A Howell

..Gene expression profiling is beginning to appear in the breast cancer clinic but it is not yet fully evaluated. This review explores the questions that must be addressed before this technology can become an everyday clinical tool...

..However, considerable controversy exists regarding the cancer risks in women who test positive for the family mutation...

..It seems likely that herceptin will add to conventional therapies and thus will be the paradigm for the introduction of other biological therapies to improve cure rates...

..What is now needed is for other groups to repeat this observation and, if found, to examine the characteristics of the tumours producing this phenomenon in order to develop hypotheses about its cause and possible treatments...

..Nearly all data available indicate that AIs are superior to tamoxifen. The important question is whether survival is improved when they are used as adjuvant therapy?..

..The ongoing clinical development programme for fulvestrant will more fully the role of this valuable new agent in the treatment of postmenopausal ABC...

..Anastrozole should be the preferred initial treatment for postmenopausal women with localised hormone-receptor-positive breast cancer...

..At present concerns about deleterious vascular side effects are confined to HRT and SERMs. However, we have few long-term data using AIs for the treatment and prevention of breast cancer...

..These results strongly suggest that screening younger women with a family history of breast cancer leads to improved survival. More precise estimates of the benefit will accrue from further follow-up and other such studies...

..These data confirm that fulvestrant is an additional, effective, and well-tolerated treatment for advanced breast cancer in postmenopausal women whose disease progressed on prior endocrine therapy...

..We conclude that early anti-oestrogen treatment should prevent breast cancer in very high-risk women...

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..These data and the newer treatments available indicate a need to re-think our general approach to endocrine therapy and endocrine prevention...

..Increasingly women at high risk of breast cancer are opting for risk reducing surgery. The aim of this study was to assess the effectiveness of this approach in women at high risk in both carriers and non-carriers of BRCA1/2...

..26), BRCA2 (P = 0.16) or BRCA negative (P = 0.30) samples. Hence, the RASSF1A p.A331S polymorphism is not confirmed as a significant germline contributor to familial breast cancer susceptibility...

..01) and metastatic breast cancer (Rs=0.617; P<0.05). The ability to meet or exceed energy requirements led to gains in body fat among patients with metastatic breast cancer and NSCLC, but did not prevent loss of FFM in these groups...

..The results reveal anastrozole to be an effective and valuable first- and second-line therapy in postmenopausal women with ABC and visceral metastases, showing similar CB to other endocrine therapies...

..0002). Our results indicate that variants in CASP8 and TNRC9/TOX3 alter the risk of disease in individuals affected with familial ovarian cancer...

..A time delay is deliberate to allow women to fully address the issues involved with a decision for surgery. Early evidence suggests that this prepares the women emotionally and physically for their surgery...

..The vast majority of women have breast reconstruction...

..These data indicate that staining with the Ki67 antibody may be useful in monitoring response to anti-oestrogen therapy...

..Older women are less likely to receive standard management for breast cancer than younger postmenopausal women. Whether differences in general health explain variations in the rates of surgery is not known...

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..0-61.6). These results demonstrate that older women in the UK are less likely to receive standard management for breast cancer, compared to younger women and this disparity cannot be explained by differences in tumour characteristics...

..To evaluate a transcriptomic approach to identify healthy women at increased risk of breast cancer due to G2-radiosensitivity and look at transcripts that are differentially expressed between individuals...

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..Finally, study of the paracrine mechanisms of growth control in the normal human breast may provide new, more specific, therapeutic targets for breast cancer prevention...

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..Post-counsel women were significantly more likely to retain information if they were sent a post-clinic letter or if they assessed their personal risk as too high initially...

..A number of computer-based models have been developed. However, use of these models can be time consuming and difficult. The Manchester scoring system was developed in 2003 to simplify the selection process without losing accuracy...

..HER-2-positive breast cancer may have a predilection for the brain, or trastuzumab therapy may change the disease pattern by prolonging survival. New strategies to address this problem require investigation in this group of patients...

