Preoperative chemotherapy for breast cancer

乳腺癌术前化疗

• 批准号: 6863195
• 负责人: LAJOS PUSZTAI
• 金额: $ 19.48万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-14 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6863195
• 关键词: antineoplastic antibiotics; antineoplastics; biotechnology; breast neoplasms; clinical research; clinical trial phase III; combination chemotherapy; cyclophosphamide; doxorubicin; drug screening /evaluation; female; fine needle aspiration; fluorouracil; gene expression profiling; genetic markers; human subject; human therapy evaluation; microarray technology; neoplasm /cancer chemotherapy; neoplasm /cancer classification /staging; neoplasm /cancer remission /regression; paclitaxel; patient oriented research; pharmacogenetics; preoperative state; women' s health

DESCRIPTION (provided by applicant): There are several chemotherapy regimens that are currently considered acceptable standard adjuvant treatment for breast cancer to improve cure rates. These include, CMF, AC, FAC, FEC, TAC, paclitaxel/AC, paclitaxel/FAC, docetaxel/AC. However, not all of these regimens are equally likely to benefit a particular individual. Clinicopathologic features of breast cancer or single gene markers have not been able to predict reliably who, as an individual, benefits from one particular regimen over another. Administration of all chemotherapy before surgery (neoadjuvant therapy) for newly diagnosed stage I-III breast cancer is safe and as effective as administration of the drugs postoperatively. A minority of patients (10-30%) experiences pathologic complete response (pCR), which is eradication of all viable invasive cancer cells from the breast and lymph nodes. This form of extreme good response correlates strongly with prolonged survival and is considered to be the most reliable early surrogate for cure. Furthermore, neoadjuvant chemotherapy provides an opportunity to study molecular predictors of response. Our hypothesis is that baseline, pretreatment gene expression profile of breast cancer holds information about sensitivity or resistance to chemotherapy. We also assume that this information can be extracted by transcriptional profiling and formalized into a predictor of complete pathologic response through mathematical transformation. In a small (n=45), prospective, single arm clinical trial we have identified a set of genes associated with response and constructed a molecular predictor of pCR to neoadjuvant weekly paclitaxel followed by FAC chemotherapy. The goal of the current proposal is to validate this gene-expression profile-based molecular predictor of pCR and to develop similar predictors for 2 other commonly used regimens, FAC and docetaxel/capecitabine followed by FEC. This program will draw on clinical resources at three institutions, U.T.M.D. Anderson Cancer Center, the Lyndon B. Johnson General Hospital (Houston, TX), and US Oncology, the largest private practice group in the country. We expect that our work will lead to the development of microarray-based clinical tests to personalize chemotherapy selection for an individual with newly diagnosed breast cancer.

描述（由申请人提供）：有几种化学疗法方案目前被认为是可接受的乳腺癌标准辅助治疗，以提高治愈率。其中包括CMF，AC，FAC，FEC，FEC，TAC，Paclitaxel/ac，Paclitaxel/fac，Docetaxel/ac。但是，并非所有这些方案都同样有可能使特定个体受益。乳腺癌或单个基因标记物的临床病理特征无法可靠地预测谁是个人，从一种特定方案中受益于另一种方案。对新诊断的I-III期乳腺癌进行手术前的所有化学疗法（新辅助治疗）的给药与术后药物的给药一样有效。少数患者（10-30％）经历了病理完全反应（PCR），这是消除乳腺癌和淋巴结的所有可行侵入性癌细胞。这种极端良好反应形式与长期生存密切相关，被认为是治愈早期最可靠的替代物。此外，新辅助化疗提供了研究反应分子预测指标的机会。我们的假设是乳腺癌的基线，预处理基因的表达谱符合有关化学疗法的敏感性或抗性的信息。我们还假设可以通过转录分析提取此信息，并通过数学转化形式地将其形式化为完全病理反应的预测指标。 在一个小的（n = 45），前瞻性的单臂临床试验中，我们确定了一组与反应相关的基因，并构建了PCR对新辅助对新辅助的每周紫杉醇的分子预测指标，然后进行了FAC化学疗法。当前建议的目的是验证基于PCR的基因表达曲线的分子预测指标，并为其他2种常用的方案，FAC和多西他赛/卡皮替滨开发相似的预测因子，然后是FEC。该计划将利用U.T.M.D.三个机构的临床资源。安德森癌症中心，林登·约翰逊综合医院（德克萨斯州休斯顿）和美国最大的私人执业小组美国肿瘤学。 我们预计我们的工作将导致基于微阵列的临床测试的发展，以个性化新诊断的乳腺癌的人的化学疗法选择。