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Eva Hadadi Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium
Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium

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Hervé Acloque INSERM U935, University Paris Saclay, Villejuif, Ile-de-France, France
Université Paris-Saclay, INRAE, AgroParisTech, GABI, Jouy-en-Josas, Ile-de-France, France

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-inflammatory, anti-oxidative, anti-angiogenic, anti-proliferative and pro-apoptotic properties (reviewed in Hill et al. 2015 ). Melatonin is also able to disrupt oestrogen-dependent cell signalling and has also been shown to slow down EMT induction in breast

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P L Jeffery Ghrelin Research Group, Hormone-dependent Cancer Programme, School of Life Sciences, Queensland University of Technology, PO Box 2434, Brisbane 4001, Australia

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R E Murray Ghrelin Research Group, Hormone-dependent Cancer Programme, School of Life Sciences, Queensland University of Technology, PO Box 2434, Brisbane 4001, Australia

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A H Yeh Ghrelin Research Group, Hormone-dependent Cancer Programme, School of Life Sciences, Queensland University of Technology, PO Box 2434, Brisbane 4001, Australia

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J F McNamara Ghrelin Research Group, Hormone-dependent Cancer Programme, School of Life Sciences, Queensland University of Technology, PO Box 2434, Brisbane 4001, Australia

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R P Duncan Ghrelin Research Group, Hormone-dependent Cancer Programme, School of Life Sciences, Queensland University of Technology, PO Box 2434, Brisbane 4001, Australia

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G D Francis Ghrelin Research Group, Hormone-dependent Cancer Programme, School of Life Sciences, Queensland University of Technology, PO Box 2434, Brisbane 4001, Australia

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A C Herington Ghrelin Research Group, Hormone-dependent Cancer Programme, School of Life Sciences, Queensland University of Technology, PO Box 2434, Brisbane 4001, Australia

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L K Chopin Ghrelin Research Group, Hormone-dependent Cancer Programme, School of Life Sciences, Queensland University of Technology, PO Box 2434, Brisbane 4001, Australia

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autocrine/paracrine pathway exists to promote cell growth in breast cancer, as appears to be the case in prostate cancer ( Jeffery et al. 2002 ). Materials and methods Cell culture Oestrogen-dependent breast cancer

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S Zanardi
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D Serrano
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A Argusti
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M Barile
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M Puntoni
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A Decensi
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Introduction Despite recent progress in treatment and therapeutic strategies, breast cancer incidence, morbidity and mortality remain a major problem in Western countries. Recent trials with selective oestrogen receptor modulators

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H S Jacobs Reproductive Endocrinology, Royal Free and University College London Medical School, The Middlesex Hospital, Mortimer Street, London W1N 8AF, UK.

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The concern that postmenopausal hormone replacement therapy (HRT) may cause cancer of the breast has lead to an enormous volume of research in epidemiology, endocrinology and tumour cell biology. The epidemiology has become extremely sophisticated because the anticipated effect is small and there are several confounding factors. The consensus today is that long-term HRT (>10 years) is associated with an increase in the risk of breast cancer which, on average, is equivalent to delaying menopause for the same period of time that the patient is on treatment. The risk is related to endogenous and exogenous oestrogen levels. Studies that have investigated individual susceptibility are reviewed, as are environmental factors such as the interaction of HRT with alcohol intake. The clinical implication of these data is that the dosage of HRT should be the smallest that is efficacious. Subcutaneous implants of oestrogen typically cause very high oestrogen levels and, in the opinion of this reviewer, should be restricted to women unable to take or absorb oestrogen by mouth or percutaneously. Finally, the issue of HRT for women with a history of breast cancer is considered. The potential is discussed for treatment of women with severe symptoms of oestrogen deficiency with a low dose of oestrogen, together with a selective oestrogen receptor modulator to protect the breast.

