Stephen R Johnston

..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...

..Curtis C, Shah SP, Chin SF et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 2012; 486:346-52...

..Toxicity was higher with the combination, including increased diarrhea and liver enzyme elevations...

..The magnitude of the benefit represents a quantum shift in how we should use endocrine therapy in future, and potentially defines a new standard of care in this setting...

..Subsequent trials will be needed to see whether combinations of novel STIs are well tolerated and how they may further enhance clinical benefit in breast cancer...

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..The steroidal AI, exemestane is also an option in non-steroidal AI-resistant disease. Clinical trials are underway to compare fulvestrant with exemestane as an appropriate therapy following the onset of AI resistance...

..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...

..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 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...

..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...

..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...

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

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

..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...

..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...

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

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..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...

..This study shows brain metastases are common phenomenon in HER2 positive advanced breast cancer patients receiving trastuzumab and also may implicate the brain as a sanctuary site for early relapse in this patient cohort...

..Regional nodal recurrence including supraclavicular node recurrence is not dealt with in this review...

..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]...

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

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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...

..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...

..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...

..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...

..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...

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..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...

..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...

..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...

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..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...

..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...