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Phenotypic and Genotypic Risk Factors for Fatigue Trajectories in Patients with Early-Stage Breast Cancer [Poster Title]

Other Titles

Rising Star Poster/Presentation

Abstract

Introduction: Cancer-related fatigue (CRF) is the most burdensome symptom in early-stage breast cancer (ESBC) patients; up to 30% report severe fatigue one-year post-diagnosis. CRF significantly impairs quality of life and functional status. Identifying risk factors for distinct fatigue trajectories can inform symptom management timing and personalization.

Purpose: Identify distinct trajectories and phenotypic and genotypic risk factors associated with high severity fatigue trajectories in women with ESBC.

Methods: This analysis of a prospective longitudinal study examined genetic underpinnings of symptoms in ESBC patients. Fatigue was assessed using the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS®29) weekly during treatment and monthly thereafter for 12 months following surgery. Group-based trajectory modeling (GBTM) identified distinct fatigue trajectories. Single nucleotide polymorphisms (SNPs) from eight inflammatory and neuroimmune genes (IL6, IL8, IL10, TNFa, CRP, NFkB1, NFkB2, BDNF) were assessed with univariate GBTM. SNPs with promising associations (p<0.20) were entered into a multivariate GBTM with backward elimination to identify final joint predictors of trajectory group membership, including interactions.

Results: Participants (n=291) had a mean age of 60.1 (SD=11.63) years and clustered into three fatigue trajectories: mild/decreasing (28.5%), mild/flat (55.6%), and moderate/flat (15.8%). While univariate analysis identified 10 SNPs across IL6, NFkB1, and NFkB2 (p<0.05), only NFkB1 variants (rs2016504, rs17250305) remained significant in the final multivariate model. Younger age and higher BMI also predicted membership in more severe fatigue trajectories (p<0.05). Notably, a significant age-by-rs2016504 interaction (p=0.027) revealed attenuation of the positive association of rs2016504 with increasing age.

Discussion: The final model contained only SNPs within the NFkB gene family, a master regulator of pro-inflammatory cytokine responses. These findings suggest that genetic variations in upstream inflammatory regulation may drive persistent fatigue and highlights NFkB signaling pathways as potential therapeutic targets. Early screening for these markers could identify patients at risk for chronic fatigue, allowing for personalized symptom management.

Notes

References:

Carreira, H., Williams, R., Dempsey, H., Stanway, S., Smeeth, L., & Bhaskaran, K. (2021). Quality of life and mental health in breast cancer survivors compared with non-cancer controls: A study of patient-reported outcomes in the United Kingdom. Journal of Cancer Survivorship: Research and Practice, 15(4), 564–575. https://doi.org/10.1007/s11764-020-00950-3

Dorland, H. F., Abma, F. I., Van Zon, S. K. R., Stewart, R. E., Amick, B. C., Ranchor, A. V., Roelen, C. A. M., & Bültmann, U. (2018). Fatigue and depressive symptoms improve but remain negatively related to work functioning over 18 months after return to work in cancer patients. Journal of Cancer Survivorship, 12(3), 371–378. https://doi.org/10.1007/s11764-018-0676-x

Hansen, J. A., Feuerstein, M., Calvio, L. C., & Olsen, C. H. (2008). Breast Cancer Survivors at Work. Journal of Occupational and Environmental Medicine, 50(7), 777. https://doi.org/10.1097/JOM.0b013e318165159e

Hollen, P. J., Msaouel, P., & Gralla, R. J. (2015). Determining issues of importance for the evaluation of quality of life and patient-reported outcomes in breast cancer: Results of a survey of 1072 patients. Breast Cancer Research and Treatment, 151(3), 679–686. https://doi.org/10.1007/s10549-015-3420-5

Joly, F., Lange, M., Dos Santos, M., Vaz-Luis, I., & Di Meglio, A. (2019). Long-Term Fatigue and Cognitive Disorders in Breast Cancer Survivors. Cancers, 11(12), 1896. https://doi.org/10.3390/cancers11121896

Description

This session examines phenotypic and genotypic risk factors for cancer-related fatigue trajectories in early-stage breast cancer patients. Findings highlight NF-κB gene variants, younger age, and higher BMI as predictors of persistent fatigue, suggesting that early genetic screening could enable personalized, timely symptom management interventions.

Author Details

Katrina Carr, BSN, RN; Susan M. Sereika, PhD; Yvette Conley, PhD, FAAN; Susan Wesmiller, PhD, RN, FAAN

Sigma Membership

Eta

Type

Poster

Format Type

Text-based Document

Study Design/Type

Longitudinal Study

Research Approach

Quantitative Research

Keywords:

Breast Cancer, Disease Risk Factors, Cancer Fatigue, Breast Cancer Patients

Conference Name

37th International Nursing Research Congress

Conference Host

Sigma Theta Tau International

Conference Location

Toronto, Ontario, Canada

Conference Year

2026

Rights Holder

All rights reserved by the author(s) and/or publisher(s) listed in this item record unless relinquished in whole or part by a rights notation or a Creative Commons License present in this item record. All permission requests should be directed accordingly and not to the Sigma Repository. All submitting authors or publishers have affirmed that when using material in their work where they do not own copyright, they have obtained permission of the copyright holder prior to submission and the rights holder has been acknowledged as necessary.

Review Type

Abstract Review Only: Reviewed by Event Host

Acquisition

Proxy-submission

Date of Issue

2026-09-05

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Phenotypic and Genotypic Risk Factors for Fatigue Trajectories in Early-Stage Breast Cancer Patients

Toronto, Ontario, Canada

Introduction: Cancer-related fatigue (CRF) is the most burdensome symptom in early-stage breast cancer (ESBC) patients; up to 30% report severe fatigue one-year post-diagnosis. CRF significantly impairs quality of life and functional status. Identifying risk factors for distinct fatigue trajectories can inform symptom management timing and personalization.

Purpose: Identify distinct trajectories and phenotypic and genotypic risk factors associated with high severity fatigue trajectories in women with ESBC.

Methods: This analysis of a prospective longitudinal study examined genetic underpinnings of symptoms in ESBC patients. Fatigue was assessed using the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS®29) weekly during treatment and monthly thereafter for 12 months following surgery. Group-based trajectory modeling (GBTM) identified distinct fatigue trajectories. Single nucleotide polymorphisms (SNPs) from eight inflammatory and neuroimmune genes (IL6, IL8, IL10, TNFa, CRP, NFkB1, NFkB2, BDNF) were assessed with univariate GBTM. SNPs with promising associations (p<0.20) were entered into a multivariate GBTM with backward elimination to identify final joint predictors of trajectory group membership, including interactions.

Results: Participants (n=291) had a mean age of 60.1 (SD=11.63) years and clustered into three fatigue trajectories: mild/decreasing (28.5%), mild/flat (55.6%), and moderate/flat (15.8%). While univariate analysis identified 10 SNPs across IL6, NFkB1, and NFkB2 (p<0.05), only NFkB1 variants (rs2016504, rs17250305) remained significant in the final multivariate model. Younger age and higher BMI also predicted membership in more severe fatigue trajectories (p<0.05). Notably, a significant age-by-rs2016504 interaction (p=0.027) revealed attenuation of the positive association of rs2016504 with increasing age.

Discussion: The final model contained only SNPs within the NFkB gene family, a master regulator of pro-inflammatory cytokine responses. These findings suggest that genetic variations in upstream inflammatory regulation may drive persistent fatigue and highlights NFkB signaling pathways as potential therapeutic targets. Early screening for these markers could identify patients at risk for chronic fatigue, allowing for personalized symptom management.