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W R Miller
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Glorianne Lazaro
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Chris Smith
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Lindy Goddard
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Nicola Jordan
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Richard McClelland
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Peter Barrett-Lee School of Pharmacy and Pharmaceutical Sciences, Velindre Cancer Centre, Cardiff University, Redwood Building, Cardiff, Wales CF10 3NB, UK

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Robert I Nicholson
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Stephen Hiscox
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Introduction Molecular and biological profiling has identified a subset of oestrogen receptor-positive (ER+) luminal breast cancers that co-expresses the epidermal growth factor receptor 2 (ERBB2/‘HER2’) protein ( Guiu et al . 2012 ). HER2

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Minlu Zhang Department of Cancer Control and Prevention, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, People’s Republic of China
Department of Biostatistics, School of Public Health and Key Lab of Health Technology Assessment, National Health and Family Planning Commission of the People’s Republic of China, Fudan University, Shanghai, People’s Republic of China

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Peng Peng Department of Cancer Control and Prevention, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, People’s Republic of China

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Kai Gu Department of Cancer Control and Prevention, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, People’s Republic of China

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Hui Cai Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

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Guoyou Qin Department of Biostatistics, School of Public Health and Key Lab of Health Technology Assessment, National Health and Family Planning Commission of the People’s Republic of China, Fudan University, Shanghai, People’s Republic of China
Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai, People’s Republic of China

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Xiao Ou Shu Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

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Pingping Bao Department of Cancer Control and Prevention, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, People’s Republic of China

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node status ( Arriagada et al . 2006 ), clinical stage ( Zahl & Tretli 1997 , Natarajan et al . 2009 ), oestrogen receptor (ER) status ( Hess et al . 2003 , Dignam et al . 2009 ) and molecular subtypes ( Mulligan et al . 2008 , O’Brien et al

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Xiong Wang Department of Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, China
Department of Pharmacy, Tongren hospital affiliated to Wuhan University (the third hospital of Wuhan), Wuhan, China

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Li Ma Department of Pharmacy, Tongren hospital affiliated to Wuhan University (the third hospital of Wuhan), Wuhan, China

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Qiao-yan Ding Department of Pharmacy, Tongren hospital affiliated to Wuhan University (the third hospital of Wuhan), Wuhan, China

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Wen-yu Zhang College of Pharmacy, The Ohio State University, Columbus, Ohio, USA

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Yong-gang Chen Department of Pharmacy, Tongren hospital affiliated to Wuhan University (the third hospital of Wuhan), Wuhan, China

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Jin-hu Wu Department of Pharmacy, Tongren hospital affiliated to Wuhan University (the third hospital of Wuhan), Wuhan, China

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Hong-feng Zhang Department of Pathology, the central hospital of Wuhan, Tongji medical college, Huazhong University of Science and Technology, Wuhan, China

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Xiu-li Guo Department of Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, China

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Institute, Beijing, China. Prolactinoma animal models Oestrogen-treated rats and intragastric administration The oestrogen-treated rat is a well-known model of pituitary lactotroph hyperplasia and hyperprolactinaemia ( Heaney et al. 1999 ). The

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J Marsden
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N P M Sacks
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M P Schrey
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K V Patel
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T J Powles
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J Chang
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W R Miller Breast Research Unit, Western General Hospital, Edinburgh, UK.

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Both mammary adipose tissue and breast cancers have the ability to aromatize androgens into oestrogens. Such potential may maintain the growth of hormone-dependent tumours. It has therefore been important to determine the effects of new aromatase inhibitors such as formestane, exemestane, anastrozole and letrozole on oestrogen biosynthesis and concentrations of endogenous hormones within the breast. Studies based on in vitro incubations of breast cancer and cultures of mammary adipose tissue fibroblasts demonstrate that these drugs are highly effective inhibitors, with IC50 values ranging between 1 and 50 nM (although the relative efficacy varies between tissues and test systems). Despite this potential, in vitro incubations of breast tissues from patients treated with type II inhibitors such as aminoglutethimide and letrozole can display paradoxically high aromatase activity; this appears to be caused by the reversible nature of the inhibition, coupled with induction/stabilization of the aromatase enzyme. To assess in situ effects within the breast, postmenopausal women with large primary breast cancers have been treated neoadjuvantly with aromatase inhibitors using a protocol that included (i) breast biopsy before treatment, (ii) definitive surgery after 3 months of treatment and (iii) infusion of [3H]androstenedione and [14C]oestrone in the 18 h immediately before biopsy and surgery. With this study design, it has been shown that drugs such as letrozole profoundly inhibit in situ aromatase activity and reduce endogenous oestrogens within the breast.

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Catrin Lutz C Lutz, Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, Netherlands

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Hendrik A Messal H Messal, Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, Netherlands

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Damir Vareslija D Vareslija, School of Pharmacy and Biomolecular Sciences, RCSI, Dublin, Ireland

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Stefan Prekovic S Prekovic, Center for Molecular Medicine, UMC Utrecht, Utrecht, Netherlands

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The breast epithelium, vital for mammary gland function, is influenced by oestrogen through the ER signalling pathway. Luminal breast cancer, characterised by ER expression, comprises the majority of all breast cancers and presents significant clinical challenges due to therapy resistance and recurrence. Despite advancements in understanding luminal disease, improving long-term survival and reducing relapse of breast cancer patients by predicting therapy efficacy and understanding resistance mechanisms remain critical challenges. This review discusses luminal breast cancer biology, focusing on molecular classification of the primary disease, metastatic spread, and experimental models.

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A O Mueck Section of Endocrinology and Menopause, Women's University Hospital, Tuebingen, Germany. endo.meno@med.uni-tuebingen.de

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H Seeger Section of Endocrinology and Menopause, Women's University Hospital, Tuebingen, Germany. endo.meno@med.uni-tuebingen.de

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Endometrial carcinoma is listed under the absolute contraindications to hormone therapy (HT). According to current opinion, HT after stage I or II is still considered an option, and continuous combined oestrogen/progestogen replacement therapy (CCEPT) would be recommended. However, up to now, only observational studies have been put forward. Although none of these studies have established an increased rate of recurrence or mortality, alternatives such as phytopreparations and tibolone, or particular psychotherapeutic drugs, such as venlafaxine, should be considered for the relief of climacteric complaints. Progestogen-only therapy (PT) particularly has been considered. However, the currently discussed possible progestogen effects regarding an increased risk of breast cancer have to be taken into account. Indeed, the wider discussion about the gestagen effects regarding the risk of breast cancer is to be considered. Generally, after hysterectomy, at least for patients with cardiovascular risk factors, the preference today is to use low-dose oestrogen therapy (patches or gels) instead of CCEPT, and this is also now recommended for patients after endometrial cancer. This is to be noted because of the risk factors for endometrial carcinoma, such as hypertension, obesity, polycystic ovary syndrome (PCO) and diabetes mellitus. However, each form of HT should be only exceptionally recommended, and the patients must be informed about the risks that exist and the use of alternatives.

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