Aromatase Inhibitor Associated Musculoskeletal Symptoms (AIMSS)

The goal of this clinical trial is to learn whether transcutaneous auricular vagus nerve stimulation, also called taVNS, can help relieve aromatase inhibitor-related joint and muscle pain in adult women with hormone receptor-positive breast cancer. The main questions this study aims to answer are: 1. Does taVNS reduce pain caused by aromatase inhibitor treatment? 2. Does taVNS improve quality of life, mood symptoms, and the need for pain medicine? 3. What side effects or medical problems occur during treatment? Researchers will compare active taVNS with sham stimulation. Participants in both groups will receive mild electrical stimulation around the ear, but the sham stimulation will be applied to an area not expected to activate the vagus nerve. Participants will: 1. Be randomly assigned to active taVNS or sham stimulation 2. Receive one 30-minute treatment session every day for 28 days 3. Complete pain, mood, and quality-of-life questionnaires before treatment, after treatment, and during follow-up 4. Report pain medicine use and any side effects 5. Provide small blood samples to measure inflammatory markers, T-cell profiles, and tumor markers Participants will be followed for up to 6 months after treatment. For some participants who do not have enough pain relief after taVNS, an optional second-stage study may be offered. In this stage, participants may receive low-dose interleukin-2, also called IL-2, by injection every other day for 2 weeks.

Both Tart Cherry and Omega 3 FAs have better side effect profiles compared to other commonly used medications for AIMSS, such as nonsteroidal anti-inflammatories, steroids, and serotonin norepinephrine reuptake inhibitors. Additionally, in our clinics we often find that patients tend to be more receptive to taking a supplement as opposed to an additional medication. Further, both Tart Cherry concentrate and fish oil have beneficial properties for helping with joint stiffness in general, in addition to other health issues like insomnia. There is preliminary evidence in mouse models that when given together, these supplements may have an even greater anti-inflammatory effect than when taken separately14. Although to our knowledge, no human studies have tested this hypothesis. This study has been designed to test the hypothesis that Tart Cherry and fish oil when given in combination over a 12-week period could produce beneficial changes in joint function when compared to Tart Cherry or fish oil in isolation in an obese breast cancer population experiencing AIMSS. Secondary outcomes to be assessed include pain, functional performance, quality of life and cognition.