CLO22-059: Chemotherapy Timing and Outcomes in Early Breast Cancer

Background: Chemotherapy efficacy and tolerability can vary up to 10-fold depending on dose time due to circadian variations in physiology. Existing data indicate that evening platinum and late night or early morning anthracycline or taxane chemotherapy may be superior. The objective of this study is to assess the relationship between dose timing and outcomes in breast cancer patients. Methods: 153 patients who had neoadjuvant chemotherapy in 2014-2020 were included. Chemotherapy administration was defined as AM when at least 70% of doses were given before noon and PM when at least 70% were after noon. Mixed AM or PM labels were used for rates of 50-70%. Patient/tumor characteristics, hospitalizations, weight loss, treatment changes, pathology, and disease recurrences were collected. Stratification occurred by stage, age, receptor status, and treatment. Univariate and multivariate logistic models were used to investigate the relationship between endpoints and dosing time. Contingency tables using chi-squared tests and ANOVA tests were constructed to investigate the relationship between timing and categorical and continuous variables, respectively. Results: Patients with hormone receptor positive/HER2 negative tumors were more likely to have AM dosing. Mixed AM patients had more dose reductions (OR 4.48, 95% CI 1.70-11.83, p = 0.002) and early treatment terminations (OR 3.76, 95% CI 1.20-11.79, p = 0.023) than PM patients. Recurrence rates also differed (AM 27.2%, mixed AM 0%, mixed PM 8.1%, PM 18.5%, p=0.043). Due to the small number of AM patients (n=11), an analysis was performed with two groups: AM (50% or more doses before noon) or PM (50% or more doses after noon). Dose reductions remained more frequent AM patients (OR 2.6, 95% CI 1.20-5.62, p=0.015) while differences for early termination or recurrence were no longer significant. The average age was older in AM (54.5 v. 50.3) but other characteristics including receptor status were well-balanced. Other variables including hospitalization, treatment delays, and weight loss were not significant. Conclusions: Timing may be important in breast cancer treatment. In this study, patients in the PM group had fewer dose reductions. Early treatment termination and recurrences also varied according to dose time. These findings align with our hypothesis though prospective study is needed. Our study is limited by the small number of AM patients. Future investigation of mixed timing would be of interest.