Prediction model incorporating dynamic changes in serum tumor markers for evaluating the efficacy of neoadjuvant chemotherapy in patients with breast cancer: a retrospective cohort study

结合血清肿瘤标志物动态变化的预测模型用于评估乳腺癌患者新辅助化疗的疗效:一项回顾性队列研究

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Abstract

BACKGROUND: Current prediction models for the efficacy of neoadjuvant chemotherapy (NAC) in patients with breast cancer (BC) include only static measurements of serum tumor markers, while the dynamic measurement data of these markers have not been fully utilized. This study aimed to develop and validate a prediction model for evaluating the efficacy of NAC in BC patients on the basis of dynamic changes in CEA, CA125, and CA15-3 levels. METHODS: We retrospectively screened 565 patients with BC who received NAC at our department from December 2016 to November 2021. A total of 446 patients were included and randomly divided into a training cohort (n = 312) and a test cohort (n = 134) at a 7:3 ratio. Least absolute shrinkage and selection operator (LASSO) regression with tenfold cross-validation was applied to select the most relevant features, and multivariate logistic regression was used to construct the predictive model on the basis of the selected features. The performance of the model was evaluated by the area under the receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis (DCA). RESULTS: A nomogram integrating age, human epidermal growth factor receptor 2 (HER2) status, pre-chemotherapy levels of CEA, principal component 1 (PC1) for CEA, PC2 for CA125, and PC2 for CA15-3 was developed for the dynamic CEA&CA125&CA15-3 model. Another nomogram integrating estrogen receptor (ER) status, HER2 status, and pre-chemotherapy CEA levels was developed for the pre-chemotherapy CEA&CA125&CA15-3 model. The area under the receiver operating characteristic curve (AUC) of the dynamic model was 0.739 (95% CI 0.680-0.797) in the training cohort and 0.712 (95% CI 0.613-0.811) in the test cohort. The AUC was 0.658 (95% CI 0.593-0.722) in the training cohort and 0.715 (95% CI 0.624-0.807) in the test cohort for the pre-chemotherapy model. Compared with the pre-chemotherapy model, the dynamic model demonstrated significantly improved predictive accuracy. Our dynamic model also exhibited good predictive performance in subgroup analyses. CONCLUSIONS: This study developed and validated nomogram models using clinicopathological features and serum tumor marker characteristics to predict NAC efficacy in BC patients. Although the dynamic model demonstrated comparable discriminative ability (AUC) to the pre-chemotherapy model in the test cohort, it showed significantly improved performance in net reclassification. While promising, this model requires further validation in multi-center prospective studies before clinical application.

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