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Study Objective  Dehydroepiandrosterone ( DHEA ) and its sulfated form ( DHEAS )—jointly referred to as  DHEA (S)—are neurosteroids known to regulate brain development and function that have been found to be positively correlated with cognitive function. It is unknown whether prechemotherapy plasma  DHEA (S) levels are associated with the onset of cancer‐related cognitive impairment ( CRCI ). The objective of this study was to evaluate whether an association exists between prechemotherapy plasma  DHEA (S) levels and onset of  CRCI  in patients with breast cancer receiving chemotherapy.    Design  Multicenter, prospective cohort study.    Setting  Two specialized cancer centers in Singapore.    Patients  Eighty‐one patients with early‐stage breast cancer (stages I– III ) who had no prior exposure to chemotherapy and/or radiotherapy and were scheduled to receive anthracycline‐based or taxane‐based chemotherapy treatment with curative intent.    Measurements and Main Results  Patients completed assessments for self‐perceived and objective cognitive function at three time points: prechemotherapy (T1), during chemotherapy (T2), and after chemotherapy (T3). Plasma samples were collected prior to chemotherapy, and  DHEA (S) levels were quantified by using ultra–high‐performance liquid chromatography–tandem mass spectrometry. Multivariable logistic regression was used to adjust for clinically important factors and to evaluate the association between prechemotherapy plasma  DHEA (S) levels and  CRCI . Mean ±  SD  age was 48.9 ± 9.3 years, with 27.8% of patients experiencing clinically significant cognitive impairment based on global Functional Assessment of Cancer Therapy–Cognitive Function scores. The mean ±  SD  prechemotherapy plasma  DHEAS  and  DHEA  levels were 1.61 ± 0.91 μmol/L and 19.21 ± 13.13 nmol/L, respectively. 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.    Conclusion  Our findings suggest that patients with higher prechemotherapy  DHEAS  levels had lower odds of developing self‐perceived cognitive impairment. Future studies are required to further investigate the effect of  DHEA (S) on specific cognitive domains and to validate our findings in independent cohorts.

pharmacotherapy: the journal of human pharmacology and drug therapy

Prechemotherapy Levels of Plasma Dehydroepiandrosterone and Its Sulfated Form as Predictors of Cancer‐Related Cognitive Impairment in Patients with Breast Cancer Receiving Chemotherapy