Both real and sham acupuncture led to sustained improvements in breast cancer survivors’ perceived cognitive difficulties vs usual care — but only real acupuncture improved objective measures of cognitive performance, according to the ENHANCE clinical trial.

The fact that real and sham acupuncture had similar benefits for patients’ subjective complaints may be because even the sham version offers personal attention, relaxation, and a sense of being cared for, Jun Mao, MD, explained during a press briefing at San Antonio Breast Cancer Symposium (SABCS) 2025, where he presented the research.

However, the findings suggest that compared with sham treatment, the specific needling aspects of real acupuncture may improve objective measures of cognition, said Mao, who is chief of integrative medicine and wellness services at Memorial Sloan Kettering Cancer Center in New York City.

More than 40% of breast cancer survivors have persistent cancer-related cognitive difficulties that can take a toll on quality of life. Survivorship guidelines from the National Comprehensive Cancer Network recommend nondrug interventions — but also acknowledge there is “very limited” evidence to guide such strategies, Mao noted.

Similarly, insomnia has been estimated to affect 60% of breast cancer survivors, and research shows that it often co-exists with, and may worsen, cognitive difficulties.

In a prior study, Mao’s team found that acupuncture improved insomnia and its associated cognitive complaints among breast cancer survivors.

To further evaluate the impact on cognition, the ENHANCE trial enrolled 260 women (mean age, 56 years) with a history of stage 0 to III breast cancer who had completed active treatment within the past 2 years, had no evidence of disease, and reported at least moderate cognitive difficulties and insomnia. Just over half (54%) had received chemotherapy, and 63% were on hormonal therapy.

Participants were randomly assigned in a 2:1:1 ratio to real acupuncture, sham acupuncture, or usual care as directed by their physician (with the same contact frequency as the acupuncture groups).

Women in both the real and sham acupuncture groups had sessions once a week for 10 weeks. Sham acupuncture mimicked the overall experience of treatment, including time, attention, and relaxation, but used nonpenetrating needles on areas of the skin that are not traditional acupuncture points.

Cognitive function was assessed at baseline, at 10 weeks, and again at 26 weeks to evaluate durability of effects.

After 10 weeks, both real and sham acupuncture improved participants’ perceived cognitive impairment (PCI) (primary outcome) as measured by the Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog PCI), a validated patient-reported outcomes tool.

The minimum clinically important improvement on the FACT-Cog PCI is 7.4 points: Real and sham acupuncture improved that measure by 10.3 points and 10.5 points, respectively — roughly double the 4.8-point improvement seen in the usual-care group.

The benefit with acupuncture over usual care persisted at 26 weeks, but there was no difference between real and sham acupuncture at either time point.

“The story was very different,” Mao said, when looking at objective cognitive function as measured by the Hopkins Verbal Learning Test-Revised (HVLT-R) — which gauges memory, learning, and attention using standardized tasks.

While sham acupuncture had no effect overall, real acupuncture improved participants’ objective cognitive performance at 10 weeks and 26 weeks — with about a 4-point difference in HVLT-R total recall scores (P = .034) vs sham.

There was no difference, however, between real acupuncture and usual care, with objective cognitive performance improving to a similar degree in both groups over time.

Only 59 women, or 30% of trial participants, met criteria for objective cognitive impairment at baseline. And in that subgroup, Mao reported, real acupuncture was associated with a trend toward improving objective cognitive performance compared with sham acupuncture and usual care.

He acknowledged several limitations to the study, including the well-educated population (77% had at least a college education) and the fact that it was conducted at a large, urban academic medical center.

And because participants had both cognitive difficulties and insomnia, Mao said, the results may not apply to women who have cognitive complaints but no sleep disturbances.

Another key issue is whether the acupuncture protocol used in this trial can be reproduced in the real world, said briefing moderator Virginia Kaklamani, MD, SABCS co-director and leader of the breast cancer program at Mays Cancer Center, UT Health San Antonio.

“The results might be different for a patient getting acupuncture out in the community by someone that’s not trained,” Kaklamani cautioned.

She also pointed to some practical barriers, including limited availability of acupuncture in some geographic areas and lack of insurance coverage.

Nonetheless, Kaklamani said that when a patient with breast cancer shows an interest in supportive care like acupuncture, she encourages it — given the potential for symptom improvement at a low risk for harm.

In the ENHANCE trial, side effects from real acupuncture were infrequent and mostly mild, with bruising being the most common at just under 5%.

Based on Mao’s experience, interest in acupuncture may be growing. He said that demand for acupuncture among patients at his center has risen over the years such that there is now a 2-month wait list.

He also noted that, at least in New York City, insurance companies are beginning to cover acupuncture for patients with cancer.

This study was funded by grants from the National Cancer Institute and the National Institutes of Health. Mao reported receiving grants from Tibet Cheezheng Tibetan Medicine Co., Ltd., and Zhongke Health International LLC. He also reported being a co-founder of the online platform Greatly Health. Kaklamani disclosed financial relationships with AstraZeneca, Daiichi Sankyo, and Gilead, among others.