Background
Objective, treatment-independent markers of cancer-related fatigue are needed to advance clinical trials. We evaluated physical, neurocognitive, and serologic markers for correlation with self-reported fatigue before and after (neo)adjuvant chemotherapy for early-stage breast cancer.
Methods
Women with stage I-III breast cancer consented to assessment before and after completing 4 cycles of dose-dense doxorubicin/cyclophosphamide. Assessment included self-reported fatigue (Brief Fatigue Inventory), depression (CES-D), Pittsburgh Sleep Quality Index, and 28 objective measures: grip strength, 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), adjusted for depression, timing pre-/post-chemotherapy, menopausal status, obesity, and education. P values were adjusted to control the False Discovery Rate.
Results
Of 28 subjects, 3 withdrew without completing baseline assessments. Pre- and post-chemotherapy data were available to evaluate physical measures (25 subjects, age 50.6±9.5 years), neurocognitive tests (22 subjects), and serologic markers (10 subjects). On covariate-adjusted analysis, interleukin (IL)-12 was associated (p<0.01) with fatigue at both assessments. Serum eotaxin (p<0.01), IL-1RA (p<0.01), MCP1 (p<0.01), and performance on 2 neurocognitive (trailmaking) tests (p<0.01, p=0.02) were inversely associated with fatigue before chemotherapy but not afterwards, while daily energy expenditure, serum MCP1 and serum MIP-1a were associated (each p<0.01) with fatigue after chemotherapy but not before. The association between energy expenditure and fatigue was detectable only if an actively athletic subject with outlier values of energy expenditure was excluded.
Conclusion
Serum IL-12 merits confirmatory testing as an objective, treatment-independent measure of fatigue in early-stage breast cancer.