Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
Department of Pathology, Memorial Sloan Kettering Cancer, 1275 York Avenue, New York, NY, 10065, USA.
Breast Cancer Res Treat. 2019 Aug;177(1):61-66. doi: 10.1007/s10549-019-05295-9. Epub 2019 May 29.
Human epidermal growth factor receptor 2 (HER2)-positive breast cancers are known to have significant clinical and pathological response to neoadjuvant systemic therapy (NST). The aim of this study was to identify factors associated with pathological complete response (pCR), defined as no residual invasive carcinoma in the breast and axillary lymph nodes (ypT0/is ypN0), among patients with HER2-positive breast cancer and to compare pCR rates between breast cancers with HER2 protein overexpression by immunohistochemistry (IHC) versus HER2 gene amplification by fluorescence in situ hybridization (FISH) in the absence of protein overexpression by IHC.
We conducted a retrospective review of HER2-positive breast cancer patients treated with NST and surgery at Memorial Sloan Kettering Cancer Center between January 2013 and May 2018. Estrogen receptor (ER), progesterone receptor (PR), and HER2 status were assessed according to the 2018 ASCO/CAP guidelines.
During the study period, 560 patients were identified. Of 531 patients with IHC results available, 455 patients had HER2 IHC 3+, and 76 had IHC < 3+ but HER2 amplification detected by FISH. The overall pCR rate was 59% (330/560). The pCR rate among patients with HER2 protein overexpression (IHC 3+) was 67%, compared to 17% among patients with HER2 amplification by FISH (IHC < 3+). On univariate and multivariate analyses, HER2 protein overexpression by IHC (IHC 3+) was a significant predictor of pCR, along with grade 3 histology, PR-negative status, and dual anti-HER2 therapy.
Although both HER2 IHC and FISH are standard HER2 testing methods in breast cancer, achievement of pCR is associated with HER2 IHC expression level, among other factors.
人表皮生长因子受体 2（HER2）阳性乳腺癌对新辅助全身治疗（NST）具有显著的临床和病理反应。本研究的目的是确定与病理完全缓解（pCR）相关的因素，pCR 定义为乳腺和腋窝淋巴结（ypT0/is ypN0）中无残留浸润性癌，该研究纳入了 HER2 阳性乳腺癌患者，并比较了免疫组织化学（IHC）检测到的 HER2 蛋白过表达与 IHC 无蛋白过表达时荧光原位杂交（FISH）检测到的 HER2 基因扩增的乳腺癌之间的 pCR 率。
我们对 2013 年 1 月至 2018 年 5 月期间在 Memorial Sloan Kettering 癌症中心接受 NST 和手术治疗的 HER2 阳性乳腺癌患者进行了回顾性研究。根据 2018 年 ASCO/CAP 指南评估雌激素受体（ER）、孕激素受体（PR）和 HER2 状态。
在研究期间，共确定了 560 例患者。在可获得 IHC 结果的 531 例患者中，455 例患者的 HER2 IHC 为 3+，76 例患者的 HER2 IHC 为<3+但 FISH 检测到 HER2 扩增。总体 pCR 率为 59%（330/560）。HER2 蛋白过表达（IHC 3+）患者的 pCR 率为 67%，而 FISH（IHC<3+）检测到 HER2 扩增的患者的 pCR 率为 17%。在单因素和多因素分析中，HER2 蛋白过表达（IHC 3+）是 pCR 的显著预测因子，与组织学 3 级、PR 阴性状态和双抗 HER2 治疗有关。
尽管 HER2 IHC 和 FISH 都是乳腺癌的标准 HER2 检测方法，但 pCR 的实现与其他因素一起与 HER2 IHC 表达水平相关。
