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C J Fabian
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B F Kimler
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M S Mayo
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S A Khan
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Breast tissue and duct fluid provide a rich source of biomarkers to both aid in the assessment of short-term risk of developing breast cancer and predict and assess responses to prevention interventions. There are three methods currently being utilized to sample breast tissue in asymptomatic women for risk assessment: nipple-aspirate fluid (NAF), random periareolar fine-needle aspiration (RPFNA) and ductal lavage. Prospective single-institution trials have shown that the presence of atypical cells in NAF fluid or RPFNA specimens is associated with an increased risk of breast cancer. Furthermore, RPFNA-detected atypia has been observed to further stratify risk based on the commonly used Gail risk-assessment model. A prospective trial evaluating risk prediction on the basis of atypical cells in ductal-lavage fluid is ongoing. The ability of other established non-genetic biomarkers (mammographic breast density; serum levels of bioavailable estradiol, testosterone, insulin-like growth factor-1 and its insulin like growth factor binding protein-3) to stratify risk based on the Gail model is as yet incompletely defined. Modulation of breast intra-epithelial neoplasia (i.e. hyperplasia with or without atypia) with or without associated breast-tissue molecular markers, such as proliferation, is currently being used to evaluate response in Phase II chemoprevention trials. RPFNA has been the method most frequently used for Phase II studies of 6–12 months duration. However, ductal lavage, RPFNA and random and directed core needle biopsies are all being utilized in ongoing multi-institutional Phase II studies. The strengths and weaknesses of each method are reviewed.

Article Type:
Review Article
DOI:
https://doi.org/10.1677/erc.1.01000
Volume/Issue:
Volume 12: Issue 2
Free access
M K Wu Department of Medical Genetics, Lady Davis Institute Jewish General Hospital, McGill University, Department Endocrinology and Diabetes, Lady Cilento Children's Hospital, School of Medicine, University of Queensland, Queensland Children's Medical Research Institute, Department of Histopathology, King Edward Memorial Hospital, John Hunter Children's Hospital, School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, School of Paediatrics and Child Health, University of Western Australia, Department of Paediatric Endocrinology and Diabetes, Princess Margaret Hospital for Children, Child and Adolescent Health Service, Genetics and Epigenetics in Health and Disease Genetics and Genomic Medicine Programme UCL Institute of Child Health Great Ormond Street Hospital for Children, The Scripps Research Institute, Departments of Oncology and Experimental Medicine, McGill University, Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montréal, Quebec, Canada

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L de Kock Department of Medical Genetics, Lady Davis Institute Jewish General Hospital, McGill University, Department Endocrinology and Diabetes, Lady Cilento Children's Hospital, School of Medicine, University of Queensland, Queensland Children's Medical Research Institute, Department of Histopathology, King Edward Memorial Hospital, John Hunter Children's Hospital, School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, School of Paediatrics and Child Health, University of Western Australia, Department of Paediatric Endocrinology and Diabetes, Princess Margaret Hospital for Children, Child and Adolescent Health Service, Genetics and Epigenetics in Health and Disease Genetics and Genomic Medicine Programme UCL Institute of Child Health Great Ormond Street Hospital for Children, The Scripps Research Institute, Departments of Oncology and Experimental Medicine, McGill University, Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montréal, Quebec, Canada

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L S Conwell Department of Medical Genetics, Lady Davis Institute Jewish General Hospital, McGill University, Department Endocrinology and Diabetes, Lady Cilento Children's Hospital, School of Medicine, University of Queensland, Queensland Children's Medical Research Institute, Department of Histopathology, King Edward Memorial Hospital, John Hunter Children's Hospital, School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, School of Paediatrics and Child Health, University of Western Australia, Department of Paediatric Endocrinology and Diabetes, Princess Margaret Hospital for Children, Child and Adolescent Health Service, Genetics and Epigenetics in Health and Disease Genetics and Genomic Medicine Programme UCL Institute of Child Health Great Ormond Street Hospital for Children, The Scripps Research Institute, Departments of Oncology and Experimental Medicine, McGill University, Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montréal, Quebec, Canada
Department of Medical Genetics, Lady Davis Institute Jewish General Hospital, McGill University, Department Endocrinology and Diabetes, Lady Cilento Children's Hospital, School of Medicine, University of Queensland, Queensland Children's Medical Research Institute, Department of Histopathology, King Edward Memorial Hospital, John Hunter Children's Hospital, School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, School of Paediatrics and Child Health, University of Western Australia, Department of Paediatric Endocrinology and Diabetes, Princess Margaret Hospital for Children, Child and Adolescent Health Service, Genetics and Epigenetics in Health and Disease Genetics and Genomic Medicine Programme UCL Institute of Child Health Great Ormond Street Hospital for Children, The Scripps Research Institute, Departments of Oncology and Experimental Medicine, McGill University, Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montréal, Quebec, Canada
Department of Medical Genetics, Lady Davis Institute Jewish General Hospital, McGill University, Department Endocrinology and Diabetes, Lady Cilento Children's Hospital, School of Medicine, University of Queensland, Queensland Children's Medical Research Institute, Department of Histopathology, King Edward Memorial Hospital, John Hunter Children's Hospital, School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, School of Paediatrics and Child Health, University of Western Australia, Department of Paediatric Endocrinology and Diabetes, Princess Margaret Hospital for Children, Child and Adolescent Health Service, Genetics and Epigenetics in Health and Disease Genetics and Genomic Medicine Programme UCL Institute of Child Health Great Ormond Street Hospital for Children, The Scripps Research Institute, Departments of Oncology and Experimental Medicine, McGill University, Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montréal, Quebec, Canada

