Study shows brain abnormalities in breast cancer patients treated with chemotherapy

- By Michelle Brandt

Shelli Kesler

Shelli Kesler

A neuroimaging study from the Stanford University School of Medicine has found that when asked to perform certain tasks, women who have undergone chemotherapy for breast cancer had significantly less activation of a part of the brain known to play a critical role in planning, attention and memory than did breast cancer patients without such treatment, as well as healthy women.

The research, published Nov. 14 in the Archives of Neurology, advances previous findings about the effects of chemotherapy and breast cancer on brain function. It provides “further evidence that primary breast cancer may cause measurable brain injury,” the study authors wrote, adding that women treated with chemotherapy experience additional brain abnormalities and cognitive difficulties.

The study also shows an association between breast cancer patients’ self-reported cognitive impairment and abnormalities in brain function. Among patients who received chemotherapy, complaints about their cognitive ability significantly correlated with lower activation of these parts of the brain, the study found.

“This shows that when a patient reports she’s struggling with these types of problems, there’s a good chance there has been a brain change,” said lead author Shelli Kesler, PhD, assistant professor of psychiatry and behavioral sciences. “Yet these women are often dismissed as imagining or exaggerating the problems.”

Kesler, whose research focuses on ways to predict which cancer patients might experience impairments, said it was important for patients and physicians to have an increased awareness of the issue — “not only to validate the patients’ experience, but to also increase the likelihood that they’ll receive proper, supportive services and treatments for their cognitive difficulties.”

The study involved 25 female breast cancer patients who underwent chemotherapy and surgery, 19 breast cancer patients who had surgery only and 18 healthy females who served as controls. Participants were screened to ensure they had no neurological, psychiatric or medical conditions known to affect cognitive function.

The researchers used functional magnetic resonance imaging to determine which parts of the women’s brains activated when they performed a card-sorting task that measures problem-solving skills. The researchers also used a questionnaire to assess patients’ perception of their cognitive abilities.

Kesler and her colleagues replicated previous findings by showing that cancer patients demonstrated significantly reduced activation in two parts of the prefrontal cortex, including one that is responsible for working memory, cognitive control and monitoring. In new findings, they showed that women in the chemotherapy group demonstrated significantly reduced activation of an additional region of the prefrontal cortex, which Kesler and colleagues describe as “potential neurotoxic brain injury,” and that decreased levels of activation significantly correlated with increases of the patients’ self-reported executive dysfunction.

“When women are reporting cognitive problems, there is a biological change that corresponds,” Kesler said.

Women in the chemotherapy group were also found to make more errors on the card-sorting task and take longer to complete it than healthy women and cancer patients who hadn’t had chemotherapy. “Cancer patients may have brain changes, but the changes don’t necessarily impact them functionally,” Kesler said. “But when you add chemotherapy to that, the changes are so severe that the patients can’t compensate for it anymore.”

Kesler’s next step is to conduct a longitudinal study of cancer patients during which researchers would target this region in pre-treatment brain scans and predict which women might be most vulnerable to cognitive problems.

Co-authors of the paper include Jamie Kent, PhD, postdoctoral scholar in psychiatry and behavioral sciences, and senior author Ruth O’Hara, PhD, associate professor of psychiatry and behavioral sciences. The work was supported by the National Institutes of Health.

Information about the Department of Psychiatry and Behavioral Sciences, which also supported this research, is available at

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2023 ISSUE 1

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