- Study Protocol
- Published:
Young, Empowered & strong (YES): a study protocol paper for a randomized controlled trial of an mHealth symptom monitoring and self-management intervention for adolescent and young adult (AYA) breast cancer survivors
樱花视频 volume听25, Article听number:听126 (2025)
Abstract
Background
Compared to older adults with breast cancer (BC), adolescents and young adults (AYAs) develop more aggressive disease necessitating more intensive therapy with curative intent, which is disruptive to planned life trajectories. The burden of unmet needs among AYA BC survivors exists in two domains: (1) symptoms (e.g., sexual problems, anxiety, fatigue, stress, hot flashes) and (2) AYA concerns (e.g., fertility, genetics, relationships, economic attainment). Improved attention to concerns and symptoms may improve symptom management and quality of life. The Young, Empowered and Strong (YES) trial tests the efficacy of a 9-month, multicomponent digital health intervention that includes monthly assessments of prevalent symptoms, a chat room, and journal to engage and support AYAs with BC by providing tailored information, resources, and support outside of the clinical setting.
Methods
YES is a multicenter, randomized controlled trial across three academic institutions in the United States with 400 participants randomized to either the YES intervention or usual care arm. Inclusion criteria include biologically female; 15鈥39 years of age at diagnosis of stage 0-III BC; within 3 years of diagnosis; no known evidence of recurrence; no prior history of new malignancy since initial BC diagnosis; and ability to access medical records from treatment site. All participants complete REDCap surveys at baseline, and at 3, 6, and 9 months post-enrollment. The primary outcome is quality of life as measured by the Quality of Life in Adult Cancer Survivors Scale (QLACS), with changes from baseline to 6-months in QLACS scores, compared by arm. Secondary outcomes include patient reported AYA concerns/needs, emotional symptoms, general health, physical symptoms, and health behaviors,
Discussion
Study findings will provide valuable insight into the ability of the YES digital health intervention to address symptoms and concerns of AYA BC survivors and assist them to track and self-manage their own symptoms, concerns, and needs related to their cancer outside of the clinic.
Trial registration
Clinicaltrials.gov, NCT04906200, registered May 13, 2021.
Background
Approximately 13,000 new cases of breast cancer are reported in the United States (U.S.) annually among individuals younger than 40 years, representing 15% of all new adolescent and young adult (AYA) cancers [1]. Incidence rates of invasive breast cancer among this age group have been increasing since 2004, with AYAs experiencing biologically more aggressive tumors at more advanced stages compared to older adults [2]. While advances in treatment have improved outcomes, AYAs with breast cancer remain at higher risk of experiencing a recurrence or dying from their breast cancer compared to older adults with the disease [3]. Disparities in disease and mortality outcomes are amplified in AYAs from under-represented sociodemographic groups such as racial, ethnic, sexual and gender minorities, those with low educational and financial attainment, and those living in rural areas [1, 4].
AYAs diagnosed with breast cancer often experience disruptions in planned life trajectories due to intensive treatment, associated disease symptoms, and treatment-related side effects [5]. While acute physical complaints generally resolve following initial treatment, the long-term physical, emotional, and psychosocial impacts may worsen or only become evident following the completion of active treatment [6]. Compared to older populations, AYAs are more likely to suffer medically and psychosocially during breast cancer treatment and beyond. Many experience an influx of unmet needs (e.g., body image, menopausal symptoms, mental health, fatigue, sexual dysfunction) and concerns (e.g., fear of recurrence, employment, fertility, financial attainment, relationships) unique to or accentuated by their age [6,7,8]. Beyond causing distress, these needs and concerns influence longer-term treatment decisions including adherence to risk-reducing adjuvant endocrine therapy and health behaviors [9]. Thus, improved attention to AYA breast cancer concerns and symptoms in survivorship may improve not only symptom management and health-related quality of life (QOL), but disease and overall mortality outcomes. However, the healthcare system is not equipped to meet the intensive needs of AYAs with breast cancer who are no longer receiving active cancer treatment, but are struggling with the aftermath as most of the previous focus has been on physical QOL and not psychosocial care [10, 11]. While there is a great need to enhance the survivorship care of all patients with cancer, it is especially true for AYAs with breast cancer, given their unique and serious concerns. Importantly, the needs of AYAs from diverse sociodemographic backgrounds are particularly unmet, and improving their outcomes remains critical to mitigate disparities [12]. Therefore, strategies to empower patients with the tools, skills, and support they need to fully recover have the potential to improve wellbeing for the large and growing population of AYA survivors of breast cancer, and may generalize to AYA survivors of other cancers.
