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Hereditary Breast Cancer Genetics and Risk Prediction Techniques

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Breast Cancer Management for Surgeons

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Abstract

Around 10% of individuals with breast cancer carry an inherited germline cancer susceptibility mutation, of which BRCA1 and BRCA2 confer the highest risk. Increased familial breast cancer risk is also observed in families testing negative for high-risk germline mutations, suggesting that polygenic interactions of multiple lower-penetrance susceptibility alleles, in addition to traditional breast cancer risk factors, are important causes of familial breast cancer.

Hereditary breast cancers are a significant subgroup of the overall breast cancer disease burden due to their specific management implications. Furthermore, inherited cancer models have heralded new paradigms in our understanding of both somatic and inherited cancer development. This chapter will outline the basics of oncogenesis, key concepts in genetics and inherited breast cancer susceptibility genes. It will discuss risk prediction techniques and, finally, approaches to genetic testing in breast cancer.

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Abbreviations

ACGH:

Array comparative genome hybridisation

CNV:

Copy number variation

CS:

Cowden syndrome

ER:

Oestrogen receptor

FISH:

Fluorescence in situ hybridisation

GWAS:

Genome-wide association study

HER2:

Human epidermal growth factor receptor 2

LFS:

Li-Fraumeni syndrome

MLPA:

Multiplex Ligation-dependent Probe Amplification

MSS:

Manchester scoring system

NCCN:

National Comprehensive Cancer Network (USA)

NGS:

Next-generation sequencing

NICE:

National Institute of Health and Care Excellence (UK)

PJS:

Peutz-Jeghers syndrome

PR:

Progesterone receptor

SNP:

Single nucleotide polymorphism

TNT:

Triple-negative tumour

TSG:

Tumour suppressor gene

VUS:

Variant of unknown significance

WES:

Whole exome sequencing

WGS:

Whole genome sequencing

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Authors and Affiliations

  1. Guy’s and St. Thomas’ NHS Foundation Trust, Department of Clinical Genetics, Guy’s Hospital, London, UK

    Helena Carley MBChB(Hons) BSc(Hons)

  2. Clinical Genetics, Guy’s Hospital, Great Maze Pond, SE1 9RT, London, UK

    Anju Kulkarni MBBS, BSc, MD(Res), FRCP

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  1. Helena Carley MBChB(Hons) BSc(Hons)
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  2. Anju Kulkarni MBBS, BSc, MD(Res), FRCP
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Correspondence to Anju Kulkarni MBBS, BSc, MD(Res), FRCP .

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Editors and Affiliations

  1. The Medical School Department of Oncology, University of Sheffield, Sheffield, United Kingdom

    Lynda Wyld

  2. Athens University Medical School, Athens, Greece

    Christos Markopoulos

  3. Helsinki University Hospital, Helsinki, Finland

    Marjut Leidenius

  4. Department of Oncology & Radiotherapy, Gdańsk Medical University Department of Oncology & Radiotherapy, Gdańsk, Poland

    Elżbieta Senkus-Konefka

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Carley, H., Kulkarni, A. (2018). Hereditary Breast Cancer Genetics and Risk Prediction Techniques. In: Wyld, L., Markopoulos, C., Leidenius, M., Senkus-Konefka, E. (eds) Breast Cancer Management for Surgeons. Springer, Cham. https://doi.org/10.1007/978-3-319-56673-3_5

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