2011-05-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/644908摘要：研究目標:經由最近所發展之基因體微陣圖譜訊息方法，乳癌可分成luminal A、luminal B、Her-2 和basal-like 四種分子形態。這些研究成果也證實luminal A 乳癌，相對於其他次主群乳癌，有較好之預後，但對術前化療反應反而較差。雖然多數研究其預測乳癌預後之方法，大多採用合併多數基因表現之方法，雖可預測早期乳癌之存活率，但這些方法卻因非常昂貴，並不能推廣到多數患者。同時，這些方法也未在台灣乳癌患者去驗證實用性。最重要的是，這些微陣基因方法，通常使用腫瘤組織去決定多基因表現，但宿主因素並無考慮在此研究方法中。我們最近的研究顯示，與tamoxifen 代謝有關之CYP19, ESR1, 和CPY2D6 單核核酸基因多型性，可能與乳癌患者對抗雌性激素治療反應和預後不同有高相關性。研究假說:我們認為同形態luminal A，但卻有不同預後及臨床表現之台灣乳癌患者，必定存著我們所未知基因體改變，基因體表現圖譜和基因體多形性之訊息。研究目標及研究方法:在本研究計畫中，我們將從組織庫中選擇，已追蹤多年且具有完整臨床特徵，復發形態和預後之luminal A 形態乳癌患者。並根據腫瘤組織特徵及患者預後，並參考術後追加網路預測系統(www. adjuvantonline.com)。將這些患者分成四組，即低復發率但預後不好、低復發率且預後良好、高復發率但預後良好、和高復發率且預後不好等四組，每組50 位患者，共200 位患者。我們主要目標如下：(1) 釐清這四組不同預後之luminal A 形態乳癌患者的基因體改變和基因體圖譜。(2) 探索並發現那些基因體多形性可預測luminal A 形態乳癌患者對藥物治療之效果及預後。(3) 探討和廓劃出這四組之間可能存在之基因體拷貝和基因體喪失現象。(4) 藉由整合基因體改變，基因體表現圖譜和基因體多形性微陣分析之多基因平台方法，將幫助我們找出特別基因，並釐清其功能性和生物重要性。預期研究結果:我們相信此研究計畫將幫助我們完整分析及廓劃luminal A形態乳癌患者之基因體改變，基因體表現圖譜和基因體多形性。並藉由此研究計畫所衍生之生物標記和治療標靶藥物，進一步幫助我們預測luminal A形態乳癌患者的預後並改善治療效果。<br> Abstract: Background:Recent development of microarray expression profile characterizes breastcancers into different subtypes, including luminal A, luminal B, Her-2 and basal-likesubtypes. Many studies suggested luminal A breast cancers, compared to othersubtypes, carry a better prognosis, but do not respond well to neoadjuvantchemotherapy. Although there are several assays using multiple gene expression topredict the survival of early breast cancers, these tests are still too expensive for manypatients to afford and not validated in Taiwanese patients. And importantly, these testsonly use tumor tissue for determination of multigene expression, i.e., host factor wasnot incorporated in these assays. Our recent study have demonstrated that germlineSNP of metabolizing genes, such as CYP19, ESR1, and CPY2D6 of tamoxifen, showthat patients with different genotype may carry different response to this anti-estrogentreatment and hence different prognosis.Hypothesis:We hypothesize that, in luminal A-type Taiwanese breast cancer patients, there ispresence of the uncovered genetic alterations, genes expression profiles, and genomicpolymorphism responsible for differential clinical behaviors of this group of patients.Specific aims and methods:In this proposal, we will choose breast cancer tissues with long duration offollow up from our tissue bank. Only luminal A subtype breast cancers will beincluded. Tumors will be separated into four groups: low recurrence risk but worseoutcome, low recurrence risk and good outcome, high recurrence risk but goodoutcome, high recurrence risk and poor outcome. Fifty cases will be collected for eachgroup, altogether 200 cases. Our specific aims are: (1) To identify genetic changes andexpression profiles associated with different outcome of four groups. (2) To determinethe role of germline polymorphisms in prognostication and predicting response totherapy (3) To explore and compare overall copy number aberration as well as loss ofheterozygosity of the entire human genome between four groups. (4) To integrate thedataset from three microarray platforms, and allow us identify specific subsets genesand functionally analyze and validate their biologic significances.Anticipated results:We believe this project will help us comprehensively discover germline geneticalterations, genomic polymorphism, and genes expression profiles for luminal Abreast cancer, and help us predict the prognosis and treatment response, and thusimprove the treatment outcome of this group of tumors.uminal A 乳癌基因體改變基因體表現圖譜和基因體多形性luminal A breast cancergenetic alterationsgenomic polymorphismand genes expression profiles