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Cancer

Cover image for Cancer

1 February 2008

Volume 112, Issue S3

Pages i–iv, 673–729

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  1. Supplement

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    2. Supplement
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      Endocrine and targeted manipulation of breast cancer: Summary statement for the Sixth Cambridge Conference (pages 673–678)

      Steven E. Come, Aman U. Buzdar, James N. Ingle, Stephen R. D. Johnston, Angela M. Brodie, R. Charles Coombes, William R. Miller, Kathleen I. Pritchard, Eric P. Winer, Jo Anne Zujewski and Paul E. Goss

      Version of Record online: 10 DEC 2007 | DOI: 10.1002/cncr.23194

      This summary provides conclusions and recommendations from the Sixth Cambridge Conference on Endocrine and Targeted Manipulation of Breast Cancer, which was convened to assess the most recent data in the field, articulate current best practices, and identify the next steps to advance both patient care and research.

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      Preclinical modeling of endocrine response and resistance : Focus on aromatase inhibitors (pages 679–688)

      Luciana F. Macedo, Gauri Sabnis and Angela Brodie

      Version of Record online: 10 DEC 2007 | DOI: 10.1002/cncr.23191

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      By using a breast cancer intratumoral aromatase model, the authors demonstrated that the transition from a responsive state to a letrozole-resistant state was associated with molecular mechanisms of adaptation that involved the activation of growth factor receptor pathways, particularly the HER-2/Raf/mitogen-activated protein kinase signaling pathway. Blockade of the crosstalk between the HER-2 signaling pathway and the estrogen receptor with signal-transduction inhibitors or pure antiestrogen fulvestrant restored the response to aromatase inhibitors.

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      Predicting response and resistance to endocrine therapy : Profiling patients on aromatase inhibitors (pages 689–694)

      William R. Miller, Alexey Larionov, Thomas J. Anderson, John R. Walker, Andreas Krause, Dean B. Evans and J. Michael Dixon

      Version of Record online: 10 DEC 2007 | DOI: 10.1002/cncr.23187

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      Microarray analysis of RNA from sequential biopsies of breast cancers that were taken before and after 10 to 14 days of neoadjuvant treatment with the aromatase inhibitor letrozole suggested that 1) classic estrogen-dependent and proliferation genes are unlikely to be robust markers of hormone response or resistance, and 2) resistance to endocrine therapy is heterogeneous.

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      Pharmacogenomics of tamoxifen and aromatase inhibitors (pages 695–699)

      James N. Ingle

      Version of Record online: 10 DEC 2007 | DOI: 10.1002/cncr.23192

      Pharmacogenomics examines the relation between a patient's genetic makeup and response to a given drug and forms the basis for true personalized medicine. Pharmacogenomic studies are beginning to yield important findings relating to tamoxifen and are under way for aromatase inhibitors, the 2 most important classes of drugs in the endocrine therapy of breast cancer.

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      Summary of aromatase inhibitor clinical trials in postmenopausal women with early breast cancer (pages 700–709)

      Aman U. Buzdar, R. Charles Coombes, Paul E. Goss and Eric P. Winer

      Version of Record online: 10 DEC 2007 | DOI: 10.1002/cncr.23193

      Several studies have evaluated the safety and efficacy of aromatase inhibitors (AIs) for the treatment of early breast cancer in postmenopausal women. The results from these studies suggest that AIs should be considered when planning a patient's course of endocrine therapy.

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      Enhancing endocrine response with novel targeted therapies : Why have the clinical trials to date failed to deliver on the preclinical promise? (pages 710–717)

      Stephen R. D. Johnston, Alexandra Leary, Lesley-Ann Martin, Ian E. Smith and Mitch Dowsett

      Version of Record online: 10 DEC 2007 | DOI: 10.1002/cncr.23190

      Signal transduction inhibitors (STIs) are being combined with endocrine therapies in an effort to enhance endocrine responsiveness and delay the emergence of acquired resistance to hormonal therapy. Although these agents have shown early promise in selected breast cancer models, the clinical results have been disappointing to date. Ongoing combination trials and recommendations for future trials are discussed.

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      Combining endocrine agents with chemotherapy: Which patients and what sequence? (pages 718–722)

      Kathleen I. Pritchard

      Version of Record online: 10 DEC 2007 | DOI: 10.1002/cncr.23189

      In metastatic breast cancer and in the adjuvant setting, it would be most useful to have trials that evaluated the order of sequential hormone therapy and chemotherapy versus concurrent administration of hormone and chemotherapy. To the author's knowledge, few trials of this type have been conducted to date, but when they have, the combined response rate, response duration, and overall survival were not different.

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      Current NCI-sponsored Cooperative Group trials of endocrine therapies in breast cancer (pages 723–729)

      Jennifer Eng-Wong and Jo Anne Zujewski

      Version of Record online: 10 DEC 2007 | DOI: 10.1002/cncr.23188

      NCI-sponsored Cooperative Group phase 3 trials are evaluating several endocrine treatment strategies. Ongoing trials are evaluating new agents, optimal timing of treatment as well as determination of which hormone-responsive tumors benefit from inclusion of chemotherapy.

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