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Nelson Rangel Department of Medical Sciences, University of Turin, Turin, Italy
Natural and Mathematical Sciences Faculty, Universidad del Rosario, Bogotá, Colombia

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Milena Rondon-Lagos School of Biological Sciences, Universidad Pedagógica y Tecnológica de Colombia, Tunja, Colombia

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Laura Annaratone Department of Medical Sciences, University of Turin, Turin, Italy

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Simona Osella-Abate Department of Medical Sciences, University of Turin, Turin, Italy

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Jasna Metovic Department of Medical Sciences, University of Turin, Turin, Italy

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Maria Piera Mano Department of Surgical Sciences, University of Turin, Turin, Italy

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Luca Bertero Department of Medical Sciences, University of Turin, Turin, Italy

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Paola Cassoni Department of Medical Sciences, University of Turin, Turin, Italy

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Anna Sapino Department of Medical Sciences, University of Turin, Turin, Italy
Pathology Unit, Fondazione del Piemonte per l’Oncologia (FPO) Candiolo Cancer Institute (IRCCS), Candiolo, Italy

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Isabella Castellano Department of Medical Sciences, University of Turin, Turin, Italy

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Introduction Oestrogen receptor (ER) and progesterone receptor (PgR) are expressed in most breast cancers (BCs) (~75%) and both have wide prognostic and predictive utility ( Early Breast Cancer Trialists’ Collaborative Group 2011 ). In

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Dennis H Dowhan Institute for Molecular Bioscience, School of Chemistry and Molecular Biosciences, Prince Henry's Institute for Medical Research, Laboratory for Cancer Medicine, Dame Roma Mitchell Cancer Research Laboratories, University of Sydney Western Clinical School, The University of Queensland, Brisbane, Queensland 4072, Australia

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Matthew J Harrison Institute for Molecular Bioscience, School of Chemistry and Molecular Biosciences, Prince Henry's Institute for Medical Research, Laboratory for Cancer Medicine, Dame Roma Mitchell Cancer Research Laboratories, University of Sydney Western Clinical School, The University of Queensland, Brisbane, Queensland 4072, Australia

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Natalie A Eriksson Institute for Molecular Bioscience, School of Chemistry and Molecular Biosciences, Prince Henry's Institute for Medical Research, Laboratory for Cancer Medicine, Dame Roma Mitchell Cancer Research Laboratories, University of Sydney Western Clinical School, The University of Queensland, Brisbane, Queensland 4072, Australia

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Peter Bailey Institute for Molecular Bioscience, School of Chemistry and Molecular Biosciences, Prince Henry's Institute for Medical Research, Laboratory for Cancer Medicine, Dame Roma Mitchell Cancer Research Laboratories, University of Sydney Western Clinical School, The University of Queensland, Brisbane, Queensland 4072, Australia

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Michael A Pearen Institute for Molecular Bioscience, School of Chemistry and Molecular Biosciences, Prince Henry's Institute for Medical Research, Laboratory for Cancer Medicine, Dame Roma Mitchell Cancer Research Laboratories, University of Sydney Western Clinical School, The University of Queensland, Brisbane, Queensland 4072, Australia

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Peter J Fuller Institute for Molecular Bioscience, School of Chemistry and Molecular Biosciences, Prince Henry's Institute for Medical Research, Laboratory for Cancer Medicine, Dame Roma Mitchell Cancer Research Laboratories, University of Sydney Western Clinical School, The University of Queensland, Brisbane, Queensland 4072, Australia

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John W Funder Institute for Molecular Bioscience, School of Chemistry and Molecular Biosciences, Prince Henry's Institute for Medical Research, Laboratory for Cancer Medicine, Dame Roma Mitchell Cancer Research Laboratories, University of Sydney Western Clinical School, The University of Queensland, Brisbane, Queensland 4072, Australia

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Evan R Simpson Institute for Molecular Bioscience, School of Chemistry and Molecular Biosciences, Prince Henry's Institute for Medical Research, Laboratory for Cancer Medicine, Dame Roma Mitchell Cancer Research Laboratories, University of Sydney Western Clinical School, The University of Queensland, Brisbane, Queensland 4072, Australia

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Peter J Leedman Institute for Molecular Bioscience, School of Chemistry and Molecular Biosciences, Prince Henry's Institute for Medical Research, Laboratory for Cancer Medicine, Dame Roma Mitchell Cancer Research Laboratories, University of Sydney Western Clinical School, The University of Queensland, Brisbane, Queensland 4072, Australia

