Ebook Breast cancer management for surgeons: Part 1

Lynda Wyld · Christos Markopoulos
Marjut Leidenius · Elżbieta Senkus-Konefka Editors

Breast Cancer
Management for
Surgeons
A European
Multidisciplinary Textbook

123


Breast Cancer Management for Surgeons


Lynda Wyld
Christos Markopoulos
Marjut Leidenius
Elżbieta Senkus-Konefka
Editors

Breast Cancer
Management for
Surgeons
A European Multidisciplinary Textbook


Editors
Lynda Wyld
The Medical School Department of Oncology
University of Sheffield

Sheffield, United Kingdom

Christos Markopoulos
Athens University Medical School
Athens, Greece

Marjut Leidenius
Helsinki University Hospital
Helsinki, Finland

Elżbieta Senkus-Konefka
Department of Oncology & Radiotherapy
Gdańsk Medical University Department of Oncology
& Radiotherapy
Gdańsk, Poland

ISBN 978-3-319-56671-9    ISBN 978-3-319-56673-3 (eBook)
/>Library of Congress Control Number: 2017959196
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V

Foreword
Foreword by:
Professor Vassilios Papalois
Imperial College Healthcare NHS Trust, London, UK
Secretary General of the European Union of Medical
Specialist (UEMS)
It is a great honour to offer this forward for this
world class textbook for the multidisciplinary
management of breast cancer for surgeons. I will
first address with great pleasure the fact that this is
a European textbook reflecting the widely known
and well respected experience and expertise of
Colleagues across Europe with whom I had the
real privilege to work closely when I was President
of the Section of Surgery of the Union of European
Medical Specialists (UEMS) and over the last two
years as UEMS Secretary General.
The UEMS is an organisation with almost 60 years of
history, representing, through their National Medical Associations, 39 Countries in the EU and beyond,
a total of 1.6 million medical specialists. The UEMS
work on the ground is being done by 43 Specialist
Sections that also collaborate though 15 Multidisciplinary Joint Committees for areas of practice which
are of interest to more than one Section.

The UEMS prides itself for being an organisation
that develops real projects for real people in real life!
The development of the UEMS European Training
Requirements (ETRs) and Exams are two flagship
projects for the UEMS. The ETRs and the Exams are
developed by the UEMS Sections in close collaboration with the relevant European Scientific Societies.
This is being done through a truly wide and in depth
consultation across Europe that embraces Universities, Scientific Societies and Professional Colleges
and Associations; the final product has the review
and approval of the National Medical Associations
represented in the UEMS. I cannot really think of a
more robust process for developing such quality
control projects as the UEMS ETRs and Exams aiming to advance and harmonise specialist practice in
Europe that will of course translate into top class
clinical care for patients.
The Divisions of Breast Surgery of the Section of
Surgery of the UEMS has been one of the most
active and productive players in the field of UEMS
ETRs and Exams. They have also gone one step further and they have produced superb educational
material in support of Colleagues across Europe
who wish to ensure that their knowledge is up to
speed and meets the standards of the UEMS ETRs

and are also robustly prepared to apply for the relevant UEMS Exams. The superb textbook that you
have in your hands is testimony to this great effort.
I truly enjoyed reading each chapter that is written
most clearly and elegantly and addresses all elements of modern practice: evidence based
approach, multidisciplinary/ team work, state of
the art experience, expertise and clinical pathways
as well as constructive use of technology.

I was particularly impressed by the fact that the
textbook combines scientific accuracy and robustness with the authors’ genuine interest and truly
humane approach for the patients. The textbook is
inspired by the Hippocratic (and pan-European!)
values of medical humanism.
I believe that Colleagues of all specialties and ranks
who are actively involved in breast cancer treatment will find this textbook a powerful ally and
compelling navigator that will guide them through
the complexities of this ever evolving area of multidisciplinary practice that affects the lives of millions of patients around the world.
Congratulations and Kudos to the Editors and the
Authors!
Enjoy sailing through its pages!


Preface from the UEMS – EBS – Division of
Breast Surgery
A few years ago, EUSOMA (the European Society
of Breast Cancer Specialists) published a position
paper on “Guidelines on the standards for the
training of specialized health professionals dealing with breast cancer”. Theoretical and practical
requirements for the training of a “breast surgeon” were described in detail, as well as an
assessment strategy – specialist exams – on how a
candidate could be qualified as a “specialist in
breast surgery”.
Following that, the UEMS (European Union of
Medical Specialists) expressed its support for proposals in the guidelines, and as a result, the breast
surgery working group was established in the
UEMS Section of Surgery, and the breast surgery
examination was launched in 2010.
The exam is part of the series of professional examinations offered by the European Board of Surgery

(EBS) and results in the award of a European
Board of Surgery Qualification (EBSQ) in breast
surgery examination. Graduates of the exam may
use the post-nominal FEBS or Fellow of the European Board of Surgery. Considering the recognized success of the project, the UEMS proceeded
in 2015 to officially upgrade the breast surgery
working group to a full division within the European Board of Surgery, the Division of Breast Surgery, recognizing its status as an increasingly
important specialist group of surgeons.
The EBSQ in breast surgery exam is organized
twice per year, and respected and recognized
breast surgeons from all over Europe are invited to
act as examiners. In our common effort to improve
the quality of health services for breast cancer
patients across Europe, we strongly believe that the
EBSQ exams play an important role. A breast surgeon holding an EBSQ diploma has official recognition that she/he meets EBSQ application
requirements with regard to specialist education,
training and experience and has up-to-date knowledge of breast cancer management.

This textbook, written by European-based breast
cancer specialists from all management disciplines
involved in modern breast cancer care, will serve as
the syllabus for the EBSQ in breast surgery exam.
Breast surgeons have a leading role in the management of patients with breast cancer, and all current
necessary knowledge for evidence-­
based breast
cancer management is included in its chapters. Furthermore, this textbook will also serve as a helpful
reference tool in everyday practice for everyone
involved in the care of breast cancer patients.
On behalf of the UEMS-EBS-Division of Breast
Surgery, I would like to express my deep appreciation to the editors and co-authors of the book for all
their efforts and to Springer for this great edition.

