight into the potential for an SMS-based conversational agent to improve sleep in BC survivors with sleep disturbances.

e13172 Background: The Association of Cancer Care Centers (ACCC) launched a quality improvement initiative in 2018 to address suboptimal germline BRCA1/2 testing rates and identify barriers impeding testing for patients with early-stage or metastatic breast cancer. Between 2018 and 2023, changes in clinical guidelines led to expanded testing criteria and increased referrals for genetic testing. A follow-up survey in 2023 aimed to assess changes in testing practices and challenges faced by cancer care teams, considering the evolving landscape of genetic testing and the impact of the COVID-19 pandemic. Methods: In 2018, a survey of 95 oncology providers was conducted to explore provider characteristics, testing characteristics, and challenges/barriers to germline BRCA 1/2 testing. The survey was conducted again in 2023 for comparative analysis with a response of 115 oncology providers. The surveys explored provider characteristics, testing practices, and challenges/barriers to germline BRCA1/2 testing. To comprehensively understand the patient's perspective, an additional survey was conducted in October 2023, involving 61 individuals recently diagnosed with breast cancer to evaluate the patient experience with germline BRCA 1/2 testing and subsequent follow-up. Results: The adoption of expanded testing criteria, which influenced changes in clinical guidelines, has led to a substantial increase in referrals for genetic testing. The utilization of genetic testing by medical oncologists experienced a notable surge with 64% of survey respondents in 2023 reporting that medical oncologists most often initiated tests for germline BRCA1/2 mutations, compared to 29% in 2018. Patients’ awareness and engagement were high, with 82% undergoing germline BRCA1/2 testing, 48% undergoing testing at diagnosis, 33% before treatment, and 13% during treatment. In 2023, 23% of providers reported routinely ordering germline BRCA1/2 testing for patients with early-stage breast cancer, marking a threefold increase from the 2018 survey results. For patients with metastatic breast cancer, 41% of providers routinely ordered BRCA mutation testing, a threefold increase from 14% in 2018. While testing rates improved, challenges and barriers persist such as patient concerns (47%), access to genetic counselors (42%), turnaround time for test results (36%), and reimbursement issues (28%). Conclusions: The comparative analysis revealed a moderate improvement in germline BRCA1/2 testing practices, with increased provider engagement and patient awareness. Despite progress, challenges persist, needing multi-pronged efforts to enhance testing uptake and distribute critical information on testing to patients. The results indicate positive trends but underscore the importance of addressing barriers for comprehensive patient care.

Importance There has been little consideration of genomic risk of recurrence by breast cancer subtype despite evidence of racial disparities in breast cancer outcomes. Objective To evaluate associations between clinical trial end points, namely pathologic complete response (pCR) and distant recurrence–free survival (DRFS), and race and examine whether gene expression signatures are associated with outcomes by race. Design, Setting, and Participants This retrospective cohort study used data from the Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis 2 (I-SPY 2) multicenter clinical trial of neoadjuvant chemotherapy with novel agents and combinations for patients with previously untreated stage II/III breast cancer. Analyses were conducted of associations between race and short- and long-term outcomes, overall and by receptor subtypes, and their association with 28 expression biomarkers. The trial enrolled 990 female patients between March 30, 2010, and November 5, 2016, with a primary tumor size of 2.5 cm or greater and clinical or molecular high risk based on MammaPrint or hormone receptor (HR)-negative/ ERBB2 (formerly HER2 or HER2 / neu )–positive subtyping across 9 arms. This data analysis was performed between June 10, 2021, and October 20, 2022. Exposure Race, tumor receptor subtypes, and genomic biomarker expression of early breast cancer. Main Outcomes and Measures The primary outcomes were pCR and DRFS assessed by race, overall, and by tumor subtype using logistic regression and Cox proportional hazards regression models. The interaction between 28 expression biomarkers and race, considering pCR and DRFS overall and within subtypes, was also evaluated. Results The analytic sample included 974 participants (excluding 16 self-reporting as American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, or multiple races due to small sample sizes), including 68 Asian (7%), 120 Black (12%), and 786 White (81%) patients. Median (range) age at diagnosis was 47 (25-71) years for Asian, 49 (25-77) for Black, and 49 (23-73) years for White patients. The pCR rates were 32% (n = 22) for Asian, 30% for Black (n = 36), and 32% for White (n = 255) patients ( P = .87). Black patients with HR-positive/ ERBB2 -negative tumors not achieving pCR had significantly worse DRFS than their White counterparts (hazard ratio, 2.28; 95% CI, 1.24-4.21; P = .01), with 5-year DRFS rates of 55% (n = 32) and 77% (n = 247), respectively. Black patients with HR-positive/ ERBB2 -negative tumors, compared with White patients, had higher expression of an interferon signature (mean [SD], 0.39 [0.87] and −0.10 [0.99]; P = .007) and, compared with Asian patients, had a higher mitotic score (mean [SD], 0.07 [1.08] and −0.69 [1.06]; P = .01) and lower estrogen receptor/progesterone receptor signature (mean [SD], 0.31 [0.90] and 1.08 [0.95]; P = .008). A transforming growth factor β signature had a significant association with race relative to pCR and DRFS, with a higher signature associated with lower pCR and worse DRFS outcomes among Black patients only. Conclusions and Relevance The findings show that women with early high-risk breast cancer who achieve pCR have similarly good outcomes regardless of race, but Black women with HR-positive/ ERBB2 -negative tumors without pCR may have worse DRFS than White women, highlighting the need to develop and test novel biomarker-informed therapies in diverse populations.

