SURGICAL FOUNDATIONS MICHAEL S. SABEL Essentials of BREAST SURGERY MOSBY ELSEVIER
Surgical Foundations:
Essentials of Breast
Surgery
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Surgical Foundations:
Essentials of Breast
Surgery
Michael S. Sabel, MD, FACS
Associate Professor of Surgery
Division of Surgical Oncology
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan
1600 John F. Kennedy Blvd.
Ste 1800
Philadelphia, PA 19103-2899
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
ISBN: 978-0-323-03758-7
Copyright # 2009 by Mosby, Inc., an affiliate of Elsevier Inc.
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The Publisher
Library of Congress Cataloging-in-Publication Data
Sabel, Michael S.
Essentials of breast surgery / Michael S. Sabel. – 1st ed.
p. ; cm. – (Surgical foundations)
Includes bibliographical references and index.
ISBN 978-0-323-03758-7 (alk. paper)
1. Breast–Cancer–Surgery. 2. Breast–Surgery. I. Title. II. Series: Surgical foundations.
[DNLM: 1. Breast–surgery. 2. Breast Diseases–surgery. 3. Breast Neoplasms–therapy.
WP 910 S115e 2009]
RD667.5.S23 2009
616.990449059–dc22
2009004600
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Developmental Editor: Martha Limbach
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Design Direction: Steve Stave
Marketing Manager: Brenna Christensen
Printed in the United States of America
Last digit is the print number: 9
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Dedication
To my wonderful wife, Janeel, who was
extremely understanding when family time
needed to be compromised, and to my beauti-
ful children, Alex and Madison, although they
weren’t quite as understanding. Also, to my
parents, Steven and Rhoda, who through
their love and patience got me to the point
where I can hopefully make them proud.
v
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Preface
The management of both benign and malig-
nant breast disease represents a major portion
of a surgeon’s responsibility, yet often com-
prises only a minor portion of their training.
The diagnostic workup and treatment of
breast disease is constantly changing and
increasingly complex, making it extremely
challenging for the surgical trainee or practi-
cing general surgeon to keep up with changes
in the field. Surgeons will see an extremely
high volume of patients with complaints
related to the breast, and it is imperative
that they allay fears, palliate symptoms, and
not miss diagnosing malignant disease.
Surgeons must also identify patients at high
risk of developing breast cancer so that
appropriate screening and prophylactic mea-
sures may be considered. The management of
malignant breast disease is increasingly multi-
faceted. The days of the surgeon seeing the
patient, completing surgical therapy, and then
referring the patient to other specialists have
passed; today the surgeon needs to work
in concert with radiologists, pathologists,
medical and radiation oncologists, plastic
surgeons, and other medical professionals to
formulate an appropriate diagnostic and ther-
apeutic plan. Multidisciplinary management
of the breast cancer patient is critical and often
guided by the surgeon even though surgery
may not be the first modality employed.
Any surgeon dealing with breast disease is in
need of a strong grasp of not only the anatomy
and physiology of the breast, but the potential
and limitations of breast imaging, benign and
malignant breast histology, genetics, cancer
biology, and an understanding of all treatment
modalities such as radiation and systemic
therapies. However, most textbooks on breast
disease are meant for clinicians and researchers
from multiple disciplines, containing extre-
mely thorough reviews of the research, the
evolution of treatment, and the randomized
trials that led us to this point. This can be
too confusing and overwhelming for the
surgeon in training or the practicing general
surgeon who must also focus on diseases
outside of the breast. Surgical Foundations:
Essentials of Breast Surgery captures the true
essentials of the management of breast disease
in an easily readable and absorbable format.
The principles of multimodality therapy
(chemotherapy, radiation therapy, hormonal
therapy) are explained from a surgical perspec-
tive, as are the basics of breast anatomy and
physiology, the diagnostic workup and
management of benign breast disease, and risk
stratification and reduction. Our goal is a
textbook that surgery residents, surgical oncol-
ogy fellows, and breast surgery fellows can
utilize in training (and beyond) and that
practicing general surgeons can use to enhance
their management of breast disease. Easy to
read, with a list of key topics to help focus the
reader and a liberal use of tables, boxes, and
figures to reinforce the information in each
chapter, this textbook will hopefully be a
useful resource to any surgeon responsible for
the management of diseases of the breast,
particularly breast cancer.
vii
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Contents
1
Anatomy and Physiology of the Breast.......................................................1
2
Principles of Breast Cancer Screening .......................................................19
3
The Breast Mass, Breast Biopsies, and Benign Lesions
of the Breast................................................................................................41
4
Breast Pain and Fibrocystic Disease...........................................................67
5
Management of Nipple Discharge.............................................................73
6
Infectious and Inflammatory Diseases of the Breast ................................83
7
Gynecomastia .............................................................................................91
8
Identifying and Managing the High-Risk Patient...................................101
9
Reading the Pathology Report .................................................................123
10
Workup and Staging of the Breast Cancer Patient .................................133
11
Management of Ductal Carcinoma In Situ and Paget Disease...............143
12
Surgical Management of Primary Breast Cancer.....................................157
13
Regional Management of Breast Cancer .................................................179
14
Principles of Breast Reconstruction .........................................................209
15
Principles of Radiation Therapy for Primary Breast Cancer...................231
16
Principles of Adjuvant Chemotherapy for Breast Cancer ......................247
17
Principles of Adjuvant Hormonal Therapy .............................................267
ix
18
Neoadjuvant Therapy...............................................................................279
19
Locally Advanced and Inflammatory Breast Cancer ..............................289
20
Surveillance of the Patient with Breast Cancer after Treatment ............297
21
Management of Breast Cancer Recurrence..............................................307
22
Breast Cancer in Special Populations ......................................................323
23
Other Tumors of the Breast .....................................................................335
Subject Index ............................................................................................341
x
CONTENTS
1
Anatomy and Physiology
of the Breast
DEVELOPMENT OF THE BREAST
Embryology
Development during Puberty
ANATOMY OF THE ADULT
BREAST
Muscular Anatomy of the Chest
Wall
Fascia of the Breast and Chest
Wall
Neural Anatomy of the Breast
and Chest Wall
Vascular Anatomy
Lymphatic Anatomy
Anatomy of the Axilla
PHYSIOLOGY OF THE BREAST
Hormones Affecting the Breast
The Breast during the Menstrual
Cycle
The Breast after Menopause
The Breast during Pregnancy
Lactation
Key Points
Know the development of the breast from intrauterine
development through puberty.
Describe the anatomy of the breast and the relationship of the breast to the
chest wall and axilla.
Understand the segmental distribution of the ductal-lobular units and the
pathway of milk from the lobules to the nipple
Name the muscles of the chest wall and axilla, their blood supply and
innervation, and the impact of a nerve injury.
Understand the arterial supply and venous and lymphatic drainage of the
breast and how this impacts breast pathology and surgery.
Describe the anatomy of the axilla, the boundaries of the “axillary pyramid,”
and the groupings of the lymph nodes in the axilla.
Understand the hormones that can affect breast physiology and how
lactation occurs.
Know the changes that the breast undergoes during the menstrual cycle,
during pregnancy, and after menopause.
1
Development of the Breast
The
breast
undergoes
multiple
changes
throughout life, from intrauterine life to senes-
cence. The development of the breast has sev-
eral
implications
that
impact
the
breast
surgeon. These include not only developmental
anomalies that the breast surgeon may face, but
also the routine surgical approach to both
benign and malignant disease. Although the
majority of growth occurs with puberty, the
development and differentiation of the breast
are truly completed by the end of the first term
of pregnancy. This is relevant to the develop-
ment of cancer, because breast cancer risk is
clearly and inversely related to the age at which
pregnancy first occurs. It is possible that this is
secondary to an increased risk of carcinogenesis
when the pre-parity, undifferentiated, and pro-
liferating mammary epithelium is exposed to
carcinogens, as compared to the effect of these
same carcinogens on the differentiated breast.
Embryology
Breast development takes place in several
stages (Box 1–1). Essentially, the breast arises
from a single ectodermal bud. At approxi-
mately the fifth to sixth week of fetal life,
a
milk
streak
develops
as
an
ectodermal
thickening, extending from the axilla to the
pelvis. This is also referred to as the galactic
band. By the ninth week, most of this has atro-
phied except for a mammary ridge in the pec-
toral region. It is here that a mass of basal cells
proliferates to form the nipple bud. By the 12th
week, squamous cells from the surface begin to
invade the nipple bud. While the epithelial
cells grow downward as mammary ducts, ter-
minating in lobular buds, the mesenchymal
cells differentiate into smooth muscle of the
nipple and areola. The anlage of the lactiferous
ducts invades the mesodermal connective tis-
sue by 16 to 24 weeks.
The fact that the entire gland thus originates
as a large dermal and subcutaneous organ from
a single focus on the skin is relevant to the
breast surgeon. One can think of the breasts
as modified eccrine glands. This is pertinent to
the lymphatic drainage, and has implications
for lymphatic mapping and sentinel lymph
node biopsy (see Chapter 13). Failure of some
of these steps to take place can result in con-
genital abnormalities of the breast (Box 1–2).
Most of these are quite rare; however, ectopic
breast tissue may be found in 1% to 6% of indi-
viduals and is commonly encountered by the
breast surgeon. Ectopic breast tissue is a result
of a failure of the milk streak to completely
atrophy. The ectopic tissue is usually located
in the axilla, and women may present with
complaints of a mass or pain in this area. Both
benign fibrocystic changes and cancer can arise
in this tissue.
During the second trimester, the breast con-
tinues to develop with the appearance of sweat
glands, sebaceous glands, and apocrine glands,
which will develop into the Montgomery
glands around the nipple. The epithelial buds
begin to branch into between 15 and 25
branches. Until this point, all of this has
occurred independent of the placental sex hor-
mones. In the third trimester, these hormones
can enter the fetal circulation and stimulate
BOX 1–1 STAGES OF
EMBRYOLOGIC BREAST
DEVELOPMENT
Ridge stage (<5-mm embryo)
Milk hill stage (7 to 8 weeks, 5- to 10-mm
embryo)
Thickening of the mammary anlage in
the region of the thorax
Regression of the remainder of the milk
streak
Mammary disc stage (10-mm embryo)
Invagination into the chest wall
mesenchyme
Lobule stage (11- to 25-mm embryo)
Tridimensional growth
Cone stage (10 to 14 weeks, 25- to 30-
mm embryo)
Flattening of the ridge
Budding stage (12 to 16 weeks, 30- to
70-mm embryo)
Mesenchymal cells differentiate into
smooth muscle of nipple and areola
Epithelial buds develop
Indentation stage (70 mm to 10 cm)
Branching stage (16 weeks, 10-cm fetus)
Epithelial buds branch into 15 to 25
strips of epithelium
Differentiation of hair follicle, sebaceous
gland, and sweat gland elements
Apocrine glands develop to form
Montgomery glands around the nipple
Canalization stage (20 to 32 weeks of
gestation)
First stage dependent on hormonal
influences
Placental sex hormones induce
canalization of the branched epithelial
tissues
End-vesicle stage (newborn)
Development of lobuloalveolar
structures containing colostrum
2
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
the branched epithelial tissues to canalize. The
ends of these branches differentiate into lobu-
loalveolar structures that contain colostrum.
