Fatigue During and After Breast Cancer Therapy-A Prospective Study

J Pain Symptom Manage. 2017 Mar;53(3):551-560. doi: 10.1016/j.jpainsymman.2016.09.011. Epub 2016 Dec 29.


Context: Chronic fatigue (CF) in breast cancer (BC) survivors is multifactorial and may be caused by immune activation triggered by BC or its treatment. In the Neoadjuvant Avastin in Breast Cancer study, BC patients received neoadjuvant chemotherapy (FEC100→taxane) ± bevacizumab, a monoclonal antibody with fatigue as a potential side effect.

Objectives: To examine fatigue levels and prevalence of CF before and during chemotherapy and at follow-up, and their associations with C-reactive protein (CRP) and clinical variables.

Methods: Eighty-four HER2-negative patients with cT2-4N0-3M0 BC responded to questionnaires and had CRP measured before treatment (T0), after FEC100 (T1), after taxanes before surgery (T2), and at two-year follow-up (T3).

Results: The prevalence of CF increased from 8% at T0 to 36% at T3, P < 0.0001. Fatigue levels peaked during chemotherapy from 12.0 at T0 to 20.0 at T2, and declined to 16.7 at T3, P < 0.001. Women with CF at T3 had higher fatigue levels at T0, T2, and T3 than those without CF (P ≤ 0.01). Psychological distress (P = 0.03) and pain (P = 0.04) at T3 were associated with CF at T3. Only psychological distress remained a significant predictor in multivariate analysis. CRP increased from T0 to T1 (P < 0.01) and declined to baseline values at T3, but changes were not associated with bevacizumab treatment. No association was found between bevacizumab or CRP, and fatigue levels or CF.

Conclusion: Neither bevacizumab treatment nor low-grade systemic inflammation as measured by CRP was associated with the increased fatigue levels and raised prevalence of CF, observed during and after BC therapy. Increased fatigue levels at baseline and psychological distress at T3 were associated with CF at T3.

Trial registration: ClinicalTrials.gov NCT00773695.

Keywords: Breast cancer; C-reactive protein (CRP); bevacizumab; chronic fatigue; fatigue.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / epidemiology
  • Adenocarcinoma / physiopathology
  • Adenocarcinoma / psychology
  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use*
  • Bevacizumab / adverse effects
  • Bevacizumab / therapeutic use
  • Biomarkers / blood
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / physiopathology
  • Breast Neoplasms / psychology
  • C-Reactive Protein / metabolism
  • Fatigue / epidemiology*
  • Fatigue / etiology
  • Fatigue / physiopathology
  • Fatigue / psychology
  • Female
  • Follow-Up Studies
  • Humans
  • Inflammation / epidemiology
  • Inflammation / physiopathology
  • Inflammation / psychology
  • Longitudinal Studies
  • Middle Aged
  • Pain / epidemiology
  • Pain / physiopathology
  • Pain / psychology
  • Prevalence
  • Prospective Studies
  • Stress, Psychological / epidemiology
  • Stress, Psychological / physiopathology
  • Stress, Psychological / psychology
  • Treatment Outcome


  • Antineoplastic Agents
  • Biomarkers
  • Bevacizumab
  • C-Reactive Protein

Associated data

  • ClinicalTrials.gov/NCT00773695