Purpose: The neutralizing peptibody trebananib prevents angiopoietin-1 and angiopoietin-2 from binding with Tie2 receptors, inhibiting angiogenesis and proliferation. Trebananib was combined with paclitaxel+/-trastuzumab in the I-SPY2 breast cancer trial. Patients and methods: I-SPY2, a phase II neoadjuvant trial, adaptively randomizes patients with high-risk, early-stage breast cancer to one of several experimental therapies or control based on receptor subtypes as defined by hormone receptor (HR) and HER2-status and MammaPrint risk (MP1, MP2). The primary endpoint is pathological complete response (pCR). A therapy "graduates" if/when it achieves 85% Bayesian probability of success in a phase III trial within a given subtype. Patients received weekly paclitaxel (plus trastuzumab if HER2- positive) without (control) or with weekly intravenous trebananib, followed by doxorubicin/cyclophosphamide and surgery. Pathway-specific biomarkers were assessed for response prediction. Results: There were 134 participants randomized to trebananib and 133 to control. Although trebananib did not graduate in any signature [phase III probabilities: HR-negative (78%), HRnegative/HER2-positive (74%), HR-negative/HER2-negative (77%), and MP2 (79%)], it demonstrated high probability of superior pCR rates over control (92%-99%) among these subtypes. Trebananib improved 3-year event-free survival (hazard ratio 0.67), with no significant increase in adverse events. Activation levels of the Tie2 receptor and downstream signaling partners predicted trebananib response in HER2-positive disease; high expression of a CD8 T cell gene signature predicted response in HR-negative/HER2-negative disease. Conclusions: The Ang/Tie2 axis inhibitor trebananib combined with standard neoadjuvant therapy increased estimated pCR rates across HR-negative and MP2 subtypes, with probabilities of superiority >90%. Further study of Ang/Tie2 receptor axis inhibitors in validated, biomarker-predicted sensitive subtypes is warranted.

346 Background: More than 150,000 women live with incurable metastatic breast cancer (MBC) in the U.S. today. Survival for patients with MBC has greatly improved over recent decades, but studies exploring aspects of breast cancer survivorship (quality of life, health outcomes, coping, etc.) disproportionately focus on patients with non-metastatic disease. In an effort to better serve patients with MBC at our large tertiary cancer center, we launched a project to understand the preferences, perceived barriers, and unmet needs of this unique population. Methods: We employed focus groups to qualitatively examine patients living with metastatic breast cancer at all points in their journey with advanced cancer. Two experienced patient advocates provided feedback on the protocol. We invited 37 patients with metastatic breast cancer to participate in focus groups of 2-4 subjects. A researcher moderated these recorded conversations, asking subjects to discuss their memories of being diagnosed with MBC, their everyday experience of living with MBC, and their hopes and fears as they look forward. Written transcripts of the studies are coded using the Atlas.ti qualitative research software with intercoder reliability calculated among three coders. Recurrent themes are identified and described. Results: 32 patients participated in 13 focus groups. The majority of patients were white (88%), with an average age of 59 (median 61). Median time since diagnosis with metastatic disease was 57 months (4.75 years). 84% of patients had estrogen-receptor positive MBC, 28% had HER2-positive MBC, and none had triple negative disease. Initial themes identified include a desire for more information about treatments (new drugs, clinical trials, symptom management), and about planning in the face of uncertainty (especially financial, but also regarding end-of-life challenges, relationship changes). Patients also commonly expressed a need for more connection to fellow patients who can provide guidance and support. Analysis of data and formulation of findings are still ongoing, and will be completed by the end of 2023. Publication is planned for early 2024. Conclusions: Metastatic breast cancer cancer survivors continue to have unmet physical, practical, emotional, and spiritual needs. These needs change throughout a patient’s journey. The knowledge gained from exploring these needs will inform projects and management changes designed to better serve our patients by adapting existing services and creating new ones.