This colostral milk is stimulated by the placen-
tal hormones and can be expressed for 4 to 7
days after birth, in both male and female
newborns (often referred to as “witch’s milk”).
During these final weeks of development, the
mammary gland mass increases fourfold and
the
nipple-areolar
complex
develops
and
becomes pigmented. Shortly after birth there
is withdrawal of the placental hormones, caus-
ing colostral secretion to stop and involution
of the breast.
After birth, mammary gland development
does very little more other than keeping pace
with the growth of the body. During early
childhood, there is further canalizing and
branching of the vesicles, but no significant
changes will take place until puberty.
Development during Puberty
Under the influence of gonadotropin-releasing
hormone from the hypothalamus, puberty
begins in children between 8 and 12 years
of age. This leads to the release of follicle-
stimulating hormone (FSH) and luteinizing
hormone (LH) from the pituitary gland, result-
ing in maturation of the ovarian follicles and
the secretion of estrogens. As puberty begins,
the circulating estrogen causes the ductal
epithelium and surrounding stroma to grow.
These ducts begin to extend into the superficial
pectoral fascia and arborize within the sup-
porting stroma to form collecting ducts and ter-
minal duct lobular units. These ultimately form
buds that precede further breast lobules. Sur-
rounding the ducts, vascularity increases and
connective tissues increase in volume and elas-
ticity, replacing adipose tissue and providing
support for the developing ducts (Fig. 1–1).
In addition to the development of pubic hair,
breast budding is one of the first signs of adoles-
cence in girls, along with the adolescent
growth spurt, beginning anywhere between
age 8 and 13 years. Although there are many
ways one can define the stages of breast devel-
opment from puberty to adulthood, the most
commonly used system is the Tanner phases,
which is based on the external appearance of
the breast (Table 1–1). Approximately a year or
2 following menarche, the breasts acquire their
mature structure (Tanner stage 5).
Anatomy of the Adult Breast
The adult breast sits atop the anterior chest
wall (Fig. 1–2). Superiorly, the breast extends
to the second intercostal space, while inferi-
orly it extends to the inframammary fold,
located at the sixth or seventh intercostal
space. The medial margin is at the lateral mar-
gin of the sternum, and the lateral margin sits
at the midaxillary line. The shape of the breast
is not spherical, but rather that of a teardrop,
with an extension of breast tissue toward the
axilla known as the tail of Spence. This is an
important concept to keep in mind when
performing a mastectomy (see Chapter 12:
Surgical Management of Breast Cancer). These
are the classic descriptions of the boundaries
of the breast, but breast tissue can extend
BOX 1–2 ABNORMAL BREAST
DEVELOPMENT
Accessory Nipple (Polythelia)
Ectopic nipple tissue due to failure of
complete regression of the milk streak
May occur anywhere from axilla to groin
Accessory Mammary Gland
(Polymastia)
Accessory breast tissue due to failure of
complete regression of the milk streak
Most often in axilla; may enlarge during
pregnancy
Hypoplasia
Underdevelopment of the breast, which
may be unilateral or bilateral with
asymmetry
Poland’s syndrome
Unilateral hypoplasia of the breast, thorax,
and pectoralis muscles
Can also be associated with hand
abnormalities (symbrachydactyly,
hypoplasia of the middle phalanges, and
central skin webbing)
Hyperplasia
Overdevelopment of the breast; may be
unilateral or bilateral with asymmetry
Amazia
The nipple is present but there is no
underlying breast tissue
Congenital Amastia
Absent breast and nipple
Acquired Amastia
Iatrogenic amastia due to excisional
biopsy of the breast bud
Can also result from radiation or trauma
(burn)
3
1—ANATOMY AND PHYSIOLOGY OF THE BREAST
beyond these described boundaries. Ductal tis-
sue can extend as high as the clavicle, beyond
the inframammary fold, into the axilla, or
beyond the border of the latissimus dorsi.
The two breasts may be widely separated on
the chest, or partially synthesized at the mid-
line, although ducts do not communicate
across the midline of the chest.
On average, the breast is 10 to 12 cm in
diameter and 5 to 7 cm thick at its center.
The contour of the breast is typically conelike
with breast tissue projecting into the axilla as
the axillary tail of Spence. The volume of the
breast can range from 21 to 2000 mL, with
an average of 400 mL. The volume fluctuates
with the menstrual cycle (see later). The breast
Figure 1–1. Schematic draw-
ing illustrating mammary gland
development. Anterior and lat-
eral views of the breast are
shown in columns 1 and 2. The
microscopic
appearances
of
the
ducts
and
lobules
are
illustrated in columns 3 and 4,
respectively.
A,
Prepubertal
(childhood).
B,
Puberty.
C,
Mature
(reproductive).
D,
Pregnancy.
E,
Lactation.
F,
Postmenopausal
(senescent)
state. (From Copeland EM III,
Bland KI. The breast. In Sabiston
DC Jr, ed. Essentials of sur-
gery. Philadelphia: WB Saunders,
1987.)
TABLE 1–1 Tanner Stages
Stage
Approximate Age
Description
Stage 1
Puberty
Preadolescent, with slight elevation of the papilla
Stage 2
11.1 1.1 yr
Elevation of the breast and papilla as a small mound
Increase in size of the areola
Stage 3
12.2 1.1 yr
Further enlargement of the breast
Stage 4
13.1 1.2 yr
The areola and papilla form a secondary mound above the breast
Stage 5
15.3 1.7 yr
Areola recedes into the general contour of the breast
4
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
is more conical in the nulliparous woman and
more pendulous in women who have had chil-
dren. The contour and volume of the breast,
however, vary greatly among individuals, and
may vary from left to right. More than half of
women have volume differences of greater
than 10% and more than one fourth of
women have volume differences greater than
20%. These differences are typically not appre-
ciated by most women.
The breast comprises three major structures:
the skin, the subcutaneous tissue, and the
fibroglandular breast tissue. The skin of the
breast is thin and contains hair follicles, seba-
ceous glands, and eccrine sweat glands. The
nipple-areolar complex is typically located
over the fourth intercostal space (in the non-
pendulous breast). Both the nipple and areola
consist of a keratinizing stratified squamous
epithelium with a dense basal melanin deposi-
tion, which accounts for the pigmentation. It
can range from 15 to 60 mm in diameter.
Within the nipple are multiple sensory nerve
endings,
including
Ruffini-like
bodies
and
end bulbs of Krause. Within the dermis are
radially arranged smooth muscle fibers that
contract with stimulation, hardening and ele-
vating the nipple. The areola has hair follicles,
sebaceous glands, and sweat glands. At the
periphery of the areola are the Morgagni tuber-
cles, elevations formed by openings of the
ducts of the Montgomery glands. These glands
are a cross between sweat and mammary
glands, and are capable of producing milk.
Underneath the skin is the subcutaneous fat,
which contributes to the size of the breast and
which fluctuates with the amount of total
body fat. Beneath this is the superficial pecto-
ral fascia (Fig. 1–3). The gland of the breast lies
within the superficial fascia, with the anterior
layer between the skin and the mammary
gland, and the posterior layer between the
gland and the fascia of the pectoralis major
muscle. Connecting these two fascial layers
are fibrous bands (Cooper suspensory liga-
ments).
Cooper’s
ligaments
help
give
the
breast its shape and anchor the gland to the
skin. They are particularly dense at the lower
periphery of the breast, where they maintain
the inframammary fold.
The breasts maintain mobility on the chest
wall because of the retromammary bursa.
Between the posterior layer of the superficial
pectoral fascia and the pectoralis major muscle
fascia is a cleft known as the retromammary
space, or retromammary bursa. The deep surface
Figure 1–2.
The breast tis-
sue typically extends from the
2nd rib to the inframammary
fold at the 6th or 7th rib, and
from the lateral border of the
sternum
to
the
midaxillary
line. The breast is teardrop
shaped, with an extension of
breast tissue extending into
the axilla, known as the axil-
lary tail or the tail of Spence.
(From
Bloom
N,
Beattie
E,
Harvery J. Atlas of cancer sur-
gery.
Philadelphia:
Elsevier,
2000.)
5
1—ANATOMY AND PHYSIOLOGY OF THE BREAST
of the breast rests on portions of the deep
investing fasciae of the pectoralis major, serra-
tus anterior, and external oblique muscles, as
well as the upper extent of the rectus sheath.
As the breast tissue develops through the
layers of the superficial fascia, they remain rel-
atively close to the skin. This is especially true
at the nipple-areolar complex. These relation-
ships are all important when performing a
mastectomy.
The fibroglandular tissue, or parenchyma, of
the breast, is divided into 15 to 20 segments
that converge at the nipple in a radial arrange-
ment (Fig. 1–4). These segments are not always
evenly distributed around the breast. The
upper half of the breast, particularly the upper
outer quadrant, tends to contain more glandu-
lar tissue than does the remainder of the
breast. Each segment contains a lobe made of
20 to 40 lobules, each consisting of 10 to 100
alveoli. Two-millimeter ducts drain each seg-
ment into subareolar lactiferous sinuses of 5
to 8 mm in diameter. Ten major collecting
milk ducts then open at the nipple. The ductal-
lobular unit is the biologically active unit of
the breast. The epithelial lining of the lobule
consists of superficial (luminal) A cells that
are involved in milk synthesis. The B cells
(basal) have stem cell activity. Finally there
are myoepithelial cells located around the
alveoli and small excretory mild ducts between
the inner aspect of the basement membrane
and the tunica propria. These cells are not
innervated, but rather are stimulated to con-
tract by the hormones prolactin and oxytocin.
Muscular Anatomy of the
Chest Wall
Underneath the breast lies the musculature of
the chest wall and upper abdomen (Table 1–2).
The pectoralis major muscle broadly originates
over the medial half of the clavicle, lateral
sternum, and sixth and seventh ribs, and then
converges to an insertion point on the greater
tubercle of the humerus. It is fan shaped and
made of two divisions. The clavicular division
originates from the clavicle. The costosternal
division
originates
from
the
sternum
and
costal cartilages, and
is the larger of the
two divisions. When the deep pectoral fascia
has been reflected laterally, the natural cleavage
between the clavicular and costosternal por-
tions of the pectorals major can be appreciated.