Serial symptom monitoring using electronic patient-reported outcome systems (ePROs) has resulted in greater attention to and better management of symptoms [13] as well as improved QOL [14]. Interventions promoting the self-management of symptoms among patients with cancer have been developed and tested in various ways among different patient populations across the cancer trajectory [15,16,17]. These interventions have been delivered using a range of modalities, including nurse-led classes, phone calls, videos, web-based platforms, mobile applications (鈥渁pps鈥), and written information, and most have included content promoting the self-management of symptoms. Many have reported positive effects, including decreases in symptom frequency, distress, and severity, as well as an improvement in QOL both during and post-treatment [15,16,17]. Recently, randomized controlled trials have tested ePROs to screen for distress, address emotion regulation, and support adherence to prescribed treatment [13]. Utilizing ePROs in the tracking of unmet needs, concerns, and experienced symptoms among AYAs with breast cancer may assist in providing an accessible way to identify and improve equity in survivorship care among underserved groups, especially those living in rural areas [12].
Based on our previous experience designing supportive care interventions for AYAs with breast cancer [18], we developed Young, Empowered and Strong (YES), a mobile app- and web-based educational and supportive care intervention for AYAs with newly diagnosed, early stage breast cancer. The YES study aims to determine the efficacy of the YES intervention compared to usual care in improving QOL and AYA breast cancer concerns and symptoms at 6-months post-randomization, also determining the sustainability of intervention effects at 9-months. We have hypothesized that participants randomized to YES will report better QOL, fewer unaddressed AYA breast cancer concerns, and fewer/less severe symptoms at 6- and 9-months compared to participants randomized to usual care. As an exploratory aim, we will determine potential moderators and mediators of intervention efficacy and investigate the potential effects of the intervention on inflammatory, genetic, and other biomarkers overall and by sociodemographic characteristics of interest.
Methods/design
Study design
The YES study is a multicenter, two arm, unblinded randomized controlled trial, enrolling 400 AYAs diagnosed with breast cancer (see Fig.听1). The study will compare the YES (intervention) arm to a usual care (control) arm. Randomization is 1:1 and stratified via a REDCap randomization feature by age at diagnosis (30鈥39 vs. <29 years), time since diagnosis (鈮1 year [365 days] vs. >1 year), and study site (the Ohio State University [OSU], Dana-Farber Cancer Institute [DFCI] or Columbia University Medical Center [CUMC]) to ensure balance between study arms. Participants from both arms are sent REDCap surveys at baseline, 3, 6, and 9 month timepoints via email; dried blood spot kits are distributed for blood sample collection at baseline and 6 months. Participants from both study arms are compensated with a $20 gift card after completing each of the four REDCap surveys (i.e., baseline, 3, 6, and 9 months; see Table听1). Participants randomized to YES are granted access to the YES supportive care portal at baseline for a total of 12 months and are sent portal assessments at baseline and every 4 weeks for 6 months. Participants randomized to usual care are sent REDCap surveys at 3, 6, and 9 months (see Fig.听1) and are offered access to the YES portal for 3 months at the end of their 9 month study period.
Participating sites
Participants are enrolled at three sites in the United States: OSU (Ohio), DFCI (Massachusetts), and CUMC (New York). These sites include diverse racial, ethnic, sexual and gender minority groups, those with lower educational attainment, and those living in urban and rural areas. Each site鈥檚 principal investigator (PI) ensures that their site adheres to study protocols. The OSU Institutional Review Board IRB (#OSU-21035) is the IRB of record with DFCI and CUMC IRBs relying on its oversight. The OSU Institutional IRB also reviews the intervention progress and acts as a data monitoring committee.
