Introduction

Methods

Conclusions and Future Directions

Acknowledgements Funding: NCI CA168886 (MCJ) and REACH Funding

§  The preliminary research shows that PGE2 is associated with CRCI domains predominately in verbal memory. Motor function had trending results. The domains of executive function, visual memory, and sustained attention were not significant or trending.

§  A greater sample size will be needed in order to provide definitive data as well as more information on the role of PGE2 in CRCI.

§  EP receptors and inflammatory factors will also be assessed for their role in PGE2-associated CRCI.

Cross-Sectional Study Design: Cognitive testing and concentrations of PGE2 were assessed in 19 female breast cancer patients undergoing chemotherapy.

Cognitive Assessment with CANTAB Computerized Battery: •  Motor function was assessed using the Motor Screening Test, which asked

patients to touch crosses that appeared on the screen. •  Verbal Recognition Memory assessed immediate and delayed memory

under conditions of free recall, and free and forced choice recognition after a 25 minute delay.

•  The Delayed Matching to Sample test assessed visual memory and asked subjects to identify a matching pattern identical to the sample after a series of delays.

•  Executive function was examined using the One Touch Stockings of Cambridge test, which is a spatial planning and orientation task.

•  The Rapid Visual Information Processing test assessed visual sustained attention and processing speed.

PGE2 Concentration Measures: •  Blood samples were collected in serum tubes and spun at 1600g for 15

minutes before serum was obtained and aliquoted and stored at 80 ̊C until processing. PGE2 concentrations in serum samples were then quantified using a colorimetric ELISA assay (Enzo Life Sciences).

Statistical Analysis: •  PGE2 concentrations (pg/mL) were log transformed. Pearson correlations

between log transformed PGE2 and cognitive outcomes were performed. •  All two-sided values of p<0.05 were considered significant and p<0.20 were

interpreted as trending.

Hypothesis

Study Population and Demographic Characteristics (N=19)

Associations Between Prostaglandin E2 (PGE2) and Cognitive Function in Breast Cancer Patients Receiving Chemotherapy

Raven Shah1, Michelle Shayne, M.D.2,4, Alissa Huston, M.D.2,4, Nikki Murray, M.S.1, Sharon Hyland, N.P.4, Deborah Cory-Slechta, Ph.D.3, Michelle Janelsins, Ph.D., M.P.H.1,4

1Department of Surgery, Cancer Control, 2Department of Medicine, Hematology & Oncology, 3Department of Environmental Medicine, 4Wilmot Cancer Center

Purpose:

§  To examine the associations between PGE2 concentrations and cognitive function in breast cancer patients receiving chemotherapy.

Background:

§  Cognitive impairments experienced by cancer patients (e.g. problems with memory, processing speed, attention, concentration, and executive function) occurs in up to 80% of patients during chemotherapy treatments and can persist for years post-treatment. The etiology of chemotherapy-related cognitive difficulties is unknown and no guidelines for treatment exist.

§  A possible mechanism of induction of chemotherapy-related cognitive impairment (CRCI) involves the inflammatory response and the lipid-mediated signaling molecule, PGE2.

§  An understanding of the mechanisms that correspond to the appropriate proteins and signaling molecules involved in the pathway may enable the identification of people at risk of developing CRCI and may aide in intervention development to alleviate CRCI.

Results Associations of PGE2 Concentrations and Cognitive

Test Performance

Proposed Pathway of PGE2-mediated CRCI

Increased PGE2 levels will be associated with poorer cognitive performance in breast cancer patients

receiving chemotherapy.

Results

Cognitive Test Pearson

Correlation (r value)

Significance (p value)

Motor Mean Latency -0.339 0.156

Verbal Recognition Memory Recall of Total

Correct Words 1 -0.325 0.175

Verbal Recognition Memory Free Recall of

Total Novel Words1 0.480 0.037*

Verbal Recognition Memory Recall of Total

False Positives1 0.435 0.064

Minimum Maximum Mean Std. Deviation

Age 35 74 51.95 10.93

Stage of Disease Frequency Percent 1 1 5.3 2 7 36.8 3 3 15.8 4 8 42.1

Stage of Breast Cancer

Age of Patient Population

Education Level Frequency Percent Graduate Degree 6 31.6 2-4 yr. Degree 10 52.7 HS/GED 1 5.3 No HS or GED 1 5.3 Unknown 1 5.3

Education Level

Cancer Control Psychoneuroimmunology Lab

1p<0.05 refers to testing the subject immediately after they see the list of words *p<0.05

•  Motor function is negatively correlated with PGE2 indicating that increased PGE2 is associated with reduced latency of response.

•  Verbal memory function testing showed that increased PGE2 was associated with less total recall of words and increased total novel words and increased false positives.

•  No significant or trending results were observed in the visual memory, sustained attention or executive function tests.