Pectoralis major muscle
Pectoralis major fascia
Intercostal muscles
Parietal pleura
Visceral pleura
Stroma
Cooper’s ligament
Lactiferous sinus
Lactiferous duct
Retromammary bursa
Lobule of gland
Internal mammary lymph nodes
Lymphatic vessels
Subcutaneous
fatty tissue
Figure 1–3. Tangential and sagittal view of the breast. The breast lies in the superficial fascia just deep to the
dermis, attached to the skin by the suspensory ligaments of Cooper. The retromammary bursa separates it
from the investing fascia of the pectoralis major muscle. Cooper’s ligaments form fibrosepta in the stroma that
provide support for the breast parenchyma. From 15 to 20 lactiferous ducts extend from lobules comprised of
glandular epithelium to openings located on the nipple. Subcutaneous fat and tissue are distributed around the
lobules of the gland and account for much of its mass. (From Copeland EM III, Bland KI. The Breast, 3rd ed. Phi-
ladelphia: WB Saunders, 2004.)
6
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
Separation of this cleavage can provide access
to the axillary fat pad. The pectoralis major acts
primarily in flexion, adduction, and medial rota-
tion of the arm at the shoulder joint (bringing
the arm across the chest).
The cephalic vein runs along the upper lat-
eral border of the pectoralis major muscle
and sits between the pectoralis major and del-
toid muscle (Fig. 1–5).
Underneath the pectoralis major muscle is
the
pectorals
minor
muscle,
arising
from
the medial surfaces of the third, fourth, and
fifth ribs and inserting as a tendon into the
coracoid process of the scapula. The pectoralis
minor helps depress the shoulder inferiorly.
However, except for the loss of some mass
on the anterior thoracic wall, no significant
disability comes from the loss of the pectoralis
minor muscle. The functional loss following
division or removal of the pectoralis minor
muscle is small and well tolerated. This should
be kept in mind when performing an axillary
dissection in a patient with clinically involved
nodes, because division of the pectoralis minor
results in minimal morbidity but does allow
for a more extensive dissection of the high
level II and level III axillary nodes.
The serratus anterior muscle arises from a
series of digitations from the lateral aspect of
Nipple
Areolus
Lactiferous ampulla
Lactiferous ampulla
Peripheral lobules with
secretory acini and
minor interlobular ducts
Distal/central
major mammary ducts
Distal/central
major mammary
ducts
Cooper’s
ligament
Figure 1–4. The secretory acini of the lobular tissue
open into small intralobular ducts, which then drain
into major lobar ducts. These ducts are organized
into 16 to 18 lobular groupings separated by Coop-
er’s ligaments. As they approach the nipple, they
dilate into lactiferous ampullae, just below the nip-
ple-areolar complex, before traversing the nipple.
There may be as many as 18 openings at the apex
of the nipple, although two major ducts may con-
verge into one ampulla. (From Copeland EM III,
Bland KI. The Breast, 3rd ed. Philadelphia: WB Saun-
ders, 2004.)
TABLE 1–2 Muscular Anatomy Relevant to Breast Surgery
Muscle
Attachments
Innervation
Action
Pectoralis major
Clavicle, sternum, and costal
cartilages 1 to 6 to the greater
tubercle of the humerus
Medial and lateral
pectoral nerves
Flexion, adduction, and
medial rotation of the
arm
Pectoralis minor
Ribs 2, 3, 4, and 5 to the coracoid
process of the scapula
Medial pectoral nerve
Inferior depression of the
shoulder
Serratus anterior
Ribs 1 to 8 to the anteromedial
border of the scapula
Long thoracic nerve
Abduction and lateral
rotation of the scapula,
fixation of the scapula
Latissimus dorsi
Spinous processes T-6 to T-12, L-1
to L-5, sacrum, and lilac crest to
the intertubercular groove of the
humerus
Thoracodorsal nerve
Extension, adduction and
medial rotation of the
arm
Subscapularis
Scapula to the lesser tubercle of
the humerus
Subscapular nerve
Medial rotation and
adduction of the arm
Coracobrachialis
Coracoid process of the scapula to
the medial humerus
Musculocutaneous
nerve
Flexion and adduction
of the arm
Subclavius
First rib of costochondral junction
to the clavicle
Subclavian nerve
Depression of the clavicle
Rectus
abdominis
Pubis to cartilage of ribs 5, 6, and 7
Intercostal nerves,
iliohypogastric nerve,
ilioinguinal nerve
Tension of the anterior
abdomen, flexion of the
vertebral column
External
abdominis
oblique
Ribs 5 to 12 to the linea alba,
pubis, inguinal ligament, and
iliac crest
Respiration, increased
abdominal pressure
(micturition, defecation)
7
1—ANATOMY AND PHYSIOLOGY OF THE BREAST
the upper eight ribs. It inserts into the verte-
bral border of the scapula on its costal surface
and stabilizes the scapula on the chest wall.
The functional deficit of losing function of
the serratus anterior is an inability to raise the
arm above the level of the shoulder. The serra-
tus anterior is also important in stabilization
of the scapula on the thorax, and an injury
to the long thoracic nerve, which innervates
the serratus anterior, can result in a “winged
scapula.”
The latissimus dorsi muscle has a wide ori-
gin from the spinous processes and supraspi-
nous ligaments of the thoracic (7-12), lumbar,
and sacral vertebrae. It inserts into a 2.5-cm
insertion
in
the
bicipital
groove
of
the
humerus. The narrow tendon of the latissimus
dorsi forms the posterior axillary fold. The
latissimus dorsi functions to extend, internally
rotate, and adduct the humerus.
The subclavius muscle arises from the costo-
chondral junction of the first rib. At the tendi-
nous part of the lower border of this muscle,
the clavipectoral fascia forms a well-developed
band stretching from the coracoid process to
the first costochondral junction. This costo-
coracoid
ligament
(the
Halsted
ligament)
defines the point anatomically where the axil-
lary vessels enter the thorax (under the clavi-
cle, over the first rib).
These muscles also form a compartment
between the chest wall and the arm, known
as the axilla. This is of obvious importance to
the breast surgeon because the axillary lymph
nodes reside here. The nerves and vessels to
some of these muscles run through the axilla,
and can be injured during axillary dissection.
The axilla is described in more detail later.
One muscular abnormality that can occur in
this region is the presence of the Langer axil-
lary arch (Fig. 1–6). This represents a portion
of the latissimus dorsi muscle that arises sepa-
rately and crosses the base of the axilla superfi-
cially, passing deep to the pectoralis major
muscle to the coracoid process. This band of
tissue occurs in 7% of cases and can often
cause confusion when performing an axillary
dissection.
Pectoralis major
Cephalic vein
Deltoid
Musculocutaneous
nerve
Coracobrachialis
Axillary vein
Biceps
Brachial vein
Brachial
artery
Median
nerve
Ulnar
nerve
Basilic
vein
2nd intercostobrachial
nerve
Latissimus
dorsi
Long thoracic nerve
Long thoracic vein
Intercostal nerve
Serratus
anterior
Rectus
abdominus
Figure 1–5. Muscular anatomy of the chest wall. (From Bloom N, Beattie E, Harvery J. Atlas of Cancer Surgery.
Philadelphia: Elsevier, 2000.)
8
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
The skeletal component of the thoracic wall
consists of 12 thoracic vertebrae, 12 ribs and
their costal cartilages, and the sternum. The
intercostal spaces between the ribs are filled
with the external, internal, and innermost or
intimal intercostal muscles. The external inter-
costal muscles are the most superficial layer,
running from the tubercles of the ribs toward
the costochondral junction. The internal inter-
costal muscles run downward and posterior,
from the sternum toward the angle of the ribs.
The intercostal veins, arteries, and nerves pass
in the plane that separates the internal intercos-
tal muscle from the intimal layer.
Fascia of the Breast and Chest Wall
As stated earlier, the breast is enveloped by the
superior pectoral fascia, with the anterior layer
ventrally and a posterior layer dorsally. Con-
necting these two fascial layers are Cooper’s sus-
pensory ligaments, the fibrous bands that
provide support of the breast. Above the breast,
the superior pectoral fascia is continuous with
the superficial cervical fascia. At the inferior
aspect of the breast, the anterior and posterior
layers of the superior pectoral fascia rejoin and
are continuous with Camper’s and Scarpa’s
superficial abdominal fascia at the inframam-
mary fold.
The proximity of the breast parenchyma to
the skin is of critical importance to the breast
surgeon. The ducts and lobules of the breast
extend to the anterior layer of the superficial
fascia and extend directly to the nipple-areolar
complex. Preserving the nipple areolar complex,
as is done in a “subcutaneous mastectomy,” will
leave breast tissue. For this reason the nipple-
areolar complex is routinely removed with a
mastectomy, although some surgeons have
begun examining the possibility of preserving
just the areola or the entire nipple-areolar com-
plex (see Chapter 12). The anterior layer of the
superior pectoral fascia may be absent in some
patients; in others, only a few millimeters from
the overlying dermis may be present. Raising a
flap below the fascia will also leave residual
breast tissue, which is often done when “thick
flaps” are maintained.
Leaving residual breast tissue has important
implications if a mastectomy is being per-
formed to prevent either a recurrence (as in
the case with invasive or intraductal cancer)
or a primary cancer (as with a prophylactic
mastectomy). It is important that the surgeon
operate between the dermis and the superficial
fascia. This not only minimizes residual breast
tissue, but allows the surgeon to operate in an
almost bloodless plane, leaving the blood ves-
sels and lymphatics passing in the deeper layer
of the superficial fascia undisturbed.
The deep pectoral fascia covers the pectoralis
major muscle and is attached to the sternum
and clavicle. Inferiorly it is continuous with
the deep fascia of the abdominal wall. As with
the superficial fascia, the ducts and lobules are
in close proximity to the deep fascia, so the fas-
cia should be removed with a mastectomy (or
during a lumpectomy for a posterior tumor).
The clavipectoral fascia runs deep to the
pectoralis major muscle and envelops the pec-
toralis minor muscle. Superiorly, this fascia
thickens and attaches to the clavicle. Surgically,
this is an important landmark because this fas-
cia forms the “roof” of the axillary space; it is
also known as the axillary fascia. This fascia
covers the serratus anterior and envelops the
axillary vessels, forming the vascular sheath.
The fatty areolar tissue posterior to the clavipec-
toral fascia encompasses the large axillary lym-
phatics
and
axillary
lymph
nodes.
When
performing a sentinel lymph node biopsy, the
surgeon needs to incise this fascia in order to
reach the lymph nodes. When performing an
axillary
lymph
node
dissection,
the
flaps
should be raised above this fascia.
Neural Anatomy of the Breast
and Chest Wall
There are several motor and sensory nerves
that the breast surgeon needs to be familiar
with. Segmental thoracic nerves provide the
cutaneous sensation to the breast via anterior
Langer
axillary arch
Figure 1–6. The Langer axillary arch is a portion of
latissimus dorsi muscle that arises separately and
crosses the axilla superficially before joining the
coracoid process. This band of muscle can cause
confusion during an axillary lymph node dissection.
