Abstract 438P
Background
Given that CRF is characterized by a lack of energy, it is postulated that mitochondrial dysfunction may contribute to its etiology. Using mitochondrial DNA (mtDNA) copy number and displacement-loop (D-loop) mutation status, this study aims to evaluate mtDNA content between fatigue subclasses, over the course of chemotherapy.
Methods
In a prospective cohort study, early-stage breast patients’ fatigue levels were assessed using the validated Multi-Dimensional Fatigue Symptom Inventory–Short Form (MFSI-SF) and their blood was drawn before, during and after treatment. Relative mtDNA copy number was determined via real-time quantitative polymerase chain reaction while mitochondrial genome was sequenced directly for D-loop mutations at nucleotide positions 303, 489 and 514. Subclasses of extent of fatigue was derived using latent class analysis, based on magnitude of change in sub-domain scores after treatment, with respect to baseline. Clinically relevant factors that differentiate the identified subclasses were then compared between the fatigued groups.
Results
A total of 133 patients (mean age ± SD: 51.2 ± 8.8 years, median mtDNA: 71.0) were classified into two fatigue subclasses: mild fatigue (75.2%) and fatigued group (24.8%) respectively. Based on mtDNA trajectory, patients who are predisposed to CRF started off with lower baseline values and experienced slower recovery. Median mtDNA content was reduced over 12 weeks after initiation of chemotherapy (p < 0.001) and was reported to be consistently lower in fatigued group (T2: 48.0 vs 56.0; T3: 61.4 vs 66.0) although the difference was not found to be statistically significant. The proportion of patients with D-loop mutation status was comparable between fatigued group and mild fatigue (303: 81.8% vs 73.0%, 489: 45.5% vs 47.0% and 514: 45.5% vs 53.0%). However, no association was reported between mtDNA levels over time or D-loop mutation with CRF status.
Conclusions
mtDNA content and D-loop mutation status do not sufficiently differentiate fatigue subclasses, suggesting that future research may be needed to study the differential expression of mitochondrial dysfunction-related genes and the pathways they may perturb.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
National University of Singapore.
Funding
National Medical Research Council.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
27P - The prognostic value of neutrophil to lymphocyte ratio (NLR) and 18F-FDG PET SUV in breast cancer patients underwent neoadjuvant chemotherapy
Presenter: Soong June Bae
Session: Poster display session
Resources:
Abstract
28P - Accuracy of core biopsy in predicting pathologic complete response in the breast in patients with complete/near complete clinical and radiological response (Complete Responders in the Breast – CRBr): A feasibility study
Presenter: Nisha Hariharan
Session: Poster display session
Resources:
Abstract
29P - Tumour response to neoadjuvant chemotherapy in breast cancer: Routine pathologic markers improve the predictive power of a cell-loss metric based on release of thymidine kinase 1 into blood
Presenter: Bernhard Tribukait
Session: Poster display session
Resources:
Abstract
30P - Comparison of metabolic changes between neoadjuvant chemotherapy and neoadjuvant endocrine therapy in premenopausal women with ER positive, HER2 negative breast cancer
Presenter: Ho-hyun Ryu
Session: Poster display session
Resources:
Abstract
31P - Circulating miR-155 as a potential therapeutic monitoring marker in breast cancer
Presenter: Sumadi Lukman Anwar
Session: Poster display session
Resources:
Abstract
32P - Profile of breast cancer epidemiology in Sanglah General Hospital, Denpasar, Bali from 2012 to 2019
Presenter: Citra Aryanti
Session: Poster display session
Resources:
Abstract
33P - Contrast enhanced chest CT in patients with breast cancer: Comprehensive imaging analysis and correlation with biological markers
Presenter: Bo Hwa Choi
Session: Poster display session
Resources:
Abstract
34P - Verification of metabolic regulatory mechanisms in androgen receptor-positive triple negative breast cancer
Presenter: Yuka Asano
Session: Poster display session
Resources:
Abstract
35TiP - Ribociclib plus goserelin with hormonal therapy versus physician choice chemotherapy in pre-/perimenopausal patients with HR+, HER2– inoperable locally advanced breast cancer (ABC): RIGHT choice study
Presenter: Yen-Shen Lu
Session: Poster display session
Resources:
Abstract
36TiP - A prospective study to assess response to neoadjuvant hormonal therapy in postmenopausal women with hormone-receptor positive breast cancer at a regional cancer centre in South India
Presenter: Shina Goyal
Session: Poster display session
Resources:
Abstract