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      Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2009

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          Abstract

          The 11 th St Gallen (Switzerland) expert consensus meeting on the primary treatment of early breast cancer in March 2009 maintained an emphasis on targeting adjuvant systemic therapies according to subgroups defined by predictive markers. Any positive level of estrogen receptor (ER) expression is considered sufficient to justify the use of endocrine adjuvant therapy in almost all patients. Overexpression or amplification of HER2 by standard criteria is an indication for anti-HER2 therapy for all but the very lowest risk invasive tumours. The corollary is that ER and HER2 must be reliably and accurately measured. Indications for cytotoxic adjuvant therapy were refined, acknowledging the role of risk factors with the caveat that risk per se is not a target. Proliferation markers, including those identified in multigene array analyses, were recognised as important in this regard. The threshold for indication of each systemic treatment modality thus depends on different criteria which have been separately listed to clarify the therapeutic decision-making algorithm.

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          Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.

          The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence in women with estrogen receptor-positive, lymph node-negative breast cancer treated with adjuvant tamoxifen. The relationship between the RS and chemotherapy benefit is not known. The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy-treated patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B20 trial. Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS. A total of 651 patients were assessable (227 randomly assigned to tamoxifen and 424 randomly assigned to tamoxifen plus chemotherapy). The test for interaction between chemotherapy treatment and RS was statistically significant (P = .038). Patients with high-RS (> or = 31) tumors (ie, high risk of recurrence) had a large benefit from chemotherapy (relative risk, 0.26; 95% CI, 0.13 to 0.53; absolute decrease in 10-year distant recurrence rate: mean, 27.6%; SE, 8.0%). Patients with low-RS (< 18) tumors derived minimal, if any, benefit from chemotherapy treatment (relative risk, 1.31; 95% CI, 0.46 to 3.78; absolute decrease in distant recurrence rate at 10 years: mean, -1.1%; SE, 2.2%). Patients with intermediate-RS tumors did not appear to have a large benefit, but the uncertainty in the estimate can not exclude a clinically important benefit. The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative, estrogen receptor-positive breast cancer, but also predicts the magnitude of chemotherapy benefit.
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            Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis.

            Herein we report that the VEGFR/PDGFR kinase inhibitor sunitinib/SU11248 can accelerate metastatic tumor growth and decrease overall survival in mice receiving short-term therapy in various metastasis assays, including after intravenous injection of tumor cells or after removal of primary orthotopically grown tumors. Acceleration of metastasis was also observed in mice receiving sunitinib prior to intravenous implantation of tumor cells, suggesting possible "metastatic conditioning" in multiple organs. Similar findings with additional VEGF receptor tyrosine kinase inhibitors implicate a class-specific effect for such agents. Importantly, these observations of metastatic acceleration were in contrast to the demonstrable antitumor benefits obtained when the same human breast cancer cells, as well as mouse or human melanoma cells, were grown orthotopically as primary tumors and subjected to identical sunitinib treatments.
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              Gene-expression signatures in breast cancer.

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                Author and article information

                Journal
                Ann Oncol
                annonc
                annonc
                Annals of Oncology
                Oxford University Press
                0923-7534
                1569-8041
                August 2009
                17 June 2009
                17 June 2009
                : 20
                : 8
                : 1319-1329
                Affiliations
                [1 ]International Breast Cancer Study Group, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
                [2 ]European Institute of Oncology, Milan, Italy
                [3 ]Breast Cancer Research Program, Mayo Clinic Cancer Center, Rochester, MN, USA
                [4 ]Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA
                [5 ]International Breast Cancer Study Group, School of Public Health, University of Sydney, Sydney, New South Wales, Australia
                [6 ]Breast Center, Kantonsspital, St Gallen, Switzerland
                [7 ]Tumor and Breast Center ZeTuP, St Gallen, Switzerland
                Author notes
                [* ] Correspondence to: Prof. A. Goldhirsch, International Breast Cancer Study Group, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy. Tel: +39-02-57489439; Fax: +39-02-94379273; E-mail: aron.goldhirsch@ 123456ibcsg.org
                [†]

                See appendix for members of the Panel.

                Article
                10.1093/annonc/mdp322
                2720818
                19535820
                8589875c-32b4-4c87-938d-9763976ecd5d
                © The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

                The online version of this article has been published under an open access model. users are entitle to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and the European Society for Medical Oncology are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

                History
                : 12 May 2009
                : 12 May 2009
                Categories
                Special Article

                Oncology & Radiotherapy
                early breast cancer,therapies,st gallen consensus
                Oncology & Radiotherapy
                early breast cancer, therapies, st gallen consensus

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