9
1—ANATOMY AND PHYSIOLOGY OF THE BREAST
and lateral perforating branches. The most
sensitive portion of the breast is the nipple,
which is innervated by branches of the fourth
thoracic nerve. The surgeon should be aware
that these nerves approach the nipple medi-
ally and laterally. For this reason, circumareo-
lar incisions in the superior or inferior aspect
of the nipple are less likely to disturb the nip-
ple’s sensory innervation.
The pectoralis major muscle is innervated by
the medial and lateral pectoral (anterior thoracic)
nerves. What is often confusing is that these
names come from their origin from the medial
and lateral cords of the brachial plexus, and
not their position on the chest wall (Fig. 1–7).
The lateral pectoral nerve actually innervates
the medial portion of the pectoralis, and
courses medial to the pectoralis minor muscle
to reach its destination. The nerve passes over
the first part of the axillary vein medial to
the pectoralis minor muscle, and its branches
pierce the clavipectoral fascia to enter the deep
surface of the muscle. The pectoralis major
muscle is mainly innervated by the lateral
pectoral nerve, as this innervates the clavicular
and sternal origins of the pectoralis major
muscle.
The medial pectoral nerve innervates the lat-
eral portion of the muscle; the lower third and
the costoabdominal insertions of the pectoralis
major muscle. It courses lateral (or in some
cases through) the pectoralis minor muscle
(which it also innervates). By understanding
the anatomy of the pectoral nerves, it is possi-
ble to perform an axillary lymph node dissec-
tion without sacrificing the innervation. If one
of these nerves is cut, the denervated portions
of the muscle become flaccid and atrophic.
The long thoracic nerve (also called the exter-
nal respiratory nerve of Bell) innervates the ser-
ratus anterior muscle. Arising from the fifth,
sixth, and seventh cervical nerves, it passes
deep to the axillary artery and vein, staying
close to each segment of the thoracic wall. As
it passes caudally, it gives branches to each seg-
ment of the serratus anterior muscle. The long
thoracic nerve is superficial to the deep fascia
investing
the
serratus
anterior.
During
an
2nd intercostobrachial
nerve
Thoracodorsal vein,
artery & nerve
Subscapularis
Latissimus
dorsi
Subscapular
nerves
Long
thoracic nerve
Long
thoracic vein
Axillary
vein
Subclavius
Subclavian vein
Subclavian artery
Thoracoacromial artery
Lateral cord of
brachial plexus
Shoulder
joint capsule
Conjoined
tendon
Pectoralis major
Musculocutaneous
nerve
Coracobrachialis
First rib
Medial & lateral
pectoral nerves
Pectoralis
minor
Pectoralis
major
Figure 1–7. Neurovascular anatomy of the axilla. (From Bloom N, Beattie E, Harvery J. Atlas of Cancer Surgery.
Philadelphia: Elsevier, 2000.)
10
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
axillary dissection, the nerve can be seen by
stripping the fascia away from the serratus ante-
rior. Dissection directly on top of the serratus
anterior (between the muscle and superficial
fascia) will be medial to the nerve, pulling it
into the specimen and increasing the likeli-
hood of injury. The result of this would be an
inability to raise the arm above the level of
the shoulder, as well as a winged scapula.
The thoracodorsal nerve innervates the latissi-
mus dorsi muscle. It arises from the posterior
cord of the brachial plexus, runs beneath or
dorsal to the axillary vein along the posterior
axillary wall, and passes through the fibrofatty
tissue of the axilla to the upper portion of the
muscle. Injury to this nerve denervates the
latissimus dorsi, which weakens extension,
internal
rotation,
and
adduction
of
the
humerus. Although this is extremely well toler-
ated by most patients, every attempt should be
made to preserve the nerve during axillary dis-
section both to lessen functional loss and pre-
serve the muscle for reconstructive purposes.
An important nerve to preserve during sur-
gery is the nerve to the subscapularis muscle.
This muscle passes between the subscapular
fossa and the lesser tubercle of the humerus.
It is seen at the posterior wall of the axilla,
inferior to the axillary vein. The nerve sits on
the upper anterior surface of the muscle and
can be injured when dissecting the fascia from
the muscle inferior to the vein. Injury to this
nerve denervates the muscle, affecting medial
rotation of the arm. As the muscle both stabi-
lizes the humerus in the glenoid fossa and
assists
with
flexion,
extension,
abduction,
and adduction of the arm, palsy can produce
significant morbidity.
The intercostobrachial nerve is a sensory
nerve that runs through the axilla and inner-
vates the skin of the axilla and upper medial
aspect
of
the
arm.
The
intercostobrachial
nerve is the posterior ramus of the lateral per-
forating
branch
of
the
second
intercostal
nerve. It appears in the second intercostal
space and courses anterior to the long thoracic
nerve
and
thoracodorsal
nerve.
Often
it
divides early, giving the appearance of two
nerves. It is important because the nerve is
always exposed during an axillary dissection.
Although many surgeons routinely divide this
nerve, it is possible to dissect these nerves out
and preserve them (see Chapter 13). The nerve
typically innervates the upper arm, but can
extend as far as the level of the elbow, so divi-
sion can sometimes result in a significant area
of numbness.
Vascular Anatomy
The breast is supplied by multiple sources
(Fig. 1–8). Multiple muscle-perforating branches
of the thoracoabdominal artery perforate the
pectoralis major muscle to enter the breast.
The inner quadrants also receive blood flow
from the perforating branches of the internal
mammary arteries. These penetrate each inter-
costal space and the pectoralis major muscle
to reach the breast. The outer quadrants receive
blood from branches of the lateral thoracic
artery, which both penetrate and come around
the pectoralis major. Additional blood supply
comes from lateral cutaneous branches of the
posterior
intercostal
arteries.
All
of
these
arteries connect with each other by collateral
branches in both the breast and overlying skin.
Overall, 60% of the breast is supplied by the
internal mammary artery, 30% of the breast is
supplied by the lateral thoracic artery, and
10% is supplied by minor contributions from
the thoracoacromial, intercostals, subscapular,
and thoracodorsal arteries.
The venous drainage does not completely
follow
the
arterial
supply.
Rather,
venous
Pectoral branch
Thoracoacromial artery
Axillary
artery
Lateral
thoracic
artery
Intercostal
branches
of arteries
Anterior
intercostal
perforating
arteries
Internal
mammary
artery
Figure 1–8. Arterial distribution of blood to the
breast. The breast receives its blood supply via three
major routes: (1) medially from anterior perforating
intercostal branches off of the internal thoracic
artery, (2) laterally from branches of the thoracoacro-
mial trunk or lateral thoracic artery (both of which
come off the axillary artery), and (3) lateral cutane-
ous branches off of the intercostal arteries. (From
Copeland EM III, Bland KI. The Breast, 3rd ed.
Philadelphia: WB Saunders, 2004.)
11
1—ANATOMY AND PHYSIOLOGY OF THE BREAST
drainage heads toward an anastomotic circle
in
the
subcutaneous
tissue
beneath
and
around the areola. This plexus then drains
centrifugally toward the periphery via large
subcutaneous veins. These veins then travel
with the arteries supplying the breast. When
venous flow increases, as with lactation, these
veins become more apparent.
Lymphatic Anatomy
The lymphatic drainage of the breast is through
two sets of lymphatic vessels; the superficial
(also known as subepithelial or subdermal)
and the deep (Fig. 1–9). The subepithelial
plexus of lymphatic vessels exists throughout
the entire body surface. These vessels are valve-
less, allowing lymph to flow in any direction,
although it does so sluggishly. The subepithelial
plexus connects to subdermal lymphatic vessels
by vertical lymphatics. The subdermal vessels
do have valves. Thus lymph flows unidirection-
ally from the superficial to the deep plexus.
In the breast, the subepithelial and subdermal
plexuses are confluent with the subareolar
plexus. Also draining into the subareolar plexus
are the fine lymphatics of the lactiferous ducts
and the lymphatics of the areola and nipple.
It is because of these connections between the
subareolar plexus and the subepithelial and
subdermal lymphatics that subareolar or periar-
eolar injection of tracers during intraoperative
lymphatic mapping and sentinel lymph node
biopsy is possible.
From the deep lymphatics, the lymph flow
moves centrifugally toward the axillary and
internal mammary lymph nodes. Approxi-
mately 3% of the lymph from the breast goes
to the IM chain, which can come from all
quadrants of the breast, not just the inner
quadrants.
The
internal
mammary
nodes
(IMN) are found with the internal mammary
artery and vein within the intercostal spaces
at the sternal border, deep to the intercostal
muscles and within the extrapleural fat. Most
of the nodes are in the upper parasternal area
(upper three interspaces); however, the num-
ber of nodes is variable and can extend as
low as the fifth intercostal space and as high
as the retroclavicular region. The other 97%
of lymph flows to the axillary lymph nodes.
Anatomy of the Axilla
The anatomy of the axilla and axillary lymph
nodes is obviously crucial to the breast sur-
geon. The axilla is typically thought of as a
four-walled pyramid that sits between the
upper arm and the chest (Fig. 1–10). The
dome-shaped base of the pyramid is the arm-
pit, made of the axillary fascia and the skin.
The apex of the pyramid is an aperture that
extends into the posterior triangle of the neck
through the cervicoaxillary canal. This canal is
M
M
T
M
I
II
III
Figure 1–9. Lymphatic drainage of the breast.
(From Copeland EM III, Bland KI. The Breast, 3rd ed.
Philadelphia: WB Saunders, 2004.)
Lateral wall:
humerus
(thin strip)
Anterior wall:
pectoralis major
and minor
Medial wall:
serratus anterior
Posterior wall:
subscapularis,
latissimus and
teres major
Base: skin and
axillary fascia
Apex: aperature into
posterior triangle
of neck
Bounded by clavicle,
scapula and 1st rib.
Figure 1–10. The axillary pyramid.
12
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
bounded by the clavicle anteriorly, the scapula
posteriorly, and the first rib medially. Almost
all of the structures heading toward the upper
extremity pass through the cervical axillary
canal. This leaves the four walls. The anterior
wall is the pectoralis major and minor mus-
cles. The posterior wall is the subscapularis
muscle (and to a lesser extent the teres major
and latissimus dorsi muscles and tendons).
The medial wall is the serratus anterior muscle.
The lateral wall is a thin strip of humerus
between the insertions of the muscles of the
anterior and posterior walls.
Coming through the apex of the pyramid
are the great vessels and nerves of the upper
extremity, enclosed within a layer of fascia,
the axillary sheath. The sheath is dense con-
nective tissue extending from the neck, but
gradually disappears as the nerves and vessels
begin to branch. Throughout their course in
the axilla, the axillary artery and vein are asso-
ciated with the cords of the brachial plexus
(medial, lateral, and posterior).