Professor Christos J. Markopoulos
President of the Division of Breast Surgery
at the Section of Surgery of the UEMS-EBS


VII

Preface from the European Society of Surgical
Oncology
Half a million women develop breast cancer, and
100,000 women die of the disease each year in
Europe. This represents a massive health burden
but one where outcomes are steadily improving.
Outcomes continue to vary widely across Europe
due to differences in early detection and wide
variance in therapy schedules. Breast cancer surgeons play a leading role in the delivery of care to
women with breast cancer, and over 60% of breast
cancers are cured by surgery alone. However, the
increasingly complex treatment schedules require
that surgeons have in-depth knowledge of
evidence-­based multidisciplinary practice.
Harmonization of outcomes across Europe
requires education, training and quality assurance.
Specialist breast units are being set up across
Europe as per European Parliament resolutions
and European guidelines for quality assurance. A
programme of breast unit quality assurance is in
progress in the EU at the moment. This critically
important action, implemented by the European
Union, would be entirely useless if there was no

quality assurance of surgical management and
training in breast surgery.
ESSO (the European Society of Surgical Oncology) is committed to this task. Numerous courses
and masterclasses have been organized, specialists
have set up a network to facilitate training across
Europe, grants are available to train young breast
surgeons, and the UEMS examination is solidly in
place to certify competence and multidisciplinary
understanding.

This textbook summarizes the expected knowledge which any breast cancer surgeon has to possess in order to pass the exam.
I congratulate the editors and all contributors to
this ambitious editorial and educational project; it
is here to reassure all breast cancer patients that
they will receive the best management possible
today and to lay the foundations for future research.
Professor Riccardo A. Audisio
Immediate Past President of ESSO


IX

Contents
I
1

Basic Science
Gross Anatomy of the Breast and Axilla...........................................................................................................

3

Peter Palhazi
2
Physiology and Developmental Stages of the Breast..............................................................................11

Theodore G. Troupis, Adamantios Michalinos, George Skandalakis, and Panayiotis Skandalakis
3

Breast Cancer Epidemiology....................................................................................................................................19
R.M. Parks, M.G.M. Derks, E. Bastiaannet, and K.L. Cheung

4
Effect of Oestrogen Exposure, Obesity, Exercise and Diet
on Breast Cancer Risk....................................................................................................................................................31

Eleni Th. Petridou, Marios K. Georgakis, and Constantine N. Antonopoulos
5
Hereditary Breast Cancer Genetics and Risk Prediction Techniques.............................................43

Helena Carley and Anju Kulkarni

II

Screening, High Risk Lesions, and Risk ­Management

6

Screening for High-Familial-­Risk Women........................................................................................................59
Athina Vourtsis

7

Risk-Reducing Breast and Ovarian Surgery for Women at High Familial Risk........................69
Inkeri Schultz and Kerstin Sandelin

8
The Role of Breast Cancer Chemoprevention in High-Risk Women................................................79

Lynda Wyld
9

Molecular Profiling of Breast Cancer and DCIS............................................................................................89
Christos Markopoulos

10Pathology of High-Risk Breast Lesions..............................................................................................................103

Sarah E. Pinder and Abeer M. Shaaban
11

Ductal Carcinoma in Situ.............................................................................................................................................115
Stacey A. Carter, Sarah E. Pinder, and Alastair M. Thompson

12

Imaging of the Breast....................................................................................................................................................127
Petra Steyerova

13

Breast Cancer Screening..............................................................................................................................................147

John Mathew and Mark Sibbering

III

Early Breast Cancer: Diagnosis and ­Management

14
Clinical Presentation, Diagnosis and Staging of Breast Cancer........................................................159

Janez Zgajnar


X
Contents

15

Pathology of Breast Cancer.......................................................................................................................................177
Frederique Penault-Llorca and Nina Radosevic-Robin

16

The Breast and Oncoplastic Multidisciplinary Team................................................................................193
Fiona MacNeill, Marios Konstantinos Tasoulis, and Melissa Ley Hui Tan

17

Surgery to the Breast: Mastectomy......................................................................................................................203
Petros Charalampoudis and Tibor Kovacs

18

Surgery to the Breast: Breast Conservation Techniques........................................................................213
Marjut Leidenius

19

Oncoplastic Breast-Conserving Therapy..........................................................................................................229
Elias E. Sanidas and Florian Fitzal

20
Fat Transfer in Oncoplastic and Reconstructive Breast Surgery.......................................................245

Riccardo Bonomi, I. Fabio Rapisarda, Gilles Toussoun, and Loraine Kalra
21
Breast Surgery after Primary Systemic Treatment.....................................................................................255

Thorsten Kuehn
22
Surgery for Locally Recurrent Breast Cancer.................................................................................................263

Roberto Agresti, Andrea Spano, Giulia Bianchi, and Giovanna Trecate
23
Management of the Axilla: Sentinel Lymph Node Biopsy....................................................................275

Leif Bergkvist and Jan Frisell
24
Axillary Node Clearance..............................................................................................................................................285

Tuomo J. Meretoja

25

Axillary Management in the Neoadjuvant Setting....................................................................................291
K. Wimmer, F. Fitzal, R. Exner, and M. Gnant

26
Axillary Reverse Mapping: ARM.............................................................................................................................303

Isabel T. Rubio, Ernest J.T. Luiten, and V. Suzanne  Klimberg

IV

Reconstructive Surgery

27

Immediate Reconstruction: General and Oncological Considerations........................................315
Maria João Cardoso and Giuseppe Catanuto

28
Delayed Breast Reconstruction: General and Oncological Considerations..............................325

Zoltán Mátrai
29

Breast Implants: Design, Safety and Indications for Use.......................................................................355
Jana de Boniface and Inkeri Schultz

30
Specific Implant-Based Techniques for Breast Reconstruction.........................................................365