..These include alternating and sequential treatments, preferably with treatments changed before overt progression occurs...

..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 results are consistent with the suggestion that E2 may act to stimulate proliferation indirectly via a paracrine mechanism involving IGFs in normal as well as malignant human breast epithelial cells...

..Epithelial cells, which are the putative target cells for carcinogenesis in the breast, are therefore prone to promutagenic damage as a result of exposure to an environmental nitrosamine...

..Since weight gain impacts on survival, patients should be counselled to reduce energy intake and exercise during and after adjuvant treatment...

..Both questionnaires were found to have good predictive value and could be used in patients with advanced cancer to help screen out those with an affective disorder...

..The lack of survival benefit and excess toxicity seriously limits the wider application of this regime. It should not be used in place of standard dose palliative chemotherapy for metastatic breast cancer...

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..Fulvestrant might also have potential as a follow-on therapy after tamoxifen in an adjuvant setting and help alleviate some of the concerns surrounding long-term (up to 5 years) tamoxifen therapy...

..Among the patients with operable disease, there was no difference in overall survival (P = 0.42), relapse free survival (P = 0.69), and survival from the start of endocrine therapy (P = 0.85) according to body weight...

..005) without any significant increase in toxicity as assessed from animal weight. A PaTrin-2-temozolomide combination may therefore be beneficial in the treatment of human breast cancers...

..The problems of adherence to energy restriction in humans are well known...

..In this study, we report the implementation and screening results from the largest English Cancer Network...

..To establish the uptake of contralateral risk reducing mastectomy in women informed of their risks and options at time of diagnosis of their primary unilateral breast cancer...

..These observations may be accounted for by shared environmental factors within families or a common predisposing gene with low penetrance...

..Although it is probable that women are helped by genetic counselling and if at substantial risk, annual mammography, the psychological impact of assigning true risk and the value of mammography need to be evaluated...

..In an attempt overcome these negative aspects of tamoxifen therapy, 'pure' anti-oestrogens have been developed and are currently being investigated for the treatment of breast cancer...

..The authors reported the overall survival results from these studies...

..The ATAC trial provides the most mature data of any AI trial and has enabled the evaluation of a full risk:benefit profile of anastrozole...

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..Further research will define the role of this exciting new agent in the endocrine treatment of breast cancer...

..Sequencing options for the future are also discussed because non-steroidal AIs are increasingly used early in the treatment sequence...

..New approaches are required, however, not only to prevent the disease but to devise methods for their assessment that do not require very large and expensive clinical trials...

..85; odds ratio (95% CI) = 1.42 (1.01-2.01) (p = 0.044). Significant weight gain between the ages of 20 and 40 and the prevalence of central obesity amongst FH women suggest the need for weight management within FH clinics...

..Ongoing trials are investigating the efficacy of fulvestrant after failure on aromatase inhibitors and evaluating its use in combination with therapies that target growth factor receptor signaling pathways...

..Current and planned endocrine prevention trials in populations of pre- and postmenopausal women at risk of breast cancer are summarized and endocrine therapy after primary surgery and for advanced disease discussed...

..Other similar oestrogen antagonists are undergoing research and development, with a few currently being evaluated in phase II trials...

..Here, we summarize data supporting the difference between the two types of treatment and attempt to account for the underlying mechanisms that favour AIs...

..To describe and compare women's risk perceptions and recall of breast cancer risk information in a cohort of first-time attendees at a family history clinic...

..04 and p = 0.047, respectively) and benefit (p = 0.037 and p = 0.031, respectively) to the study. Taking these factors into account when advising women at the start of a chemoprevention trial may be helpful in improving compliance...

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..The emergence of aromatase inhibitors as an alternative to tamoxifen for the treatment of breast cancer is challenging the management of the disease and influencing the change of regulatory guidelines...

..This suggests that the response to oestrogen in normal breast is highly dependent upon epithelial-stromal/myoepithelial interactions which maintain the tissue microenvironment during epithelial cell proliferation...

