HER2表达异质性与激素受体水平：影响HER2阳性乳腺癌新辅助治疗疗效的关键病理学预测因素

TL;DR - A WeChat interpretation of a Modern Pathology study (Hu et al., 2026) that borrows the ecological quadratic entropy (QE) index to quantify intratumoral HER2 protein expression heterogeneity, showing it independently predicts failure to achieve pathologic complete response (pCR) after neoadjuvant anti-HER2 therapy. Note: this is a quantitative pathology/biostatistics metric, not an AI/ML method.

• In 295 HER2-positive patients treated with trastuzumab-based NAT (82% with pertuzumab), overall pCR was 51.86%; HER2-homogeneous tumors (HQE=0, 201 cases) reached 64.7% pCR vs. only 24.5% for heterogeneous tumors (HQE>0), and higher HER2-HQE was an independent risk factor for not achieving pCR on multivariate analysis.
• HER2-HQE was computed from the proportions of IHC 0/1+, 2+, and 3+ tumor cells and stratified by terciles (low 0.001–0.160, mid 0.161–0.240, high >0.240); it correlated negatively with the IHC 3+ cell fraction and positively with ER/PR expression (P<0.001), plus higher clinical N stage (P=0.033).
• Downstaging by AJCC anatomic stage fell across HQE strata (85.7% / 81.1% / 66.7% for zero/low/mid) but only 32.3% in the high-HQE group (not significant, P=0.102), suggesting HER2-HQE >0.24 as a candidate threshold for limited benefit from standard anti-HER2 regimens.
• Stratified analysis: in the IHC 3+ <95% subgroup, ER level (11–69%, OR=29.43, P=0.001) and low HQE (OR=13.86, P=0.007) were independent predictors; in the highly homogeneous ≥95% subgroup only continuous ER stratification (notably 0–10%) retained predictive value, while FISH amplification level (4–6 vs >6 signals/cell) showed no pCR/RCB difference.