The adverse prognostic impact of reduced chemotherapy dose intensity appears attenuated in early breast cancer patients with treatment-relevant neutropenia: a retrospective cohort study

PURPOSE: Maintaining a relative dose intensity (RDI) ≥ 85% during chemotherapy is established as a critical threshold for optimal outcomes in early breast cancer. This study investigates whether the prognostic impact of reduced RDI differs based on the presence of chemotherapy-induced neutropenia requiring treatment modifications (rCIN). METHODS: We analyzed 730 patients with early breast cancer receiving anthracycline/cyclophosphamide and taxane-based chemotherapy at the University Hospital Tübingen between 2014 and 2021. rCIN was defined as any dose reduction > 15%, delay ≥ 5 days, or discontinuation attributed to neutropenia per Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Patients were stratified into four groups based on RDI (≥ 85% vs. < 85%) and rCIN status. Differences in overall survival (OS) and disease-free survival (DFS) were assessed by Kaplan-Meier analysis, and predictors of DFS were evaluated by Cox regression. RESULTS: rCIN occurred in 21.8% of patients, with 59.7% of rCIN patients receiving RDI < 85% versus 16.1% of non-rCIN patients (p < 0.001). Despite lower RDI, rCIN patients maintained similar pathological complete response rates after neoadjuvant therapy. In Kaplan-Meier analysis, patients with RDI < 85% without rCIN had significantly worse DFS and OS than the reference group with RDI ≥ 85% without rCIN (DFS p = 0.003; OS p = 0.002), while patients with RDI < 85% with rCIN showed comparable survival to high-RDI groups (all pairwise p > 0.170). Direct comparison between the two reduced-RDI groups was not statistically significant for either DFS or OS (DFS p = 0.055; OS p = 0.159). Cox regression confirmed RDI < 85% as a negative prognostic factor (HR 2.53; 95% CI 1.38-4.65; p = 0.003). The rCIN × RDI < 85% interaction term was not statistically significant (HR 0.44; 95% CI 0.12-1.60; p = 0.212). CONCLUSIONS: In this retrospective cohort, reduced RDI was associated with poorer outcomes, particularly in patients without rCIN. By contrast, patients with RDI < 85% and rCIN showed no significant differences in Kaplan-Meier survival, and similar pathological complete response rates were observed despite lower RDI in the neoadjuvant subgroup. These findings are hypothesis-generating and require confirmation in larger prospective studies.