The axilla is enveloped in fascia. The most
significant fascia is the clavipectoral fascia.
This fascia extends from the clavicle toward
the floor of the axilla (the axillary fascia). It
encloses both the subclavius muscle and the
pectoralis minor muscle. The upper portion
of the clavipectoral fascia is known as the cos-
tocoracoid membrane. The lower portion is
sometimes called the suspensory ligament of
the axilla or the coracoaxillary fascia. A dense
condensation
of
the
clavipectoral
fascia,
extending from the medial end of the clavicle
to the first rib, is known as Halsted’s ligament.
This ligament covers the subclavian artery
and vein as they cross the first rib and is an
important landmark when performing a level
III axillary lymph node dissection.
Within the pyramid, in addition to the great
vessels and nerves and their branches, are the
axillary lymph nodes. We tend to group the
lymph nodes by their anatomic location, hav-
ing been arbitrarily divided into levels based
on their relation to the pectoralis minor mus-
cle. The level I lymph nodes lie lateral to the
muscle, the level II nodes like directly beneath
the muscle, and the level III nodes are medial
to the medial border of the pectoralis minor.
However, the lymph nodes are better categor-
ized by several groups (Fig. 1–11):
The lateral group, or axillary vein group,
consists of four to six nodes that lie medial
or posterior to the axillary vein. These
lymph nodes receive most of the lymph
draining from the upper extremity.
The anterior group, or external mammary
group, consists of four or five lymph
nodes that lie along the lower border of
the pectoralis minor muscle in association
with the lateral thoracic vessels. These
lymph nodes receive the major portion
of the lymph draining from the breast.
The posterior, or scapular, group consists of
six or seven nodes that lie along the poste-
rior wall of the axilla at the lateral border
of the scapula. These nodes receive lymph
primarily from the posterior neck and trunk.
The central group consists of three or four
lymph
nodes
that
lie
within
the
fat
beneath
the
pectoralis
minor
muscle.
These lymph nodes receive drainage from
the lateral, anterior, and posterior groups.
The subclavicular, or apical, nodes consist
of 6 to 12 lymph nodes that sit at the apex
of the axilla, superior to the pectoralis
muscle and along the medial side of the
axillary vein. These receive drainage from
all of the other lymph node groups.
The interpectoral nodes, or Rotter’s nodes,
consist of one to four nodes between the
pectoralis major and minor muscles and
drain into the central and subclavicular
nodes) (Table 1–3).
Thus the level I lymph nodes, those nodes
lateral or below the lower border of the pector-
alis minor muscle, include the external mam-
mary, axillary vein, and scapular lymph node
groups. The level II lymph nodes, located deep
Supraclavicular node
Subclavian v.
Coracoid process
Axillary v.
Thoracodorsal v.
Central node
Systemic route
Apical
(subclavicular) node
Lateral (axillary)
node group
Subscapular v.
Posterior (subscapular)
node group
External mammary
(anterior) node group
Pectoralis minor
(tendon, muscle)
I
I
I
II
III
Figure 1–11. The major lymph node groups of the
axilla. The Roman numerals indicate the three levels
of the axillary nodes in relation to the pectoralis
minor muscle. (From Copeland EM III, Bland KI. The
Breast, 3rd ed. Philadelphia: WB Saunders, 2004.)
13
1—ANATOMY AND PHYSIOLOGY OF THE BREAST
to the pectoralis minor muscle, include the
central and some of the subclavicular lymph
node groups. The remainder of the subclavicu-
lar lymph nodes are the level III lymph nodes,
located medial to the pectoralis minor.
The locations of the axillary groups and the
flow of the lymph are important in regard to
metastatic dissemination of breast cancer. Typ-
ically there is unidirectional flow toward the
regional lymph nodes; however, when the
lymphatics are blocked by neoplasm, flow
can reverse, leading to endolymphatic metas-
tases of both the dermis and breast paren-
chyma. Therefore the presence of metastases
in the regional nodes, which can obstruct the
lymphatic vessels, will increase the likelihood
of parenchymal metastases (manifesting as in
breast
recurrences)
and
dermal
metastases
(e.g., chest wall recurrences after mastectomy).
Physiology of the Breast
The purpose of the breast is milk production
for the sustenance of the newborn. The secre-
tory units of the breast are the alveoli, small
saccules
off
of
the
lactiferous
ducts.
The
growth of these secretory units and their pro-
duction of milk is controlled by an intricate
network of hormones. Fluctuation of these
hormones and changes in their relative ratios
cause several histologic changes in the breast,
not just during pregnancy but also during the
menstrual cycle. Changes occur in both the
epithelium and the stroma and profoundly
influence the morphology of the breast.
Hormones Affecting the Breast
See Table 1–4.
TABLE 1–3 Major Lymph Node Groups of the Axilla
Group
Location
Nodes
Drainage From
Lateral (axillary vein)
Medial-posterior to axillary vein
4 to 6
Upper extremity
Anterior (external mammary)
Along lower border of pectoralis minor
4 to 5
Breast
Posterior (scapular)
Lateral border of scapula
6 to 7
Posterior neck/trunk
Central
Beneath pectoralis minor
3 to 4
Lateral, anterior, and
posterior groups
Subclavicular (apical)
Apex of axilla
6 to 12
All other groups
Interpectoral (Rotter’s)
Between pectoralis major and minor
1 to 4
TABLE 1–4 Hormones Influencing Breast Development During Pregnancy
Hormone
Effect During Development
Effect During Pregnancy and Lactation
Estrogen
Causes ductal growth during adolescence
Required for lobuloalveolar growth
Progesterone
Required for lobuloalveolar
differentiation and growth
Glucocorticoids
Contributes to ductal growth in puberty
Enhances lobuloalveolar growth
Stimulus for lactation
Growth hormone
Contributes to ductal growth in puberty
Stimulus for lactation
Maintains mammary epithelial
cell survival
Insulin
Enhances growth of mammary
epithelium
Enhances ductal alveolar growth
Prolactin
Contributes to ductal growth in puberty
Required for lactogenesis and maintenance
of lactation
Human placental
lactogen
Stimulates alveolar growth and lactogenesis
Thyroid hormones
Increases epithelial secretory response
to prolactin
Oxytocin
Causes contraction of myoepithelial cells
and milk ejection
14
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
Estrogen
Estrogen stimulates the growth of the breast at
puberty. However, while development is depen-
dent on estrogen, estrogen alone will have no
effect. In the presence of other hormones, such
as hydrocortisone, insulin, or growth hormone,
it leads to growth of the ductal system.
Progesterone
Progesterone also stimulates breast growth at
puberty, but unlike estrogen, which works pri-
marily on the ducts, progesterone induces devel-
opment of the terminal ducts and lobuloalveolar
structures.
As
with
estrogen,
this
response
requires the presence of other hormones, specif-
ically growth hormone and insulin.
Prolactin
Prolactin is produced by lactotrophs in the pitu-
itary
gland.
Prolactin
stimulates
mammary
growth and differentiation and ultimately milk
production. The synthesis of prolactin is stimu-
lated by a wide variety of hormones and neuro-
transmitters (Box 1–3). Thyrotropin releasing
hormone (TRH) is the primary stimulator of pro-
lactin secretion, dopamine is the primary inhibi-
tion. However, prolactin can also be produced
by cells in the breast; thus prolactin can not
only behave as a classic hormone, but also as a
paracrine or autocrine factor. The extrapituitary
prolactin is not regulated by TRH or dopamine
but is controlled by progesterone.
Oxytocin
Oxytocin is a peptide hormone secreted by the
pituitary gland. Oxytocin is released in response
to a variety of stimuli. Suckling results in
oxytocin release and may also be a conditioned
reflex in response to an infant’s cry. Oxytocin
receptors are located on the myoepithelial cells
located in the basement membrane of the
alveoli and intralobular ducts. These receptors
increase in number at parturition. When oxyto-
cin binds to these receptors, contraction of the
myoepithelial cells occurs.
Human Placental Lactogen
Human placental lactogen (hPL) is produced by
the placenta and serum levels continue to rise
throughout pregnancy. The major role of hPL
is related to breast growth and differentiation
during pregnancy. After delivery, the decrease
in the serum concentration is rapid.
The Breast during the Menstrual
Cycle
Follicular Phase
The follicular phase of the menstrual cycle is
defined as the first day of menstruation until
ovulation. It is initiated by a rise in follicle-
stimulating hormone (FSH) levels at the first
day of the cycle. This is triggered by a decrease
in progesterone and estrogen (which act to
inhibit FSH secretion). FSH stimulates the
development of follicles and their secretion
of estrogen (Fig. 1–12).
In the breast, the increased estrogen levels
initiate
cellular
mitoses,
RNA
synthesis,
increased nuclear density, and other changes
within the epithelial cells. In addition, estro-
gen has a histamine-like effect on the mam-
mary
microcirculation.
This
leads
to
an
increased blood flow to the breast in the 3 to
4 days before menstruation. The breast can
increase in volume from 15 to 30 cm3 due to
both the increasing interlobular edema and
the enhanced cellular proliferation.
Estrogen inhibits the secretion of FSH, and
FSH levels decrease. Estrogen levels peak toward
BOX 1–3 HORMONES AND
NEUROTRANSMITTERS AFFECTING
PROLACTIN PRODUCTION
Thyrotropin releasing hormone (TRH)
[stimulatory]
Vasoactive intestinal peptide (VIP)
[stimulatory]
Dopamine [inhibitory]
Estrogen [stimulatory]
Insulin [stimulatory]
EGF [stimulatory]
Relaxin [stimulatory]
Follicular phase
Ovulation
Estrogen
Progesterone
FSH
LH surge
Luteal phase
Figure 1–12. Changes in hormone levels with the
menstrual cycle.
15
1—ANATOMY AND PHYSIOLOGY OF THE BREAST
the end of the follicular phase of the menstrual
cycle, which exerts a positive feedback on lutei-
nizing hormone (LH). There is a dramatic pre-
ovulatory LH surge at this point, which is
required for ovulation. The LH causes the follicle
to swell and rupture, with expulsion of the
oocyte, and corona radiate into the peritoneal
cavity and ultimately into the fallopian tube.
Luteal Phase
The luteal phase is initiated by the surge in LH.
During the luteal phase, progesterone synthesis
is maximum. The major effects of the LH surge
are the conversion of granulose cells from pri-
marily androgen-converting cells to predomi-
nantly progesterone-synthesizing cells. At this
point there is increased progesterone secretion
with some estrogen secretion.
In the breast, the progestogens trigger the
mammary ducts to dilate and the alveolar epi-
thelial cells to differentiate into secretory cells.
The breast epithelial cell proliferation increases
during the luteal phase of the menstrual cycle.
Menstruation
The high progesterone levels exert a negative
feedback on GnRH, and as this decreases so
does FSH and LH secretion. Ultimately there
is a decrease in estrogen and progesterone
levels, which removes the inhibition of FSH,
which begins to rise once again to initiate the
next menstrual cycle.
