Abstract P2-12-08: Chemotherapy-induced fatigue and mitochondrial function in early stage breast cancer
Authors: Herath Kanchana , Dranka Brian P , Lessmann George M , McAllister Donna , Hoffmann Raymond G , Kalyanaraman Balaraman , Chitambar Christopher R , Peswani Namrata I 
Published: May 2015

Introduction

Patients with early stage breast cancer receiving chemotherapy (CT) may experience persistent fatigue. The mechanisms for fatigue are not well understood. We hypothesized that CT-induced fatigue may involve perturbations in mitochondrial function. We therefore examined the development of fatigue in patients during adjuvant or neoadjuvant CT and measured mitochondrial function in their peripheral blood mononuclear cells (PBMCs).

Methods

Females with Stage I-III breast cancer patients, ages 35-75 years, were enrolled in an IRB-approved study. Patients with coexisting illnesses associated with chronic fatigue were excluded. Patients self-reported fatigue severity using the 14-question Fatigue Symptom Inventory (FSI) that rates fatigue intensity on a 10-point scale. Data [FSI and PBMCs] were collected prior to CT, mid-point in the course of CT, 2 - 3 weeks after completion of CT, and 3 and 6 months later. Mitochondrial function in PBMCs from patients was measured using a Seahorse Bioscience XF24 analyzer at corresponding times.

Results

Results on CT-induced fatigue are available for 67 patients. The overall fatigue score for each patient was measured as the sum of the scores for all 14 questions in the FSI. The average fatigue score for the 67 patients prior to chemotherapy was 20. Baseline fatigue scores for patients who had adjuvant CT were much greater than for patients receiving neoadjuvant CT (R2=1). Patient fatigue scores doubled after starting chemotherapy (average score 40, p &lt; 0.001). Even though fatigue scores improved after treatment completion (average score 26 at 6 months), the scores did not return to baseline 6 months later (p=0.02).

In our population, CT-induced fatigue did not correlate with patient age regardless of the CT regimen [r=0.3 and r= -.2, for doxorubicin plus cyclophosphamide (AC) vs docetaxel plus cyclophosphamide (TC) groups, respectively)] or a decrease in hemoglobin (r= -.3 and r=0.03, for AC and TC, respectively). None of these correlations could explain more than 9% of the change in treatment-induced fatigue (p=0.2).

Preliminary analysis of mitochondrial function in 12 patients shows that 9 patients had a decrease in mitochondrial reserve capacity with an increase in CT-induced fatigue following completion of 4 cycles of CT. 3 patients had a decrease in mitochondrial reserve capacity but reported no significant change in their fatigue scores. Mitochondrial function data on all patients have been collected and are presently being analyzed.

Conclusion

Our study shows that early stage breast cancer patients treated with adjuvant or neoadjuvant CT may experience fatigue that can persist for months after completion of treatment and cannot be explained by the CT regimen, age, or anemia. Our initial results suggest a link between CT-induced fatigue and changes in mitochondrial function in some patients. Mitochondrial function analysis and its correlation with fatigue for all 67 patients will be completed and reported at SABCS. Mitochondrial function may prove to be a biomarker for CT-induced fatigue in certain patients and may help identify patients for whom interventions that stimulate mitochondria biogenesis, including pharmacologic agents and exercise, may be beneficial in ameliorating this side-effect.

Citation Format: Kanchana Herath, Brian P Dranka, George M Lessmann, Donna McAllister, Raymond G Hoffmann, Balaraman Kalyanaraman, Christopher R Chitambar, Namrata I Peswani. Chemotherapy-induced fatigue and mitochondrial function in early stage breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-12-08.