Lorna J. Cook and Michael Douek
31
Specific Autologous Flap Techniques.................................................................................................................381

Sinikka Suominen and Maija Kolehmainen


XI
Contents

32
Goldilocks Procedure....................................................................................................................................................393

Fiona MacNeill
33

Nipple Reconstruction..................................................................................................................................................401
Valentina Lefemine and Kelvin F. Gomez

34

Complications of Breast Surgery and Their Management....................................................................411
Michalis Kontos and Christos Markopoulos

V

Adjuvant Therapy for Early Breast Cancer

35

Adjuvant Endocrine Therapy....................................................................................................................................427

Manuela Rabaglio and Monica Castiglione
36

Adjuvant Chemotherapy.............................................................................................................................................439
Giuseppe Curigliano, Angela Esposito, and Carmen Criscitiello

37
Adjuvant Molecular Therapies in Breast Cancer.........................................................................................447

A. Prove, L.-A. Teuwen, and L. Dirix
38
Primary Systemic Therapy for Breast Cancer.................................................................................................453

Cornelia Liedtke and Hans-Christian Kolberg
39

Radiotherapy for Breast Cancer.............................................................................................................................463
Barbara Alicja Jereczek-Fossa, Maria Cristina Leonardi, and Samantha Dicuonzo

VI

Breast Cancer in Special Groups

40
Breast Cancer in Special Groups: Young Women with Early Breast Cancer...............................487

Rossella Graffeo and Olivia Pagani
41

Hereditary Breast Cancer............................................................................................................................................499

Teresa Ramón y Cajal, Anna Virgili, and Nuria Dueñas
42
Breast Cancer in Special Groups: Breast Cancer in Pregnancy..........................................................511

Matteo Lambertini, Hatem A. Azim Jr, and Fedro Alessandro Peccatori
43
Fertility Preservation in Women with Breast Cancer................................................................................521

Anna Rachelle Mislang, Matteo Lambertini, and Laura Biganzoli
44
Breast Cancer in Older Patients..............................................................................................................................529

Anne Shrestha and Lynda Wyld
45
Breast Cancer in the Male Patient.........................................................................................................................541

M. Umit Ugurlu and Bahadir M. Gulluoglu
46
Sarcoma of the Breast...................................................................................................................................................551

Erkki Tukiainen and Andrew Lindford
47
Desmoid (Aggressive) Fibromatosis of the Breast.....................................................................................559

Nicholas C. Eastley, Jaroslaw Krupa, and Robert U. Ashford


XII

Contents

VII Advanced Breast Cancer
48

Locally Advanced Breast Cancer............................................................................................................................567
Elżbieta Senkus and Aleksandra Łacko

49
Metastatic Breast Cancer: Prognosis, Diagnosis and Oncological Management..................579

Elżbieta Senkus and Aleksandra Łacko
50

The Role of Surgery in Metastatic Disease to the Bone..........................................................................595
Amit Kumar and Robert U. Ashford

51
Roles of Surgery and Modern Radiation Techniques in Metastatic
Disease Affecting the Brain.......................................................................................................................................603

Garth Cruickshank
52
Local Therapies for Liver Metastases from Breast Cancer....................................................................613

Robert P. Jones, Hassan Z. Malik, and Carlo Palmieri
53
Role of Surgery in Lung Metastases from Breast Cancer.......................................................................619

Michael Shackcloth and Susannah Love

54
Surgery for Locally Advanced Breast Cancer.................................................................................................625

Jaroslaw Skokowski and Pawel Kabata
55
The Role of Surgery to the Primary Cancer in Stage IV Disease........................................................633

Seema A. Khan and Patience Odele
56

Palliative Care.....................................................................................................................................................................641
Tiina Saarto

57
Supportive Care................................................................................................................................................................649

Renata Zaucha

VIIISurvivorship
58
Breast Cancer Survivorship: Chronic Post-operative Pain
and Sensory Changes....................................................................................................................................................659

Tuomo J. Meretoja
59

 reast Cancer Survivorship: Psychological Distress, Body Image, Sexuality
B
and Importance of the Clinical Consultation.................................................................................................663
Louise Fairburn, Christopher Holcombe, and Helen Beesley

60
Bone Health in Patients with Breast Cancer...................................................................................................673

Amy Kwan and Janet E Brown
61
Nursing Issues and the Role of the Specialist Nurse in Breast Care...............................................681

Victoria Harmer
62

Breast Cancer-Related Lymphedema..................................................................................................................689
Heli Kavola and Sinikka Suominen


XIII
Contents

IX

Quality Assurance

63

Research and Audit in Advancing the Quality of Breast Cancer Care...........................................703
Petra G. Boelens, Elma Meershoek-Klein Kranenbarg, Esther Bastiaannet,
Cornelis van de Velde, and Riccardo A. Audisio

XAppendix
64

MCQ Self-Test......................................................................................................................................................................715
Lynda Wyld and Christos Markopoulos




Supplementary Information
Index...........................................................................................................................................................................................721


Contributors
Roberto Agresti, MD

Giulia Bianchi, MD

Fondazione IRCCS Istituto Nazionale dei Tumori
Surgery – Breast Surgery Unit
Milan, Italy


Medical Oncology Unit
Department of Medical Oncology
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Italy


Constantine N. Antonopoulos, MD, PhD, FEBVS
National and Kapodistrian University of Athens
Medical School, Department of Hygiene,

Epidemiology and Medical Statistics
Athens, Greece


Laura Biganzoli, MD

Robert U. Ashford, MBBS, FRCS, MD

Petra G. Boelens

University Hospitals of Leicester NHS Trust
Department of Orthopaedics, Leicester Royal Infirmary
Leicester, UK


Department of Surgery
Leiden University Medical Center
Leiden, The Netherlands


Riccardo A. Audisio

Jana de Boniface, MD, PhD

St Helens and Knowsley Teaching Hospitals NHS Trust
University of Liverpool, Department of Surgery
Liverpool, Merseyside, UK