In the breast, the rapid decline in the circu-
lating levels of estrogen and progesterone lead
to a regression of the secretory activity of the
epithelium. The tissue edema is reduced, with
the minimum breast volume observed 5 to 7
days after menstruation.
The Breast after Menopause
Menopause typically occurs when a woman is
in her late 40s and early 50s; it is associated
with a variety of symptoms related to the loss
of estrogen and progesterone. These include
hot flashes, night sweats, mood disturbances
and difficulty sleeping, and vaginal dryness.
The breasts will also undergo changes with
menopause. The loss of hormonal stimulation
produces a decrease in the absolute number of
lobular units, as well as a diffuse atrophy of the
residual lobular units. This results in a decrease
in the glandular tissue, which is replaced with
fatty tissue. This decrease in breast density
makes it easier to detect breast cancer on mam-
mography, which is why sensitivity increases
with age. The duct system remains intact. The
loose paralobular and intralobular connective
tissue become progressively collagenized and
less cellular. The loss of strength of the connec-
tive tissue results in an increase in size and sag
to the breasts. However, these changes of atro-
phy are variable and incomplete. Some women
in their 60s and 70s still have a lobular appear-
ance similar to a premenopausal state.
We tend to associate fibrocystic disease with
the menstrual cycle, matching the increase in
pain and palpable masses to the changes in
hormone levels. It would therefore seem logi-
cal that fibrocystic disease should resolve with
menopause, but this is not always the case. For
some women, the breasts can become more
tender with menopause, with an increase in
“lumpiness” or cysts.
The Breast during Pregnancy
It is not until pregnancy that the breast attains
its maximum development. In the pregnant
patient, there is marked growth of the ducts,
lobules, and alveoli under the influence of
luteal and placental sex steroids and prolactin.
During the first 3 to 4 weeks of pregnancy,
under the influence of estrogen, there is growth
and branching of the ducts, as well as increased
lobule formation. By the second month, the
breasts have enlarged dramatically. The super-
ficial veins dilate and there is increased pig-
mentation of the nipple-areolar complex. The
breasts become tender and the nipples become
sore. This can begin just a few weeks after
conception.
Estrogen and progesterone prohibit the hypo-
thalamus from producing prolactin-inhibiting
factor (PIF). With this influence gone, prolactin
is released and this continues progressively dur-
ing pregnancy, although increase in prolactin
levels is slow during the first trimester.
In the second trimester of pregnancy, the
effects of progesterone cause the lobular for-
mation to exceed the ductal sprouting. During
this time, prolactin levels continue to rise and
by the third trimester, blood levels of prolactin
are three to five times higher than normal.
At this point the alveoli contain colostrum,
but no fat. The breast continues to enlarge, but
this is not due to epithelial proliferation but
rather the filling of the alveoli with colostrum,
as well as the hypertrophy of myoepithelial cells.
In the third trimester of pregnancy, the
stroma surrounding the lobules diminishes to
16
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
make room for the hypertrophied lobules. As
pregnancy continues, colostrum composed of
desquamated epithelial cells and fluid accumu-
lates. This is released in the immediate post-
partum period.
Lactation
During pregnancy, prolactin is being produced,
starting during the eighth week of pregnancy
and increasing until birth. During that time,
the high levels of estrogen and progesterone
block the prolactin receptors and inhibit milk
production. After birth, there is a decline in
the serum levels of estrogen and progesterone
over several days. This removes the inhibition
of milk production and lactogenesis begins.
Prolactin is one of two hormones responsi-
ble for milk production, with the other being
oxytocin. Prolactin levels were increasing until
birth, and after delivery begin to decline. If the
mother is not nursing, the prolactin levels will
drop slowly (>14 days). In the nursing mother,
prolactin will also drop, but much more
slowly, dependent on the time that the infant
nurses. Prolactin drives the synthesis and
secretion of milk into the alveolar spaces.
When the myoepithelial cells contract, the
milk passes through the ductal system and
out of the breast.
Oxytocin is the second hormone responsible
for milk production and delivery. When an
infant suckles at the mother’s breast, this causes
the increase in both prolactin, to stimulate
more production, and oxytocin, to increase
milk delivery.
During the first few days after delivery, the
body does not produce milk but rather a liquid
substance called colostrum. This is high in
immunoglobulins, which
help
protect
the
infant against infections at a time when the
infant’s own immune system has not fully
developed. Colostrum may help decrease the
infant’s chances of developing asthma and
other allergies.
When breast-feeding stops, it may take sev-
eral months for milk production to completely
stop. The breasts usually return to their previ-
ous size, although they may be smaller after
breast-feeding is completed.
Suggested Readings
1. Abramson RG, Mavi A, Cermik T, et al. Age-related
structural and functional changes in the breast:
Multimodality correlation with digital mammogra-
phy, computed tomography, magnetic resonance
imaging and positron emission tomography. Semin
Nucl Med 2007;37(3):146–153.
2. Anderson E. The role of oestrogen and progester-
one receptors in human mammary development
and tumorigenesis. Breast Cancer Res 2002;4(5):
197–201.
3. Aupperlee M, Kariagina A, Osuch J, Haslam SZ.
Progestins and breast cancer. Breast Dis 2005-2006;
24:37–57.
4. Kass R, Mancino AT, Rosenbloom A, et al. Breast
physiology: Normal and abnormal development
and function. In Bland KI, Copeland EM, eds. The
Breast: Comprehensive Management of Benign and
Malignant Disorders. St. Louis: Elsevier, 2004.
5. Romrell LJ, Bland KI. Anatomy of the breast, axilla,
chest wall and related metastatic sites. In Bland KI,
Copeland
EM,
eds.
The
Breast:
Comprehensive
Management of Benign and Malignant Disorders.
St. Louis: Elsevier, 2004.
6. Russo J, Russo IH. Development of the human
breast. Maturitas 2004;49(1):2–15.
7. Osborne MP. Breast anatomy and development.
In Harris JR, Lippman ME, Morrow M, Osborne CK,
eds. Diseases of the breast, 3rd ed. Philadelphia:
Lippincott Williams & Wilkins, 2004.
17
1—ANATOMY AND PHYSIOLOGY OF THE BREAST
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2
Principles of Breast Cancer
Screening
MODALITIES OF BREAST
IMAGING
Mammography
Ultrasound
Magnetic Resonance Imaging
Positron Emission Tomography
PRINCIPLES OF BREAST CANCER
SCREENING
Key Points
Describe how mammography is performed for screening
and additional techniques used for diagnostic mammography.
Know the differences between film and digital mammography.
Be familiar with the BI-RADS system and the abnormalities
on mammogram that warrant close observation versus biopsy.
Describe how ultrasound is performed and its indications.
Know the strengths and limitations of breast MRI in both screening
and diagnosis.
Understand the principles of cancer screening.
Breast imaging has changed the management
of breast disease dramatically over the past
few decades. Not only has screening changed
the face of breast cancer, but improvements
in technology and newer modalities have
altered the approach to the diagnosis of breast
abnormalities. Understanding the indications,
benefits and limitations of the various modal-
ities used in the evaluation of the breast is crit-
ical to the breast surgeon.
Modalities of Breast Imaging
Mammography
Technique
Mammography is by far the most important
imaging modality used today for the evaluation
of breast disease. Mammography is used both
for screening the asymptomatic woman and
helping diagnose women who present with a
19
complaint
regarding
the
breasts.
When
a
screening mammography is performed, two
standard views are used; the mediolateral
oblique (MLO) view and the craniocaudal
(CC) view (Fig. 2–1). The MLO view com-
presses the breast along a plane of approxi-
mately 45 degrees extending from the upper
inner quadrant to the lower outer quadrant,
with the x-ray tube rotated parallel to the
pectoralis muscle fibers. The natural mobility
of the breast is used to get as much breast
tissue as possible included, and when done
properly in the MLO view, shows both axil-
lary tail and abdominal wall. The CC view
positions the breast directly on top of the
x-ray cassette holder, with the x-ray tube
positioned for superior to inferior imaging.
For both the MLO and CC views, maximum
compression of the breastis necessary todecrease
the thickness of the breast, and to make the
breast more uniform in appearance, spreading
out
overlapping
structures.
If
there
is
an
abnormality detected on a screening mammo-
gram, or if a diagnostic mammogram is being
performed, additional views beyond the MLO
and CC views are often necessary (Table 2–1).
These are done under the direct supervision of
the radiologist, who reviews the results of the
procedure with the patient at the time of the
examination.
Digital Mammography
Standard mammography uses film for the
acquisition of the image, display for the radiol-
ogist, and storage. In contrast to what some
people believe, both traditional and digital
mammography use x-rays to obtain the image
(Fig. 2–2). The difference is that with digital
mammography the image is stored on a com-
puter rather than film. This does have several
advantages, however. On the computer screen,
the image can be manipulated. Postexpo-
sure processing may be performed to adjust
A
B
Figure 2–1. The MLO view (A) compresses the breast along a plane of approximately 45 degrees extending
from the upper inner quadrant to the lower outer quadrant, with the x-ray tube rotated parallel to the pectoralis
muscle fibers. When done properly, the MLO view shows both axillary tail and abdominal wall. The CC view
(B) positions the breast directly on top of the x-ray cassette holder, with the x-ray tube positioned for superior
to inferior imaging. The CC and MLO views of the right breast are negative for malignancy. (Image courtesy of
Dr. Alexis Nees, Department of Radiology, University of Michigan.)
20
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
contrast, brightness, and magnification with-
out the need to obtain additional images.
There is greater contrast resolution than with
film, and less “noise,” which may enhance
sensitivity and specificity. It also allows for
the rapid and easy transmission of images so
that second reads can be easily obtained.
Digital mammography is not without its
drawbacks
as
well.
Primarily,
the
cost
is
significant; in addition to the new machines,
monitors and digital workstations are needed
for the radiologists. As the transition is made
from film to digital imaging, problems may
arise when trying to compare a digital image
to a previous mammogram on film. Plus, the
spatial resolution is less than that of film mam-
mography, which can limit the evaluation of
microcalcifications or the margins of masses.
TABLE 2–1 Additional Views Obtained During Diagnostic Mammography
Magnification
views
Magnified views are taken of a specific area, with increased resolution to better look
at the lesion.
Spot compression
views
A small compression paddle is used to spread out the tissue, bringing the area
of concern closer to the film.
Exaggerated CC
views
Typically the CC view starts at the medial aspect and includes as much of the lateral
breast as possible. However, in some women, additional views are obtained to
include the entire lateral half of the breast.
Rolled views
The breast tissue is reoriented about the axis of the nipple to determine whether an
abnormality is real or simply overlapping tissue.
Tangential views
For palpable lesions, a metallic BB is placed on the skin and then the area is rolled,
placing it tangential to the x-ray beam.
