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可接受的乳腺癌标准辅助治疗，可提高治愈率。这些包括CMF、AC、FAC、FEC、TAC、紫杉醇/AC、紫杉醇/FAC、多西紫杉醇/AC。然而，并非所有这些方案都同样可能使特定个体受益。乳腺癌的临床病理特征或单基因标记尚无法可靠地预测作为个体的谁从一种特定的治疗方案中获益而不是另一种。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且有效。少数患者 (10-30%) 经历病理完全缓解 (pCR)，即根除乳腺和淋巴结中所有存活的侵袭性癌细胞。这种极其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方法。此外，新辅助化疗提供了研究反应分子预测因子的机会。我们的假设是，乳腺癌的基线、治疗前基因表达谱包含有关化疗敏感性或耐药性的信息。我们还假设该信息可以通过转录分析来提取，并通过数学转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，我们鉴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 和多西紫杉醇/卡培他滨，然后是 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：U.T.M.D.安德森癌症中心、林登·约翰逊综合医院（德克萨斯州休斯顿）以及美国最大的私人诊所集团美国肿瘤科。 我们期望我们的工作将促进基于微阵列的临床测试的发展，为新诊断乳腺癌的个体提供个性化的化疗选择。