Eligibility
Participants are eligible to enroll if they meet the following criteria: biologically female; age 15鈥39 years at diagnosis of a stage 0-III breast cancer; within 3 years of their breast cancer diagnosis; no known evidence of breast cancer recurrence (local or distant) or second primary breast cancer; no prior history of new other malignancy since their breast cancer diagnosis (other than non-melanoma skin cancer); able to speak, understand, and read English; cognitively able to complete study requirements; ability to access medical records from the participant鈥檚 site institution; willing to provide cell phone number and email address and are willing to receive email, mobile push notifications, and/or text messages from the study team with their own smartphone or one provided by the study team. For potential participants under 18 years, we obtain assent and permission from a parent/guardian for participation. Pregnant survivors are also eligible for the YES trial, given that fertility and pregnancy are important AYA issues. Patients are excluded if they are under age 15 or over age 42; stage IV or have metastatic breast cancer; or are biologically male.
Recruitment
Recruitment began in May 2021; potential participants are identified through the screening of program and clinic lists, electronic medical records, and referral of patients from providers. A HIPAA waiver was requested to conduct the prescreening of patients within each clinic, with each maintaining a list of patients they have screened and approached. Importantly, we also maintain a list of individuals who decline study participation and their reasons why. At each site, AYA patients fitting prescreening eligibility criteria are approached in-person during clinic visits or remotely via phone/email. For all potential participants screened, the following patient and clinical cancer characteristics are abstracted from medical records: age at diagnosis, race, ethnicity, zip code, gender/gender identity, language spoken, insurance status, months since diagnosis, T, N, M stage, grade, estrogen- and progesterone-receptor status, HER2-neu status, number of positive lymph nodes, breast and ancillary surgeries, reconstruction, adjuvant therapies, ovarian suppression, type of endocrine therapy prescribed, height, and weight at the time of recruitment/chart abstraction and at baseline. These data are used to characterize participant populations at each institution.
We also utilize study flyers/information sheets (see Additional File 1) that are distributed in clinics, at community events and through our community partners, and/or mailed or emailed to potential participants. All aspects of recruitment, the consent process, and study/YES portal setup can be done remotely via phone or Zoom. Each site conducts in-clinic and/or remote consent processes based on current institutional standards. Study teams follow up with three additional contact attempts, if needed, over a 6-week period to allow for sufficient time to respond. Following confirmation of eligibility, patients and coordinators review the consent documents together, and are asked to provide informed consent by email via REDCap with electronic signature.
After consenting, participants are prompted by email or text to complete the baseline survey via REDCap and are given a dried blood spot (DBS) kit by mail (in self-addressed, postage-paid packaging) or in clinic to self-collect a blood specimen. Blood specimen collection also occurs at 6 months using the same procedures. The baseline REDCap survey and the DBS sample (if the participant has agreed to give a blood sample) are required to randomize participants. We have implemented robust procedures designed to maximize survey response rates and DBS kit completion (e.g., monitoring survey non-response, reminder emails and phone calls, small incentives). Participants are then informed of their randomization allocation by study staff. Those randomized to the YES intervention arm are onboarded to the YES portal by study staff. All participants can withdraw from the study at any time by contacting study staff.
Overview of the YES intervention
The YES intervention is an interactive mHealth intervention designed to engage and support young women newly diagnosed with early-stage breast cancer to self-monitor and manage concerns and symptoms outside of a clinical setting. The YES portal uses serial symptom monitoring with electronic patient-reported outcome systems (ePROs) to address the unmet needs of a growing population of AYAs with breast cancer during the survivorship period, a demographic amenable to technology-based solutions. By reporting concerns (e.g., fertility, genetics, body image, diet and nutrition, physical activity, weight management, survivorship care, recurrence concerns, financial concerns) and symptoms (e.g., sexual problems, anxiety, fatigue, stress, sleep problems, hot flashes, musculoskeletal complaints) at each timepoint, participants are provided with tailored education and resources. Importantly, ePROs are tracked over time, generating graphs of symptom/concern presence and monthly changes in frequency/severity, useful to participants. YES can be accessed via mobile phone, tablet, laptop, or desktop computer and includes tips, participant-triggered informational sheets, assessments, additional guidance and opportunities, helpful websites, the YES Chat (anonymized participant group chat), an optional journal activity, symptom and concern tracking graphs, previously triggered informational sheet library, information about the study, and account and notification settings.
