Real, Placebo Acupuncture Improve Cognitive Outcomes in Breast Cancer Survivors

Both real and sham acupuncture were linked to clinically meaningful and sustained increases to perceived cognitive impairment in breast cancer survivors vs usual care, but real acupuncture was associated with greater gains in objective cognitive function, according to data shared at the 2025 San Antonio Breast Cancer Symposium from the phase 2 ENHANCE trial (NCT04837820).

These data suggest that the overall acupuncture experience may improve perceived cognitive impairment, while the specific needling components may provide additional benefit for objective cognitive outcomes among breast cancer survivors.

From baseline to week 10, real acupuncture and sham acupuncture produced similar improvements in subjective cancer-related cognitive dysfunction as measured by the FACT-Cog PCI, with mean increases of 10.3 points (95% CI, 7.8-12.7) and 10.5 points (95% CI, 7.1-13.9), respectively.

Usual care demonstrated a smaller mean increase of 4.8 points (95% CI, 2.25-7.37). Because the minimum clinically important improvement is 7.4 points, both real and sham procedures exceeded this threshold, whereas UC did not. Real acupuncture was significantly more effective than usual care at week 10 (mean difference, 5.5; P = .003) and week 26 (mean difference, 5.5; P = .002). Differences between real and sham acupuncture were not statistically significant at either timepoint.

Across all participants, mean change in the Hopkins Verbal Learning Test (HVLT) Total Recall Score from baseline increased in the acupuncture group to 3.94 at week 10 and 4.36 at week 26. The usual care group improved to 3.49 at week 10 and showed its largest increase at week 26 with a score of 4.83. In contrast, the sham group showed a slight decline at week 10 with a mean change of –0.15, followed by improvement to 0.51 at week 26. The difference between real and sham acupuncture arms at week 10 was statistically significant (P = .034).

Among the 59 participants with objective cognitive impairment, the HVLT Delayed Recall Score improved across all groups. The real acupuncture group showed the greatest gains, with a mean change of 8.00 at week 10 that increased to 10.53 at week 26. The sham and usual care groups demonstrated similar improvements at week 10, with mean changes of 5.29 and 5.31, respectively.

By week 26, the usual care group continued to improve to 7.50, whereas the sham group declined to 2.93. All values represent mean change and standard error. Regarding statistical comparisons, the difference between the real and sham acupuncture groups at week 26 was not statistically significant (P = .075).

“I think we need to listen to women,” Jun J. Mao, MD, MSCE stated during a question-and-answer portion of his presentation. “If they complain to you that they have cognitive difficulty, we shouldn’t just say, ‘Oh my God, it’s in your head, your cognition is actually fine,’ because that will not help any women with breast cancer. But as the study has shown, maybe using a therapeutic approach to listen, validate, care, and provide a process for them to start feeling better—I think that’s really important, and aggressively addressing their symptoms.”

Study Design and Patient Demographics

Participants in the real acupuncture group received 10 weekly sessions lasting 20 to 30 minutes, using acupoints for cognition and sleep along with additional points for comorbid symptoms, totaling 10 to 26 points; electroacupuncture (EA) at 2 Hz was applied when clinically indicated. The sham group followed a similar schedule but received needling at non-acupuncture, non-trigger point locations, with needles taped to the skin without manual stimulation and without EA. The usual care group continued standard medical care and was contacted at the same frequency as the acupuncture groups for study assessments.

Subjective cancer-related cognitive difficulties (CRCD) were measured with the perceived cognitive impairment subscale of the FACT-Cog PCI, an 18-item measure scored from 0 to 72, with higher scores indicating better function and a clinically meaningful improvement defined as 7.4 pts or greater. Objective CRCD was evaluated by blinded assessors using the normed Total Recall T-score from the HVLT-Revised (HVLT-R), which involves recalling 12 words across 3 trials followed by a delayed recall after 20 to 25 minutes.

A total of 260 participants were included in the ITT analysis. Treatment adherence exceeded 80% in both the real and sham acupuncture groups, and 91.2% of participants completed data collection at week 10. The mean age was 56.6 years (SD, 10.4). Most participants had attained a college-level education or higher (194; 76.9%), and just over half had received chemotherapy (139; 53.5%). The mean time since cancer diagnosis was 4.7 years (SD, 2.8). The racial distribution included 78.8% White, 10.4% Black or African American, 6.9% Asian, and 3.8% identifying as another or more than 1 race. Current hormonal therapy included none in 37.3%, tamoxifen in 37.3%, and aromatase inhibitors in 25.4%.

Limitations

Several limitations should be noted. The COVID-19 pandemic introduced additional variability related to patient stress and disruptions in care. Participants were breast cancer survivors experiencing both CRCD and insomnia, and the majority had a college-level education or higher, which may limit generalizability. Only about 30% met criteria for objective cognitive impairment at baseline. In addition, the study was conducted at a large, urban academic cancer center, further narrowing the applicability of the findings to more diverse clinical settings.

Disclosures: Jun J. Mao reports grants from Tibet Cheezheng Tibetan Medicine Co. Ltd. and Zhongka Health International LLC. He is also a co-founder of Greatly Health. These disclosures are unrelated to the submitted work.

Reference

Mao JJ, Li X, Li Y. Effects of Acupuncture vs Sham Acupuncture and Usual Care on Cancer-Related Cognitive Difficulties Among Breast Cancer Survivors: The ENHANCE Randomized Clinical Trial. Presented at: San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, TX. Abstract GS3-04.