IRS Proteins and Trastuzumab Resistance
研究概览
地位
条件
详细说明
Twenty percent of invasive breast cancers overexpress Her2 neu. These breast cancers are more aggressive with a higher relapse rate and shortened overall survival. Trastuzumab is a humanized monoclonal antibody FDA approved for the treatment of Her2 overexpressing breast cancer. Trastuzumab is an active single agent for treating metastatic breast cancer and when combined with chemotherapy improves time to progression and overall survival in women with metastatic her2 overexpressing breast cancer. In the adjuvant setting recent clinical trials have demonstrated improved relapse free survival in patients with high risk node negative and node positive breast cancer. In the neoadjuvant setting in patients with locally advanced breast cancer the response rates are very high with complete pathologic responses in 50-60 % of patients. Although trastuzumab is an essential agent for optimal treatment of Her2 positive breast cancer, not all patients respond and in the metastatic setting trastuzumab is not curative indicating that resistance develops. The mechanism of such resistance is unknown.
The fact that not all HER2-expressing breast cancer tumors respond to Herceptin treatment, and most tumors eventually develop resistance to this drug, underscores the need for additional research into how HER2 functions to promote aggressive behavior in tumors and why some tumors become resistant to Herceptin. Recent reports have implicated the IGF-1 signaling pathway in both the mechanism of HER2 action and in resistance to Herceptin. The IRS proteins are the major downstream effectors of the IGF-1 receptor and they play a critical role in determining the cellular response to IGF-1 stimulation. Therefore, the IRS proteins may also be signaling modifiers of the HER2 receptor and may contribute to Herceptin resistance that results from compensatory signaling through the IGF-1R.
研究类型
注册 (实际的)
联系人和位置
学习地点
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Massachusetts
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Worcester、Massachusetts、美国、01655
- University of Mass Medical School
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
取样方法
研究人群
描述
Inclusion Criteria:
- Women age 18-70 with breast cancer who have signed an IRB approved consent form.
- Biopsy proven breast cancer with her 2 overexpression by fluorescence in situ hybridization (FISH).
- Newly diagnosed patients with Stages 1,2 and 3 breast cancer who will be receiving neoadjuvant chemotherapy prior to breast surgery
- Normal Left ventricular ejection fraction, as measured by echocardiogram or MUGA scan
- Normal bone marrow, kidney and liver function
- No evidence of distant metastatic disease
Exclusion Criteria:
- Patients with significant cardiac disease including abnormal LVEF, symptomatic coronary artery disease, uncontrolled hypertension.
- Prior treatment with chemotherapy.
- Any cancer other than previously treated skin cancer.
- Breast cancer in a previously irradiated breast.
学习计划
研究是如何设计的?
设计细节
队列和干预
团体/队列 |
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1
This is a tissue acquisition and collection protocol that will analyze potential cellular changes that occur after treatment with trastuzumab.
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研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
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A tissue acquisition and collection protocol that will analyze potential cellular changes that occur after treatment with trastuzumab to try to elucidate the mechanism of trastuzumab resistance in patients with HER2-positive breast cancer.
大体时间:2-years
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2-years
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合作者和调查者
调查人员
- 首席研究员:Kathryn L Edmiston, MD、University of Massachusetts, Worcester
出版物和有用的链接
一般刊物
- Mohsin SK, Weiss HL, Gutierrez MC, Chamness GC, Schiff R, Digiovanna MP, Wang CX, Hilsenbeck SG, Osborne CK, Allred DC, Elledge R, Chang JC. Neoadjuvant trastuzumab induces apoptosis in primary breast cancers. J Clin Oncol. 2005 Apr 10;23(11):2460-8. doi: 10.1200/JCO.2005.00.661. Epub 2005 Feb 14.
- Hurley J, Doliny P, Reis I, Silva O, Gomez-Fernandez C, Velez P, Pauletti G, Powell JE, Pegram MD, Slamon DJ. Docetaxel, cisplatin, and trastuzumab as primary systemic therapy for human epidermal growth factor receptor 2-positive locally advanced breast cancer. J Clin Oncol. 2006 Apr 20;24(12):1831-8. doi: 10.1200/JCO.2005.02.8886. Epub 2006 Mar 20. Erratum In: J Clin Oncol. 2006 Jul 20;24(21):3515. Powell, Jodeen E [added].
- Coudert BP, Largillier R, Arnould L, Chollet P, Campone M, Coeffic D, Priou F, Gligorov J, Martin X, Trillet-Lenoir V, Weber B, Bleuse JP, Vasseur B, Serin D, Namer M. Multicenter phase II trial of neoadjuvant therapy with trastuzumab, docetaxel, and carboplatin for human epidermal growth factor receptor-2-overexpressing stage II or III breast cancer: results of the GETN(A)-1 trial. J Clin Oncol. 2007 Jul 1;25(19):2678-84. doi: 10.1200/JCO.2006.09.9994. Epub 2007 May 21. Erratum In: J Clin Oncol. 2007 Nov 1;25(31):5048.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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