BACKGROUND HER2-positive (HER2+) breast cancer (BC) comprises all the four PAM50 molecular subtypes. Among these, the HER2-Enriched (HER2-E) appear to be associated with higher pathological complete response (pCR) rates following anti-HER2-based regimens. Here, we present a meta-analysis to validate the association of the HER2-E subtype with pCR following anti-HER2-based neoadjuvant treatments with or without chemotherapy (CT). METHODS A systematic literature search was performed in February 2019. The primary objective was to compare the association between HER2-E subtype (versus others) and pCR. Selected secondary objectives were to compare the association between 1) HER2-E subtype and pCR in CT-free studies, 2) HER2-E subtype within hormone receptor (HR)-negative and HR+ disease and 3) HR-negative disease (versus HR+) and pCR in all patients and within HER2-E subtype. A random-effect model was applied. The Higgins' I2 was used to quantify heterogeneity. RESULTS Sixteen studies were included, 5 of which tested CT-free regimens. HER2-E subtype was significantly associated with pCR in all patients (odds ratio [OR] = 3.50, p < 0.001, I2 = 33%), in HR+ (OR = 3.61, p < 0.001, I2 = 1%) and HR-negative tumors (OR = 2.28, p = 0.01, I2 = 47%). In CT-free studies, HER2-E subtype was associated with pCR in all patients (OR = 5.52, p < 0.001, I2 = 0%) and in HR + disease (OR = 4.08, p = 0.001, I2 = 0%). HR-negative status was significantly associated with pCR compared to HR + status in all patients (OR = 2.41, p < 0.001, I2 = 30%) and within the HER2-E subtype (OR = 1.76, p < 0.001, I2 = 0%). CONCLUSIONS The HER2-E biomarker identifies patients with a higher likelihood of achieving a pCR following neoadjuvant anti-HER2-based therapy beyond HR status and CT use. Future trial designs to escalate or de-escalate systemic therapy in HER2+ disease should consider this genomic biomarker.

中文翻译：

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HER2阳性乳腺癌中富含HER2的亚型和病理完全缓解：系统评价和荟萃分析。

背景技术HER2阳性（HER2 +）乳腺癌（BC）包含所有四种PAM50分子亚型。其中，富含HER2的（HER2-E）似乎与基于抗HER2的治疗方案后较高的病理完全缓解（pCR）率相关。在这里，我们提出了一项荟萃分析，以验证在使用或不使用化学疗法（CT）的抗HER2新辅助治疗后，HER2-E亚型与pCR的关联。方法于2019年2月进行了系统的文献检索。主要目的是比较HER2-E亚型（相对于其他）与pCR之间的关联。选择的次要目标是在无CT研究中比较1）HER2-E亚型与pCR之间的关联，2）所有患者以及HER2-E亚型内的激素受体（HR）阴性和HR +疾病内的HER2-E亚型，以及3）HR阴性疾病（相对于HR +）和pCR。应用随机效应模型。希金斯的I2用于量化异质性。结果包括16项研究，其中5项测试了无CT方案。在所有患者中，HER2-E亚型均与pCR显着相关（比值[OR] = 3.50，p <0.001，I2 = 33％），HR +（OR = 3.61，p <0.001，I2 = 1％）和HR-阴性肿瘤（OR = 2.28，p = 0.01，I2 = 47％）。在无CT研究中，所有患者（OR = 5.52，p <0.001，I2 = 0％）和HR +疾病（OR = 4.08，p = 0.001，I2 = 0％）HER2-E亚型均与pCR相关。 。与所有患者的HR +状态相比，HR阴性状态与pCR显着相关（OR = 2.41，p <0.001，I2 = 30％），并且在HER2-E亚型中（OR = 1.76，p <0.001，I2 = 0％）。结论HER2-E生物标志物鉴定出在新辅助抗HER2辅助治疗后，除心率状态和CT使用外，更有可能实现pCR的患者。将来将HER2 +疾病的全身治疗升级或降低的试验设计应考虑该基因组生物标志物。