..Only 30 patients (43% of cases) were detected as 'cases' by both questionnaires and this finding warrants further investigation...

..Future clinical studies will evaluate fulvestrant in adjuvant and neoadjuvant settings, together with its optimal sequencing in relation to tamoxifen and other endocrine therapies...

..We conclude that proliferation is negatively related to age and is influenced by the menstrual cycle but that additional as yet unknown factors must account for a large part of the variability seen in the data...

..Intermittent energy restriction may be a potential strategy for the primary prevention of breast cancer...

..Thus the effectiveness of chemotherapy may be enhanced and treatment duration shortened by the use of G-CSF infusions. Further studies of this promising approach are warranted...

..Consequently, inhibition of stem-cell self-renewal pathways should be explored because of the likelihood that residual stem cells might be resistant to current therapies...

..These data suggest prevention of weight gain between age 18 years and menopause or weight loss and maintenance during these years reduces risk of postmenopausal breast cancer...

..We aimed to determine whether p21(CIP1) or p27(KIP1) could induce a terminally differentiated phenotype in breast cells, and to examine if CDKI expression is regulated by basement membrane interactions...

..Recent candidate and genome-wide association studies have identified variants altering susceptibility to breast cancer...

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..We conclude that reduced expressions of genes in the lipid metabolism and glycolytic pathways are detectable in breast tissue following DER, and these may represent targets for DER mimetics as effective chemoprophylactic agents...

..It may be possible to increase effectiveness of ED by additional preventive agents or by lifestyle alterations...

..However, immunohistochemical offers a rapid and convenient method for assessing potential utility of O6-alkylating agents or O6-alkylguanine DNA-alkyltransferase inactivating agents in future studies of breast cancer treatment...

..The Gail, Claus, and Ford models all significantly underestimate risk, although the accuracy of the Claus model may be improved by adjustments for other risk factors...

..Further studies are required in order to determine its value for preventing complications of bone disease and possibly as an adjuvant to surgery for breast cancer...

..Low phenylalanine (phe) and tyrosine (tyr) diets limit tumour growth in animal models and may offer a novel cancer therapy. We studied the efficacy and acceptability of a low phe and tyr diet in patients with advanced cancer...

..Overall, the data suggest a direct role for ARF haploinsufficiency in melanoma predisposition and co-operation between ARF and CDKN2A in tumour formation, consistent with recent observations in Cdkn2a-specific knockout mice...

..Split-dose DTIC therefore does not appear to be a clinically effective approach to overcome O(6)-alkylating agent resistance in advanced breast cancer...

..Although the high contralateral breast cancer risk is confirmed by this study there is no real evidence for an increase in ipsilateral recurrence or new primary breast cancers in mutation carriers up to the 10-year point...

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..The aim of this study was to clarify these relationships, as circulating IGF-related peptides are potential surrogates of predisposition to common chronic diseases...

..The data suggest a model where scattered steroid receptor-positive cells are stem cells that self-renew through asymmetric cell division and generate patches of transit amplifying and differentiated cells...

..These interactions might explain resistance to endocrine treatments and offer solutions in terms of novel therapeutic targets...

..The reasons are complex and include differences in study design, lack of standardisation between assays, and variations in IGFBP-3 proteolytic activity--these are discussed in this commentary...

..The role of screening in this group of patients has not yet been assessed, but an international study combining CT with genomic and proteomic assessment is planned...

..Recommendations are made regarding terminology, indications, regimen, diagnosis before treatment, monitoring of efficacy, tumor localization, surgery, pathologic evaluation, and postoperative treatment...

..In view of the increased use of hormone therapies in an adjuvant and preventative setting their impact on cognitive functioning should be investigated more thoroughly...

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..Finally, recent results suggest that anastrozole may be superior to tamoxifen as adjuvant therapy for early stage disease in postmenopausal women with hormone-responsive disease...

..Management recommendations have been summarised in two algorithms, one for women experiencing a premature menopause and the other for postmenopausal women requiring adjuvant aromatase inhibitor therapy...