- 學位論文
分子檢測方法應用於乳癌的診斷和治療
The molecular assays used in breast cancer diagnosis and treatment
摘要
乳癌好發於全球，其發生率已超過肺癌成為第一位。基於生活型態、飲食文化差異，遲婚和晚生育，開發中國家其乳癌發生率與已開發國家的差異縮少。乳癌的診斷和治療發展是科學界頭號重要項目，病理學上使用TMN分期，Nottingham grading system等系統使報告內容更精準描述病程；隨後發展出乳癌亞型，由Perou et al. (2000)首次利用cDNA微陣列分析 (cDNA microarrays)對基因組進行分析，結合乳癌的生物標記 (IHC4)，被公認的四種亞型為Luminal A、Luminal B、Her2-enriched 和Triple-negative breast cancer (TNBC)。結合乳癌治療和分型系統可發展出不同的治療藥物，包括荷爾蒙治療和標靶治療：荷爾蒙治療是為阻斷雌激素與帶有雌激素受體的腫瘤細胞之間的相互作用；標靶治療則針對HER2基因過度表達、PIK3CA基因突變和遺傳性因子BRCA 基因突變作為目標。對於藥物的抗藥性或是傳導路徑的突變已逐漸被做為研究的焦點，因此藉由多基因表達平台能更精準評估復發的風險和輔助治療的措施，四個多基因平台: Oncotype Dx、MammaPrint、EndoPredict和Prosigna (PAM50) 使乳癌在診斷和治療上更精準且更全面性，本文也會描述其使用的檢驗方法。
並列摘要
Breast cancer has become the commonest cancer worldwide, surpassing lung cancer in recent years. Different lifestyle habits, diet, culture, delayed marriage and childbirth, have contributed the increasing incidence of breast cancer, even in developing countries. The diagnosis and treatment of breast cancer have become a priority in the scientific field. Pathologists use TNM staging and the Nottingham grading system, which accurately describe the disease progression. Subsequently, breast cancer subtyping has been established. Perou et al. (2000) first used cDNA microarray analysis to study the genome, after multiple studies and integration with breast cancer biomarkers (IHC4). Four subtypes are now recognized: Luminal A, Luminal B, Her2-enriched, and Triple-negative breast cancer (TNBC). The combination of breast cancer treatment and subtyping systems has led to the development of different drug treatments, including hormone therapy and targeted therapy. Hormone therapy aims to block the interaction between estrogen with estrogen receptors in the tumor cell. Targeted therapy targets HER2 gene overexpression, PIK3CA and BRCA gene mutations. As drug resistance or pathway mutations gradually become a focus of research, the use of multi-gene expression can more accurately assess the risk of recurrence and assist in treatment measures. Four multi-gene platforms, Oncotype Dx, MammaPrint, EndoPredict, and Prosigna (PAM50), have made breast cancer diagnosis and treatment more accurate and comprehensive. This article will also describe the testing methods used.