Department of Medical Oncology, National Taiwan University Hospital, Taipei, Taiwan.
Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Breast. 2022 Feb;61:35-42. doi: 10.1016/j.breast.2021.11.016. Epub 2021 Nov 29.
Targeted therapies against human epidermal growth factor receptor 2 (HER2) are associated with increased interstitial lung disease (ILD). Trastuzumab, lapatinib, pertuzumab, and trastuzumab emtansine have markedly extended HER2 breast cancer survival but current knowledge on how these HER2-targeted agents induce interstitial lung disease is still poorly defined due to limited cases in the literature. Physicians mostly managed this complication by dose interruption, dose de-escalation, or discontinuation with success. In 2019, the FDA had granted accelerated approval on trastuzumab deruxtecan (T-Dxd) in HER2 breast cancer in the late line setting. Severe ILD incidence rate was over ten percent and led to fatal outcomes in 2.2% of patients in the T-Dxd trial. Searching for biomarkers to detect ILD incidence before it becomes clinically fulminant or for treatment response monitoring is of high clinical value. A Case of life-threatening trastuzumab-induced ILD was encountered in our facility. The ILD was confirmed to be antineutrophil cytoplasmic antibody (ANCA) pulmonary capillaritis. The biomarker of neutrophil extracellular traps (NETs), serum MPO-DNA complex, showed a good correlation with the clinical severity. Soon after B cell depleting agent rituximab usage, the serum MPO-DNA outperformed ANCA autoantibody and maintained its correlation with clinical severity. In addition to the trastuzumab-induced ILD case, a prospective cohort in our facility also confirmed the usefulness of MPO-DNA in monitoring vasculitis activity. We postulated that upfront testing with biomarkers of vasculitis during HER2 targeted treatment with high ILD incidence may be beneficial in the future.
针对人类表皮生长因子受体 2（HER2）的靶向治疗与间质性肺病（ILD）的增加有关。曲妥珠单抗、拉帕替尼、帕妥珠单抗和曲妥珠单抗emtansine显著延长了 HER2 乳腺癌的生存时间，但由于文献中有限的病例，目前对这些 HER2 靶向药物如何引起间质性肺病的了解仍不明确。医生主要通过中断剂量、降低剂量或停药来成功治疗这种并发症。2019 年，FDA 批准在晚期 HER2 乳腺癌中加速批准曲妥珠单抗 deruxtecan（T-Dxd）。ILD 的严重发生率超过 10%，在 T-Dxd 试验中，2.2%的患者发生致命结局。寻找生物标志物来检测ILD 发病前的临床爆发或治疗反应监测具有很高的临床价值。我们的机构遇到了一例危及生命的曲妥珠单抗诱导的ILD。ILD 被确认为抗中性粒细胞胞质抗体（ANCA）肺毛细血管炎。中性粒细胞胞外陷阱（NETs）的生物标志物，血清 MPO-DNA 复合物，与临床严重程度有很好的相关性。在使用 B 细胞耗竭剂利妥昔单抗后，血清 MPO-DNA 优于 ANCA 自身抗体，并保持与临床严重程度的相关性。除了曲妥珠单抗诱导的 ILD 病例外，我们机构的一项前瞻性队列研究还证实了 MPO-DNA 在监测血管炎活动中的有用性。我们推测，在高ILD 发生率的 HER2 靶向治疗期间，使用血管炎的生物标志物进行预先检测在未来可能是有益的。
