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已知HER2阳性乳腺癌对于术前辅助全身治疗（化疗和抗HER2治疗）的临床和病理完全缓解率显著较高。不过，现有两种标准HER2检测方法：免疫组织化学法（IHC）检测HER2蛋白表达、荧光原位杂交法（FISH）检测HER2基因扩增，不同HER2检测方法对于HER2阳性乳腺癌术前新辅助全身治疗病理完全缓解率的影响尚不明确。 2019年5月29日，施普林格·自然《乳腺癌研究与治疗》在线发表美国哈佛大学麻省总医院、纽约纪念医院斯隆凯特林癌症中心的研究报告，探讨了不同HER2检测方法对于HER2阳性乳腺癌术前新辅助全身治疗病理完全缓解率的影响。 该单中心回顾研究对2013年1月～2018年5月纽约纪念医院斯隆凯特林癌症中心接受术前新辅助全身治疗和手术治疗的560例HER2阳性乳腺癌患者进行回顾分析，根据2018年美国临床肿瘤学会和美国病理医师学会指南，对雌激素受体、孕激素受体和HER2状态进行分析，比较IHC检测HER2蛋白过度表达（3+）乳腺癌与IHC检测HER2蛋白未过表达（<3+）而FISH检测HER2基因扩增乳腺癌的病理完全缓解率。病理完全缓解定义为：术前辅助全身治疗后，乳房和腋窝淋巴结病理检查无残留浸润癌。 结果，获得531例患者的IHC检测结果，其中455例IHC检测HER2蛋白表达为3+、76例IHC检测HER2蛋白表达<3+而FISH检测HER2基因扩增。所有560例患者的病理完全缓解率为59%（330例）。IHC检测HER2蛋白过度表达（IHC3+）与FISH检测HER2基因扩增（IHC<3+）患者相比，病理完全缓解率显著较高（67%比17%）。 根据单因素和多因素分析，IHC检测HER2蛋白过度表达（IHC3+）是病理完全缓解、组织学分级3级、孕激素受体阴性、双重（曲妥珠单抗＋帕妥珠单抗）抗HER2治疗的显著预测因素。 因此，该研究结果表明，虽然IHC和FISH都是乳腺癌的标准HER2检测方法，但是病理完全缓解与IHC检测HER2蛋白表达水平显著相关。那么，如果IHC检测HER2蛋白表达水平不高，那么有没有必要进行昂贵的FISH检测、有没有必要进行昂贵的双重（曲妥珠单抗＋帕妥珠单抗）抗HER2治疗？这些问题值得开展进一步研究深入探讨。 Breast Cancer Res Treat. 2019 May 29. Pathologic complete response rate according to HER2 detection methods in HER2-positive breast cancer treated with neoadjuvant systemic therapy. Melissa Krystel-Whittemore, Jin Xu, Edi Brogi, Katia Ventura, Sujata Patil, Dara S. Ross, Chau Dang, Mark Robson, Larry Norton, Monica Morrow, Hannah Y. Wen. Massachusetts General Hospital, Boston, USA; Memorial Sloan Kettering Cancer, New York, USA. PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. KEYWORDS: Pathologic complete response; HER2 assessment; Neoadjuvant systemic therapy; HER2-positive breast cancer; Human epidermal growth factor receptor 2 DOI: 10.1007/s10549-019-05295-9
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