IRS Proteins and Trastuzumab Resistance

Significant progress has been made in the treatment of women with Her2 positive breast cancer who are treated with trastuzumab, a humanized monoclonal antibody that inhibits Her2. Despite this progress not all patients with Her2 positive metastatic breast cancer respond to trastuzumab and patients with metastatic disease who do respond usually develop progressive disease during treatment with trastuzumab. The mechanism of such resistance is unknown. We propose to investigate the mechanism of trastuzumab resistance in Her2 positive breast cancer. The hypothesis to be examined in the basic science section of this study is that IRS-1 and IRS-2 are modifiers of HER2 signaling and that these adapter proteins could be predictive indicators of treatment response to Herceptin in patients that are candidates for this targeted therapy. The connection between IRS-1 and IRS-2 expression and Herceptin response and clinical outcome in HER2 positive human breast tumors will be evaluated to determine if IRS expression correlates with resistance to Herceptin therapy and with the aggressive behavior of these tumors. This study will establish if the IRS proteins influence HER2 function in tumors and if they are predictive markers for evaluating treatment options for HER2 positive patients.

Sex

Female

Minimum age

18 Years

Maximum age

70 Years

Inclusion Criteria:

1. Women age 18-70 with breast cancer who have signed an IRB approved consent form.
2. Biopsy proven breast cancer with her 2 overexpression by fluorescence in situ hybridization (FISH).
3. Newly diagnosed patients with Stages 1,2 and 3 breast cancer who will be receiving neoadjuvant chemotherapy prior to breast surgery
4. Normal Left ventricular ejection fraction, as measured by echocardiogram or MUGA scan
5. Normal bone marrow, kidney and liver function
6. No evidence of distant metastatic disease

Exclusion Criteria:

1. Patients with significant cardiac disease including abnormal LVEF, symptomatic coronary artery disease, uncontrolled hypertension.
2. Prior treatment with chemotherapy.
3. Any cancer other than previously treated skin cancer.
4. Breast cancer in a previously irradiated breast.

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