- 期刊
案例報告：原發性EGFR T790M和L858R突變之肺腺癌患者使用Afatinib和抗雌激素療法
Treatment With Afatinib and Anti-Estrogen Therapy in Patient With de Novo EGFR T790M and L858R Mutations Lung Adenocarcinoma: A Case Report
摘要
過去關於T790M突變研究，主要圍繞在tyrosine kinase inhibitors（TKIs）治療後產生抗藥性；原發性T790M突變伴隨其他敏感性突變的研究有限，且未有明確顯著的療效藥物。本案例為1名有高血壓病史的76歲亞洲女性，2008年先診斷為乳癌（estrogen receptor positive [ER+], progesterone receptor positive [PR+], and human epidermal growth factor receptor (EGFR) 2 negative [Her 2-]）。左側乳房經手術切除併腋窩淋巴結清除術，且完成化療及放射治療，再以anastrozole作為停經後的乳癌輔助療法。2014年被診斷為原發性肺腺癌第4期，EGFR基因檢測為雙突變基因：原發性exon 20 T790M和exon 21 L858R，使用afatinib 40 mg為第一線治療，病情以response evaluation criteria in solid tumours（RECIST）評估標準為持續穩定，至今使用afatinib超過52個月。病人對於afatinib的治療反應與過去研究相異，探討病人相關用藥與其他可能因子。推測部分原因可能和原發性T790M突變頻率有關，另一因素根據過去文獻提出乳癌病人使用抗雌激素療法，能降低第二個原發性肺癌死亡率的風險。本篇將同時探討抗雌激素療法（anti-estrogen therapy）與EGFR-TKIs協同治療的臨床實證。
並列摘要
In the past, the T790M mutation study mainly focused on the acquired resistance after tyrosine kinase inhibitors (TKIs) treatment; the study of de novo T790M mutation with other sensitive mutations was limited, there was no significant therapeutic agent. Our patient was a 76-year-old asian female with hypertension. In 2008, she was first diagnosed with breast cancer (estrogen receptor positive [ER+], progesterone receptor positive [PR+], and human epidermal growth factor receptor (EGFR) 2 negative [Her 2-]). She underwent left mastectomy combined with axillary lymph node dissection and completed chemotherapy and radiotherapy. Following, anastrozole was administered as adjuvant chemotherapy for postmenopausal breast cancer. In 2014, she was diagnosed with stage 4 primary lung adenocarcinoma and EGFR gene testing found dual mutations: exon 20 (de novo T790M) and 21 (L858R). Afatinib 40 mg was used as first-line therapy and the condition was continuously stabilized as per response evaluation criteria in solid tumours (RECIST) evaluation criteria, afatinib has been used for more than 52 months. The patient's treatment responses to afatinib differed from those reported in previous studies and we examined drugs used by the patient and other possible factors. It is suggested that part of the reason may be related to the frequency of de novo T790M mutation, another factor that previous studies have examined patients with breast cancer who were administered anti-estrogen therapy and found that it can decrease the risk of patients dying from a second primary lung cancer. This article will explore the clinical evidence of anti-estrogen therapy and EGFR-TKIs synergistic treatment.