Paul Goss

..g., node-positive disease, prior chemotherapy). Both the efficacy and safety of letrozole for the adjuvant treatment of breast cancer are reviewed...

..We hope the findings of our Commission and our recommendations will inspire Latin American stakeholders to redouble their efforts to address this increasing cancer burden and to prevent it from worsening and threatening their societies...

..Less toxicity on bone is compatible with one hypothesis behind MA.27 but requires confirmation. Exemestane should be considered another option as up-front adjuvant therapy for postmenopausal hormone receptor-positive breast cancer...

..MA17 showed improved outcomes in postmenopausal women given extended letrozole (LET) after completing 5 years of adjuvant tamoxifen...

..We investigated the efficacy and safety of adjuvant lapatinib for patients with trastuzumab-naive HER2-positive early-stage breast cancer, started at any time after diagnosis...

..The studies suggest that VN/14-1 may be a useful novel therapy for ER-positive breast cancer...

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..To compare time to progression (TTP) with a steroidal aromatase inhibitor (AI) atamestane (ATA) combined with toremifene (TOR; complete estrogen blockade) versus letrozole (LET) in receptor-positive advanced breast cancer (ABC)...

..This study was designed to compare the effects of exemestane with the nonsteroidal aromatase inhibitors anastrozole and letrozole on serum and urine levels of biomarkers of bone turnover in healthy postmenopausal women...

..Our objective was to determine the effects of liarozole alone or in combination with tamoxifen on the N-methyl-N-nitrosourea (MNU)-induced rat mammary carcinoma model, as well as on the uterus in ovariectomized immature rats...

..This report presents updated findings from the trial...

..When the trial was unblinded, patients who received placebo (PLAC) were offered LET...

..ATA is distinct from LET on end-organ function and this favorable profile makes clinical testing of this steroidal aromatase inhibitor of interest in the clinical setting...

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..A trial examining the merits of > 5 years of treatment with an AI, MA.17R, is ongoing, as are a number of other trials of duration of therapy. This article reviews results from MA.17 and the design of these trials of duration...

..Further studies of combinations of AIs with anti-estrogens on end-organ function are merited...

..Aromatase inhibitors prevent more contralateral breast cancers and cause fewer side effects than tamoxifen in patients with early-stage breast cancer...

..MA.17 randomized postmenopausal women after 5 years of tamoxifen, to letrozole or placebo. We present outcomes according to tumor receptor status...

..The re-randomization of MA.17 patients to an additional 5 years of letrozole or to no treatment will provide further insights into the benefits and side effects of long-term treatment...

..This is the first demonstration that extended adjuvant therapy after standard tamoxifen in postmenopausal women with early breast cancer has a clinically significant impact on outcome...

..The hope is that continued advances in endocrine therapy will translate into improved survival among both pre- and postmenopausal women with receptor-positive breast cancer...

..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...

..Our improved understanding of the biology of breast cancer and the use of biomarkers for identification of specific subtypes is allowing us to bring patient-specific novel therapies such as lapatinib to the clinic...

..In particular, targeted therapies either alone or in combination with AIs may improve clinical outcomes--the results of ongoing clinical trials will shape the future treatment of breast cancer...

..Cardiac toxicity is rarely seen with lapatinib. This paper reviews lapatinib-associated toxicities and provides practical management recommendations based on available data...

..We first compared breast density among white, African American, and Asian women and then correlated breast density and race with age, body mass index (BMI), and breast or cup size...

..In this manuscript, the rationale for targeting the insulin-like growth factor system is reviewed in addition to a summary of the available clinical trial data...

..This article reviews the problem of resistance to hormonal therapy and addresses potential approaches to overcome intrinsic or acquired mechanisms of resistance...

..Areas of active investigation include the mechanisms of resistance to endocrine therapy with tamoxifen and AIs and clinical strategies to overcome this resistance...