Karolinska University Hospital

Department of Breast and Endocrine Surgery
Stockholm, Sweden


Hatem A. Azim Jr, MD, PhD

Riccardo Bonomi, MD

2BrEAST Data Centre, Department of Medicine
Institut Jules Bordet, and l'Université Libre de Bruxelles
(U.L.B.)
Brussels, Belgium


Western Sussex Hospital Foundation Trust
Worthing Hospital
Worthing, West Sussex, UK


Nuovo Ospedale-Santo Stefano Istituto Toscano Tumori
Department of Medical Oncology
Prato, Italy


Janet E Brown, MD
Esther Bastiaannet, PhD
Leiden University Medical Center
Department of Surgery
Leiden, The Netherlands

University of Sheffield
Academic Unit of Clinical Oncology
Sheffield, UK


Maria-João Cardoso, MD, PhD
Helen Beesley, D.Clin.Psychol
University of Liverpool
Institute of Psychology Health and Society
Liverpool, Merseyside, UK


Leif Bergkvist, MD, PhD
Västmanland County Hospital Västerås
Center for Clinical Research
Uppsala University and Department of Surgery
Västerås, Sweden


Champalimaud Foundation, Breast Unit
Lisbon, Portugal


Helena Carley, MBChB (Hons), BSc (Hons)
Guy’s and St. Thomas’ NHS Foundation Trust
Department of Clinical Genetics, Guy’s Hospital
London, UK

XV
Contributors

Stacey A. Carter, MD

Marloes Gertruda Maria Derks, MD

Baylor College of Medicine, Department of Surgery
Houston, TX, USA


Leiden University Medical Center
Department of Surgery
Leiden, Zuid-Holland, The Netherlands


Monica Castiglione, MD
IBCSG (International Breast Cancer Study Group)
Berne, Switzerland


Samantha Dicuonzo, MD
European Institute of Oncology
Milan, Italy


Giuseppe Catanuto, MD, PhD
Azienda Ospedaliera Cannizzaro
U.O.C. Multidisciplinare di Senologia

Catania, Italy


Luc Dirix

Petros Charalampoudis, MD, FRCS, FEBS

Michael Douek, MD, FRCS

Guy’s and St. Thomas’ NHS Foundation Trust
King’s College London, Breast Unit
(Guy’s and St. Thomas’ NHS Foundation Trust)
Division of Cancer Studies (King’s College London)
London, UK


Guy’s and St. Thomas’ Hospital-London
Research Oncology
London, UK


Kwok-Leung Cheung, DM, FRCSEd, FACS
University of Nottingham
School of Medicine, Royal Derby Hospital Centre
Derby, UK


Lorna J. Cook, BA, MBBS, FRCS
Guy’s and St. Thomas’ Hospital-London
Lavant, West Sussex, UK

Medical Oncology, EUSOMA Breast Unit
Wilrijk Antwerp, Belgium


Nuria Dueñas, MD
Hospital de Sant Pau
Department of Medical Oncology
Barcelona, Catalonia, Spain
ndueñ

Nicholas Eastley, MBCHB, BMedSci, MRCS
University Hospitals of Leicester NHS Trust
Department of Orthopaedics, Leicester Royal Infirmary
Leicester, UK


Angela Esposito
Carmen Criscitiello
Istituto Europeo di Oncologia
Division of Early Drug Development
for Innovative Therapies, Division of Pharmacy
Milan, Italy


Istituto Europeo di Oncologia
Division of Early Drug Development
for Innovative Therapies
Division of Pharmacy

Milan, Italy


Garth Cruickshank, PhD, MBBS, FRCS

Ruth Exner, MD

University of Birmingham, Institute of Cancer and
Genomic Sciences and Department of Neurosurgery
Queen Elizabeth Hospital Birmingham
Edgbaston, Birmingham, West Midlands, UK


Department of Surgery and
Comprehensive Cancer Center
Medical University of Vienna
Vienna, Austria


Giuseppe Curigliano, MD, PhD

Louise Fairburn, D.Clin.Psychol, MSc, BA (Hons)

Istituto Europeo di Oncologia
Division of Early Drug Development
for Innovative Therapies
Milan, Italy


Royal Liverpool and Broadgreen

University Hospitals NHS Trust
Liverpool Cancer Psychology S­ ervice
Prescot Street, Liverpool, UK



XVI
Contributors

Florian Fitzal, FEBS

Christopher Holcombe, MD, FRCS

Medical University of Vienna
Department of Surgery and
Comprehensive Cancer Center
Vienna, Austria


Royal Liverpool University Hospital
Department of Breast and Endocrine Surgery
Linda McCartney Centre
Liverpool, Merseyside, UK


Jan Frisell, MD, PhD

Barbara Alicja Jereczek-Fossa, MD, PhD

Department of Molecular Medicine and Surgery

Karolinska Institutet
Stockholm, Sweden

European Institute of Oncology
Milan, Italy


Department of Breast and Endocrine Surgery
Karolinska University Hospital
Stockholm, Sweden


Marios K. Georgakis, MD
National and Kapodistrian University of Athens
Medical School, Department of Hygiene,
Epidemiology and Medical Statistics
Athens, Greece


Michael Gnant, MD
Department of Surgery and
Comprehensive Cancer Center
Medical University of Vienna
Vienna, Austria


Kelvin Francis Gomez, MBChB, MD, FRSCEd
Nevill Hall Hospital
Department of Breast Surgery,
Abergavenny, Wales, UK

Rossella Graffeo, MD
Institute of Oncology (IOSI) and
Breast Unit of Southern Switzerland (CSSI)
Bellinzona, Switzerland


Bahadir M. Gulluoglu, MD, FACS
Marmara University School of Medicine
Department of General Surgery,
Breast and Endocrine Surgery Unit
Istanbul, Turkey


Victoria Harmer, DHC, MBA,
BSc(Hons) Dip, RN AKC
Breast Care, Imperial College Healthcare NHS Trust
Department of Breast Care,
Charing Cross Hospital
London, UK


