UAB 0467 PHASE II TRIAL OF LETROZOLE WITH BEVACIZUMAB IN WOMEN WITH BREAST CANCE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本研究的主要目的是确定来曲唑和贝伐珠单抗联合新辅助治疗在病理学证实的乳腺浸润性导管癌或浸润性小叶癌（肿瘤为雌激素受体阳性）患者中的病理学应答。次要目的包括评价1）临床反应; 2）耐受性和毒性; 3）用于预后价值的特异性生物标志物和作为对治疗的反应/抗性的标志物;和4）18 F-FDG PET扫描“代谢反应”与客观反应率和反应持续时间参数之间的相关性。据推测，雌激素治疗的疗效与ER+和/或PR+乳腺癌的女性可以通过贝伐单抗，重组人源化抗体血管内皮细胞生长因子的手段增强。 患者必须年满60岁，通过乳房X线检查和/或超声检查发现可测量的疾病，ECOG体能状态评分为0、1或2，方可入组。在开始治疗之前，患者将进行PET扫描。仅当PET扫描提示有转移时，才进行胸部、腹部和骨盆的标准CT评价以及骨扫描。将获得血细胞计数、UA、24小时尿液、尿蛋白/肌酐比值和血生化。还将获得乳房X线照片和超声检查，并将其用作基线评价。 在诊断时将进行标准活检，以提供足够的组织用于诊断以及允许生物标志物和雌激素/孕酮表达的测定。患者将每日口服来曲唑，每3周一次接受贝伐珠单抗IV输注。在第6周，患者将进行首次缓解评价，包括乳房X线检查/乳房超声检查和PET扫描。将进行活检以评价生物标志物。客观缓解或病情稳定的患者将继续接受相同的方案，每6周一次重新分期，共18周，或直至观察到进展。在最后一次评估后，将由外科医生决定是否对原发性肿瘤进行再次手术。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The primary objective of this study will be to determine the pathological response to neoadjuvant therapy using a combination of Letrozole and Bevacizumab in patients with pathologically confirmed invasive ductal carcinoma or invasive lobular carcinoma of the breast whose tumors are estrogen receptor positive. Secondary objectives include evaluating 1) clinical response; 2) tolerability and toxicity; 3) specific biomarkers for prognostic value and as markers for response/resistance to the therapy; and 4) the correlation between 18 F-FDG PET scan "metabolic response" with objective response rate and duration of response parameters. It is hypothesized that the efficacy of hormonal therapy in women with ER+ and/or PR+ breast cancer can be augmented by means of Bevacizumab, a recombinant humanized antibody to vascular endothelial cell growth factor. To be enrolled, patients must be 60 years or older, have measurable disease by mammogram and/or ultrasound, and ECOG performance status 0, 1 or 2. Prior to starting therapy, patients will have a PET scan. Standard CT evaluations of the chest, abdomen and pelvis, and bone scan will be done only if there is suggestion of metastasis in the PET scan. Blood counts, UA, 24-hour urine, urinary protein/creatinine ratio, and blood chemistries will be obtained. Mammogram and ultrasound of the breast will also be obtained and used as baseline evaluations. Standard biopsies will be performed at the time of diagnosis in order to provide adequate tissue for diagnosis as well as to allow assays of biomarkers and estrogen/progesterone expression. Patients will take oral Letrozole daily and receive Bevacizumab IV infusions every 3 weeks. At 6 weeks patients will have the first evaluation of response including mammogram/ultrasound of the breast and a PET scan. A biopsy will be performed for evaluation of biomarkers. Patients with objective response or stable disease will continue the same regimen with restaging every 6 weeks for a total of 18 weeks, or until progression is observed. Definitive surgery of the primary tumor will be performed at the discretion of the surgeon after the last evaluation.