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Development and validation of a nomogram for predicting grade 4 neutropenia in patients with breast cancer undergoing
Jing Shi1,2,3, Fuxing Zhao2, Tianlei Qiu2
1School of Clinical Medicine of Qinghai University, Affiliated Hospital of Qinghai University Xining 810000, Qinghai, China.
Background:
Grade 4 neutropenia is a severe toxicity associated with anthracycline-based chemotherapy in patients with breast cancer. This study aimed to develop and validate a clinical prediction model for this adverse event during the first cycle of anthracycline-based chemotherapy.
Methods:
In this multicenter retrospective study, female patients with breast cancer who received their first cycle of anthracycline-based chemotherapy between January 2017 and December 2023 were included. Patients were randomly assigned into training and internal validation cohorts in a 2:1 ratio. An independent external validation cohort comprised patients treated between January 2024 and December 2025. Predictors were selected using multivariable logistic regression with a backward stepwise approach, and a nomogram was constructed. Model performance was assessed in terms of discrimination, calibration, and clinical utility using decision curve analysis (DCA).
Results:
A total of 672 patients were analyzed, with 518 in the training and internal validation cohort and 154 in the external validation cohort. Four independent predictors of grade 4 neutropenia were identified: age, body mass index (BMI), Ki67 index, and chemotherapy regimen. The model achieved area under the curve (AUC) values of 0.757, 0.759, and 0.731 in the training, internal validation, and external validation cohorts, respectively, demonstrating good discriminative ability. Calibration plots demonstrated satisfactory agreement between predicted and observed risks across all cohorts, and DCA confirmed the clinical utility of the model.
Conclusion:
We developed and externally validated a robust nomogram for predicting grade 4 neutropenia in patients with breast cancer undergoing their first cycle of anthracycline-based chemotherapy. This user-friendly tool may assist clinicians in identifying high-risk patients prior to treatment initiation, enabling timely preventive intervention.