Robert P. Jones, BSc (Hons), MBChB, PhD, MRCS
University of Liverpool
Institute of Translational Medicine
Liverpool, UK


Pawel Kabata, MD, PhD

Department of Surgical Oncology
Medical University of Gdansk
Gdansk, Poland


Loraine Kalra, MBBS, MS, MRCS, EBSQ
Royal Victoria Infirmary
Queen Victoria Road
Newcastle Upon Tyne NE1 4LP, UK


Heli Kavola, MD, PhD
Helsinki University Hospital
Department of Plastic Surgery
Helsinki, Finland


Seema Ahsan Khan, MD
Co-leader Women’s Cancer Research Program
Robert H. Lurie Comprehensive Cancer Center
Northwestern Hospital, Department of Surgery
Chicago, IL, USA


V. Suzanne Klimberg, MD
Breast Surgical Oncology, University of Arkansas
for Medical Sciences (UAMS)
Winthrop P. Rockefeller Cancer Institute
Division of Breast and Surgical Oncology
Little Rock, AR, USA

Hans-Christian Kolberg, MD
Marienhospital Bottrop gGmbH
Obstetrics and Gynecology/Breast Cancer Center/
Gynecologic Cancer Center
Bottrop, Germany



XVII
Contributors

Maija Kolehmainen, MD

Valentina Lefemine, MD, FRCS

Helsinki University Hospital, Helsinki University
Department of Plastic Surgery
Helsinki, Finland


Nevill Hall Hospital
Department of Breast surgery
Abergavenny, Wales, UK


Michalis Kontos, MD, PhD

Marjut Leidenius, MD, PhD

National and Kapodistrian University of Athens
1st Department of Surgery
Athens, Greece


Department Head, Helsinki University Hospital
Comprehensive Cancer Center, Breast Surgery Unit
Helsinki, Finland


Tibor Kovacs, PhD, FRCS, EBSQ

Maria Cristina Leonardi, MD

Guy’s and St. Thomas’ NHS Foundation Trust
Breast Unit, King’s College London
London, UK


European Institute of Oncology
Milan, Italy


Cornelia Liedtke, MD, PhD
Jaroslaw Krupa, MD, PhD
University Hospitals of Leicester NHS Trust
Department of Breast Surgery, Glenfield Hospital
Leicester, UK

Klinik für Frauenheilkunde und Geburtshilfe
Universitätsklinikum Schleswig-Holstein/
Campus Lübeck
Lübeck, Germany


Thorsten Kuehn, MD

Andrew Lindford, MBBS, MRCS, FEBOPRAS, PhD

Department of Gynecology
Esslingen, Germany


Helsinki University Hospital
Department of Plastic Surgery
Helsinki, Finland


Anju Kulkarni, MBBS, BSc, MD(Res), FRCP
Clinical Genetics, Guy’s Hospital
London, UK


Amit Kumar, BSc, MBBS, FRCS Ed (Tr & Orth)
University Hospitals Leicester NHS Trust
Department of Orthopaedics
Leicester, UK

Amy Kwan, MBBS, BSc
University of Sheffield
Academic Unit of Clinical Oncology
Sheffield, UK


Susannah Love, BA (Hons), MBBS, MRCS
Liverpool Heart and Chest Hospital
Department of Thoracic Surgery
Liverpool, UK


Ernest J.T. Luiten, MD
Amphia Hospital
Department of Oncologic Breast Surgery
Breda, The Netherlands


Fiona MacNeill, MD, MBBS, FRCS, FEBS
Royal Marsden Hospital
London, UK


Aleksandra Łacko, MD, PhD
Department of Clinical Oncology
Wroclaw Medical University
Wrocław, Poland

Matteo Lambertini, MD
Institut Jules Bordet and l'Université Libre
de Bruxelles (U.L.B.), Breast Data Centre
Department of Medicine
Brussels, Belgium


Hassan Z. Malik, MBChB, MD
School of Cancer Studies
Institute of Translational Medicine
University of Liverpool
North Western Hepatobiliary Unit
Aintree University Hospital
Liverpool, UK



XVIII
Contributors

Christos Markopoulos, MD, PhD

Peter Palhazi, MD

Medical School - National and Kapodistrian
University of Athens
2nd Department of Propedeutic Surgery - Breast Unit
Athens, Greece

Department of Anatomy
Histology and Embryology, Semmelweis University
Budapest, Hungary


Carlo Palmieri, MBBS, PhD
John Mathew, DM, FRCS
Royal Derby Hospital, Breast Unit
Derby, UK


Zoltán Mátrai, MD, PhD, FEBS
National Institute of Oncology
Center of Surgical Oncology
Department of Breast and Sarcoma Surgery
Budapest, Hungary


Elma Meershoek-­Klein Kranenbarg
Datacenter, Department of Surgery
Leiden University Medical Center
Leiden, The Netherlands


Tuomo J. Meretoja, MD, PhD
Helsinki University Hospital
Comprehensive Cancer Center
Breast Surgery Unit
Helsinki, Finland

Adamantios Michalinos, MD, PhD
Department of Anatomy
National and Kapodistrian University of Athens
Helsinki, Finland


Anna Rachelle Mislang, MD, FRACP (Australia)
Nuovo Ospedale-Santo Stefano Istituto Toscano Tumori
Department of Medical Oncology
Prato, Italy


Patience Odele, MD
Northwestern Hospital
Department of Surgery
Chicago, IL, USA


Olivia Pagani, MD
Institute of Oncology (IOSI) and
Breast Unit of Southern Switzerland (CSSI)
Bellinzona, Switzerland


Molecular and Clinical Cancer Medicine
Institute of Translational Medicine
University of Liverpool
Liverpool, UK
Liverpool and Merseyside Breast Academic Unit

The Linda McCartney Centre
Royal Liverpool University Hospital
Liverpool, UK
Academic Department of Medical Oncology
Clatterbridge Cancer Centre NHS Foundation Trust
Wirral, UK


Ruth Parks, BMedSci, MBBS, MRCS
University of Nottingham, School of Medicine
Royal Derby Hospital Centre
Derby, UK


