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Dynamic changes in ER, PR, HER2, Ki-67, and AR before and after neoadjuvant therapy in breast cancer and their clinicopathological significance: a single-center real-world study
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DOI：10.1186/s12885-026-16672-1.png)
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Abstract
En 中文
Biomarker dynamics after neoadjuvant therapy (NAT) may affect molecular subtype classification and treatment decisions. Although previous studies have described receptor conversion after NAT, the clinical significance of integrated biomarker remodeling, including ER, PR, HER2, Ki-67, and AR, particularly in relation to multiple pathological response indicators in real-world clinical practice, remains incompletely understood. We retrospectively analyzed 644 patients with breast cancer who received neoadjuvant therapy followed by surgery. Changes in ER, PR, HER2, Ki-67, and AR were evaluated using McNemar’s test and the Wilcoxon signed-rank test. Multivariable logistic regression was used to assess associations between biomarker evolution and treatment response, including pCR, Miller–Payne grade, ypT stage, and ypN status, with emphasis on residual disease. Exploratory analyses also evaluated biomarker-change patterns according to pretreatment Nottingham grade. A sensitivity analysis was performed using the more stringent pCR definition of ypT0 ypN0. ER, PR, and HER2 conversion rates were 13.4%, 17.7%, and 12.0%, respectively. HER2 change was predominantly loss-driven (9.1% vs. 2.9% gain). Directional analysis showed that bidirectional ER remodeling was associated with improved pathological response, while PR and HER2 conversion were mainly related to baseline subtype and MP grade. Ki-67 and AR significantly decreased after NAT (P < 0.001 and P = 0.017). Baseline molecular subtype and Ki-67 independently predicted pCR, whereas AR was not significantly associated (P = 0.882). Applying the more stringent ypT0 ypN0 definition reduced the pCR rate from 37.6% to 36.5% but did not materially alter the multivariable results. In patients with residual invasive breast carcinoma, the magnitude of Ki-67 decline differed across ypT groups (P = 0.034) and was smaller in Grade III than in Grade I–II tumors (P = 0.010). Biomarker remodeling after NAT may reflect therapy-associated biological changes, although the underlying mechanisms remain to be elucidated. HER2 changes are predominantly loss-driven, and ER shows response-associated bidirectional remodeling. Post-NAT biomarker reassessment may provide complementary information for molecular stratification and individualized post-neoadjuvant treatment planning. Dynamic changes in Ki-67 may provide additional information for pathological-response stratification in patients with residual disease, whereas baseline AR showed limited independent predictive value.
Keywords:
Breast cancer
Neoadjuvant therapy
HER2
Ki-67
Receptor conversion
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