..Alternative strategies are needed. We hypothesized that augmentation of SSRI/SNRI therapy with hypnotic agents would optimize hot flash therapy by improving sleep and quality of life...

..A better understanding of mechanisms responsible for tumor dormancy and recurrence will be important for improving care of patients at risk for late-developing metastases...

..Both tumor and host signatures are being pursued to this end. Optimizing, expanding and extending endocrine therapy is likely to add further to patient outcome...

..Our aim was to assess the cardiovascular risk associated with celecoxib in 3 dose regimens and to assess the relationship between baseline cardiovascular risk and effect of celecoxib on cardiovascular events...

..We studied the effects of EXE, its principal metabolite, 17-hydroexemestane (17-H-EXE), and LET on bone and lipid metabolism in ovariectomized (OVX) rats...

..The efficacy and long-term toxicity data from the aromatase inhibitor prevention trials, and the identification of risk profiles from trial results, are awaited with interest...

..Breast cancer incidence increases with age and more than 1,300 women age 70 years or older were enrolled onto MA.17, making it ideal to explore the benefits, toxicities, and quality of life (QOL) impact of letrozole on older women...

..3 study of exemestane with or without celecoxib against placebo. The efficacy and toxicity results of these studies, and the identification of risk profiles from them, are awaited with interest...

..The aromatase inhibitors offer us the first ever tool to render women virtually free of estrogen and are potentially an exciting tool for the prevention of breast cancer...

..CONCLUSION: Adjuvant chemotherapy causes cognitive dysfunction, fatigue, and menopausal symptoms in women with breast cancer. Priority should be given to the study of strategies that might reduce these toxic effects...

..In this paper, the available data on SERMs including tamoxifen and raloxifene in breast cancer prevention and the data pointing to the efficacy of aromatase inhibitors in this setting are outlined...

..The aromatase inhibitor letrozole, by suppressing estrogen production, might improve the outcome after the discontinuation of tamoxifen therapy...

..These are to determine the end-organ effects of the inhibitors and include measurements of quality of life, bone and lipid metabolism, and endometrial effects. This review addresses the clinical implications of these studies of AIs...

..We examined factors associated with cause-specific death in a large cohort of breast cancer patients treated with extended adjuvant endocrine therapy...

..Potentially, E(2) + SCH 57068 could be combined for the treatment and prevention of breast cancer or as a novel hormone replacement therapy...

..CONCLUSION: These analyses suggest that, at least out to about 48 months, longer duration of letrozole treatment is associated with greater benefit in the extended adjuvant therapy setting...

..We conclude that although the decision to release the results of the interim analysis of MA17 and allow patients on placebo to take letrozole was justified, methods for analyzing and interpreting interim results can be improved...

..Several pharmacological and clinical considerations suggest that GC/MS/MS should become the preferred method for monitoring aromatase inhibitor therapy...

..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...

..17B evaluated bone turnover markers and bone mineral density (BMD) in postmenopausal women randomly assigned to MA.17, a placebo-controlled trial of letrozole after standard adjuvant tamoxifen...

..To evaluate the impact of letrozole compared with placebo after adjuvant tamoxifen on quality of life (QOL) in the MA.17 trial...

..Pilot studies of chemoprevention are also being undertaken. The aromatase inhibitors are an important new addition to the armamentarium of breast cancer therapy...

..373; P = 0.036) and apoptotic index (r = 0.495; P < 0.004). CONCLUSION: Dietary flaxseed has the potential to reduce tumor growth in patients with breast cancer...

..Outstanding issues to optimize AI therapy include identifying the optimal duration, agent, and patients for these therapies...

..Nevertheless, the superior clinical efficacy and survival data of letrozole suggest that it has the potential to displace tamoxifen as the gold standard in breast cancer treatment in the coming years...

..These observations indicate that OCT3 protein is selectively expressed in human breast cancer cells, and its expression may be implicated in mammary gland tumorigenesis via up-regulating FGF-4 expression...