Cognitive Problems May Be Present Before Chemotherapy in Women With Breast Cancer

This abstract will be presented at a press conference hosted by C. Kent Osborne, M.D., director of the Lester and Sue Smith Breast Cancer Center at Baylor College of Medicine, on Friday, Dec. 7 at 7:30 a.m. CT in Room 217 A-C of the Henry B. Gonzales Convention Center. Reporters who cannot attend in person can call in using the following information:• U.S./Canada (toll free): 1 (800) 446-2782• International (toll call): 1 (847) 413-3235

Newswise — SAN ANTONIO — Women undergoing chemotherapy who experience cognitive problems, commonly referred to as “chemo brain,” displayed alterations in neurocognitive responses prior to undergoing treatment, according to data presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium, held here Dec. 4-8.

Bernadine Cimprich, Ph.D., R.N., associate professor emerita at the University of Michigan School of Nursing in Ann Arbor, and colleagues found that pretreatment neurocognitive compromise and fatigue were key contributors to the cognitive effects often attributed to chemotherapy.

“For a long time, women undergoing treatment for breast cancer have reported cognitive problems such as trouble thinking clearly, remembering things, and carrying out jobs and other responsibilities, which we have attributed to chemotherapy or ‘chemo brain,’” Cimprich said. “Research shows that these problems do occur in some women during chemotherapy, but we still do not understand what the underlying causes are.”

Cimprich and her colleagues reasoned that the mental demand and stress of a breast cancer diagnosis could play a role in these early cognitive problems. They tested neurocognitive responses using functional magnetic resonance imaging (fMRI) on 28 women who received adjuvant chemotherapy, 37 who received radiotherapy and 32 healthy controls. Before treatment and one month after treatment, the participants performed a verbal working memory task with varying levels of demand for cognitive control during fMRI scanning. They also provided self-reports of fatigue.

Women who underwent chemotherapy reported a significantly higher level of fatigue and performed less accurately on the cognitive tests before treatment and one month after treatment. In addition, greater fatigue correlated with poorer test performance and more cognitive problems reported over time.

Brain imaging before treatment showed reduced function in regions needed to perform the task in both patient groups when compared with controls, with more compromise seen in women awaiting chemotherapy. Women who were less successful in recruiting the brain regions needed for the task before treatment were more likely to suffer greater fatigue over time, regardless of treatment group.

“Our initial findings showed that the level of worry interfered with patients’ ability to do a task,” Cimprich said. “The level of worry had a key role in the cognitive problems with these women before treatment, and this worry was related to fatigue.”

Scores for cognitive testing from women who underwent radiation treatment fell between those of women who underwent chemotherapy and those of the healthy women.

“Women faced with the decision to undergo chemotherapy should know that cognitive problems, should they occur, may not always stem from chemotherapy,” Cimprich said. “Women should not avoid accepting recommendations for lifesaving chemotherapy for fear of ‘chemo brain.’”

Cimprich recommended existing interventions to combat stress after a breast cancer diagnosis, including mindfulness intervention, psychological support, cognitive behavior interventions and exercise.

“It might be possible to diminish worry and fatigue and maintain strong brain function during the course of treatment using these interventions,” Cimprich said.

The research was funded by the National Institutes of Health.

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The mission of the 2012 CTRC-AACR San Antonio Breast Cancer Symposium is to produce a unique and comprehensive scientific meeting that encompasses the full spectrum of breast cancer research, facilitating the rapid translation of new knowledge into better care for patients with breast cancer. The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio, the American Association for Cancer Research (AACR) and Baylor College of Medicine are joint sponsors of the San Antonio Breast Cancer Symposium. This collaboration utilizes the clinical strengths of the CTRC and Baylor and the AACR’s scientific prestige in basic, translational and clinical cancer research to expedite the delivery of the latest scientific advances to the clinic. For more information about the symposium, please visit www.sabcs.org.

Abstract:Publication Number: S6-3

Title: Neurocognitive impact in adjuvant chemotherapy for breast cancer linked to fatigue: A Prospective functional MRI study

Bernadine Cimprich1, Daniel F Hayes2, Mary K Askren6, Mi Sook Jung1, Marc G Berman7, Lynn Ossher3, Barbara Therrien1, Patricia A Reuter-Lorenz3, Min Zhang4, Scott Peltier5 and Douglas C Noll5. 1Nursing, University of Michigan, Ann Arbor, MI; 2Internal Medicine, University of Michigan, Ann Arbor, MI; 3Psychology, University of Michigan, Ann Arbor, MI; 4Biostatistics, University of Michigan, Ann Arbor, MI; 5Biomedical Engineering, University of Michigan, Ann Arbor, MI; 6Integrated Brain Imaging Center, University of Washington, Seattle, WA and 7Rotman Research Institute at Baycrest, University of Toronto, Canada.

Body: Background: Our previous research showed evidence of compromised cognitive function prior to adjuvant chemotherapy for breast cancer, with fatigue as a contributory factor. Fatigue is a common symptom reported by women treated for breast cancer, yet its association with neurocognitive function has not been systematically examined. In this prospective study, weexamined possible alterations in neurocognitive responses, namely, working memory, from pre- to post- adjuvant treatment during functional magnetic resonance imaging (fMRI) and further investigated whether early fatigue might be linked to cognitive alterations over time.

Methods: Women treated with either adjuvant chemotherapy (anthracyline-based combination regimen, n=29) or radiotherapy (n=37) for localized breast cancer (Stages 0-IIIa) and age-matched healthy controls (n=32) were enrolled. Participants performed a verbal working memory task (VWMT) with varying levels of demand for cognitive control during fMRI scanning and provided self-reports of fatigue (FACT-F) at two time points coincident with pre- and one-month post chemotherapy assessments. Imaging data were analyzed with general linear models using SPM5; comparative statistics were used to determine group differences, and correlational analyses addressed relationships of fatigue and neurocognitive measures.

Findings: The chemotherapy group reported significantly greater severity of fatigue (p < .05) and erformed less accurately on the VWMT both pre- and one-month post-treatment than the other groups. Greater fatigue was correlated with poorer performance on the VWMT at both time points across groups, with stronger correlation post-treatment (r = -.22, p = .03). A 2 time-point (pre- vs post-treatment) x 2 group (chemotherapy vs. controls) x 2 demand-level contrasts (high minus low vs. medium minus low) analytic model showed a significant group x time interaction (p < .05), mainly due to lower pre-treatment activation in an area of the prefrontal cortex supporting working memory, the anatomical left inferior frontal gyrus (LiFG), at higher task demand in the chemotherapy group. The radiotherapy group scored between the other two groups with intermediate activation of those contrasts. Of interest, lower pre-treatment activation in the LiFG in the high-low demand contrast predicted severity of fatigue across all participants at the post-treatment assessment (r = -.27, p < .01), linking early compromise in neurocognitive performance with greater fatigue over time.

Discussion: Neurocognitive alterations during a working memory task and greater fatigue were evident before any adjuvant chemotherapy for breast cancer. Notably, functional alterations in working memory processes were evident with fMRI before adjuvant chemotherapy and predicted severity of post-treatment fatigue. Importantly, across all participants, greater fatigue over time was correlated with reduced cognitive performance. Taken together, these findings indicate that pre-treatment neurocognitive compromise and fatigue are key contributors to the cognitive impact often attributed solely to chemotherapy. Early therapeutic interventions targeting fatigue may improve cognitive function and reduce the distress of "chemo brain" throughout the course of adjuvant treatment.