Substantial improvements in the early detection and treatment of breast cancer have led to improvements in survival, but breast cancer remains a significant cause of morbidity and mortality in women. In 2012, the mammalian target of rapamycin (mTOR) inhibitor everolimus was approved by the U.S. Food and Drug Administration for the treatment of advanced breast cancer in patients resistant to endocrine therapy. Although everolimus is generally well tolerated, mTOR inhibitor-associated pneumonitis is one of the most common adverse drug events leading to treatment discontinuation. To date, the underlying pathophysiology of this toxicity is unclear, and this uncertainty may hinder the optimization of management strategies. However, experiences from breast cancer and renal cell carcinoma clinical trials indicate that mTOR inhibitor-associated pneumonitis can be effectively managed by early detection, accurate diagnosis, and prompt intervention that generally involves everolimus dose reductions, interruptions, or discontinuation. Management can be achieved by a multidisciplinary approach that involves the collaborative efforts of nurses, oncologists, radiologists, infectious disease specialists, pulmonologists, clinical pharmacists, and pathologists. Comprehensive education must be provided to all health care professionals involved in managing patients receiving everolimus therapy. Although general recommendations on the management of mTOR inhibitor-associated pneumonitis have been published, there is a lack of consensus on the optimal management of this potentially serious complication. This article provides an overview of mTOR inhibitor-associated pneumonitis, with a focus on the detection, accurate diagnosis, and optimal management of this class-related complication of mTOR inhibitor therapy.
Implications for practice: This article summarizes the pathogenesis, clinical presentation, incidence, detection, and optimal management of everolimus-related noninfectious pneumonitis in breast cancer. In particular, this article provides a detailed overview of the important aspects of the detection, accurate diagnosis, and appropriate management of mammalian target of rapamycin inhibitor-associated pneumonitis. In addition, this article emphasizes that effective management of this adverse drug event in patients with breast cancer will require a multidisciplinary approach and collaboration among various health care professionals.
摘要
在乳腺癌早期检测和治疗中取得的重大改善使生存率有所提高, 但是乳腺癌仍然是导致女性病损和死亡的一个重要原因。2012年, 美国食品药品监督管理局批准将哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂依维莫司用于在内分泌疗法耐药性患者中治疗晚期乳腺癌。尽管依维莫司的耐受性普遍良好, 但是mTOR抑制剂相关性非感染性肺炎是导致治疗停止的最常见不良药物事件之一。迄今为止, 此毒性的基础病理生理学尚不明确, 而此不确定性可能会阻碍管理策略的优化。然而, 从乳腺癌和肾细胞癌临床试验中获得的经验表明, 通过早期检测、准确诊断和及时干预（通常包括减少依维莫司剂量以及中断或停止给药）可有效管理mTOR抑制剂相关性非感染性肺炎。可通过多学科方法管理疾病, 该方法需要护士、肿瘤医师、放射科医师、传染病专科医生、肺病医生、临床药剂师和病理学家的协同努力。必须向接受依维莫司的患者管理中涉及的所有医疗保健专业人士提供全面教育。尽管已发布了对mTOR抑制剂相关性非感染性肺炎管理的一般建议, 但是对于此可能发生的严重并发症的最佳管理, 人们尚未达成共识。本文概述了mTOR抑制剂相关性非感染性肺炎, 重点是针对mTOR抑制剂治疗中此类别相关性并发症的检测、准确诊断和最佳管理。
对临床实践的提示：本文总结了乳腺癌患者中依维莫司相关性非感染性肺炎的发病机理、临床表现、发病率、检测和最佳管理。本文特别概述了哺乳动物雷帕霉素靶蛋白抑制剂相关性非感染性肺炎的检测、准确诊断和恰当管理的重要方面。此外, 本文还着重指明, 在乳腺癌患者中有效管理此不良药物事件需要多学科方法和各种医疗保健专业人士的合作。
Keywords: Adverse drug event; Breast cancer; Everolimus; Pneumonitis.
© AlphaMed Press 2018.