At inception, the YES intervention was designed as a web-based portal accessible via tablet, mobile, or computer browser (see Additional File 1 for screenshots of old YES) with a separate website hosting the YES Chat. In mid-2023, the study team was notified that the vendor who created and hosted the web-only YES portal was being terminated and would no longer support the existing portal infrastructure as of April 2024. Beginning in August 2023, all sites paused recruitment while the YES portal was rebuilt with a new vendor, with an addition of a concurrent mobile app version, including an integrated YES Chat feature. At the time of the pause, a total of 250 participants were enrolled in the study, with 110 randomized to the intervention arm. During this pause, participants actively randomized to the intervention arm were able to access the original YES app. Recruitment resumed in March 2024; the new mobile app with the web version was released in April 2024 (see Additional File 1 for screenshots of new YES). After resuming recruitment in March 2024, 150 participants were enrolled, with 68 randomized to the intervention arm as of December 2024.
Intervention development
The YES pilot study (NCT03913936), enrolled 30 AYA breast cancer survivors (mean鈥=鈥36 years at diagnosis), including women at a range of times from diagnosis and of diverse backgrounds [19]. Over a 4-week period, participants were invited to engage with YES over time, with 80% completing the pilot and over 50% indicating they had read all information provided. The top concerns/symptoms triggered within the pilot included sexual health, anxiety, fatigue, stress and mindfulness, depression and sadness, mental health services, emotional health in survivorship, sleep problems, vaginal dryness and pain, and hot flashes and excessive sweating [19]. We used feedback from the pilot to revise the YES intervention and study procedures, with a focus on participant engagement, including a patient-centered plan to optimize timing and minimize the burden of assessments, as well as strategies to promote improved engagement.
Intervention procedures
Participants randomized to the YES portal intervention arm are notified of their assignment post-randomization and are asked to download the YES portal mobile app to their smartphones and/or access the YES portal via their internet browser, with the assistance of study staff. Participants activate their account via an email sent by study staff, and after confirming their date of birth, log themselves into the portal. The same login is used for both the mobile app and web browser versions of the YES portal, as they are synchronous. Participants are walked through the features of the portal and instructed to contact the study staff if any issues should arise.
Participants randomized to YES are prompted by text messages, mobile push notifications, and/or emails every 4 weeks for 6 months to complete monthly YES assessments, which include AYA breast cancer-specific concerns, symptoms, and psychosocial distress measures. Participants have 10 days to complete their monthly YES assessment. If they do not complete the assessment in the first 7 days, a reminder text message and email are sent, notifying participants that their assessment is expiring in 3 days. If the participant still does not complete their assessment, they receive a final notification notifying them that their assessment is expiring in 24听h. Every monthly assessment takes approximately 20听min to complete.
During the last three months of the 9-month study period, participants no longer complete monthly portal assessments, but receive intermittent reminders about portal features and resources. Participants are also sent engaging reminders intermittently throughout the study to encourage them to engage with the YES portal between assessments, review their tailored information, monitor their concerns and symptoms over time, and utilize the supportive resources that are readily available. Participants鈥 use of portal components and the evaluation of the sustainability of effects on AYA concerns, symptoms, and quality of life continue through 9-months.
Intervention components
YES intervention materials include the following components: (1) YES welcome letter and welcome guide (i.e., a walkthrough of using the mobile app and web portal features); (2) portal assessments (ePROs and distress); (3) anonymous participant chatroom; (4) optional, ad-hoc journaling feature; (5) triggered symptom informational resource sheets based on assessment responses; (6) questions to consider with their care team resource; (7) helpful books and websites resource; and (8) rotating tip/thought of the week. All resources and materials are accessed via the portal on demand and hard copies can be printed.
Survivorship concerns and symptom assessments are sent to participants in the intervention arm via the YES portal every 4 weeks for 6 months including AYA breast cancer-specific concerns (AYA HOPE Study questionnaire with additional items), symptoms, and psychological distress.
