Project description:We studied the effect on tumour response to neoadjuvant therapy of the substitution of lapatinib for trastuzumab in combination with weekly paclitaxel after doxorubicin plus cyclophosphamide treatment, and of the addition of lapatinib and trastuzumab combined after doxorubicin plus cyclophosphamide treatment in patients with HER2-positive operable breast cancer to determine whether there would be a benefit of dual HER2 blockade in these patients.
Project description:This randomized phase II trial studies how well paclitaxel with or without carboplatin and/or bevacizumab followed by doxorubicin and cyclophosphamide works in treating patients with breast cancer that can be removed by surgery. Drugs used in chemotherapy, such as paclitaxel, carboplatin, doxorubicin, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Bevacizumab may stop the growth of tumor cells by blocking blood flow to the tumor. Giving chemotherapy together with bevacizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
Project description:The human breast cancer (BR) data set (endpoints D and E) was contributed by the University of Texas M. D. Anderson Cancer Center (MDACC, Houston, TX, USA). Gene expression data from 230 stage I-III breast cancers were generated from fine needle aspiration specimens of newly diagnosed breast cancers before any therapy. The biopsy specimens were collected sequentially during a prospective pharmacogenomic marker discovery study between 2000 and 2008. These specimens represent 70-90% pure neoplastic cells with minimal stromal contamination. Patients received 6 months of preoperative (neoadjuvant) chemotherapy including paclitaxel, 5-fluorouracil, cyclophosphamide and doxorubicin followed by surgical resection of the cancer. Response to preoperative chemotherapy was categorized as a pathological complete response (pCR = no residual invasive cancer in the breast or lymph nodes) or residual invasive cancer (RD), and used as endpoint D for prediction. Endpoint E is the clinical estrogen-receptor status as established by immunohistochemistry. RNA extraction and gene expression profiling were performed in multiple batches over time using Affymetrix U133A microarrays. Genomic analysis of a subset of this sequentially accrued patient population were reported previously. For each endpoint, the first 130 cases were used as a training set and the next 100 cases were used as an independent validation set. Gene expression data from 230 stage I-III breast cancers