Molecular evolution of breast cancer

Authors

  • Peter T Simpson,

    1. The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, London, UK
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    • These authors contributed equally to the writing of this review

  • Jorge S Reis-Filho,

    1. The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, London, UK
    2. IPATIMUP—Institute of Molecular Pathology and Immunology, University of Porto, Portugal
    3. School of Health Sciences, University of Minho, Braga, Portugal
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    • These authors contributed equally to the writing of this review

  • Theodora Gale,

    1. The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, London, UK
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  • Sunil R Lakhani

    Corresponding author
    1. Molecular and Cellular Pathology, School of Medicine, University of Queensland, Royal Brisbane and Women's Hospital and Queensland Institute of Medical Research, Brisbane, Australia
    • Head, Molecular and Cellular Pathology, School of Medicine, University of Queensland, Mayne Medical School, Herston Road, Herston, Brisbane, QLD 4006, Australia.
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Abstract

Molecular analysis of invasive breast cancer and its precursors has furthered our understanding of breast cancer progression. In the past few years, new multi-step pathways of breast cancer progression have been delineated through genotypic–phenotypic correlations. Nuclear grade, more than any other pathological feature, is strongly associated with the number and pattern of molecular genetic abnormalities in breast cancer cells. Thus, there are two distinct major pathways to the evolution of low- and high-grade invasive carcinomas: whilst the former consistently show oestrogen receptor (ER) and progesterone receptor (PgR) positivity and 16q loss, the latter are usually ER/PgR-negative and show Her-2 overexpression/amplification and complex karyotypes. The boundaries between the evolutionary pathways of well-differentiated/low-grade ductal and lobular carcinomas have been blurred, with changes in E-cadherin expression being one of the few distinguishing features between the two. In addition, lesions long thought to be precursors of breast carcinomas, such as hyperplasia of usual type, are currently considered mere risk indicators, whilst columnar cell lesions are now implicated as non-obligate precursors of atypical ductal hyperplasia (ADH) and well-differentiated ductal carcinoma in situ (DCIS). However, only through the combination of comprehensive morphological analysis and cutting-edge molecular tools can this knowledge be translated into clinical practice and patient management. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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