Symptoms
The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is a patient-centered, standardized self-report measure that enables patients to report symptoms and adverse events (AEs). This measure demonstrates favorable validity, reliability, and responsiveness in a large heterogeneous sample of U.S.-based cancer patients actively undergoing treatment [20]. PRO-CTCAE items salient to AYA breast cancer survivors, as confirmed in our pilot study [19], are collected. The PRO-CTCAE items use conditional branching for symptoms and AEs that contain multiple attributes (e.g., if a participant reports a symptom, she is asked to quantify the severity and extent to which the symptom interfered with her daily activities; if she does not report a symptom, these items are skipped). We also asked participants to choose the face that best represents how they feel using a publicly available five emoji Likert scale.
Psychological distress
The Patient Health Questionnaire-9 (PHQ-9) is a brief tool that assesses depressive symptoms, which are common among cancer survivors [21, 22]. Participants are asked to answer 9 items about how they have felt in the past two weeks, set on a 4-point Likert scale (0鈥=鈥塶ot at all to 3鈥=鈥塶early every day). Scores on the PHQ-9 range from zero to 27, with scores indicating: 0鈥4 no/minimal depression, 5鈥9 mild depression, 10鈥14 moderate depression, 15鈥19 moderately severe depression, and 20鈥27 severe depression. At each assessment, participants are flagged for an alert value if their total score is 鈮モ15 or if they marked 鈥1鈥 or greater on the single item concerning suicidal ideation (i.e., participants had thoughts that they would be better off dead or of hurting themselves in some way).
Participant responses to the PHQ-9 are monitored by pre-programmed automatic alerts in the YES portal, which notify study staff at DFCI, OSU, or CUMC within 1听day that a participant needs a follow-up with one of the clinical investigators at the appropriate site. If the total score is 鈮モ15, but the response to item #9 is 0, site staff follow-up with the participant鈥檚 treating clinician within 1 business day. If the participant indicated 1 (several days), 2 (more than several days), or 3 (nearly every day) on item #9, site staff alert the site PI/covering clinician/study staff at each site informing them that a patient has endorsed the suicidal ideation item on the PHQ-9. The participant鈥檚 electronic health record is reviewed for a prior or current history of depression or other psychiatric conditions, medications, and notes about whether the participant is currently under care for depression or anxiety symptoms. The site PI/covering clinician/study staff designated at each site who routinely handles participant depressive symptom alerts calls the participant as soon as possible. If the clinician/study staff knows the participant and/or is trained in addressing suicidality, they will assess and triage the participant, if appropriate.
Measures
Participant REDCap surveys
Surveys are sent via REDCap at baseline prior to randomization, 3 months, 6 months, and 9 months based on the participant鈥檚 enrollment date. See Table听1 for REDCap surveys by timepoint.
Sociodemographic information
Sociodemographic information including race, ethnicity, sexual and gender identification, education, income, occupation, household size, number of children, marital status, employment status, and insurance status is collected.
Quality of life
The primary outcome of QOL is measured using the Quality of Life in Adult Cancer Survivors (QLACS) for long-term cancer survivors comprises 47 items scored on a 1 (never) to 7 (always) scale [23, 24]. These items are grouped into 12 domains including generic (negative feelings, positive feelings, cognitive problems, sexual problems, physical pain, fatigue, social avoidance) and cancer-specific domains (financial problems, family-related distress, distress about recurrence, appearance concerns, benefits of having cancer). A generic summary score is calculated by adding the 7 constituent domain scores (reversing the score for positive feelings), so that a lower score corresponds to higher QOL. A cancer-specific summary score is calculated by adding the constituent domain scores of all but the 鈥渂enefits鈥 domain. The psychometric properties of the QLACS for breast cancer survivors who are newly-post primary treatment have been studied, and the instrument has been used in younger women, including validation in AYA women [24, 25].
Health status
The EQ-5D-5 L is a summary measure of health status to evaluate health and healthcare includes 5 functional dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). The EQ-5D-5 L can be used to generate and evaluate quality adjusted life years. There is also a visual analog scale (EQ-VAS) that asks participants to rate how good or bad their health is today on a zero (worst health imaginable) to 100 (best health imaginable) scale [26].
