Real and sham acupuncture were more effective in improving perceived cognitive impairment in breast cancer survivors compared with usual care, while real acupuncture was superior to sham acupuncture in improving objective cognitive function, according to results from the randomized phase II ENHANCE clinical trial, presented at the San Antonioium Breast Cancer (December 2, December 9SA). 2025.
More than 40% of breast cancer survivors experience cancer-related cognitive difficulties, sometimes referred to as “brain fog” or “chemobrain,” according to Jun J. Mao, MD, MSCE, the Laurance S. Rockefeller Chair in Integrative Medicine and chief of the Integrative Medicine and Wellness Service at Sloceran Memorial. “Cognitive difficulties associated with cancer can make it more difficult to perform daily tasks and can reduce overall quality of life,” Mao explained. “Unfortunately, there are very few evidence-backed treatments for this problem.”
Previously, Mao and his colleagues found that insomnia was associated with cognitive difficulties in over 1,000 breast cancer survivors and that, in a previous trial, acupuncture improved insomnia and may improve cognitive function compared to cognitive behavioral therapy for insomnia (CBT-I). To further test the effectiveness of acupuncture in improving cognitive function for breast cancer patients, researchers designed a three-arm study that compared real acupuncture with sham acupuncture and usual care provided at the physician’s discretion. Virtual acupuncture is designed to mimic the experience of real acupuncture with a similar overall relaxation experience, but there are a few key differences: Virtual acupuncture uses points on the body that are not considered classic acupuncture points, and the needles do not penetrate the skin.
Acupuncture should be considered as a complex intervention involving both the needle and the care provided. Simply believing that you are receiving a helpful treatment and relaxing by lying down for 20-30 minutes can have potential therapeutic benefits even if the needles are not inserted or placed at specific therapeutic points. By comparing real acupuncture with virtual acupuncture, rather than just usual care, we were able to better understand whether the benefits were due to the acupuncture technique itself or the overall experience.”
Jun J. Mao, MD, MSCE, Laurance S. Rockefeller Chair in Integrative Medicine and Chief of Integrative Medicine and Wellness Service, Memorial Sloan Kettering Cancer Center
The clinical trial involved 260 women with a history of stage 0-3 breast cancer who completed treatment, had no signs of cancer, and reported moderate or greater cancer-related cognitive difficulties and insomnia. Participants were randomly assigned to receive real acupuncture (129), sham acupuncture (70), or usual care (61). Real or sham acupuncture treatments were administered once weekly for 10 weeks, and cognitive function was assessed at baseline, 10 weeks, and 26 weeks.
Perceived cognitive function was measured using the Functional Assessment of Cancer Therapy – Cognitive Function (FACT-Cog PCI), a validated patient-reported outcome measure that asks patients to complete a survey about how they feel their memory, attention, and ability to perform daily tasks is affected. Objective cognitive function was measured via the Hopkins Verbal Learning Test-Revised (HVLT), which measures memory, learning, or attention performance using standardized tasks.
“These two measures capture different aspects of cognition and often do not align,” Mao said. “In our study, among participants who reported moderate to severe cognitive difficulties and met enrollment eligibility, only 30% met criteria for objective cognitive impairment as measured by the HVLT. This discrepancy highlights the importance of using both tools together as they provide a more complete picture.”
After 10 weeks, those who received real acupuncture and sham acupuncture showed a clinically significant improvement in perceived cognitive impairment as measured by FACT-Cog PCI scores: a 10.3-point improvement and a 10.5-point improvement, respectively, compared with a 4.8-point improvement in the usual care group. Real acupuncture also showed a twofold improvement in reducing perceived cognitive impairment compared to usual care at both 10 weeks and 26 weeks, while the difference between real and sham acupuncture was not significant at any point.
“The fact that real and virtual acupuncture produced similar results in improving perceived cognitive function may be because virtual acupuncture, while not stimulating the body in the same way, still provides benefits such as personal attention, relaxation, and a sense of care, which can improve how people feel,” Mao explained.
While real acupuncture improved HVLT scores, sham acupuncture made no difference in objective cognitive function. At week 10, real acupuncture was significantly better than sham acupuncture with a 4-point difference in HVLT scores. Overall, real acupuncture and usual care showed similar results in improving objective cognitive function. However, in the subset of patients found to have impaired objective cognition at baseline, real acupuncture was associated with a promising trend toward improved memory compared to usual care and sham acupuncture.
“Previous research using brain scans in people with memory problems or pain suggests that actual acupuncture may more effectively stimulate specific areas of the brain involved in memory, attention and learning,” Mao explained. “While our study also suggests that acupuncture may have potential benefit in improving objective cognitive function for people with some impairment, future studies are needed to specifically verify this.”
Adverse events were mostly mild and limited to the actual acupuncture arm with bruising being the most common (3.1% of participants). In addition to acupuncture, the study also found that insomnia was significantly associated with objective cognitive performance, and that sleep fragmentation—the number of awakenings and time awake—was significantly associated with worse performance on objective cognitive tests.
“Cognitive difficulties for women with breast cancer are complex and involve finding ways to deal with both distress related to perceived cognitive abilities and objective functioning,” Mao said. “While this trial showed that the ability of acupuncture to improve a patient’s perceived cognitive difficulty is likely due to the process of receiving acupuncture care rather than specific acupuncture techniques, it still makes sense for women with breast cancer to try a course of acupuncture to see if it can help improve their sense of cognitive difficulty. Patients with objective cognitive impairment will provide more convincing evidence.”
Limitations of this study include a small sample of patients who met criteria for objective cognitive impairment at baseline. The trial was also conducted at a single, large, urban academic cancer center with participants limited to female breast cancer survivors, so results may not be generalizable to male survivors, survivors of other types of cancer, or survivors in community or rural settings. The trial was conducted during the COVID-19 pandemic, which may have introduced other variables related to a patient’s stress and care.
This study was funded by grants from the National Cancer Institute and the National Institutes of Health Cancer Support Center. Mao states that he receives funds from Tibet Cheezheng Tibetan Medicine Co., Ltd. and Zhongke Health International LLC for other work. He is also the co-founder of Greatly Health.
