microRNA of Human Epidermal Growth Factor Receptor 2 （HER2）Positive Patient Treated With Herceptin

Study Overview
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Brief Summary
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This projective observational study is planned to enroll more than 300 advanced breast cancer patients, who were proved as Her-2 positive using fluorescence in situ hybridization (FISH) and / or immunohistochemistry, and 100 healthy donors as control. Before treatment, the plasma microRNA will be collected and detected by microRNA extraction kit and quantitative polymerase chain reaction (qPCR), respectively. After analyzed their microRNA expression by microRNA predictive model, previously reported by our team, all of enrolled patients will be classified as probable sensitive group or probable resistant group. Herceptin combined with other chemotherapy will be the backbone of salvage treatment and used for at least 3 months; the change of local masses and metastasis lesions after treatment will be documented to evaluate the response. Based on these results, investigator aim to construct a mathematical predictive model by analyzing the correlation of baseline microRNA expression level and the prognosis of patients. And a diagnosis microRNA kit will be planned and manufactured

Official Title
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A Perspective Study of the Predictive Value of microRNA in Patients With HER2 Positive Advanced Stage Breast Cancer Who Were Treated With Herceptin

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Capecitabine
* Drug: Trastuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patients signed the written informed consent female patient who is ≥ 18yrs, HER2 positive: immunohistochemistry (+++) or FISH (+) stage IV the patients have no history of chemotherapy ,hormone therapy,radiotherapy or surgery after diagnosis of breast cancer the result of patients' blood tests are as follow: WBC≥3.0×109/L; Plt≥100×109/L;AST/SGOT or ALT/AGPT≤tripple of normal upper limit; Creatinine<double of the normal upper limit ECOG scores are 0 or 1 . The patient is able to take oral pills Exclusion Criteria: The patient was never exposed to herceptin. The patient suffered from other non-breast malignancy in the last 5 years, except for cervical carcinoma in situ, radical basal cell carcinoma or squamous cell carcinoma. The life expectancy is less than 3 months. Severe hepatic function disorder, Child Pugh grade C. Severe cardiac function disorder, cardiac function is more than grade III; Prolonged QT interval; Arrhythmia or taking anti-arrhythmia drugs; Pregnant or breast feeding female.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Herceptin probable sensitive group<br>Plasma microRNAs will be collected using microRNA extraction kit according to manufacturer's instructions; and their expression levels are analyzed by quantitative polymerase chain reaction (qPCR).According to microRNAs - herceptin predictive model(reported by our team), the patients will be considered as Herceptin probable sensitive group | Drug: Capecitabine<br>* Capecitabine will be administered orally at a dose of 2500mg/m2 daily for 3 months (Day 1 to 14 of a 21-day cycle)<br>* Other names: Xeloda;Drug: Trastuzumab<br>* patients will receive herceptin intravenous infusion at a dose of 6mg on day 1 of each cycle<br>* Other names: Herceptin;|
| Herceptin probable resistant group<br>Plasma microRNAs will be collected using microRNA extraction kit according to manufacturer's instructions; and their expression levels are analyzed by quantitative polymerase chain reaction (qPCR).According to microRNAs - herceptin predictive model(reported by our team), the patients will be considered as Herceptin probable resistant group | Drug: Capecitabine<br>* Capecitabine will be administered orally at a dose of 2500mg/m2 daily for 3 months (Day 1 to 14 of a 21-day cycle)<br>* Other names: Xeloda;Drug: Trastuzumab<br>* patients will receive herceptin intravenous infusion at a dose of 6mg on day 1 of each cycle<br>* Other names: Herceptin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progress-free survival of patients |  | progression free survival (PFS) was defined as the interval from the diagnosis of advanced breast cancer with HER2 positive to disease progression, relapse, death due to any causes or last follow-up.The follow-up interval is 2 years. | 
| overall survival of patients |  | Overall survival was defined as the interval from the diagnosis of advanced breast cancer with HER2 positive to death due to any causes or last follow-up,The follow-up interval is 2 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, herceptin, microRNA