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C J R Stewart Department of Medical Genetics, Lady Davis Institute Jewish General Hospital, McGill University, Department Endocrinology and Diabetes, Lady Cilento Children's Hospital, School of Medicine, University of Queensland, Queensland Children's Medical Research Institute, Department of Histopathology, King Edward Memorial Hospital, John Hunter Children's Hospital, School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, School of Paediatrics and Child Health, University of Western Australia, Department of Paediatric Endocrinology and Diabetes, Princess Margaret Hospital for Children, Child and Adolescent Health Service, Genetics and Epigenetics in Health and Disease Genetics and Genomic Medicine Programme UCL Institute of Child Health Great Ormond Street Hospital for Children, The Scripps Research Institute, Departments of Oncology and Experimental Medicine, McGill University, Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montréal, Quebec, Canada

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B R King Department of Medical Genetics, Lady Davis Institute Jewish General Hospital, McGill University, Department Endocrinology and Diabetes, Lady Cilento Children's Hospital, School of Medicine, University of Queensland, Queensland Children's Medical Research Institute, Department of Histopathology, King Edward Memorial Hospital, John Hunter Children's Hospital, School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, School of Paediatrics and Child Health, University of Western Australia, Department of Paediatric Endocrinology and Diabetes, Princess Margaret Hospital for Children, Child and Adolescent Health Service, Genetics and Epigenetics in Health and Disease Genetics and Genomic Medicine Programme UCL Institute of Child Health Great Ormond Street Hospital for Children, The Scripps Research Institute, Departments of Oncology and Experimental Medicine, McGill University, Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montréal, Quebec, Canada
Department of Medical Genetics, Lady Davis Institute Jewish General Hospital, McGill University, Department Endocrinology and Diabetes, Lady Cilento Children's Hospital, School of Medicine, University of Queensland, Queensland Children's Medical Research Institute, Department of Histopathology, King Edward Memorial Hospital, John Hunter Children's Hospital, School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, School of Paediatrics and Child Health, University of Western Australia, Department of Paediatric Endocrinology and Diabetes, Princess Margaret Hospital for Children, Child and Adolescent Health Service, Genetics and Epigenetics in Health and Disease Genetics and Genomic Medicine Programme UCL Institute of Child Health Great Ormond Street Hospital for Children, The Scripps Research Institute, Departments of Oncology and Experimental Medicine, McGill University, Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montréal, Quebec, Canada

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C S Choong Department of Medical Genetics, Lady Davis Institute Jewish General Hospital, McGill University, Department Endocrinology and Diabetes, Lady Cilento Children's Hospital, School of Medicine, University of Queensland, Queensland Children's Medical Research Institute, Department of Histopathology, King Edward Memorial Hospital, John Hunter Children's Hospital, School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, School of Paediatrics and Child Health, University of Western Australia, Department of Paediatric Endocrinology and Diabetes, Princess Margaret Hospital for Children, Child and Adolescent Health Service, Genetics and Epigenetics in Health and Disease Genetics and Genomic Medicine Programme UCL Institute of Child Health Great Ormond Street Hospital for Children, The Scripps Research Institute, Departments of Oncology and Experimental Medicine, McGill University, Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montréal, Quebec, Canada
Department of Medical Genetics, Lady Davis Institute Jewish General Hospital, McGill University, Department Endocrinology and Diabetes, Lady Cilento Children's Hospital, School of Medicine, University of Queensland, Queensland Children's Medical Research Institute, Department of Histopathology, King Edward Memorial Hospital, John Hunter Children's Hospital, School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, School of Paediatrics and Child Health, University of Western Australia, Department of Paediatric Endocrinology and Diabetes, Princess Margaret Hospital for Children, Child and Adolescent Health Service, Genetics and Epigenetics in Health and Disease Genetics and Genomic Medicine Programme UCL Institute of Child Health Great Ormond Street Hospital for Children, The Scripps Research Institute, Departments of Oncology and Experimental Medicine, McGill University, Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montréal, Quebec, Canada

