Preoperative prediction of breast cancer Ki-67 status via multimodal ultrasound-clinical nomogram: a single-center study.
Xiao-Kai Lu, Nian-Qiu Liu, Yi-Hang Li, Zhi-Yao Li, Dong Chen, Zhi-Rui Chuan, Yin-Xi Qu, Ying-Xian Zhang, Hai-Tao Chen, Xiao-Mao Luo
Abstract
Open AccessBackground: Breast cancer is a highly heterogeneous malignancy that poses a major health threat to women. Contemporary clinical management relies heavily on molecular subtyping, in which the Ki-67 proliferation index serves as a critical biomarker for assessing tumor aggressiveness and recurrence risk. However, conventional Ki-67 evaluation depends on invasive biopsy and immunohistochemical analysis, whose accuracy can be compromised by tumor heterogeneity-induced sampling errors and inter-observer variability. Therefore, this study aimed to develop and validate a preoperative nomogram that integrates multimodal ultrasound features with clinical parameters to enable non-invasive preoperative assessment of Ki-67 expression status in breast cancer. Methods: We retrospectively enrolled 142 consecutive breast cancer patients from The Third Affiliated Hospital of Kunming Medical University's Breast Center (March 2022 to August 2024). Preoperative multimodal ultrasound parameters (including B-mode, Doppler, and shear-wave elastography) and clinical variables were systematically documented using standardized protocols. Variables demonstrating univariate associations (P<0.10) underwent forward stepwise multivariate regression using likelihood ratio criteria. Model performance was assessed through: (I) calibration curves with Hosmer-Lemeshow test; (II) discrimination via area under the curve (AUC); and (III) clinical utility by decision curve analysis. Internal validation employed bootstrap resampling (1,000 replicates) with optimism correction using Harrell's method. Results: Univariate analysis identified six predictors associated with Ki-67 status (P<0.10): maximum lesion diameter, hyperechoic halo presence, Adler grade, Eratio, posterior echo reduction, and calcifications. Multivariate analysis confirmed four independent predictors of Ki-67 status (P<0.05): hyperechoic halo presence [adjusted odds ratio (aOR) =7.934; 95% confidence interval (CI): 2.604-24.173], posterior echo reduction (aOR =0.245; 95% CI: 0.099-0.601), calcifications (aOR =3.524; 95% CI: 1.466-8.472), and Adler grade (aOR =2.334; 95% CI: 1.222-4.456). The resulting nomogram demonstrated good discrimination (AUC =0.797; 95% CI: 0.722-0.872), with bootstrap-corrected AUC of 0.771 (95% CI: 0.673-0.879). Conclusions: The validated nomogram provides clinically useful preoperative prediction of Ki-67 status (AUC =0.797; bootstrap-corrected 0.771), with hyperechoic halo presence, posterior echo reduction, calcifications, and high Adler grade as key predictors.