Association of clinicopathological characteristics and pro-inflammatory markers with reduced relative dose intensity in breast cancer chemotherapy

Background: Chemotherapy efficacy depends on relative dose intensity (RDI) and an RDI <85% is associated with unfavourable overall survival. Clinicopathological char-
acteristics have been observed as risk factors of reduced RDI. The pro-inflammatory markers such as interleukin-6 (IL-6) and C-reactive protein (CRP), which also serve as
biomarkers of aging, have been reported to associate with RDI. We aimed to determine whether these parameters have influence on RDI in the local breast cancer (BC)
patients. Methods: This cross-sectional study recruited 172 women with stage I-IV BC receiving first-line chemotherapy between July 2018-March 2022. Sociodemographic, clinico-
pathological, and treatment data and peripheral blood samples were collected prior o chemotherapy. IL-6 and CRP levels were analyzed using quantitative ELISA. Dose
reductions and delays were captured and utilized to calculate the patient’s RDI. Multivariable logistic regression analysis was performed to determine the association between pre-chemotherapy parameters and RDI <85%. Results: Mean age was 52 years (range 32-78). The average RDI for all patients was 93% and an RDI <85% occurred in 23 (13.4%) patients. Mean IL-6 level was 1.12 pg/ml (range 0.0e27.7) and mean CRP was 10.82 mg/ml (range 0.0e151.7). Factors associated with reduced RDI were diabetes mellitus comorbidity (OR 5.13, 95% CI
1.38e19.03; p ¼0.015), triple-negative tumours (OR 4.17, 95% CI 1.09e15.89; p ¼0.037), palliative treatment setting (OR 3.75, 95% CI 1.12e12.62, p ¼0.032), and IL-6 serum level >0.485 pg/ml (OR 3.46, 95% CI 1.05e11.37; p ¼0.041).
Conclusions: The presence of diabetes mellitus comorbidity, triple-negative tumours, palliative treatment intention, and IL-6 serum level >0.485 pg/ml are associated with reduced RDI. Further investigation is warranted to confirm the association between biomarker of aging and chemotherapy delivery.