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K Hussain Department of Medical Genetics, Lady Davis Institute Jewish General Hospital, McGill University, Department Endocrinology and Diabetes, Lady Cilento Children's Hospital, School of Medicine, University of Queensland, Queensland Children's Medical Research Institute, Department of Histopathology, King Edward Memorial Hospital, John Hunter Children's Hospital, School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, School of Paediatrics and Child Health, University of Western Australia, Department of Paediatric Endocrinology and Diabetes, Princess Margaret Hospital for Children, Child and Adolescent Health Service, Genetics and Epigenetics in Health and Disease Genetics and Genomic Medicine Programme UCL Institute of Child Health Great Ormond Street Hospital for Children, The Scripps Research Institute, Departments of Oncology and Experimental Medicine, McGill University, Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montréal, Quebec, Canada

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N Sabbaghian Department of Medical Genetics, Lady Davis Institute Jewish General Hospital, McGill University, Department Endocrinology and Diabetes, Lady Cilento Children's Hospital, School of Medicine, University of Queensland, Queensland Children's Medical Research Institute, Department of Histopathology, King Edward Memorial Hospital, John Hunter Children's Hospital, School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, School of Paediatrics and Child Health, University of Western Australia, Department of Paediatric Endocrinology and Diabetes, Princess Margaret Hospital for Children, Child and Adolescent Health Service, Genetics and Epigenetics in Health and Disease Genetics and Genomic Medicine Programme UCL Institute of Child Health Great Ormond Street Hospital for Children, The Scripps Research Institute, Departments of Oncology and Experimental Medicine, McGill University, Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montréal, Quebec, Canada

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I J MacRae Department of Medical Genetics, Lady Davis Institute Jewish General Hospital, McGill University, Department Endocrinology and Diabetes, Lady Cilento Children's Hospital, School of Medicine, University of Queensland, Queensland Children's Medical Research Institute, Department of Histopathology, King Edward Memorial Hospital, John Hunter Children's Hospital, School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, School of Paediatrics and Child Health, University of Western Australia, Department of Paediatric Endocrinology and Diabetes, Princess Margaret Hospital for Children, Child and Adolescent Health Service, Genetics and Epigenetics in Health and Disease Genetics and Genomic Medicine Programme UCL Institute of Child Health Great Ormond Street Hospital for Children, The Scripps Research Institute, Departments of Oncology and Experimental Medicine, McGill University, Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montréal, Quebec, Canada

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M R Fabian Department of Medical Genetics, Lady Davis Institute Jewish General Hospital, McGill University, Department Endocrinology and Diabetes, Lady Cilento Children's Hospital, School of Medicine, University of Queensland, Queensland Children's Medical Research Institute, Department of Histopathology, King Edward Memorial Hospital, John Hunter Children's Hospital, School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, School of Paediatrics and Child Health, University of Western Australia, Department of Paediatric Endocrinology and Diabetes, Princess Margaret Hospital for Children, Child and Adolescent Health Service, Genetics and Epigenetics in Health and Disease Genetics and Genomic Medicine Programme UCL Institute of Child Health Great Ormond Street Hospital for Children, The Scripps Research Institute, Departments of Oncology and Experimental Medicine, McGill University, Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montréal, Quebec, Canada

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W D Foulkes Department of Medical Genetics, Lady Davis Institute Jewish General Hospital, McGill University, Department Endocrinology and Diabetes, Lady Cilento Children's Hospital, School of Medicine, University of Queensland, Queensland Children's Medical Research Institute, Department of Histopathology, King Edward Memorial Hospital, John Hunter Children's Hospital, School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, School of Paediatrics and Child Health, University of Western Australia, Department of Paediatric Endocrinology and Diabetes, Princess Margaret Hospital for Children, Child and Adolescent Health Service, Genetics and Epigenetics in Health and Disease Genetics and Genomic Medicine Programme UCL Institute of Child Health Great Ormond Street Hospital for Children, The Scripps Research Institute, Departments of Oncology and Experimental Medicine, McGill University, Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montréal, Quebec, Canada
Department of Medical Genetics, Lady Davis Institute Jewish General Hospital, McGill University, Department Endocrinology and Diabetes, Lady Cilento Children's Hospital, School of Medicine, University of Queensland, Queensland Children's Medical Research Institute, Department of Histopathology, King Edward Memorial Hospital, John Hunter Children's Hospital, School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, School of Paediatrics and Child Health, University of Western Australia, Department of Paediatric Endocrinology and Diabetes, Princess Margaret Hospital for Children, Child and Adolescent Health Service, Genetics and Epigenetics in Health and Disease Genetics and Genomic Medicine Programme UCL Institute of Child Health Great Ormond Street Hospital for Children, The Scripps Research Institute, Departments of Oncology and Experimental Medicine, McGill University, Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montréal, Quebec, Canada

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Article Type:
Letter
DOI:
https://doi.org/10.1530/ERC-15-0460
Volume/Issue:
Volume 23: Issue 2
Free access