A
B
Figure 2–2. Digital mammographic MLO and CC views are negative for malignancy. (Images courtesy of
Dr. Alexis Nees, Department of Radiology, University of Michigan).
21
2—PRINCIPLES OF BREAST CANCER SCREENING
Digital mammography may provide better
screening in women with dense breasts, par-
ticularly younger women. The multicenter
Digital
Mammographic
Imaging
Screening
Trial showed improved performance of digital
mammography in women who had dense
breasts, with 70% sensitivity compared with
55% sensitivity for film-screen mammography.
In addition to the previously mentioned bene-
fits of digital mammography, computer sys-
tems
have
been
designed
to
recognize
mammographic patterns and deviations from
normal patterns, which may help radiologists
identify suspicious areas. This technology is
rather new, but could possibly decrease the
time it takes to read a mammogram, as well
as improve accuracy.
Indications and Uses
Screening
The benefits of mammographic screening are
well documented. Although it was clear from
the outset that x-ray mammography could
identify cancers at a smaller size than physical
examination, it was not clear whether this
would have an impact on survival. Ultimately
this led to eight randomized trials that demon-
strated that mammographic screening can
decrease breast cancer mortality in women
age 50 and older (Table 2–2). A meta-analysis
estimated this reduction to be approximately
34% by 7 years. The overall decreases in breast
cancer–specific mortality seen over the past
decade also attest to the impact of screening.
Screening is discussed in further detail later
in the chapter.
For the benefits of screening to be optimized,
the process needs to be cost and time efficient.
The most commonly applied approach is to
separate screening from diagnosis. Thus women
come to screening centers where two views
are obtained of each breast, the medial lat-
eral oblique (MLO) and the craniocaudal (CC)
views. The patient leaves and the images are
read at a later time, allowing for efficiency and
for “double reading,” meaning two radiologists
review the films, which increases the number of
cancers detected. This may be facilitated by the
use of digital images. The main disadvantage is
that women leave, only to be called back if there
is an abnormality requiring additional diagnos-
tic images. Approximately 5% to 10% of
women are called back. This can cause undue
concern for women, even though most of the
women called back will be found to have noth-
ing (e.g., the benign overlap of tissue) or benign
findings requiring nothing or short-interval fol-
low-up. Simply receiving a telephone call that
there was an abnormality on the mammogram
can lead to increased stress in that time period
between the telephone call and when the addi-
tional imaging is done. This has prompted calls
for immediate reading, but this is not only cost-
ineffective but also pressures the radiologists to
read quickly, which leads to increased errors.
TABLE 2–2 Randomized Trials of Breast Cancer Screening
Study
Years
Mammogram
Frequency
Breast
Examination
Relative Risk (CI)
HIP Study
1963-69
2 Views
q 1 year
4 rounds
Yes
40-49
0.77 (.53,1.11)
50-64
0.80 (.59,1.08)
Edinburgh
1979-88
1 or 2 Views
q 2 years
4 rounds
Yes
45-49
0.83 (.54,1.27)
50-64
0.85 (.62,1.15)
Kopparberg
1977-85
1 View
q 2 years
4 rounds
No
40-49
0.76 (.42,1.40)
50-74
0.52 (.39,.70)
Ostergotland
1977-85
1 View
q 2 years
4 rounds
No
40-49
1.06 (.65,1.76)
50-74
0.81 (.64,1.03)
Malmo
1976-90
1 or 2 Views
q 1.5 to
2 years
5 rounds
No
45-49
0.64 (.45,.89)
50-69
0.86 (.64,1.16)
Stockholm
1981-85
1 View
q 2 year
2 rounds
No
40-49
1.01 (.51, 2.02)
50-64
0.65 (.4, 1.08)
Gothenburg
1982-88
2 Views
q 1.5 year
5 rounds
No
39-49
0.56 (.32, .98)
50-59
0.91 (.61,1.36)
CNBSS
1980-87
2 Views
q 1 year
4 to
5 years
Yes
40-49
1.07 (.75,1.52)
50-59
1.02 (.78,1.33)
22
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
Diagnostic Mammography
Diagnostic mammography is defined as the
evaluation of individuals with an abnormal-
ity of the breast, whether that is a clinical
complaint (e.g., a mass, skin changes, nipple
inversion or discharge, or breast pain) or an
irregularity detected on a screening mammo-
gram. In some cases, the goal of the diagnostic
mammogram is to characterize a specific area,
such as a palpable mass. In other cases, it is
to “screen” the breasts for an occult unsus-
pected cancer that may or may not be related
to the complaint, such as with breast pain.
When a diagnostic mammogram is per-
formed on the basis of a callback from a screen-
ing mammogram, the goal is to characterize
the suspect lesion as normal tissue, a benign
finding, or a possible breast cancer. To do this,
the radiologist obtains additional views, using
special techniques to better visualize the area
of concern (see Table 2–1). With these addi-
tional views, the goal of the radiologist is to
then classify the findings into one of five
categories known as BI-RADS; the Breast Imag-
ing Reporting and Data System (Table 2–3).
On mammography, some abnormalities that
appear benign may be malignant and vice
versa. It is very rare that the radiologist can
make a definitive diagnosis, only an estimation
of the likelihood of a specific lesion represent-
ing a cancer. The BI-RADS system helps classify
that risk, as well as provide some national uni-
formity to mammography.
Categories 1 and 2 represent a normal mam-
mogram without findings suspicious for malig-
nancy. Whereas category 1 refers to a perfectly
normal mammogram, category 2 refers to find-
ings that are clearly benign. Examples include
an
involuting,
calcified
fibroadenoma,
an
intramammary lymph node, stable, benign-
appearing
calcifications,
cysts,
lipomas,
or
hamartomas. Patients with a category 1 or
2 mammogram do not need any specific inter-
vention or follow-up. Category 3 represents
those findings that are probably benign. The
risk of malignancy for a category 3 lesion
should be less than 2%; however, short-term
follow-up is needed to assure stability. The
mammogram should be repeated 6 months
after the initial evaluation and possibly every
6 months for up to 2 years. Biopsy should
rarely be needed for a category 3 finding
unless stability cannot be assured. If the lesion
remains stable for 2 years, then it can be reclas-
sified as benign.
Categories 4 and 5 include abnormalities for
which cancer cannot be ruled out. Category 5
includes those abnormalities with classic hall-
marks of cancer. The risk of cancer should be
above 75%, and biopsy is absolutely indicated.
Category 4 therefore includes those lesions in
between probably benign and probably malig-
nant. These are the lesions that do not have
the characteristic findings of cancer but have
a good chance of representing malignancy.
Biopsy should be considered for any category
4 finding; however, this category represents
a broad range of risk (3% to 74%). Thus the
clinician needs to work with the radiologist
to assess a reasonable risk assessment and then
discuss with the patient the relative risks and
benefits of short-term observation versus tis-
sue biopsy. It is important to keep in mind
that a category 4 mammogram will have a
reading of “Suspicious abnormality—biopsy
should be considered,” so it should be well
documented as to why a patient opted not to
have a biopsy if she chooses observation.
Even though mammography cannot make a
definitive diagnosis, there are aspects that are
highly suggestive of either benign or malig-
nant lesions. These findings may help assign
relative risk and help the patient and the phy-
sician determine whether the risk of a biopsy
outweighs the risk of missing a cancer; very
few of these descriptive findings can be used
to absolutely designate a lesion as benign.
A mass is any space-occupying lesion that
can be detected in two different projections.
Lesions seen in only one projection are referred
to as densities. Masses are characterized by their
shape, density, and margin (Fig. 2–3). Masses
that are irregular or lobular are more likely to
TABLE 2–3 Breast Imaging Reporting
and Data System (BI-RADS)
Category 0
Incomplete assessment.
Additional imaging is needed.
Category 1
Negative.
The breasts are normal in appearance.
Category 2
Benign finding.
A finding is present that is
characteristic of a benign lesion.
Category 3
Probably benign finding.
A finding is present that has a high
probability of being benign.
Category 4
Suspicious abnormality.
A finding is present that has a
possibility of being cancer.
Category 5
Highly suggestive.
A lesion is present that has the
typical morphology of a cancer.
23
2—PRINCIPLES OF BREAST CANCER SCREENING
be malignant than round or oval masses.
Although mammography can rarely distin-
guish benign from malignant, there are some
lesions that can be called benign based on their
density. Lesions that are fat dense (these appear
black on a mammogram) are benign, represent-
ing either lipomas or areas of fat necrosis with
oil cyst formation. Tissue biopsy is not neces-
sary. Benign hamartomas may also have a
pathognomonic appearance and may be char-
acterized as BI-RADS category 2 (Fig. 2–4).
Finally, the margins surrounding a mass are an
important feature in analyzing a mammo-
graphic mass. Benign lesions tend to have
well-defined circumscribed margins. Cancers
on the other hand more often have indistinct
or microlobulated margins. Masses with spicu-
lated margins, forming a stellate pattern of
radiating lines, are almost always malignant
(Fig. 2–5).
Because calcium absorbs x-rays, calcifications
are easily detected by mammography, even
calcifications as small as 0.2 to 0.3 mm. Calci-
fications often form in response to cell turn-
over, which may be related to cancer but can
also be related to benign changes in the breast.
The fact that they can be seen so readily on
mammogram is why mammography is partic-
ularly useful in detecting early stage cancer,
particularly ductal carcinoma in situ (DCIS).
However, there are many different types of
calcifications, and their morphologies and dis-
tribution can provide clues to their etiology.
Some types of calcifications are clearly benign,
such as the popcorn-like macrocalcifications
seen in an involuting fibroadenoma. As a gen-
eral rule, larger, round or oval-shaped calcifica-
tions uniform in size have a higher probability
of being associated with a benign process and
smaller, irregular, polymorphic, branching cal-
cifications that are heterogeneous in size and
morphology are more often associated with a
malignant process (Figs. 2–6 and 2–7).
Calcifications
are
analyzed
according
to
their size, shape, number, location, and dis-
tribution (Table 2–4). Size is an important
characteristic because macrocalcifications are
typically associated with a benign process and
microcalcifications are associated with malig-
nancy; however, there is no strict measure-
ment cutoff between micro and macro. Most
radiologists classify calcifications of 0.5 mm or
A
B
Figure 2–3. MLO and CC views of the right breast demonstrate a spiculated mass in the upper outer quadrant.
Pathology demonstrated invasive ductal carcinoma. (Images courtesy of Dr. Alexis Nees, Department of
Radiology, University of Michigan.)
24
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
A
B
Figure 2–4. Hamartomas have a very characteristic appearance on mammography, possessing a combination
of fatty and soft tissue densities surrounded by a fibrous capsule. A, The MLO view shows the classic “breast
within a breast” appearance of hamartoma. B, The CC view. (Images courtesy of Dr. Alexis Nees, Department of
Radiology, University of Michigan.)
