Department of Pathology, "A. Businco" Oncologic Hospital, ARNA S Brotzu, Via Edward Jenner 1, 09121, Cagliari, Italy.
Dipartimento di Matematica e Informatica, University of Cagliari, Palazzo delle Scienze, Via Ospedale 72, 09124, Cagliari, Italy.
Sci Rep. 2023 Aug 8;13(1):12869. doi: 10.1038/s41598-023-40071-2.
HER2+ breast cancer (BC) is an aggressive subtype genetically and biologically heterogeneous. We evaluate the predictive and prognostic role of HER2 protein/gene expression levels combined with clinico-pathologic features in 154 HER2+ BCs patients who received trastuzumab-based neoadjuvant chemotherapy (NACT). The tumoral pathological complete response (pCR) rate was 40.9%. High tumoral pCR show a scarce mortality rate vs subjects with a lower response. 93.7% of ypT0 were HER2 IHC3+ BC, 6.3% were HER2 IHC 2+/SISH+ and 86.7% of ypN0 were HER2 IHC3+, the remaining were HER2 IHC2+/SISH+. Better pCR rate correlate with a high percentage of infiltrating immune cells and right-sided tumors, that reduce distant metastasis and improve survival, but no incidence difference. HER2 IHC score and laterality emerge as strong predictors of tumoral pCR after NACT from machine learning analysis. HER2 IHC3+ and G3 are poor prognostic factors for HER2+ BC patients, and could be considered in the application of neoadjuvant therapy. Increasing TILs concentrations, lower lymph node ratio and lower residual tumor cellularity are associated with a better outcome. The immune microenvironment and scarce lymph node involvement have crucial role in clinical outcomes. The combination of all predictors might offer new options for NACT effectiveness prediction and stratification of HER2+ BC during clinical decision-making.
人表皮生长因子受体 2（HER2）阳性乳腺癌（BC）是一种侵袭性的基因和生物学异质性亚型。我们评估了 154 例接受曲妥珠单抗为基础的新辅助化疗（NACT）的 HER2+BC 患者中 HER2 蛋白/基因表达水平与临床病理特征相结合的预测和预后作用。肿瘤病理性完全缓解（pCR）率为 40.9%。高肿瘤 pCR 患者的死亡率较低，而对治疗反应较低的患者则较高。ypT0 中有 93.7%的患者为 HER2 IHC3+BC，6.3%为 HER2 IHC 2+/SISH+，86.7%的患者为 ypN0 为 HER2 IHC3+，其余为 HER2 IHC2+/SISH+。更好的 pCR 率与浸润性免疫细胞和右侧肿瘤的高百分比相关，这可以降低远处转移和改善生存，但无发病差异。来自机器学习分析的结果表明，HER2 IHC 评分和肿瘤侧别是 NACT 后肿瘤 pCR 的强有力预测因子。HER2 IHC3+和 G3 是 HER2+BC 患者的不良预后因素，可在新辅助治疗中考虑应用。增加 TILs 浓度、降低淋巴结比值和降低残留肿瘤细胞密度与更好的预后相关。免疫微环境和淋巴结受累程度较低在临床结局中起着至关重要的作用。所有预测因素的结合可能为 NACT 效果预测和临床决策中的 HER2+BC 分层提供新的选择。