AYA concerns and needs
AYA concerns and needs are measured by items from the HOPE study questionnaire that ask patients to rate their level of concern and need for information regarding a range of AYA survivorship-focused issues including fertility, diet and nutrition, physical activity, weight management, survivorship care, recurrence concerns, and financial support for medical care [27]. We have added additional items to assess general financial concerns, body image, smoking cessation, and alcohol consumption and cancer.
Breast cancer symptoms and sleep quality
A modified 19-item version of the Breast Cancer Prevention Trial (BCPT) Symptom Checklist is used to evaluate common symptoms including hot flashes, fatigue, sexual problems, and musculoskeletal complaints [28]. The PROMIS 8-item Fatigue Scale, the Insomnia Severity Index (ISI), and the modified Self-Assessment of Sleep Survey (SASS) are used to assess fatigue and sleep quality, respectively [29,30,31].
Emotional symptoms
Emotional symptoms are assessed using the Generalized Anxiety Disorder-7 (GAD-7) and the Center for Epidemiologic Studies-Depression scale (CES-D) to measure anxiety and depressive symptoms, respectively [32, 33]. The GAD-7 is a 7-item scale that asks about anxiety symptoms in the past two weeks, while the CES-D includes 20 items that evaluate symptoms of depression in the last week.
Patient activation and self-efficacy
Patient activation is measured using the Patient Activation Measures-13 (PAM-13), a short-form version of the original 22-item scale that measures an individual鈥檚 knowledge and perceived ability for self-management of chronic health conditions, used in prior studies of cancer survivors [34]. The PROMIS 8-item Self-Efficacy Scale for managing chronic conditions is also utilized to assess participant confidence in the ability to manage their breast cancer-related symptoms [35].
Health behaviors
Smoking and alcohol use are evaluated using items selected from our cohort study of young women with breast cancer (Young Women鈥檚 Breast Cancer Study [YWS]) and our prior Smoke Free Study [36]. Physical activity is assessed using a modified version of the Godin Leisure-Time Exercise Questionnaire (GLTEQ), commonly used to estimate weekly frequencies of strenuous, moderate, and light activities and the average duration of those activities [37]. Weekly minutes of moderate and vigorous activity (MVPA) are the main measure of physical activity; however weekly minutes of vigorous activity (MVA) and the average weekly frequency of mild, moderate, and strenuous intensity exercise based on the Leisure Score Index (LSI) [38] will also be examined to evaluate change in physical activity behavior. We also included one additional item to assess changes in the frequency of exercise since breast cancer diagnosis.
Social support
The 20-item Medical Outcomes Study Social Support Survey questionnaire (MOS-SS) assesses emotional and informational support, tangible support, positive social interactions, and affection [39]. Degree of loneliness, measured by the Cancer Loneliness Scale, is a 7-item validated scale used in cancer patients and survivors that asks participants to report frequency of different types of feelings of loneliness since their cancer diagnosis [40]. Additionally, all participants are asked about their use of other informational sources and support, including whether they contact their care providers.
Fertility, family history of breast cancer, and recurrence status
We also assess fertility and gynecological status, family history of breast cancer, genetic testing history, and recurrence status using items selected from the YWS and an ongoing multi-center trial (Comparison of Operative vs. Monitoring and Endocrine Therapy [COMET]) [41, 42].
Medications and supplements
We assess current medication(s), including vitamins and supplements, with an open-ended question. We have also included a modified item to assess if participants would like to be informed of the results of the study when that information becomes available [41].
COVID-19
We have assessed the effect of COVID-19 on participants鈥 lives, their ongoing treatment, and their concerns using a series of questions adapted from other similar work in this space [43, 44].
Intervention acceptability and use
Intervention acceptability and use are assessed at 6 and 9 months among those randomized to YES only. Items evaluate the overall impact of YES, its resources, and features, specifically its symptom and concern tracking, the chatroom, and the journaling features.
Other measures and data
Remote blood collection
At baseline and 6 months, participants are given a TASSO M-20 DBS [45] kit by mail or in clinic to self-collect a blood specimen. Participants are instructed on how to self-administer the DBS kit when consented, in addition to being provided with written instructions in each kit. Samples are sent (or given) back to in self-addressed, postage-paid packaging to study staff at DFCI.