Background Decreased mammography drives breast cancer disparities. Black women have lower rates of mammography completion than White women, and this contributes to disparities in outcomes. Points of disparity along the continuum for screening mammography remain underresearched. Methods The authors compared mammography referrals for Black and White women aged 40–74 years at a heterogeneous academic medical center. Completion of steps of the screening mammography continuum was compared between Black and White women within two age cohorts: 40–49 and 50–74 years. Multivariable logistic regression was used to evaluate the association between race and mammogram completion. Results Among 26,476 women, 3090 (12%) were Black, and 23,386 (88%) were White. Among Black women aged 50–74 years who were due for mammography, 40% had referrals, 39% were scheduled, and 21% completed mammography; the corresponding values for White women were 42%, 41%, and 27%, respectively. Similar differences in referral outcomes were noted for women aged 40–49 years, although Black women had lower rates of provider‐initiated referrals (9% vs. 13%). Adjusted analyses for those aged 40–49 and 50–74 years demonstrated an association between Black race and lower rates of mammography completion (odds ratio [OR] for 40–49 years, 0.74; 95% CI, 0.57–0.95; p = .02; OR for 50–74 years, 0.85; 95% CI, 0.74–0.98; p = .02). In multivariable analyses, noncommercial insurance and higher comorbidity were associated with lower rates of mammography. Provider‐initiated referral was positively correlated to mammogram completion. Conclusions Black race was associated with 15%–26% lower mammography completion (adjusted). Both groups experienced the highest attrition after scheduling mammograms, although attrition was more precipitous for Black women. These findings have implications for future interventions, including increasing provider‐initiated referrals and decreasing barriers to attending scheduled mammograms.

Introduction: Prospective data about quality of life (QoL) in men with breast cancer (BC) are lacking. A prospective registry (EORTC10085) of men with all BC stages, including a QoL correlative study, was performed as part of the International Male Breast Cancer Program. Methods: Questionnaires at BC diagnosis included the EORTC QLQ-C30 and BR23 (BC specific module), adapted for men. High functioning and global health/QoL scores indicate high functioning levels/high QoL; high symptom-focused measures scores indicate high symptoms/problems levels. EORTC reference data for healthy men and women with BC were used for comparisons. Results: Of 422 men consenting to participate, 363 were evaluable. Median age was 67 years, and median time between diagnosis and survey was 1.1 months. A total of 114 men (45%) had node-positive early disease, and 28 (8%) had advanced disease. Baseline mean global health status score was 73 (SD: 21), better than in female BC reference data (62, SD: 25). Common symptoms in male BC were fatigue (22, SD: 24), insomnia (21, SD: 28), and pain (16, SD: 23), for which women's mean scores indicated more burdensome symptoms at 33 (SD: 26), 30 (SD: 32), and 29 (SD: 29). Men's mean sexual activity score was 31 (SD: 26), with less sexual activity in older patients or advanced disease. Conclusions: QoL and symptom burden in male BC patients appears no worse (and possibly better) than that in female patients. Future analyses on impact of treatment on symptoms and QoL over time, may support tailoring of male BC management.

e24057 Background: Colorectal cancer (CRC) survivors often experience long-term symptom toxicity after cancer treatments. We described persistent gastrointestinal (GI) toxicity related to cancer and treatments in long-term CRC survivors and assessed the risk and life impact factors of GI toxicity. Methods: A cross-sectional study utilized data from the Women’s Health Initiative (WHI) Life and Longevity After Cancer (LILAC) study that recruited postmenopausal women. CRC survivors after cancer treatments were included (N = 413). Pearson correlations/A Chi-square test and multivariable linear regression models were used to identify risk and impact factors of GI toxicity. Results: 81% of CRC survivors experienced persistent GI toxicity. Bloating/gas was the most prevalent (54.2%) and severe, followed by constipation (34.1%), diarrhea (33.4%), and abdominal/pelvic pain (28.6%). Time since cancer diagnosis (< 5 years), advanced cancer stage, low income, high psychological distress, poor dietary habits and physical activity, and impaired life impact measures (health-related quality of life, daily life interferences, and body image) were significantly associated with several GI toxicities. Fatigue and sleep disturbance were the most significantly associated with long-term GI toxicity (Table 1). Abdominal/pelvic pain significantly influenced life impact measures. Conclusions: GI toxicities are highly prevalent among CRC survivors, specifically in patients with high psychological distress. A better understanding of the long-term GI toxicity in CRC survivors and identifying those more vulnerable may inform future directions for managing CRC survivorship. An individualized, multifaceted intervention is warranted to consider psychosocial support, lifestyle intervention, and physical rehabilitation. [Table: see text]