Effects, Metabolic Mechanisms and Predictors of Response to Acupuncture in Treating Psychoneurological Symptoms Among Breast Cancer Survivors

Aim 1: compared to sham acupuncture and UC, determine the effect of acupuncture on a) the psychoneurological cluster (primary outcome) and b) pain, fatigue, and sleep disturbance as individual symptoms (secondary outcomes).

Aim 2: examine the role of methylsulfonylmethane as mediator in the mechanisms of acupuncture on the psychoneurological cluster and each individual symptom from week 0 to week 6 (primary endpoint) and to week 12 (secondary endpoint).

Aim 3: identify multilevel predictors of treatment response in the acupuncture group, including a) biological (metabolomic signature, age); 2) clinical (previous treatment) and 3) psychosocial (treatment expectancy) characteristics.

• Acupuncture (Behavioral): All participants will receive a semi-standardized acupuncture protocol with needle penetrating to the skin. Participants will receive 2 acupuncture treatments each week for 5 weeks, for a total of 10 treatments. Each acupuncture treatment will take 30 minutes.
• Sham acupuncture (Behavioral): Participants will receive no-touch control needle on non- acupuncture points, with the tip that does not contact the skin. Participants will receive 2 sham acupuncture treatments each week for 5 weeks, for a total of 10 treatments. Each sham acupuncture treatment will take 30 minutes.

Primary outcomes

• The psychoneurological symptom cluster [week 0, week 6, week 12, week 24]: Psychoneurological symptom cluster: The psychoneurological symptom cluster will be calculated as the mean of the Patient-Reported Outcomes Measurement Information System (PROMIS)-29 T-scores for Pain Interference, Fatigue, and Sleep Disturbance. Each domain is scored as a standardized T-score (approximate range 20-80), with higher scores indicating worse symptom severity. Higher composite scores indicate greater psychoneurological symptom burden.

Secondary outcomes

• PROMIS Pain Interference [week 0, week 6, week 12, week 24]: Scores range from 4-20; higher scores indicate that pain is interfering with daily activities more
• PROMIS fatigue [week 0, week 6, week 12, week 24]: Scores range from 4-20; higher scores indicate that severe fatigue
• PROMIS sleep disturbance [Scores range from 4-20; higher scores indicate that severe fatigue]: Scores range from 4-20; higher scores indicate that severe sleep disturbance
• Serum methylsulfonylmethane concentration [week 0, week 6, week 12]: Change in serum methylsulfonylmethane concentration.
• GSH/GSSG [week 0, week 6, week 12]: The ratio of glutathione and oxidized glutathione

Sex: Female, ages: 18 Years to any

Inclusion Criteria:

* ≥ 18 years of age
* With histologically confirmed Stage 0-III ER/PR-positive HER2-negative breast cancer
* Currently receiving adjuvant endocrine therapy
* Completed their primary cancer treatment (e.g., surgery, radiotherapy, chemotherapy) at least 3 months prior to recruitment
* Acupuncture-naïve
* Have self- reported pain, fatigue, and sleep disturbance in the last month with an average severity rating ≥ 3 (0-10 numeric rating scale) for at least 2 of the 3 symptoms.

Exclusion Criteria:

* Taking methylsulfonylmethane or glutathione supplements
* Physically or cognitively unable to complete the study procedures
* Pregnant