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Genetic Alterations in Normal and Malignant Breast Tissue

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Breast Cancer

Abstract

Breast cancer is a heterogeneous disease with a wide spectrum of morphological subtypes and a range of clinical behaviors. Over a long time period, pathologists have evolved a system of recording cancer-related data that reflects this heterogeneity as well as providing information relevant to prognosis and prediction of response to therapy. It is well established that subtype of breast cancer, grade, and stage (Ellis et al. 1992; Elston and Ellis 1991) provide prognostic information and the use of steroid receptor analysis as well as overexpression and amplification of HER2 provides prognostic and predictive data to manage patients (Oldenhuis et al. 2008). Nonetheless, there are limitations to these data and it is well known clinically that even within the same subtype (e.g., tubular carcinoma) or same stage of disease (e.g., lymph node positive), the behavior can be markedly different. Understanding the molecular abnormalities that drive the biology of each disease will assist our ability to specifically inhibit it.

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Abbreviations

ADH:

Atypical ductal hyperplasia

ALDH1:

Aldehyde dehydrogenase 1

ALH:

Atypical lobular hyperplasia

CAF:

Cancer associated fibroblasts

CCL:

Columnar cell lesion

CGH:

Comparative genomic hybridization

DCIS:

Ductal carcinoma in situ

ECM:

Extracellular matrix

FEA:

Flat epithelial atypia

FFPE:

Formalin fixed paraffin embedded

G6PD:

Glucose-6-phosphate dehydrogenase

HR:

Homologous recombination

HUT:

Hyperplasia usual type

ILC:

Invasive lobular carcinoma

IDC:

Invasive ductal carcinoma

LCIS:

Lobular carcinoma in situ

LOH:

Loss of heterozygosity

NS:

Normal stroma

PLC:

Pleomorphic lobular carcinoma

ROH:

Retention of heterozygosity

SNP:

Single nucleotide polymorphism

TDLU:

Terminal ductal-lobular unit

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Acknowledgments

Ana Cristina Vargas is a clinical fellow funded by the Ludwig Institute for Cancer Research. We acknowledge Prof Michael O’Hare and Dr Catherine Clarke who made a significant contribution to our studies and understanding of normal breast epithelial cell biology.

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Authors and Affiliations

  1. University of Queensland Centre for Clinical Research, School of Medicine, and Pathology Queensland, The Royal Brisbane & Women’s Hospital, Brisbane, Queensland, Australia

    Sunil R. Lakhani

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  1. Chanel E. Smart
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  2. Peter T. Simpson
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  3. Ana Cristina Vargas
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Correspondence to Sunil R. Lakhani .

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  1. Department of Pathology and Clinical Cyt, Falun Central Hospital, Falun, 791 82, Sweden

    Tibor Tot

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Smart, C.E., Simpson, P.T., Vargas, A.C., Lakhani, S.R. (2010). Genetic Alterations in Normal and Malignant Breast Tissue. In: Tot, T. (eds) Breast Cancer. Springer, London. https://doi.org/10.1007/978-1-84996-314-5_4

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