Weak circadian rhythm increases neutropenia risk among breast cancer patients undergoing adjuvant chemotherapy

• Published in: Breast cancer research and treatment 2018-04, Vol.168 (2), p.483-493
• Main Authors: Li, Wentao, Kwok, Carol Chi-Hei, Chan, Dominic Chun-Wan, Wang, Feng, Tse, Lap Ah
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Actigraphy; Adjuvant chemotherapy; Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Breast cancer; Breast Neoplasms - physiopathology; Breast Neoplasms - therapy; Cancer patients; Cancer research; Care and treatment; Chemotherapy; Chemotherapy, Adjuvant - adverse effects; Chemotherapy, Adjuvant - methods; Chemotherapy-Induced Febrile Neutropenia - epidemiology; Chemotherapy-Induced Febrile Neutropenia - etiology; Chemotherapy-Induced Febrile Neutropenia - physiopathology; Circadian rhythm; Circadian Rhythm - physiology; Circadian rhythms; Cohort Studies; Cyclophosphamide; Doxorubicin; Epidemiology; Epirubicin; Female; Fluorouracil; Health aspects; Humans; Incidence; Mastectomy; Medicine; Medicine & Public Health; Middle Aged; Neutropenia; Oncology; Prospective Studies; Risk factors; Statistical analysis; Wrist
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-017-4614-9

Purpose Severe neutropenia is a common dose-limiting side effect of adjuvant breast cancer chemotherapy. We aimed to test the hypothesis that weak circadian rhythm is associated with an increased risk of neutropenia using a cohort study. Methods We consecutively recruited 193 breast cancer patients who received adjuvant chemotherapy (5-fluorouracil, epirubicin, and cyclophosphamide followed by docetaxel; doxorubicin and cyclophosphamide; docetaxel and cyclophosphamide). Participants wore a wrist actigraph continuously for 168 h at the beginning of chemotherapy. Values of percent rhythm and double amplitude below medians represented weak circadian rhythm. Mesor measured the mean activity level and acrophase symboled the peak time of the rhythm. We used Cox proportional hazard regression model to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of grade 4 neutropenia and febrile neutropenia in relation to actigraphy-derived parameters. Results Low levels of percent rhythm (HR:2.59, 95% CI 1.50–4.72), double amplitude (HR:2.70, 95% CI 1.51–4.85), and mesor (HR: 2.48, 95% CI 1.44–4.29) were positively associated with the risk of grade 4 neutropenia during chemotherapy. Low levels of percent rhythm (HR: 2.41, 95% CI 1.02–5.69) and double amplitude (HR:2.49, 95% CI 1.05–5.90) were also associated with increased risks of febrile neutropenia. The HRs for acrophase were not statistically significant. Conclusions This study provides the first epidemiological evidence that increased risks of grade 4 neutropenia and febrile neutropenia are associated with weak circadian rhythm among adjuvant breast cancer patients. The results suggest that circadian rhythm might be one potential target for the prevention of chemotherapy-induced neutropenia among cancer patients.