Fedro Alessandro Peccatori, MD, PhD
Fertility and Procreation Unit
Division of Gynecologic Oncology
European Institute of Oncology
Milan, Italy


Frederique Penault-Llorca, MD, PhD
Departments of Pathology and Biopathology
Jean Perrin Comprehensive Cancer Centre
Clermont-Ferrand, France


Eleni Th. Petridou, MD, MPH, PhD
National and Kapodistrian, University of Athens
Medical School, Department of Hygiene,

Epidemiology and Medical Statistics
Athens, Greece


Sarah E. Pinder, MBChB, FRCPath
King’s College London, Guy’s and
St. Thomas’ Hospitals
Research Oncology, Cancer Division, Guy’s Hospital
London, UK



XIX
Contributors

A. Prove

Elias E. Sanidas, MD, FACS

Medical Oncology, EUSOMA Breast Unit
Wilrijk, Antwerp, Belgium

Heraklion Medical School
Heraklion, Crete, Greece

Breast Unit-Medical Oncology
Sint-Augustinus Cancer Centre
Iridium Network, Antwerp, Belgium

Manuela Rabaglio, MD
IBCSG (International Breast Cancer Study Group) and
University Hospital – Inselspital Berne
Department of Medical Oncology
Bern, Switzerland


Nina Radosevic-Robin, MD
Jean Perrin Comprehensive Cancer Centre
Department of Pathology and Biopathology
Clermont-­Ferrand, France


Teresa Ramón y Cajal, MD, PhD
Hospital de Sant Pau
Department of Medical Oncology
Barcelona, Catalonia, Spain


Fabio Rapisarda, MD, MSc, MCh, FEBS
Western Sussex Hospital Foundation Trust
Lyndhurst Road
Worthing, West Sussex, UK


Isabel T. Rubio, MD
Breast Surgical Oncology
Hospital Universitari Vall d’Hebron
Breast Cancer Center
Barcelona, Catalonia, Spain

Asklipeion Private Hospital
Department of Surgery
Heraklion, Crete, Greece


Inkeri Schultz, MD, PhD
Karolinska University Hospital
Department of Reconstructive Plastic Surgery
Stockholm, Sweden
Department of Molecular Medicine and
Surgery at Karolinska Institutet
Stockholm, Sweden


Elżbieta Senkus, MD, PhD
Medical University of Gdańsk
Department of Oncology and Radiotherapy
Gdańsk, Poland


Abeer M. Shaaban, MBChB, PhD, FRCPath
Queen Elizabeth Hospital Birmingham
Department of Histopathology
Birmingham, West Midlands, UK


Michael Shackcloth, MD
Liverpool Heart and Chest Hospital

Department of Thoracic Surgery
Liverpool, UK


Anne Shrestha, BMedSci, MBChB, MRCS, PGCME
The Medical School, Department of Oncology and
Metabolism, University of Sheffield
Sheffield, UK


Tiina Saarto, MD, PhD
Helsinki University and Helsinki University Hospital
Comprehensive Cancer Center
Helsinki, Finland


Mark Sibbering, FRCS

Kerstin Sandelin, MD, PhD

George Skandalakis

Department of Breast and Endocrine Surgery
Karolinska University Hospital
Stockholm, Sweden

Department of Anatomy
National and Kapodistrian University of Athens
Athens, Greece

Department of Molecular Medicine and Surgery
Karolinska Institutet
Stockholm, Sweden


Royal Derby Hospital, Breast Unit
Derby, UK


Panayiotis Skandalakis, MD, PhD
Department of Anatomy
National and Kapodistrian University of Athens
Athens, Greece



XX
Contributors

Jaroslaw Skokowski, MD, PhD

Giovanna Trecate, MD

Medical University of Gdansk
Department of Surgical Oncology
Gdansk, Pomorskie, Poland


Radiology and Magnetic Resonance Unit

Department of Radiology
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Italy


Andrea Spano, MD
Fondazione IRCCS Istituto Nazionale dei Tumori,
Surgery – Plastic and Reconstructive Surgery
Milan, Italy


Theodore G. Troupis, MD, PhD
Department of Anatomy, National and Kapodistrian
University of Athens
Athens, Greece


Petra Steyerova, MD
General University Hospital Prague
Clinic of Radiology
Breast Cancer Screening and Diagnostic Centre
Prague, Czech Republic


Erkki Tukiainen, MD, PhD

Sinikka Suominen, MD, PhD

M. Umit Ugurlu, MD, FEBS

Department of Plastic Surgery
Helsinki University Hospital
Helsinki, Finland

Marmara University, School of Medicine
Department of General Surgery
Maltepe, Istanbul, Turkey

Helsinki University, Plastic Surgery
Helsinki, Finland


Breast and Endocrine Surgery Unit
Fevzi Cakmak M. Marmara Universitesi Pendik EAH
Istanbul, Turkey


Department of Plastic Surgery, Töölö Hospital
Helsinki University Hospitals
Helsinki, Finland


Melissa Ley Hui Tan, FRCS
Royal Marsden Hospital
London, UK


Marios Tasoulis, PhD
Royal Marsden Hospital
London, UK

L-A Teuwen
Hospital: GZA Sint-Augustinus
Center for Oncological Research
Wilrijk, Antwerp, Belgium


Alastair M. Thompson, ALCM, BSc,
MB ChB, MD, FRCSEd
University of Texas MD Anderson Cancer Center
Houston, TX, USA


Gilles Toussoun
Chirurgie Plastique, Reconstructrice et Esthetique
Polyclinique du Val de Saone
Macon, France


Cornelis van de Velde
Department of Surgery
Leiden University Medical Centre
Leiden, The Netherlands


Anna Virgili, MD
Hospital de Sant Pau, Department of Medical Oncology
Barcelona, Catalonia, Spain

Athina Vourtsis, MD, PhD
Diagnostic Mammography Center
Athens, Greece


Kerstin Wimmer, MD
Department of Surgery and
Comprehensive Cancer Center
Medical University of Vienna
Vienna, Austria



