Developing a digital symptom monitoring intervention to improve adherence to endocrine therapy among breast cancer survivors

Almost two-thirds of breast cancers are the hormone-receptor positive subtype which are treated with oral endocrine therapy (ET), yet up to 50% of patients do not take these medications as prescribed resulting with increased rates of breast cancer recurrence and death. Despite robust available data supporting the efficacy of ET and the low adherence to this life-saving treatment, prior interventions have shown minimal to modest short-term benefits on improving adherence. Most of these studies only provided educational materials and did not intentionally target patients at high risk of poor adherence to ET. Therefore, a tailored intervention for breast cancer survivors that addresses multiple barriers to ET adherence is particularly beneficial for this population. We propose an iterative approach to develop and pilot test a new digital behavioral intervention for ET adherence that is developed with input from breast cancer survivors. This new digital intervention will address a major barrier to ET adherence, symptoms from ET and will promote self-efficacy in symptom monitoring among patients with non-metastatic hormone receptor positive breast cancer on ET. We will iteratively refine and tailor the digital intervention focusing on symptom monitoring and management (Aims 1 and 2). We will then test the intervention for acceptability, feasibility, and preliminary efficacy (Aim 3). This project will address quality of life (symptom burden) and care delivery (medication adherence) issues among the majority of patients with breast cancer. This intervention has great promise for reducing cancer-related symptoms burden which negatively impact quality of life and potentially improving breast cancer outcomes. Modified Specific Aims There will be approximately 317,000 new cases of invasive breast cancer in 2025.5 Of these, about 75% will have hormone receptor positive breast cancer. The cornerstone of treatment for this subtype of breast cancer is oral endocrine therapy (ET) – medication that must be taken daily for 5-10 years. ET reduces risk of death from breast cancer by 50% when taken optimally. However, 10-year survival decreases from 81% when adherent to 74% when non-adherent to ET.4 Despite the robust data regarding efficacy of ET, adherence remains as low as 50% and nonadherence to ET is a major contributing factor to relapse rates. Some of these relapses include distant relapse (i.e., the development of incurable metastatic breast cancer requiring life-long treatment), a significant issue for breast cancer survivors. In a randomized trial, among those patients who discontinued ET, 79% stopped the drug due to side effects.6 Side effects from ET are frequently cited by patients as the reason for early discontinuation of ET in observational studies.7-9 Other barriers to adherence reported by breast cancer survivors include a perception of being at low risk of recurrence and low perceived benefit of ET.10 Given the incidence of HR+ breast cancer, ET non-adherence is a significant problem as non-adherence is associated with worse outcomes.11 Thus, targeted interventions to increase adherence to ET are needed to improve breast cancer outcomes. Prior interventions designed to improve ET adherence have primarily focused on providing education and have not demonstrated significant efficacy in improving adherence. We propose a randomized, mHealth intervention trial called “EmSHAPE”- Engaging mobile health for symptom monitoring and health promotion for endocrine therapy - among patients with non-metastatic hormone receptor positive breast cancer. This innovative study will integrate social cognitive theory to ensure scientific rigor in intervention development. The research and training proposed herein will enable me to build on my oncology and epidemiology training to acquire expertise in developing culturally targeted behavioral interventions, integrating mHealth technologies into behavioral interventions, and testing behavioral interventions. Following the ORBIT model for refining and testing behavioral interventions14, we will complete Phase 1a (identifying candidate treatment components), Phase 1b (refine and finalize intervention components), and Phase-2 (pilot-test the intervention), in preparation for a future efficacy trial. The following Specific Aims are proposed to accomplish these goals: Aim 1: To develop a prototype of the EmSHAPE intervention leveraging feedback from patients with HR+ breast cancer. The intervention will incorporate existing empirically supported strategies for medication adherence and additional components based on extensive formative work. Iterative learner verification and revision will be used to refine the intervention by leveraging stakeholder input for improved comprehension and acceptability. Intervention components will be evaluated by stakeholders who will report on opportunities for additional tailoring. Aim 2: To refine and finalize the EmSHAPE protocol and mHealth platform. We will refine and finalize the functional and technical components of the mHealth platform as well as refine and finalize the EmSHAPE protocol according to feedback gathered from usability testing with breast cancer survivors on ET (n=10). Aim 3: To test feasibility, acceptability, and preliminary efficacy of the EmSHAPE intervention via a pilot randomized clinical trial. Sixty women with HR+ BC will be randomized and monitored for 12 months. We hypothesize that the intervention will be acceptable (at least 60% of eligible patients will consent and at least 60% of intervention participants will report that they are “satisfied” or “very satisfied” with the intervention) and feasible (at least 60% of participants will complete the study) to breast cancer survivors receiving ET. We also hypothesize that the intervention will result in improved objective ET adherence relative to control group as measured by using smart pill bottle caps that track medication intake. This study will lay the groundwork for a larger randomized controlled trial to determine the efficacy of this intervention relative to enhanced usual care for patients with HR+ breast cancer through R01 funding. This application is significant, as no studies to date have used a multicomponent, patient-centerred, symptom monitoring approach to address low adherence rates to ET among breast cancer survivors, despite established evidence regarding the relationship between ET adherence and survival; and innovative, as implementing a symptom monitoring intervention during cancer treatment could change clinical practice if successful, by improving patient quality of life and improving cancer outcomes. This represents an important step toward improving survival disparities among breast cancer survivors by targeting oral ET adherence and furthers the candidate’s goal of establishing an independent research program to improve cancer care delivery through the development of digital and behavioral interventions.