Abstract Background We conducted a randomized, double-blinded pilot trial to compare the impact of two electroacupuncture (EA) regimens on co-occurring neuropsychiatric symptoms among breast cancer survivors (BCS). Methods BCS who self-reported cognitive impairment, fatigue, insomnia, or psychological distress were randomized (1:1) to receive ten weekly EA to target either neuropsychiatric-specific (nEA) or non-neuropsychiatric-specific (sEA) acupoints. Primary endpoints were the within-group pre-post effect sizes (Glass’s Δ) in symptom severities, adjusted for multiple comparisons (p-adjusted). Outcomes were assessed using neurocognitive tests (CANTAB®), PROs (FACT-Cog, MFSI-SF, EORTC QLQ-C30), plasma biomarkers, and neuroimaging. Responders were defined by reliable change index (for objective cognition) or MCID (for PROs). Results Thirty-five were recruited, with 30 (86%) completing all sessions. The mean (±SD) age was 58.2 (±12.2) years, and 86% reported co-occurring symptoms. Following treatment, the nEA group demonstrated significant improvements in attention (T3: Δ = 0.562, T4: Δ = 0.708, both p-adjusted 0.05) and distress (T3: Δ = 0.764, T4: Δ = 0.711, both p-adjusted 0.05). More responders were observed after nEA treatment for objective cognition (42.9% vs 12.5%) and distress (50% vs 37.5%). nEA-treated participants showed increased gray matter volume compared to sEA (p = 0.033), which positively correlated with better attention function (r = 0.69, p = 0.020). nEA-related improvements in memory and response speed were associated with reduced connectivity in the Default Mode Network (DMN–SFG, r=-0.93, p 0.01) and increased connectivity in the Dorsal Attention Network (DAN–SMG, r = 0.86, p 0.001), respectively. All adverse events were grade 2 or lower. Conclusions EA targeting neuropsychiatric-specific acupoints suggests improvements in cognition and distress symptoms in BCS, warranting validation in larger, multicenter trials. Clinicaltrials.gov NCT05283577.
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