XXI
Contributors

Lynda Wyld, MBChB, PhD, FRCS

Janez Zgajnar, MD, PhD

E Floor, The Medical School
Department of Oncology and Metabolism
University of Sheffield
Sheffield, UK


Institute of Oncology Ljubljana
Department of Surgical Oncology
Ljubljana, ­Slovenia

Renata Zaucha, MD, PhD
Clinical Center of the Medical University of Gdansk
Department of Oncology and Radiotherapy
Gdansk, Poland



1

Basic Science
Contents
Chapter 1

Gross Anatomy of the Breast and Axilla – 3
Peter Palhazi

Chapter 2Physiology and Developmental Stages
of the Breast – 11
Theodore G. Troupis, Adamantios Michalinos,
George Skandalakis, and Panayiotis Skandalakis
Chapter 3Breast Cancer Epidemiology – 19
R.M. Parks, M.G.M. Derks, E. Bastiaannet,
and K.L. Cheung
Chapter 4Effect of Oestrogen Exposure, Obesity,
Exercise and Diet on Breast Cancer Risk – 31
Eleni Th. Petridou, Marios K. Georgakis,
and Constantine N. Antonopoulos
Chapter 5Hereditary Breast Cancer Genetics and

Risk Prediction Techniques – 43
Helena Carley and Anju Kulkarni

I


3

Gross Anatomy of the Breast
and Axilla
Peter Palhazi
1.1Overview – 4
1.2Fascial and Ligamentous Structure – 4
1.3Blood Supply – 5
1.4Innervation – 6
1.5Muscles of the Anterior Chest Wall – 7
1.6Lymphatic Drainage – 7
1.7The Anatomy of the Axilla – 9
1.8Summary – 9
References – 9

© Springer International Publishing AG 2018
L. Wyld et al. (eds.), Breast Cancer Management for Surgeons, />
1


1

4

P. Palhazi

1.1

Overview

The female breast is located on the chest wall between the
second and sixth or seventh ribs, lateral to the sternum and
medial to the anterior axillary line [1]. It is associated posteriorly with the fascia of the pectoralis major, serratus anterior, abdominal external oblique and the most cranial part of
the rectus abdominis muscles. Its ideal shape is classically
described as a combination of cone and hemisphere. Its volume is determined by the amount of fatty and glandular tissue. The glandular tissue is less dominant until the second
half of pregnancy. The gland becomes fully developed during
lactation. The fatty and glandular tissue is suspended by the
fascial-ligamentous system and the skin envelope. The quantity, quality and relationship of these four factors determine
the shape of the breast.
The glandular tissue consists of 15–20, radially located
lobes (. Fig. 1.1). They are separated from each other by cellpoor, fibrous, interlobular bundles. The lobes consist of lobules. Each lobule has its own duct. The lobules are surrounded
by dense fibrous tissue with a significant amount of fatty tissue. The 15–20 main ducts branch and finally terminate in
the terminal duct lobular unit (TDLU) that secretes milk
during lactation.
The nipple-areola complex (NAC) is located on the most
prominent part of the breast mound. Most textbooks state that
there are 15–20 main ducts with 15–20 ductal orifices on the
top of the nipple. According to classical anatomical descriptions, each lobe has its own main duct and orifice; however,
some publications state less, 5–9 nipple ductal orifices. Possible explanations for the discrepancy may be the sebaceous
glands that mimic the appearance of ducts but do not contribute to the ductal lobular infrastructure or that some ducts
bifurcate shortly after emerging from the nipple [2]. The ducts
have a zone which expands (lactiferous sinus) directly underneath the nipple [3]. They serve as a milk reservoir during
lactation; however, recent studies doubt their existence [4].
The pigmented areola contains several prominences. They are

 

TDLU-s

main lactiferous duct

..      Fig. 1.1  The lactiferous ducts of a premenopausal breast lobe are
filled with plastic. Blue colour indicates the ductal structure, while white
colour indicates the TDLUs

modified accessory glands, so-called glands of Montgomery.
Numerous sweat and sebaceous glands can be found among
these, which keep the NAC lubricated and protected.
The breast can be divided practically into six portions.
According to horizontal and vertical axes, four quadrants can
be differentiated. The central substance is located behind the
areola, while an extension of the breast extends into the axilla
(Spence’s tail).
1.2

Fascial and Ligamentous Structure

The breast integrates into the superficial fascial system [5] of
the trunk, which is located between the chest musculature
and the skin. The superficial fascia of the breast encases the
glandular tissue with its anterior and posterior lamella. The
anterior lamella is located superficial to the gland at varying
distances from the dermis. It is important to note that the
superficial fascia of the breast is not a unified demarcation
sheet, but a pitted cloak-like structure. The anterior lamella

has clinical significance during skin-sparing mastectomies.
The posterior lamella covers the undersurface of the gland
and continues as Scarpa’s fascia [6] inferiorly. Between the
posterior lamella and the pectoral fascia, the retromammary
space (Chassaignac’s bursa) can be found [7]. This space contains fine areolar tissue, which can be dissected bluntly and
serves as a pocket during sub-glandular breast augmentation.
The main suspensory ligaments of the breast course from
the pectoral fascia through the glandular tissue to the skin.
These are the so-called Cooper’s ligaments [8]. These ligaments have three distinct segments (deep, middle, superficial) created by the aforementioned anterior and posterior
lamella of the superficial fascia of the breast. The deep segment is between the pectoral fascia and the posterior lamella,
the middle segment is between the posterior and anterior
lamella, and the superficial segment is between the anterior
lamella and the skin (. Fig. 1.2). Cooper’s ligaments have significant oncologic importance. Their deep segment anchors
the breast to the pectoral fascia, so total removal of the gland
is facilitated by removal of the pectoral fascia. A tumour may
also infiltrate these ligaments causing skin retraction, which
is an important diagnostic sign of breast cancer. By contraction of the pectoralis major muscle, this skin sign can be provoked, which is an important clinical indicator of malignancy.
The posterior lamella of the superficial fascia continues as
Scarpa’s fascia inferiorly. The anterior lamella also connects
to the posterior lamella at the level of the fifth rib. This junction is fixed to the pectoral fascia, because the posterior
lamella and the pectoral fascia get close to each other side to
side. From this point several strong ligaments can be observed
towards the dermis of the inferior pole and also the inframam­
mary fold. They are considered the inframammary fold ligaments [9]. This anatomical feature may explain the fixed
position of the inframammary fold during ageing.
There is a clinically important fibrous septum in the
breast, called the septum fibrosum (. Fig. 1.3, Modified from
Wuringer) [10].
 

