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Real and sham acupuncture improved perceived cognitive function versus usual care, with real acupuncture showing greater benefits for objective cognitive outcomes.
Real and sham acupuncture were both linked to clinically meaningful and lasting improvements in perceived cognitive impairment compared with usual care for breast cancer survivors, but real acupuncture showed greater benefits for objective cognitive function, according to the study findings from ENHANCE trial.
Findings were presented at the 2025 San Antonio Breast Cancer Symposium. From baseline to week 10, real acupuncture (RA) and sham acupuncture (SA) produced similar improvements in subjective cancer-related cognitive dysfunction as measured by the FACT-Cog PCI, with mean increases of 10.3 points and 10.5 points, respectively. Usual care (UC) demonstrated a smaller mean increase of 4.8 points. Because the minimum clinically important improvement is 7.4 points, both RA and SA exceeded this threshold, whereas UC did not. RA was significantly more effective than UC at week 10 and week 26. Differences between RA and SA were not statistically significant at either timepoint.
Across all participants, mean change in the Hopkins Verbal Learning Test (HVLT — a test assessing memory by having participants recall lists of words over multiple trials and after a delay) Total Recall Score from baseline increased in the RA group to 3.94 at week 10 and 4.36 at week 26. The UC 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 acupuncture (SA) 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 RA and SA at week 10 was statistically significant.
Among the 59 participants with objective cognitive impairment, the HVLT Delayed Recall Score improved across all groups. The RA group showed the greatest gains, with a mean change of 8 at week 10 that increased to 10.53 at week 26. The SA and UC groups demonstrated similar improvements at week 10, with mean changes of 5.29 and 5.31, respectively. By week 26, the UC group continued to improve to 7.5, whereas the SA group declined to 2.93. All values represent mean change and standard error. Regarding statistical comparisons, the difference between the RA and SA groups at week 26 was not statistically significant.
“I think we need to listen to women,” Dr. Jun J. Mao, integrative medicine and acupuncture at Memorial Sloan Kettering, stated during the Q&A portion of his presentation. “If they [tell] 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.”
Participants in the RA 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; EA at 2 Hz was applied when clinically indicated. The SA 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 UC 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 three trials followed by a delayed recall after 20 – 25 minutes.
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.
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