YES portal passive data
YES portal use data are collected for those randomized to the intervention to assess participants鈥 use of the portal and engagement with its information and resources, such as journal and group chat utilization; whether they accessed their triggered specific concern and symptom information in the portal; and the completion of monthly concern and symptom assessments. We also record use of the portal among the usual care arm when offered after the completion of their study requirements.
Exit interview
Participants randomized to the YES arm are asked to complete a brief exit interview at the end of 9 months, aimed at understanding how young breast cancer survivors prefer to self-manage survivorship needs, concerns, and symptoms, as well as understand ways that the YES portal might support their self-management. Each interview lasts around 15鈥20 min.
Semi-structured interview
At the end of the study, we are selecting a sample of 30 participants (across both arms) from diverse sociodemographic backgrounds to invite them to participate in a one-time, semi-structured interview. Each interview lasts around 30鈥45 min, with participants receiving $20 compensation for their time.
Planned analyses
The primary objective of the study is to compare the intervention and usual care arms with respect to the change in QLACS scores from baseline to 6 months. We will conduct repeated measures linear modeling for the primary analysis to use all QLCAS scores collected at baseline, 3, and 6 months, even if participants are missing assessments. Mediators, such as participant intervention activation and self-efficacy, and moderators, such as loneliness and social support, will be included in longitudinal models to evaluate their relationship with QLACS scores in addition to baseline and other measures, which will be included as covariates. We anticipated that up to 20% of participants may not have QLACS scores for all three assessment timepoints, and therefore, we planned to enroll a total of 400 participants in this study to ensure adequate power to evaluate our primary outcome. We originally planned to recruit 360 participants, but this was increased to ensure sufficient number of evaluable participants. A total of 288 evaluable participants (144 in the intervention group and 144 in the control group) will provide 90% power to detect 6-point difference in the change in QLACS score from baseline to 6 months (0.38 standard deviation [SD] difference) between study arms using a two-sided, 0.05 type I error test. The 0.38 SD difference calculation is based on the assumptions that the correlation coefficient between the baseline and 6 month scores is 0.5 and the SD of the difference in scores between baseline and 6 months is 15.64. We anticipate that up to 20% of enrolled participants may not provide QLACS scores for all three assessment timepoints. We, therefore, plan to enroll a total of 400 participants in the study. Several approaches will be considered to handle missing observations (e.g., complete case analysis, multiple imputation, all available case analysis) to ensure that findings are robust and to minimize the effect of missing data on conclusions.
Secondary outcomes will further define whether the YES intervention is efficacious for specific concerns and symptoms, and if its effects are sustained at 9 months, three months after completion of the 6 month YES intervention. Secondary outcomes include changes in AYA concerns and symptom frequencies from baseline to 6 months. Repeated measures regression models, both unadjusted and adjusted, will be utilized with link functions selected based on the type of outcome data being analyzed (continuous: identity link; multivariable: cumulative logit link). Primary and secondary analyses will be repeated at 9 months to determine sustainability of the effects of the YES intervention.
We plan to explore the efficacy of the YES intervention regarding primary and secondary outcomes stratified by age (<鈥30 vs. 30鈥39 years), geography (rural vs. urban), race (Black vs. White), and other relevant subgroups as represented (e.g., ethnicity [Hispanic vs. non-Hispanic], sexual and gender identity [LGBTQ鈥+鈥塿s. other]). We will also evaluate whether inflammatory and other biomarkers are associated with certain symptoms (e.g., depression, fatigue) and if they change in response to improvements in symptoms and overall QOL.
Discussion
The YES trial tests the efficacy of a 6-month, multicomponent mHealth intervention to engage and support AYAs with breast cancer by providing tailored information, resources, and support for self-management outside of the clinical setting. A multicenter study allows for larger sample sizes, sharing of resources across collaborative sites, and benefitting from each site鈥檚 own unique patient pool, helping us to meet diversity goals originally outlined in our grant application, the American Association of Cancer Research Disparities Report, the National Comprehensive Cancer Network, and others [46]. YES was designed to be sustainable, updatable, and disseminable; if evaluated to be efficacious, we will collaborate amongst sites and our existing network of provider and patient advocacy organizations to disseminate the intervention to applicable patients.
