Long-Term Fatigue After Treatment for Breast Cancer
Nancy E. Avis, Nathaniel S. O’Connell, Shannon L. Mihalko, Jennifer H. Jordan, Amy C. Ladd, Glenn J. Lesser, Kristine C. Olson, Kathryn E. Weaver, Emily V. Dressler, Pamela J. Grizzard, Beverly Levine, Tonya L. Moore, Bonnie Ky, Mary Helen Hackney, Peter Brubaker, Kerryn W. Reding, Alexander R. Lucas, Moriah P. Bellissimo, F. Gerard Moeller, Dalane W. Kitzman, Craig A. Hamilton, Heidi D. Klepin, Joseph Yeboah, William Ntim, Vlad G. Zaha, Ralph D’Agostino, W. Gregory HundleyImportance
Patients with breast cancer (BC) may have long-term fatigue after treatment, which is associated with reduced quality of life.
Objective
To identify cardiac, psychological, and cancer treatment factors associated with fatigue before and 24 months after BC treatment.
Design, Setting, and Participants
This cohort study was conducted across multiple community hospital-based cancer centers among participants with stage I to III BC receiving potentially cardiotoxic chemotherapy or aromatase inhibitors and noncancer comparators. Participants were enrolled from May 2017 to July 2021 and followed up for 24 months. Data were analyzed between July 2023 and July 2026.
Exposures
Fatigue was assessed by the Functional Assessment of Chronic Illness Therapy Fatigue scale.
Main Outcomes and Measures
It was hypothesized that chemotherapy-associated changes in left ventricular function were associated with and mediated 2-year post-BC treatment fatigue. Outcome measures included fatigue, sociodemographic variables, hematocrit, left ventricular ejection fraction and circumferential strain, cardiovascular comorbidities, 6-minute walk distance, perceived stress, and depressive symptoms.
Results
From a total of 381 patients, patients with BC (236) and noncancer comparators (145) had a mean (SD) age of 54 (12) years. Two years after BC treatment, 33 (18.2%) receiving potentially cardiotoxic chemotherapy experienced clinically relevant fatigue (χ 2 test P < .001 relative to aromatase inhibitors or controls), and 62 (34.6%) experienced a significant increase in fatigue relative to their precancer treatment fatigue level (χ 2 test P < .001, relative to aromatase inhibitors and controls). Independent of pretreatment and posttreatment left ventricular ejection fraction, diabetes status, hypertension, tobacco use, age, body mass index, hematocrit, receipt of potentially cardioprotective medications, and chemotherapy regimens, only depressive symptoms (estimate, −0.77; 95% CI, −0.83 to −0.71; P < .001) and perceived stress (−0.32; 95% CI, −0.41 to −0.24; P < .001) were associated with and mediated 24-month post-BC treatment fatigue measures. Baseline adjusted changes in 6-minute walk distance, left ventricular ejection fraction, and left ventricular strain were not associated with 24-month post-BC treatment fatigue levels.
Conclusions and Relevance
In this cohort study of patients with BC, clinically relevant fatigue increased in 34% of patients 2 years after initiating cancer treatment mediated partly by depressive symptoms and perceived stress regardless of cardiovascular risk factors, age, or change in left ventricular ejection fraction and/or strain.
Trial Registration
ClinicalTrials.gov Identifier: