Preoperative chemotherapy for breast cancer

描述(由申请人提供)：目前有几种化疗方案被认为是可接受的乳腺癌标准辅助治疗，以提高治愈率。这些药物包括CMF、AC、FAC、FEC、TAC、紫杉醇/AC、紫杉醇/FAC、多西紫杉醇/AC。然而，并不是所有这些养生法都同样有可能使特定的个人受益。乳腺癌的临床病理特征或单基因标记物还不能可靠地预测作为一个个体，谁从一个特定的方案中受益。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和有效。少数患者(10%-30%)经历了病理完全应答(PCR)，即从乳腺和淋巴结中根除所有存活的侵袭性癌细胞。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替代治疗方法。此外，新辅助化疗为研究反应的分子预测因素提供了机会。我们的假设是，乳腺癌的基线、预处理基因表达谱包含有关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图谱来提取，并通过数学变换正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，我们确定了一组与应答相关的基因，并构建了每周一次新辅助紫杉醇和FAC化疗的PCR分子预测因子。目前提案的目标是验证这种基于基因表达谱的聚合酶链式反应的分子预测因子，并为其他两种常用方案FAC和多西他赛/卡培他滨随后的FEC开发类似的预测因子。该计划将利用三个机构的临床资源，分别是德克萨斯州德州大学安德森癌症中心、德克萨斯州休斯敦的林登·B·约翰逊综合医院和美国最大的私人执业团体美国肿瘤学。 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，使新诊断的乳腺癌患者的化疗选择个人化。

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.