Fatih Atalah, Aydın Acarbay, Akgün Karakök, İsmail Nazlı, Onur Alkan, Okan Aydın, Oğuzhan Selvi, Mehmet Beşiroğlu, Mahmut Gümüş
Among patients who were alive and evaluable at the 3-month landmark, higher MNRS was independently associated with more favorable subsequent landmark OS. MNRS may represent an exploratory and complementary approach to early risk stratification using routinely available hematologic parameters. Because both neutropenia and MCV changes may be influenced by treatment exposure and other clinical factors, prospective external validation is required before clinical application.
BACKGROUND: Predicting long-term benefit from CDK4/6 inhibitors in HR+/HER2- advanced breast cancer remains challenging in routine clinical practice. We evaluated whether a simple composite index integrating early neutropenia and mean corpuscular volume change, termed the MCV-Neutropenia Risk Score (MNRS), could improve early prognostic stratification.
METHODS: In this multicenter retrospective study, 432 patients were screened, and 273 patients who were alive and evaluable at the predefined 3-month landmark were included in the final analysis. Grade 2-3 neutropenia during the first three months and ΔMCV ≥10 fL at the landmark assessment were assigned one point each to construct the MNRS (range, 0-2). Landmark overall survival (OS), measured from the 3-month landmark, was evaluated using Kaplan-Meier estimates and Cox proportional hazards regression. Internal bootstrap validation with 1,000 resamples was performed.
RESULTS: After a median landmark follow-up of 44.9 months, 77 deaths were recorded. Grade 2-3 neutropenia occurred in 205 patients (75.1%), ΔMCV ≥10 fL in 93 patients (34.1%), and 66 patients (24.2%) had an MNRS of 2. Higher MNRS categories were associated with progressively more favorable landmark OS (log-rank p = 0.009). In the final center-stratified multivariable model, each one-point increase in MNRS was independently associated with a lower risk of death (HR 0.555, 95% CI 0.381-0.808; p = 0.002). Internal bootstrap validation supported the stability of MNRS in the multivariable model.
CONCLUSION: Among patients who were alive and evaluable at the 3-month landmark, higher MNRS was independently associated with more favorable subsequent landmark OS. MNRS may represent an exploratory and complementary approach to early risk stratification using routinely available hematologic parameters. Because both neutropenia and MCV changes may be influenced by treatment exposure and other clinical factors, prospective external validation is required before clinical application.