Breast Cancer (BC) Related Fatigue: A Longitudinal Investigation of Its Prevalence, Domains and Correlates.

Background: Fatigue is a complex and multidimensional symptom that is recognized as one of the most distressing and potentially long lasting side effects of cancer treatment (trt). Large scale data that help predict and prevent severe fatigue are lacking. Methods: We carried out a detailed longitudinal analysis of fatigue using a large ongoing national prospective clinical study (CANTO, NCT01993498) of stage I-III BC patients (pts) treated from 2012-14. Pts answered fatigue questionnaires at diagnosis (dx), 3-6 (T1) and 12 months (T2) post trt. Severe fatigue was defined by EORTC QLQ C30 scores ≥ 40 for overall fatigue and EORTC F12 ≥ 50 for physical, emotional and cognitive domains of fatigue (Giesinger, 2016). We used group based trajectory models to identify clusters of pts with high risk of severe fatigue and associated factors. Results: We analyzed 4160 pts with 1 year follow up data available, 30% were age <50, 16% were smokers, 53% received chemo- (CT), 91% radio- and 82% endocrine trt. Overall severe fatigue was reported by 23% pts at dx, increasing to 34% by T2 (p<.0001). 56% of pts with severe fatigue by T2 had not previously reported fatigue at dx. In addition, cluster techniques identified a subgroup of pts with up to 96% risk (95% CI 94-99) of reporting severe fatigue by T2. Selected factors for membership to this group included younger age (p < 0.001), comorbidities (p = 0.014), smoking (p = 0.008), HR+ BC (p = 0.025) and use of CT (p = 0.008). An interaction between severe fatigue and multiple physical and psychological symptoms was found in this subgroup (p < 0.001). We also observed differential patterns of change in prevalence of fatigue from dx to T2 by fatigue domain: from 13 to 20% for physical, 18 to 14% for emotional and 12 to 13% for cognitive fatigue (all p<.001). Consistent with overall fatigue, subgroups of pts with higher risk profiles were identified for fatigue domains. Conclusions: Our findings show that one in three pts reports severe fatigue after BC trt. We found substantial heterogeneity in how the trajectories of fatigue evolve across different subgroups of pts. Our data aid in the identification of pts who have increased risk of severe fatigue over time and highlight the need for personalized interventions to ameliorate this burdensome problem. Clinical trial identification: NCT01993498, Study Start Date: February 2012. Legal entity responsible for the study: UNICANCER. Funding: Has not received any funding. Disclosure: I. Vaz-Luis: Recipient of Susan Komen for the Cure Career Catalyst Research Grant and Foundation ARC pour la recherche sur le cancer. All other authors have declared no conflicts of interest.