Treatment-independent markers of cancer-related fatigue are needed to advance clinical trials. In the current study, the authors evaluated physical, neurocognitive, and serologic markers for correlation with self-reported fatigue before and after (neo)adjuvant chemotherapy for patients with early-stage breast cancer. Women with AJCC TNM Stage I-III breast cancer consented to assessment before and after the completion of 4 cycles of dose-dense doxorubicin and cyclophosphamide. Assessment included self-reported fatigue (using the Brief Fatigue Inventory), depression (using the Center for Epidemiologic Studies-Depression Scale [CES-D]), Pittsburgh Sleep Quality Index, and 28 objective measures (grip strength in dominant and nondominant hands, 6-minute walk, daily total energy expenditure, 14 neurocognitive tests, and 10 serologic markers). Generalized linear regression models of fatigue were constructed (1 model per marker), and adjusted for depression, timing before/after chemotherapy, menopausal status, obesity, and educational level. P values were adjusted to control the False Discovery Rate.
Of 28 subjects, 3 withdrew without completing baseline assessments. Prechemotherapy and postchemotherapy data were available for the evaluation of physical measures (25 subjects aged 50.6 ± 9.5 years), neurocognitive tests (22 subjects), and serologic markers (10 subjects). On covariate-adjusted analysis, interleukin (IL)-12 was found to be associated with fatigue at both assessments (P<.01). Serum eotaxin (P < .01), IL-1RA (P < .01), monocyte chemoattractant protein 1 (MCP-1) (P<.01), and performance on 2 neurocognitive (Trail Making) tests (P<.01 and P = .02, respectively) were found to be inversely associated with fatigue before chemotherapy but not afterward, whereas daily energy expenditure, serum MCP-1, and serum macrophage inflammatory protein 1a (MIP-1a) were found to be associated with fatigue after receipt of chemotherapy but not before (P<.01 for each). The association between energy expenditure and fatigue was detectable only if an actively athletic subject with outlier values of energy expenditure was excluded.
Serum IL-12 merits confirmatory testing as an objective, treatment-independent measure of fatigue in patients with early-stage breast cancer.