 


5
Gross Anatomy of the Breast and Axilla

It is located horizontally at the level of the fifth rib towards
the nipple. It divides the glandular tissue into an upper and
lower part. It is reinforced medially and laterally by vertical
horns. The medial horn of the septum fibrosum attaches parasternally between the second and fifth rib, while the lateral
horn attaches to the lateral margin of the pectoralis major
muscle. The septum fibrosum contains neurovascular structures supplying the NAC and gland. The thoracoacromial and
deep branches of the lateral thoracic artery travel on the cranial side of this septum, while the fourth – rarely the fifth and
sixth – intercostal artery perforator travels on the caudal side
of it. The lateral cutaneous branches of the fourth intercostal
nerve travel also along this septum. The breast can be dissected bluntly along this septum from the posterior side, so
the blood supply can be preserved to the NAC during surgery.
1.3

Blood Supply

One can divide the arterial system of the breast into superficial and deep groups. Deep vessels penetrate the breast mainly
along the septum fibrosum in the posterior to anterior direction, while the superficial ones travel in the subcutaneous
layer towards the NAC (. Fig. 1.4). The superficial and deep
 

..      Fig. 1.2  Ligaments in between the skin and the anterior lamella of
the superficial fascia of the breast. A superficial branch of the second
internal mammary artery perforator is also seen

Clavicle
Pectoral fascia

Pectoralis
major

Retromammary
space

Thoracoacromial
artery

Intercostal
artery 4
Intercostal
artery 5
Fibrous septum
Inframammary
fold ligament

..      Fig. 1.3  Schematic representation of a lateral cross-sectional view
of the fibrous septum of the breast

..      Fig. 1.4  Blood supply of the breast. Superficial and deep branches
of the lateral thoracic vessels (A), second and third internal mammary
vessel perforators (B, C), fourth intercostal vessel perforators (D)

1

6

1

P. Palhazi

vessels create an anastomosing subdermal net underneath
the areola that supplies the NAC. One of the most important
aspects of the vascular anatomy is the blood supply to the
NAC.  Blood supply of the NAC is beautifully described in
relation to oncoplastic surgery in the work of van Deventer
and colleagues (2004) [11]. Surgeons should be aware of the
common patterns and how they may vary.
The second to fourth internal mammary artery perforators belong to the superficial group. After piercing the chest
wall, they get into the subcutaneous tissue, where they travel
further towards the nipple. They are the dominant blood supply of the NAC [12], although there may be considerable
anatomic variation in the number and direction of NAC
feeding vessels which may account for some instances of
nipple necrosis following surgery.
The breast receives its blood supply laterally from the lateral thoracic artery. It travels under the lateral margin of the
pectoralis major muscle, then passes round the margin and
gets into the substance of the breast. It has two main branches.
One of them stays deep (deep group), the other becomes
superficial (superficial group) and both travel towards the
nipple.
The thoracoacromial artery (deep group) arises directly
from the axillary artery and then branches underneath the
pectoralis minor muscle. Its pectoral branches supply the
upper pole of the breast.
The second to sixth intercostal artery perforators belong

to the deep group of arteries. They are in general smaller, random vessels supplying the base of the breast. Sometimes some
of these arteries can be more prominent, in particular the
fourth intercostal artery perforator. It travels in the axis of the
central parenchyma and supplies it. Sometimes this artery
travels underneath the parenchyma and passes round the
inferior pole of the breast. In particular, the fifth to sixth intercostal artery perforators are located in the area of the inframammary fold. Although they are smaller branches, their
significance is enormous, because they serve as the blood supply to the inferior pole of the breast and hence are important
in supporting inferior nipple pedicles during breast surgery.
The veins of the breast also have superficial and deep
groups. The deep veins accompany the deep arteries. The
superficial veins accompany the superficial arteries and are
superficial to them. They create a superficial venous system.
The venous blood flows towards the axillary, internal mammary and intercostal veins. The venous plexus underneath
the areola is called the areolar venous plexus. These venous
plexuses may become more apparent after augmentation surgery because of increased venous stasis.
1.4

cervical plexus [8]. The anterior cutaneous branches of the
intercostal nerves pierce the chest wall parasternally, and
then they travel superficially to laterally and innervate the
medial part of the breast.
The lateral cutaneous branches pierce the chest wall in
the mid-axillary line and then travel towards the NAC to
innervate the outer part of the breast. The upper pole
receives its sensory innervation from the supraclavicular
nerves.
From a surgical point of view, the most important point
is to preserve the sensory innervation of the NAC, which
is ensured most commonly by the deep division of the
lateral cutaneous branches of the fourth intercostal nerve

laterally (. Figs. 1.5 and 1.7) and by the third and fourth
anterior cutaneous branches (superficial course) medially.
The aforementioned deep division of the lateral cutaneous branches travels in the pectoral fascia and then centrally pierces the gland and innervates the NAC from
posteriorly [13].
The exclusively vasomotor sympathetic fibres reach the
breast along the aforementioned nerves and vessels, while
parasympathetic fibres do not run to the breast, because
secretion is hormonally regulated.
 

ACB

LCB

Innervation

The sensory innervation of the breast is provided by the anterior and lateral cutaneous branches of the second to sixth
intercostal nerves and the supraclavicular branches of the

..      Fig. 1.5  Figure demonstrating a schematic of the nerve supply to
the breast