DataSheet_2_Case Report: Significant Efficacy of Pyrotinib in the Treatment of Extensive Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Cutaneous Metastases: A Report of Five Cases.docx

BackgroundBreast cancer (BC) is the most common tumor to develop cutaneous metastases. Most BCs with cutaneous metastasis are human epidermal growth factor receptor 2 (HER2)-positive subtypes. Although the molecular mechanisms of breast cancer metastasis to different sites and the corresponding treatment methods are areas of in-depth research, there are few studies on cutaneous metastasis.
Case PresentationFive HER2-positive BC patients with extensive cutaneous metastases were treated with a regimen containing pyrotinib, a novel small-molecule tyrosine kinase inhibitor that irreversibly blocks epidermal growth factor receptor (EGFR), HER2, and human epidermal growth factor receptor 4 (HER4), then their cutaneous metastases quickly resolved at an astonishing speed and their condition was well controlled during the follow-up period.
ConclusionsThis case series reports the significant therapeutic effect of pyrotinib on cutaneous metastases of HER2-positive BC for the first time. Based on this, we recommend that pyrotinib can be used as a supplement to trastuzumab for HER2-positive BC patients with cutaneous metastases. In addition, we should consider that the pan-inhibitory effect of pyrotinib on EGFR, HER2, and HER4 may provide a dual therapeutic effect against HER2 and mucin 1.

背景 乳腺癌（Breast Cancer, BC）是最常发生皮肤转移的实体瘤。伴皮肤转移的乳腺癌中，绝大多数为人表皮生长因子受体2（Human Epidermal Growth Factor Receptor 2, HER2）阳性亚型。尽管针对乳腺癌向不同部位转移的分子机制及其对应治疗方案的研究已较为深入，但针对皮肤转移的相关研究仍较为匮乏。
病例报告 本研究纳入5例伴广泛皮肤转移的HER2阳性乳腺癌患者，予以含吡咯替尼（pyrotinib）的治疗方案。吡咯替尼是一种新型小分子酪氨酸激酶抑制剂（small-molecule tyrosine kinase inhibitor），可不可逆性阻断表皮生长因子受体（epidermal growth factor receptor, EGFR）、HER2及人表皮生长因子受体4（Human Epidermal Growth Factor Receptor 4, HER4）的活性。治疗后，患者的皮肤转移灶以惊人的速度快速消退，随访期间病情均得到良好控制。
结论 本病例系列首次报道了吡咯替尼对HER2阳性乳腺癌皮肤转移灶的显著治疗效果。基于此，我们建议对于伴皮肤转移的HER2阳性乳腺癌患者，可将吡咯替尼作为曲妥珠单抗（trastuzumab）的补充治疗方案。此外，吡咯替尼对EGFR、HER2及HER4的泛抑制作用，或可同时针对HER2与粘蛋白1（mucin 1）发挥双重治疗效应。