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Wayne D Tilley Institute for Molecular Bioscience, School of Chemistry and Molecular Biosciences, Prince Henry's Institute for Medical Research, Laboratory for Cancer Medicine, Dame Roma Mitchell Cancer Research Laboratories, University of Sydney Western Clinical School, The University of Queensland, Brisbane, Queensland 4072, Australia

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Melissa A Brown Institute for Molecular Bioscience, School of Chemistry and Molecular Biosciences, Prince Henry's Institute for Medical Research, Laboratory for Cancer Medicine, Dame Roma Mitchell Cancer Research Laboratories, University of Sydney Western Clinical School, The University of Queensland, Brisbane, Queensland 4072, Australia

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Christine L Clarke Institute for Molecular Bioscience, School of Chemistry and Molecular Biosciences, Prince Henry's Institute for Medical Research, Laboratory for Cancer Medicine, Dame Roma Mitchell Cancer Research Laboratories, University of Sydney Western Clinical School, The University of Queensland, Brisbane, Queensland 4072, Australia

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George E O Muscat Institute for Molecular Bioscience, School of Chemistry and Molecular Biosciences, Prince Henry's Institute for Medical Research, Laboratory for Cancer Medicine, Dame Roma Mitchell Cancer Research Laboratories, University of Sydney Western Clinical School, The University of Queensland, Brisbane, Queensland 4072, Australia

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metabolism, dysregulated in nasopharyngeal carcinoma Dodd et al . (2006) PA2G4 Inhibition of heregulin-mediated MCF-7 breast cancer cell growth Zhang et al . (2008) PRKCD Pro-proliferative factor in oestrogen-dependent breast cancer cells McCracken et al

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W R Miller
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R L Sutherland
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C K W Watts
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E A Musgrove
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Céline Van Themsche Research Group in Molecular Oncology and Endocrinology, Department of Chemistry and Biology, Canada Research Chair in Molecular Gyneco-Oncology, Université du Québec à Trois-Rivières, 3351, Boul. des Forges, CP 500, Trois-Rivières, Québec, Canada G9A 5H7

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Sophie Parent Research Group in Molecular Oncology and Endocrinology, Department of Chemistry and Biology, Canada Research Chair in Molecular Gyneco-Oncology, Université du Québec à Trois-Rivières, 3351, Boul. des Forges, CP 500, Trois-Rivières, Québec, Canada G9A 5H7

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Valérie Leblanc Research Group in Molecular Oncology and Endocrinology, Department of Chemistry and Biology, Canada Research Chair in Molecular Gyneco-Oncology, Université du Québec à Trois-Rivières, 3351, Boul. des Forges, CP 500, Trois-Rivières, Québec, Canada G9A 5H7

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Caroline Descôteaux Research Group in Molecular Oncology and Endocrinology, Department of Chemistry and Biology, Canada Research Chair in Molecular Gyneco-Oncology, Université du Québec à Trois-Rivières, 3351, Boul. des Forges, CP 500, Trois-Rivières, Québec, Canada G9A 5H7

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Anne-Marie Simard Research Group in Molecular Oncology and Endocrinology, Department of Chemistry and Biology, Canada Research Chair in Molecular Gyneco-Oncology, Université du Québec à Trois-Rivières, 3351, Boul. des Forges, CP 500, Trois-Rivières, Québec, Canada G9A 5H7

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Gervais Bérubé Research Group in Molecular Oncology and Endocrinology, Department of Chemistry and Biology, Canada Research Chair in Molecular Gyneco-Oncology, Université du Québec à Trois-Rivières, 3351, Boul. des Forges, CP 500, Trois-Rivières, Québec, Canada G9A 5H7

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Eric Asselin Research Group in Molecular Oncology and Endocrinology, Department of Chemistry and Biology, Canada Research Chair in Molecular Gyneco-Oncology, Université du Québec à Trois-Rivières, 3351, Boul. des Forges, CP 500, Trois-Rivières, Québec, Canada G9A 5H7

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Introduction Most breast cancers are classified as hormone dependent due to the overexpression of oestrogen receptors (ERα in particular), compared to corresponding normal tissues ( Sommer & Fuqua 2001 ). ERα has already been validated as a

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J H H Thijssen
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M A Blankenstein
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