Serum 25-hydroxyvitamin D and cancer-related fatigue: associations and effects on depression, anxiety, functional capacity and health-related quality of Life in breast cancer survivors during adjuvant endocrine therapy

Abstract

Background: The adjuvant treatment with Aromatase Inhibitor (AI) is considered standard of care for postmenopausal breast cancer (BC) women with hormone receptor-positive (HR +), however, it often causes adverse effects such as cancer-related fatigue (CRF). The high prevalence of vitamin D deficiency in postmenopausal women who start adjuvant AI supports the hypothesis that hypovitaminosis D would be one of the biological explanations for toxicity of AI. This study aimed to identify the relationship between 25-hydroxyvitamin D [25(OH)D] and CRF, and to analyze their associations and effects on depression, anxiety, functional disability, muscle/joint aches and HRQL.

Methods: This prospective study included 89 postmenopausal women diagnosed with HR + early BC in adjuvant endocrine therapy with AI. Anthropometric and body composition assessments were performed, as well as dietary assessments by application of 24-h dietary recall, at three time points, totaling 24 months of follow-up. The women completed the Cervantes Scale (CS), Hospital Anxiety and Depression Scale (HADS) and Health Assessment Questionnaire (HAQ). The CRF was determined from the Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F). The serum 25(OH)D was determined by electrochemiluminescence, with cut-off point above 75 nmol/L adopted as sufficiency. Generalized Linear Model (GLzM) and Generalized Mixed Model (GMM) analysis were used.

Results: At baseline, 36% (n = 32) of the women presented CRF and 39.3% (n = 35) had 25(OH)D below 75 nmol/L. None of the women reached the Estimated Average Requirements (EAR) of vitamin D. The causality between 25(OH)D and CRF was not significant. Longitudinally, lower levels of 25(OH)D had a negative effect on anxiety (p = 0.020), Menopause and Health (p = 0.033) and Vasomotor scores (p = 0.007). Also, the CRF had a negative effect on anxiety (p = 0.028); depression (p = 0.027); functional disability (p = 0.022); HRQL (p = 0.007); Menopause and Health (p = 0.042), Psychological (p = 0.008) and Couple Relations (p = 0.008) domains; and on Health (p = 0.019) and Aging (p = 0.036) subdomains. Vasomotor subdomain (β = -2.279, p = 0.045) and muscle/joint aches (β = -0.779, p = 0.013) were significant with CRF only at baseline.

Conclusions: This study found negative effect of body adiposity on CRF. Still, the clinical relevance of 25(OH)D and CRF is highlighted, especially that of CRF, considering the consistent impact on several adverse effects reported by BC survivors during adjuvant endocrine therapy.

Keywords: Aromatase Inhibitors; Breast neoplasms; Cancer survivors; Fatigue; Health-related quality of life; Vitamin D deficiency.

Fig. 1

Distribution of breast cancer survivors in the FACIT-Fatigue clusters throughout the study (n = 38). Clusters developed from the 5% MCID between T0T1, T1T2, T0T2 and T0T1T2: The same, Patients who maintained the FACIT-Fatigue score between T0T1, T1T2, T0T2 or who maintained the score at all three times (T0T1T2); Better, Patients who improved the FACIT-Fatigue score between T0T1, T1T2, T0T2 or who improved at T1 and again at T2 (T0T1T2); Worse, Patients who worsened the FACIT-Fatigue score between T0T1, T1T2, T0T2 or who worsened at T1 and again at T2 (T0T1T2); V, Patients who worsened the FACIT-Fatigue score at T1 and improved at T2 (T0T1T2); Inverted V, Patients who improved the FACIT-Fatigue score at T1 and worsened at T2 (T0T1T2). Chi-square Independence Test showed that there was no association between time points of study and clusters, considering T0T1 and T1T2 [X2(2) = 4.452; p = 0.108]