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New Biomarkers Associated With Cancer-Related Cognitive Impairment Identified

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Key Points

  • Patients with early-stage breast cancer with higher plasma DHEAS levels prior to chemotherapy were found to have a lower risk of developing chemobrain in the specific domains of verbal fluency and mental acuity.
  • Conversely, DHEA levels were not associated with impairment in any cognitive subdomains.

Cognitive impairment associated with cancer—also known as “chemobrain”—has gained recognition as a complication of the disease and its treatment. With this in mind, a research team started to investigate levels of biomarkers in relation to chemobrain to better understand its cause. Their findings were published by Toh et al in Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy.

Chemobrain can be subtle yet persistent, with some patients reporting difficulties related to memory and attention months after completing their cancer treatment. Given the extent of impact from chemobrain on patients, researchers hoped to find ways to preemptively identify patients who are at higher risk of developing such symptoms with the use of a standardized, quantitative biomarker. The appropriate precautions could subsequently be taken to mitigate the side effects and help improve patients’ quality of life in the long run.

“By identifying the clinically relevant factors that predispose patients to chemobrain, more appropriate interventions can be tailored accordingly to patients who are at a higher risk of developing cognitive impairment,” explained senior study author Alexandre Chan, PharmD, MPH, FCCP, BCPS, BCOP, Associate Professor in the Department of Pharmacy at the National University of Singapore.

Study Methods

The researchers recruited 81 patients with early-stage breast cancer who had no prior exposure to chemotherapy or radiotherapy and were scheduled to receive chemotherapy treatment with curative intent. This was a multicenter, prospective cohort study conducted in the National Cancer Centre Singapore and KK Women’s and Children’s Hospital between 2011 and 2016.

To assess the extent of chemobrain, patients completed assessments for self-perceived and objective cognitive function before, during, and after chemotherapy. The validated questionnaire assessed patients on individual subdomains of mental acuity, concentration, memory, verbal fluency, functional interference, and multitasking. Conversely, the computerized neuropsychological test performed was used to assess for processing speed, response time, memory, and attention of each patient. In addition, patients also completed a series of questionnaires to assess their fatigue symptoms, anxiety symptoms, and health-related quality of life.

The team also characterized plasma levels of the biomarker dehydroepiandrosterone (DHEA) and its sulfated form (DHEAS) to be biologic determinants of chemobrain. DHEA and DHEAS are neurosteroids that help regulate brain development, but it was previously unknown whether their levels correlate with cognitive function or are associated with the onset of chemobrain. Plasma samples collected prior to chemotherapy were quantified for DHEA and DHEAS levels.

Study Findings

The study showed that patients with early-stage breast cancer with higher plasma DHEAS levels prior to chemotherapy were found to have a lower risk of developing chemobrain in the specific domains of verbal fluency and mental acuity.

Prechemotherapy DHEAS levels were found to be associated with impairment in the self-perceived cognitive domains of verbal fluency (adjusted odds ratio [OR] = 0.27, 95% confidence interval [CI] = 0.08–0.96) and mental acuity (adjusted OR = 0.25, 95% CI = 0.08–0.74). Conversely, DHEA levels were not associated with impairment in any cognitive subdomains.

Toh Yi Long, a doctoral student working with Dr. Chan, and the first author of the study, said, “Our findings suggest that patients with higher prechemotherapy DHEAS levels had lower odds of developing self-perceived cognitive impairment. However, future studies are required to further investigate the effect of [DHEA and DHEAS] on specific cognitive domains and to validate our findings in independent cohorts.”

The team is now exploring new research frontiers and looking at developing potential therapeutic interventions. These interventions may provide viable options to mitigate posttreatment complications (not limited to chemobrain) that patients with cancer are experiencing, with the overall goal of improving quality of life in cancer survivors.

Disclosure: For full disclosures of the study authors, visit accpjournals.onlinelibrary.wiley.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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