A Decensi

..Because our data are hampered by the lack of predictivity of the selected biomarkers, additional studies are necessary to assess the activity of fenretinide in preventing bladder cancer...

..In addition, the prolonged half-life of tamoxifen and metabolite provides the rationale for a weekly administration of the drug in a preventive context. However, the clinical implications of our findings remain to be defined...

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..Atherosclerosis may induce VTE, or the 2 conditions may share common risk factors. We assessed the effect of tamoxifen on VTE in a breast cancer prevention trial and studied its association with risk factors for VTE...

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..Because the effect of transdermal estradiol (E2) on CRP is unclear, we compared CRP changes after 6 and 12 months of transdermal E2 and oral CEE in a randomized 2x2 retinoid-placebo trial...

..Fenretinide induces a moderate decline of IGF-I levels in women < or = 50 years of age. The association between IGF-I change and the reduction of second breast cancers in premenopausal women warrants further study...

..We determined whether IGF-I and IGFBP-3 predict second breast cancer risk, and whether their changes during fenretinide explain observed reductions in second breast cancer in women </=50 years of age...

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..Moreover, updated results of the secondary prevention trial of 4-H PR and of the primary prevention trial of tamoxifen are presented. Finally, the rationale for a reduction of tamoxifen dose in future prevention trials is provided...

..We conclude that DNA flow cytometry and conventional cytology on epithelial cells obtained from bladder washings do not appear to provide suitable surrogate endpoint biomarkers during the early stages of bladder carcinogenesis...

..Whereas a trial of tamoxifen in women already on transdermal HRT is warranted, prescription of HRT during tamoxifen may attenuate its activity...

..Since these adverse effects may be dose related, we investigated the effect of tamoxifen on several biomarkers when the drug was given at doses lower than those currently in use...

..We conducted a long-term analysis in a subgroup of women who were regularly followed up in a single center...

..Further studies on the search of the minimal active dose of tamoxifen are warranted...

..Because toxicity may be dose-dependent, we studied the biologic activity of low concentrations of tamoxifen to determine the plausibility of a dose reduction...

..Our results support the observation that tamoxifen may be a suitable preventive option for women with multiple disease risk factors...

..CONCLUSION: Given the number of patients involved in the study and the prolonged intake of the drug, the experience on fenretinide tolerability can be considered sufficiently reassuring to justify further testing of the retinoid...

..Given that high plasma levels of IGF-I have been suggested as a risk factor for breast cancer, these findings provide further support for the potential activity of raloxifene in breast cancer prevention...

..Since low-dose tamoxifen showed a favorable modulation of breast cancer biomarkers in phase II trials, a monoinstitutional cohort of women with DIN treated with low-dose tamoxifen or no systemic treatment was analyzed...

..Studies have shown that Ki-67 response after short-term neoadjuvant aromatase inhibitors may predict recurrence in postmenopausal breast cancer, whereas its prognostic effect in premenopausal women is unknown...

..In conclusion, tamoxifen (20 mg day(-1) for 6 months) decreased plasma tHcy levels in healthy women. This effect may contribute to its protective effect on myocardial infarction...

..Current knowledge suggests that a pharmacological approach to preventing cancer, using natural or synthetic agents, could become an important way forward...

..Here, we investigate the changes in lipids and clotting profile in patients of the same trial...

..These findings suggest that, in our model, interference with the ER signalling pathway is not the only mechanism of breast cancer growth inhibition by 4-HPR...

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..Conversely, the CYP2D6*2A allele may be associated with increased efficacy of tamoxifen. These findings support the relevance of pharmaco-genomics in tailoring tamoxifen treatment...

..5-36.3) for women with low tamoxifen concentrations (< 30 ng mL-1). We conclude that tamoxifen at low doses is able to lower ultrasensitive CRP and that this might be associated with a beneficial effect on CVD...

..However, a trend towards an increase in bone resorption markers suggests the need for further assessment at different skeletal sites...

