Stephen R D Johnston

..These observations support the need for further evaluation of these markers in breast tumors as predictors of TAM resistance...

..Sustained induction of apoptosis may contribute to prolonged antagonism of E2-dependent growth, and it occurred to a greater extent following 3 months of idoxifene, compared to tamoxifen...

..This article reviews the rationale for the development of FTIs, focussing on early preclinical data in breast cancer models together with preliminary results from the first phase II study of an FTI in advanced breast cancer...

..ovarian cancer together with an improved safety profile are all strongly supportive of a positive benefit-risk profile for Caelyx in the treatment of advanced ovarian cancer following failure of first-line platinum-based therapy..

..Encouraging results from phase I and II clinical trials have emerged, creating both enthusiasm and new challenges for the optimum clinical development of this important new class of anticancer drug...

..The issue is whether the current clinical data for SERMs in advanced breast cancer are sufficiently strong to encourage that further development...

..Analysts at Lehman Brothers predicted in December 2001, that the product has a 90% chance of making it to market in 2002, with peak sales potential in this year of $800 million [434768]...

..By October 2000, preclinical investigations were ongoing in Japan. By February 2001, the drug was in phase II trials in the US for pancreatic, head and neck, lung and colorectal cancers...

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..Changes in ERalpha, PgR, and HER2 were assessed in samples from patients treated with tamoxifen...

..Enhanced G1 arrest due to modulation of cell cycle regulatory proteins may be the underlying mechanism for the positive interaction between FTIs and tamoxifen...

..These data suggest that although elevated levels of MAPK occur during LTED and influence the phenotype, this is unlikely to be the sole pathway operating to achieve adaptation...

..Thus, the resistance of these human breast cancer cells to oestrogen-deprivation appears to be due to acquired hypersensitivity which may be explained in part by increased levels of and phosphorylated ERalpha...

..These results show that ARZ is an effective antagonist of E2-stimulated breast cancer growth with similar growth-inhibitory and pharmacodynamic effects to TAM in this model...

..This article reviews the rationale for these strategies, and discusses the lessons that need to be learnt if we are to successfully integrate these new drugs with aromatase inhibitors in the clinic...

..This article reviews the pre-clinical rationale for this strategy and the clinical trials in this area...

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..Although the level of myelosuppression is lower than 3-weekly regimens, this weekly regimen cannot be recommended due to the significant non-haematological toxicities associated with the treatment...

..In contrast, SERDs may have useful efficacy following aromatase inhibitors because of their unique mechanism of action, and clinical trials to determine their optimal use or sequence are ongoing...

..The correlation of molecular and clinical results from these ongoing studies will be important to establish appropriate biological variables for selecting those patients who may benefit most from this combined approach...

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..Accounting for all available data, NICE guidance supports the appropriate roles of paclitaxel, topotecan, and pegylated liposomal doxorubicin in the treatment of advanced ovarian cancer...

..As these new therapies evolve towards the clinic, the challenge to oncologists is whether their potential seen in the laboratory can be matched by further substantial improvements in clinical outcome...

..Parallel biomarker studies are starting to elucidate predictive molecular phenotypes that may indicate likelihood of response to lapatinib, and these may direct future trials with this oral tyrosine kinase inhibitor...

..Enriching trial recruitment by molecular profiling of different ER+ subtypes will become increasingly important to maximize additional benefit that new agents may bring to current endocrine therapies for breast cancer...

..This article will review the results of clinical trials of endocrine/biological combinations conducted in early and advanced breast cancer as well as provide an update on ongoing studies...

..This study assessed the clinical efficacy of the farnesyltransferase inhibitor, tipifarnib, combined with letrozole in patients with advanced breast cancer and disease progression following antiestrogen therapy...

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..This review will discuss the small molecule signal transduction inhibitors in various stages of development and address the strategic issues relating to clinical trial design with these novel targeted agents...

..We conducted a phase II study in 76 patients with advanced breast cancer...

..We conclude that endogenous ERbeta may not play a dominant role in the modulation of the tamoxifen ERalpha complex, or in the development of tamoxifen-stimulated resistant tumor growth...

..029). Future clinical studies will evaluate fulvestrant in the neoadjuvant setting together with its optimal sequencing in relation to tamoxifen and other endocrine therapies in advanced disease...

..The objective of this evaluation was to extrapolate the findings from the MA17 trial to estimate the lifetime cost effectiveness of letrozole in this setting...

..All of this has and continues to contribute to a growing understanding of how to optimize the use of endocrine agents in both treating and preventing breast cancer...

..To estimate the cost-effectiveness of extended adjuvant letrozole in postmenopausal women with early breast cancer and estrogen or progesterone receptor-positive tumors who had completed 5 years of adjuvant tamoxifen...