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乳腺癌可接受的标准辅助治疗，以提高治愈率。包括CMF、AC、FAC、FEC、TAC、紫杉醇/AC、紫杉醇/FAC、多西紫杉醇/AC。然而，并不是所有的这些方案都对特定的个体有同样的好处。乳腺癌的临床病理特征或单基因标记还不能可靠地预测，作为个体，谁从一种特定的治疗方案中比另一种更受益。对于新诊断的I-III期乳腺癌，术前所有化疗（新辅助治疗）与术后给药一样安全有效。少数患者（10-30%）经历病理完全缓解（pCR），即从乳房和淋巴结中根除所有可存活的侵袭性癌细胞。这种形式的极好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，新辅助化疗为研究反应的分子预测因子提供了机会。我们的假设是，乳腺癌的基线、预处理基因表达谱包含了对化疗的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谱提取，并通过数学转换形式化为完整病理反应的预测因子。

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.