Abstract GS3-04: Effects of Acupuncture vs Sham Acupuncture and Usual Care on Cancer-Related Cognitive Difficulties Among Breast Cancer Survivors: The ENHANCE Randomized Clinical Trial

Abstract Background: Cancer-related cognitive difficulties (CRCD) is a common and distressing condition with limited effective treatments. This study aims to evaluate the effects of acupuncture on subjective and objective CRCD in breast cancer survivors. Methods: We conducted a 3-arm randomized clinical trial among women with a history of stage 0-III breast cancer who completed active treatment, were currently free of oncologic disease, and self-reported moderate or greater CRCD and insomnia. Participants were randomized in a 2:1:1 ratio to real acupuncture (RA), sham acupuncture (SA), or usual care (UC). Acupuncture treatments were delivered once weekly for 10 weeks. Subjective CRCD was measured by the Perceived Cognitive Impairment subscale of the Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog PCI; clinically meaningful improvement ≥7.4 points). Objective cognitive function was evaluated blindly by the normed total recall T-score from the Hopkins Verbal Learning Test-Revised (HVLT). Participants completed assessments at baseline, end of treatment at Week 10 (primary endpoint), and Week 26. Using a gatekeeping multiple-comparison procedure, RA was compared with UC and SA using linear mixed models. Results: Among 260 breast cancer survivors who participated in the trial, mean age was 56.6 years; 21.2% were non-White; 53.5% had received chemotherapy; 62.7% were on hormonal therapy at enrollment (25.4% tamoxifen and 37.3% aromatase inhibitors); mean (SD) baseline FACT-Cog PCI score and HVLT Total T-score were 36.0 (14.0) and 44.3 (11.7), respectively. Of them, 237 (91.2%) completed the primary endpoint. By Week 10 (end of treatment), participants in both RA and SA groups reported clinically meaningful improvements in perceived cognitive impairment measured by FACT-Cog PCI (RA: 10.3, 95% CI: 7.8-12.7; SA 10.5, 95% CI: 7.1-13.9), while participants in UC group had a 4.8-point improvement (95% CI, 2.25-7.37). RA was significantly more effective than UC at reducing perceived cognitive impairment at Week 10 (5.46, 95% CI, 1.95-8.56, p=0.0025) and at Week 26 (5.53, 95% CI, 2.02-9.05, p=0.0022), but difference was not significant between RA and SA at either timepoint. However, RA improved objective cognitive function measured by HVLT relative to SA at Week 10 (4.10, 95% CI: 0.32-7.87, p = 0.034). Adverse events were mostly mild, with bruising being the most common, occurring in 6 patients (3.1%) who received RA. No adverse events were reported in the SA or UC groups. Conclusion: Real and sham acupuncture produced clinically meaningful and sustained improvements in perceived cognitive impairment compared to UC, and real acupuncture was superior to SA in improving objective cognitive function. Our findings suggest that the overall process of receiving acupuncture improves subjective CRCD relative to usual care. The specific needling effects of real acupuncture confers additional benefits for objective CRCD compared to sham acupuncture among breast cancer survivors. Citation Format: J. Mao, X. Li, Y. Li, K. Liou, K. Lampson, J. Root, T. Ahles. Effects of Acupuncture vs Sham Acupuncture and Usual Care on Cancer-Related Cognitive Difficulties Among Breast Cancer Survivors: The ENHANCE Randomized Clinical Trial abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr GS3-04.