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..Synergic cytotoxicity was also demonstrated in combination with fludarabine, in both resting and stimulated CLL samples. This study entitles 4HPR to be assayed as a chemotherapeutic adjuvant for the treatment of CLL...

..Ongoing randomised trials should address this issue...

..In this group of patients, androgen priming did not seem to potentiate the effectiveness of EMP, our results being comparable to those previously reported using EMP alone...

..In conclusion, the rapid growth of information and knowledge in chemoprevention, especially for CRC, is very encouraging and gives us hope that soon this approach will be applicable in a larger scale population...

..Digital nuclear morphometric analysis can capture subtle differences along neoplastic progression. Studies showed different profiles from normal to cancer lesions. Our goal is to utilize this method as biomarker in chemoprevention trials...

..A reduced activity of methylenetetrahydrofolate reductase (MTHFR) due to frequent C677T polymorphism affects DNA synthesis, repair and methylation and may be implicated in breast cancer risk...

..The aim of this study was to assess the relationships between circulating hormones, clinical features related to breast cancer risk and mammographic density in postmenopausal women...

..Here we present an extended follow-up of the Italian trial...

..Superficial (papillary) bladder cancer is associated with progression and death from muscle-invasive bladder cancer, but no reliable predictors of the outcomes have been identified...

..We assessed the optimal biologic dose and schedule of tamoxifen in HRT users using surrogate end point biomarkers and menopausal symptoms...

..To assess the sociodemographic, health-related, and psychological factors that influence the decision of women on hormone replacement therapy (HRT) to participate in a phase III trial of low-dose tamoxifen...

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..Ki-67 expression is associated with atypia and cell yield and it might be assessed as a surrogate biomarker in early-phase chemoprevention trials...

..Furthermore, a possible protective effect of fenretinide in BRCA-mutated women was suggested. Further studies on fenretinide for the prevention of ovarian carcinoma particularly in women with genetic susceptibility appear necessary...

..Finally, new targets that interfere with the onset of ER-negative breast cancer are being sought since one-third of breast cancers will not be modulated by hormonal interventions...

..Finally, new targets that interfere with ER-negative breast carcinogenesis are being sought as one-third of breast cancers will not be preventable by hormonal interventions...

..Furthermore we studied tamoxifen effects on the cancer proliferation marker Ki-67, and on sex hormone-binding globulin (SHBG)...

..These findings support their putative role as breast cancer risk biomarker...

..Such a strategy would greatly reduce the numbers of women who would need to take tamoxifen to obtain the same absolute reduction in breast cancer. These findings are exploratory and need to be confirmed in other randomized trials...

..To assess the incidence, cofactors, and excess risk of development of non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis, attributable to tamoxifen in women...

..These effects might support an activity in prostate cancer prevention but further studies are required...

..Finally, new agents that interfere with the onset of ER-negative breast cancer are being sought for combination chemoprevention since almost a third of breast cancers will not be sensitive to hormonal modulation...

..CONCLUSION: The combination of low-dose tamoxifen and fenretinide is safe but not synergistic in lowering IGF-I levels in premenopausal women. The clinical implications require further follow-up...

..We have evaluated the quality of life through a self-administered questionnaire during a randomized study of oral CEE or transdermal E2 and fenretinide or placebo...

..024) and E2 (p=0.01), and positively with DHEA-S (p=0.016) and CTX (p=0.040). Our results provide evidence for an early endocrine effect of raloxifene which further suggests a favorable impact on breast cancer prevention...

..Under our experimental conditions, 4-HPR did not show activity in advanced ovarian cancer cells. However, clinical evidence supports further investigation of fenretinide for ovarian cancer prevention...

..Fenretinide (4HPR), a synthetic retinoid, induces apoptosis in neuroblastoma cells. A Phase I study in children with neuroblastoma was designed to determine maximum tolerated dose, toxicity, and pharmacokinetics...