PROJECT SUMMARY/ABSTRACT Chronic pain is a common symptom that affects 30-40% of cancer survivors, diminishing their quality of life, impairing physical functions, and increasing health care costs. Breast cancer survivors constitute the largest group of survivors with more than 4.1 million in the US. Nearly one in two breast cancer survivors who take a class of medication known as aromatase inhibitors are affected by a chronic painful condition, aromatase inhibitor-associated arthralgia (AIA). AIA is associated with reduced physical activity, increased risk of falls, and reduced AI adherence, leading to increased overall mortality. With insufficient relief from conventional treatments and a rapidly growing population of breast cancer survivors, there is an urgent need to develop novel, effective, and scalable pain management options. Mindfulness-Oriented Recovery Enhancement (MORE) is an innovative mindfulness-based intervention (MBI) rooted in affective neuroscience that integrates training in mindfulness, reappraisal, and savoring skills to specifically target chronic pain and related symptoms (e.g. psychological distress). Although the efficacy of MORE for pain in non-cancer populations has been established, the potential for this mindfulness intervention to address pain and comorbid symptoms in breast cancer survivors has yet to be confirmed. Therefore, a rigorous, adequately-powered randomized controlled trial is needed to conclusively determine whether MBIs such as MORE can alleviate AIA. To address this critical gap in research and clinical care, we have convened a multidisciplinary team to conduct the Enhanced Pain Coping in Cancer (EPIC) trial with the following specific aims: 1) to evaluate the specific efficacy of MORE for managing AIA among breast cancer survivors, 2) to evaluate the specific effects of MORE on comorbid symptoms, quality of life, and adherence to AIs, and 3) to elucidate the cognitive-affective mechanisms of MORE for pain management among breast cancer survivors. The MORE intervention that we will test aligns with a downward spiral of chronic pain model and neuroscience and is based on discoveries from preliminary studies. For this multisite, randomized controlled trial we will randomize 200 breast cancer survivors free of oncologic disease with AIA to one of two eight-week treatments: 1) MORE or 2) supportive group psychotherapy (SG). We will assess the primary outcome (pain-related functional interference) and secondary outcomes at baseline, week 8 (end of treatment), week 12 and week 24 (primary end point) using validated patient-reported outcomes. EPIC will address major methodological limitations of existing MBI trials including pain not being a primary outcome, no eligibility requirement for having pain, and the MBIs under investigation having been developed to target stress management rather than pain management. EPIC will provide timely clinical evidence for MORE, a neuroscience-informed, mindfulness-based int...