Adobe Flash Player is required to view this feature. If you are using an operating system that does not support Flash, we are working to bring you alternative formats. Original Article Trastuzumab plus Adjuvant Chemotherapy for Operable HER2-Positive Breast Cancer Edward H. Romond, M.D., Edith A. Perez, M.D., John Bryant, Ph.D., Vera J. Suman, Ph.D., Charles E. Geyer, Jr., M.D., Nancy E.

Davidson, M.D., Elizabeth Tan-Chiu, M.D., Silvana Martino, D.O., Soonmyung Paik, M.D., Peter A. Kaufman, M.D., Sandra M. Swain, M.D., Thomas M. Pisansky, M.D., Louis Fehrenbacher, M.D., Leila A. Kutteh, M.D., Victor G.

Vogel, M. Malayalam Script Writing Format Pdf. D., Daniel W. Visscher, M.D., Greg Yothers, Ph.D., Robert B.

In this first look at a new book, HBS professors Paul Lawrence and Nitin Nohria explore how human nature shapes business organizations. However, without other counterbalancing drives at work, this would in time lead to a tension-free, collusive set of relationships with everyone attending to everyone else's comfort. Lawrence and Nitin Nohria (2002) present in their book “Driven: How Human Nature. Shapes Our Choices” new model of motivating employees better known as “four drive model”, whose base is composed of four basic drives: the drive to acquire (earning basic goods, including those of non-material nature, as is.

Jenkins, M.D., Ph.D., Ann M. Brown, Sc.D., Shaker R. Dakhil, M.D., Eleftherios P. Mamounas, M.D., M.P.H., Wilma L. Lingle, Ph.D., Pamela M. Klein, M.D., James N. Ingle, M.D., and Norman Wolmark, M.D.

N Engl J Med 2005; 353:1673-1684 DOI: 10.1056/NEJMoa052122. Methods The National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks (group 1) with the same regimen plus 52 weeks of trastuzumab beginning with the first dose of paclitaxel (group 2).

The North Central Cancer Treatment Group trial N9831 compared three regimens: doxorubicin and cyclophosphamide followed by weekly paclitaxel (group A), the same regimen followed by 52 weeks of trastuzumab after paclitaxel (group B), and the same regimen plus 52 weeks of trastuzumab initiated concomitantly with paclitaxel (group C). The studies were amended to include a joint analysis comparing groups 1 and A (the control group) with groups 2 and C (the trastuzumab group). Group B was excluded because trastuzumab was not given concurrently with paclitaxel. Results By March 15, 2005, 394 events (recurrent, second primary cancer, or death before recurrence) had been reported, triggering the first scheduled interim analysis. Of these, 133 were in the trastuzumab group and 261 in the control group (hazard ratio, 0.48; P. Trastuzumab, a monoclonal antibody targeting the extracellular domain of the HER2 protein, was approved in 1998 as a first-line treatment in combination with paclitaxel for HER2-positive metastatic breast cancer.

The benefit of this approach in patients with metastatic disease and the poor prognosis of HER2-positive breast cancer motivated the National Cancer Institute (NCI) to sponsor two trials of adjuvant treatment with trastuzumab, led by the National Surgical Adjuvant Breast and Bowel Project (NSABP) and the North Central Cancer Treatment Group (NCCTG). NSABP trial B-31, which began accrual in February 2000, compares four cycles of doxorubicin and cyclophosphamide followed by paclitaxel (group 1) with the same chemotherapy plus 52 weeks of trastuzumab beginning on day 1 of paclitaxel therapy (group 2). NCCTG trial N9831 began enrollment in May 2000 and compares three regimens: four cycles of doxorubicin and cyclophosphamide followed by weekly paclitaxel for 12 weeks (group A), four cycles of doxorubicin and cyclophosphamide followed by 52 weeks of trastuzumab after the completion of paclitaxel therapy (group B), and four cycles of doxorubicin and cyclophosphamide followed by 52 weeks of trastuzumab beginning on day 1 of paclitaxel therapy (group C).

The control groups of the trials, as well as group 2 in trial B-31 and group C in trial N9831, differed in terms of the scheduling of paclitaxel treatment and some aspects of hormonal therapy and radiotherapy but were otherwise identical. For this reason, the NCI and the Food and Drug Administration approved a joint-analysis plan developed by the NSABP and NCCTG to combine data from group 1 and group A (referred to as the control group) for comparison with group 2 and group C (referred to as the trastuzumab group). Group B of trial N9831 was excluded because the protocol required trastuzumab to be administered after the completion of chemotherapy. The plan required a first interim analysis after the occurrence of 355 events. Before the data were locked, 2043 patients (of a planned total of 2700) were enrolled in trial B-31 and 1633 patients (of a total of 2000 for the comparison of group A with group C) were enrolled in trial N9831. In April 2005, the independent data-monitoring committees of each trial recommended closing enrollment and releasing the results.