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）：目前有几种化疗方案被认为是乳腺癌可接受的标准辅助治疗，以提高治愈率。其中包括CMF、AC、FAC、FEC、TAC、紫杉醇/AC、紫杉醇/FAC、多西他赛/AC。然而，并非所有这些方案都同样可能使特定个体受益。乳腺癌的临床病理学特征或单基因标记物尚不能可靠地预测谁作为个体从一种特定方案中获益。对于新诊断的I-III期乳腺癌，术前给予所有化疗（新辅助治疗）与术后给予药物一样安全有效。少数患者（10-30%）经历病理完全缓解（pCR），即从乳腺和淋巴结中根除所有存活的浸润性癌细胞。这种极端良好的反应与延长生存期密切相关，被认为是最可靠的早期治愈替代品。此外，新辅助化疗提供了一个机会，研究分子预测反应。我们的假设是，乳腺癌的基线、治疗前基因表达谱包含了关于化疗敏感性或耐药性的信息。我们还假设这些信息可以通过转录分析提取，并通过数学变换形式化为完整病理反应的预测因子。 在一项小型（n=45）前瞻性单臂临床试验中，我们确定了一组与反应相关的基因，并构建了新辅助每周紫杉醇随后FAC化疗的pCR分子预测因子。当前提案的目标是验证这种基于基因表达谱的pCR分子预测因子，并为其他2种常用方案（FAC和多西他赛/卡培他滨，随后FEC）开发类似的预测因子。该项目将利用三个机构的临床资源，U.T.M.D.安德森癌症中心，林登B。约翰逊总医院（休斯顿，得克萨斯州）和美国肿瘤，在该国最大的私人执业集团。 我们希望我们的工作将导致基于微阵列的临床测试的发展，为新诊断的乳腺癌患者提供个性化的化疗选择。