Since the study began in 2021 in the middle of the COVID-19 pandemic, study procedures were initially designed to reflect recommended safety measures, and as such, virtual recruitment strategies, blood collection, and survey follow-up were utilized by CUMC and DFCI until 2023. CUMC initiated hybrid procedures (in-person and remote) in 2022 followed by DFCI in early 2023. OSU procedures have always been hybrid since initiating the study at their site.
Future plans for YES involve increasing the diversity of tailored information and resources based on participant feedback and preferences collected post-study, as well as offering the YES portal and its materials in Spanish. Findings from this study will add to the literature about improving care for AYAs with breast cancer, and our hope is that, if efficacious, YES may be implemented as standard of care at our three sites and beyond. With additional research, there is also the potential to adapt YES for AYAs beyond breast cancer. We believe that study findings will provide an on-demand, supportive and educational resource for AYAs with breast cancer, allowing them to track and self-manage their own symptoms, concerns, and needs related to their cancer outside of the clinic.
Data availability
This is an ongoing study; therefore, participant materials are available at the Principal Investigator鈥檚 (PI) discretion upon reasonable request.
Abbreviations
- AYA (s):
-
Adolescent and young adults
- CUMC:
-
Weill Cornell Medical Center
- DBS:
-
Dried blood spot
- DFCI:
-
Dana-Farber Cancer Institute
- ePROs:
-
Electronic patient-reported outcome systems
- IRB:
-
Institutional review board
- OSU:
-
Ohio State University
- QOL:
-
Quality of life
- YES:
-
Young, Empowered, and Strong
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Acknowledgements
We would like to acknowledge the young breast cancer survivors who agree to participate in our study.
Funding
This study was funded by the National Cancer Institute (U01CA246648, PIs Partridge and Naughton) and the Breast Cancer Research Foundation (BCRF-23-124, PI Partridge). Dr. Partridge is also supported by Susan G. Komen and by a Clinical Research Professor Award, CRP-24-1187963-01-PROF, from the American Cancer Society. Dr. Kate Dibble was funded by the Helen Gurley Brown Presidential Initiative at Dana-Farber Cancer Institute (Helen Gurley Brown Foundation). Dr. Timiya Nolan is funded by the National Cancer Institute (K08CA245208, PI Nolan). The funders played no role in the design or conduct of this research.
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Funding acquisition: Michelle Naughton, Ann H Partridge Conceptualization: Michelle Naughton, Ann H Partridge, Shoshana Rosenberg, Timiya Nolan Methodology: Michelle Naughton, Ann H Partridge, Dawn Hershman, Shoshana Rosenberg, Timiya Nolan Administration support: Craig Snow, Kate E Dibble, Gregory J. Kirkner Data curation: Kate Dibble, Craig Snow, Ann H Partridge, Michelle Naughton, Dawn HershmanData analysis and interpretation: Nabihah Tayob Manuscript writing: All authors Final approval of manuscript: All authors Accountable for all aspects of the work: All authors.
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This study was reviewed and approved by the Ohio State University Institutional Review Board (IRB# OSU-21035, protocol date May 21, 2024, version 8). Study coordinators reviewed the consent form, verifying interest, and confirming eligibility with each potential participant.
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Not applicable.
Competing interests
Dr. Shoshana Rosenberg reports grant funding from Pfizer/Conquer Cancer. Dr. Ann Partridge reports receiving royalties from Wolters Kluwer for authorship of UpToDate and has received research funding from Novartis. The remaining authors have no conflicts of interest to disclose.
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Dibble, K.E., Rosenberg, S.M., Snow, C. et al. Young, Empowered & strong (YES): a study protocol paper for a randomized controlled trial of an mHealth symptom monitoring and self-management intervention for adolescent and young adult (AYA) breast cancer survivors. 樱花视频 25, 126 (2025). https://doi.org/10.1186/s12889-025-21288-4
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DOI: https://doi.org/10.1186/s12889-025-21288-4