Oncology Unit, ASST Bergamo Ovest, Piazzale Ospedale 1, 24047, Treviglio, BG, Italy.
Oncology Unit, Oncology Department, ASST Ospedale di Cremona, Viale Concordia 1, 26100, Cremona, Italy.
Breast Cancer Res Treat. 2017 Nov;166(2):339-349. doi: 10.1007/s10549-017-4419-x. Epub 2017 Jul 31.
HER2 gene is a member of the epidermal growth factor receptor (EGFR) family. Across different malignancies, aberrations of HER2 gene commonly correspond to gain-of-function alterations leading to increased receptor signaling.
We have reviewed the literature currently available on HER2 mutations in human breast cancer (BC) evaluating type and frequency of such mutations. The primary objective was to determine the frequency and the number of patients with HER2-mut in the series analyzed. The secondary objectives were to assess characteristics of mutated cases (ER and HER2 status and stage of disease, type of mutations, and finally the clinical outcome if reported).
We retrieved 31 published papers, and the pooled rate of HER2 mutations across 12,905 BC patients was calculated. Overall, the frequency of HER2 mutations was 2.7% with most involving the intracellular domain. About 4% of patients were finally mutated. The predictive role was not described. Only 30% of these patients were simultaneously HER2 positive and 63% were ER positive.
We have found that the prevalence of HER2 mutations is about 3%. These genic alterations are independently associated with HER2 amplification status, occurring in both ER-positive/HER2-negative diseases or HER2-enriched cancers. Ongoing trials are investigating small molecules tyrosine kinase inhibitors in patients harboring these mutations.
HER2 基因是表皮生长因子受体（EGFR）家族的成员。在不同的恶性肿瘤中，HER2 基因的异常通常对应于功能获得性改变，导致受体信号的增加。
我们回顾了目前关于人类乳腺癌（BC）中 HER2 突变的文献，评估了这种突变的类型和频率。主要目的是确定分析系列中 HER2-mut 的频率和患者数量。次要目的是评估突变病例的特征（ER 和 HER2 状态和疾病分期、突变类型，以及如果有报道则最终的临床结果）。
我们检索了 31 篇已发表的论文，并计算了 12905 例 BC 患者中 HER2 突变的总发生率。总体而言，HER2 突变的频率为 2.7%，大多数涉及细胞内结构域。最终约有 4%的患者发生突变。预测作用未被描述。只有 30%的患者同时 HER2 阳性，63%的患者 ER 阳性。
我们发现 HER2 突变的流行率约为 3%。这些基因改变与 HER2 扩增状态独立相关，发生在 ER 阳性/HER2 阴性疾病或 HER2 富集的癌症中。正在进行的试验正在研究携带这些突变的患者中小分子酪氨酸激酶抑制剂。