A
B
Figure 2–5. MLO and CC of the left breast demonstrate an irregular mass with spiculated margins and pleo-
morphic calcifications. Pathology demonstrated invasive ductal carcinoma. (Images courtesy of Dr. Alexis
Nees, Department of Radiology, University of Michigan.)
less as having a high probability of association
with cancer; calcifications of 2.0 mm or larger
are typical of a benign process. The number
of calcifications can also be used as a rough
indicator of malignancy. Rarely will four or
fewer calcifications lead to the detection of
breast cancer, even when two or three calcifi-
cations with a worrisome morphology war-
rant a biopsy. Calcifications that are irregular
in shape and size (resembling small fragments
of broken glass) are often associated with
malignancy.
Calcifications in the skin are rarely due to
cancer, although they may appear to be paren-
chymal and require incremental imaging to
prove they are in the skin. Otherwise the loca-
tion of the calcifications provides little direc-
tion. The distribution of the calcifications is
more
important.
Calcifications
in
arteries
appear as parallel lines. Calcifications contain-
ing lucent centers (“eggshell” or “rim” calcifi-
cations)
are
associated
with
calcified
fat
necrosis or cysts and are benign. Calcifications
that are fine linear or fine linear branching in
appearance (resembling the casting pattern of
a duct) are particularly worrisome for DCIS or
invasive cancer.
Architectural distortion can be either obvious or
quite subtle on mammography (Fig. 2–8). This
refers to an unusual pattern in the breast paren-
chyma. This may include spiculations or retrac-
tion. In some cases, this may be associated with
postsurgical changes or infection. Otherwise,
however, architectural distortion should prompt
a biopsy because there is strong association
with malignancy. One benign entity that can
cause architectural distortion is radial scar (see
Chapter 3) but a biopsy is necessary to establish
the diagnosis. Other worrisome findings on
mammography include evidence of skin or
nipple retraction and focal skin thickening.
Guidance of Interventional Procedures
One of the most significant advances in the
management of breast disease has been the
advent of stereotactic-guided breast biopsy.
This allows for the percutaneous biopsy of an
A
B
Figure 2–6. MLO and CC views of the right breast demonstrate benign calcifications of posttraumatic oil
cysts. (Images courtesy of Dr. Alexis Nees, Department of Radiology, University of Michigan.)
26
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
abnormality detected on mammography, elim-
inating the need for wire-localized biopsy for
many women.
Stereotactic biopsy uses radiographic imaging
to target the abnormality. The most common
approach is the use of a dedicated stereotactic
table, in which a patient is positioned prone
with the breast placed through an aperture
on the table. The breast is then compressed
and imaged with mammographic equipment
located beneath the table (Fig. 2–9). Stereotactic
biopsy can also be done upright with equipment
added onto existing mammographic equip-
ment; however, there is more patient movement
and may be increased vasovagal reactions.
Initial scout images are obtained and the
radiologist uses these to determine the lesion
position in the x- and y-axes and the shortest
skin to lesion distance. Stereotactic images are
then obtained 15 degrees from midline in both
the positive and negative directions. By calcu-
lating the shift of the lesion on these images
from the midline location, the radiologist can
determine the depth of the lesion. Once all
the coordinates have been determined, the
skin is prepped and anesthetized. After a small
incision in the skin is made with a number 11
blade, a biopsy needle (either spring-loaded or
vacuum-assisted) is introduced into the breast
and guided to the lesion using the stereotactic
images. Once confirmed, the needle is fired.
Post-fire images are obtained to confirm that
the needle is positioned within the lesion.
Specimen radiographs can also be obtained to
ensure that calcifications are in the specimen.
Typically, several biopsies of the area are
obtained. When finished, a marker clip is
inserted at the site of the biopsy. After needle
removal, pressure is held to achieve hemosta-
sis, and a sterile dressing is applied. The most
common complication is hematoma, which
occurs in less than 0.5% of cases.
It is important that the radiologist and
the surgeon follow up on the results of the
biopsy and determine whether the pathology is
concordant, meaning the histologic diagnosis is
reasonable given the appearance on mam-
mography.
A
discordant
finding
requires
a
surgical biopsy. The physicians must also appre-
ciate the limitations of percutaneous biopsy.
Patients with atypia (atypical ductal hyperplasia
[ADH], atypical lobular hyperplasia [ALH], and
lobular carcinoma in situ [LCIS]) diagnosed on
needle biopsy also require a surgical biopsy
because there may beassociatedDCIS or invasive
carcinoma missed by the needle (see Chapter 8).
Ultrasound
Ultrasound now plays a significant role in the
diagnosis and treatment of breast cancer and
many breast surgeons perform ultrasound in
their office. Even though it cannot reliably
detect microcalcifications and therefore plays
a minor role in breast cancer screening, it can
identify and characterize masses in the breast,
as well as evaluate the axillary lymph nodes.
Technique
The entire breast can be imaged with ultra-
sound, but the most common use of ultra-
sound of the breast is to evaluate a mass or
lesion that has been detected on physical
examination or on mammography. Although
it has primarily been used to differentiate solid
from cystic lesions, several criteria can be used
to help characterize solid lesions as more likely
benign or malignant. Ultrasound is performed
with high-resolution linear array transducers
with a frequency of at least 7.5 MHz. Scans
are performed around the lesion in the longi-
tudinal, transverse, and radial orientations.
Several techniques can also be used to better
characterize the mass. The transducer can be
Figure 2–7. Magnification CC view demonstrates
segmentally distributed, pleomorphic calcifications.
Pathology demonstrated DCIS and invasive ductal
carcinoma. (Image courtesy of Dr. Alexis Nees,
Department of Radiology, University of Michigan.)
27
2—PRINCIPLES OF BREAST CANCER SCREENING
used to compress the breast during evaluation
to clear or confirm the presence of artifacts.
Color Doppler imaging can be used to assess
its vascularity. When performing breast ultra-
sound, it is important to carefully document
the position of any findings, including the
depth from the skin, and label all images as
to their location and the orientation of the
transducer.
When evaluating a mass by ultrasonography,
several features of the mass must be noted
(Table 2–5). The margins of the mass are impor-
tant because ductal carcinomas may have
markedly
irregular
or
spiculated
margins.
Fibroadenomas and other benign lesions often
have smoother margins. However, there are
several types of circumscribed carcinomas,
such as medullary, mucinous (colloid), or papil-
lary
carcinomas,
which
can have
smooth
margins. The shape of the mass is also impor-
tant. A mass that is taller (anterior-posterior)
than it is wide is concerning for malignancy.
Echogenicity represents the ability of the tissue
to generate echoes on ultrasound that are
detected by the transducer and appear white
on the ultrasound image. Fluid does not pro-
duce echoes, which is why cysts appear black
on ultrasound. Benign lesions tend to have a
more homogeneous, hypoechoic appearance
(less echo, appearing darker than the surround-
ing tissue) (Fig. 2–10). The more heterogeneous
the echo texture of the mass, the more suspi-
cious for malignancy. Dense fibrosis within
some ductal carcinomas may cause massive
acoustic shadowing (Fig. 2–11). An echogenic
rim around a mass is also concerning for malig-
nancy in that this may be caused by a desmo-
plastic reaction around the tumor.
TABLE 2–4 Calcifications on Mammography
Benign Calcifications
Skin calcifications
Not in the parenchyma but may appear as such. Tangential views should help
differentiate. Typically have a lucent center that can be seen on
magnification views.
Vascular calcifications
Vascular calcifications can be seen as parallel tracks that run along a blood
vessel.
Coarse or popcorn-like
calcifications
Typically found in involuting fibroadenomas.
Rod-shaped calcifications
Large rodlike calcifications are typical of secretory disease but not of breast
cancer. They are usually >1 mm, are occasionally branching, and may have
lucent centers. They form in debris that collects in the duct lumen or cause
an inflammatory reaction around a duct.
Round calcifications
Smooth round calcifications are associated with a benign process. Variable in
size. When <1 mm they are often found in the acini of lobules. When
<0.5 mm the term punctuate is used.
Spherical or lucent-centered
calcifications
Spherical or lucent-centered calcifications can range from <1 mm to >1 cm.
They may be found as debris collected in a duct, in areas of fat necrosis, and
occasionally in fibroadenomas.
Rim or eggshell calcifications
These are thin calcifications that surround all or part of the margin of a mass.
They are typically found in the wall of cysts. Breast cancer rarely produces
this type of calcifications.
Milk or calcium calcifications
This form of calcium precipitates and settles in the bottom of cysts. Their
morphologies change between the CC and MLO views.
Dystrophic calcifications
These calcifications are irregular in shape but they are usually large, that is,
>0.5 mm in size. They often form in the irradiated breast or after trauma to
the breast.
Concerning for Malignancy
Indistinct or amorphous
microcalcifications
Round or flake-shaped calcifications that are sufficiently small or hazy such
that their morphology cannot be reliably ascertained.
Pleomorphic or
heterogeneous calcifications
A cluster of heterogeneous or pleomorphic calcifications, irregular in shape and
size, generally <0.5 mm. These raise suspicion of a malignant process.
Fine linear or branching
calcifications
Thin, irregular calcifications that appear linear from a distance. Closer
examination reveals that they are distinct and <1 mm in width. They result
from irregular calcifications of necrotic tumor in the lumen of a duct
involved by breast cancer.
28
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
The absence of a mass on ultrasound does
not preclude cancer because lobular carcino-
mas may be very difficult to detect on ultra-
sound, just as they are on mammography.
Although they may present as a well-defined
mass, more often they may appear as a vague
area of shadowing. Color Doppler imaging
may reveal some suspicious vascularity at the
periphery of the lesion.
Indications and Uses
Diagnostic Evaluation of a Breast Mass
When a patient presents with a palpable mass
or when an abnormality is detected on mam-
mography, ultrasound can be particularly use-
ful in helping to characterize it further. It is
most accurate at diagnosing simple cysts, which
Figure 2–10. Radial US image of circumscribed oval
hypoechoic mass. This is a pathologically proven
fibroadenoma. (Image courtesy of Dr. Alexis Nees,
Department of Radiology, University of Michigan.)
Figure 2–8. Spot compression magnification view
demonstrates
architectural
distortion.
Pathology
demonstrated a radial sclerosing lesion. (Image cour-
tesy of Dr. Alexis Nees, Department of Radiology,
University of Michigan.)
Figure 2–9. The stereotactic table.
TABLE 2–5 Features Suspicious for
Malignancy on Ultrasound
Likely
Benign
Likely
Malignant
Margins
Smooth
Irregular
Echogenicity
Homogenous
Heterogeneous
Shape
Ellipsoid
(transverse
greater than
anteroposterior)
Irregular
Echogenic
capsule
None or thin
Present
29
2—PRINCIPLES OF BREAST CANCER SCREENING
appear as round or oval masses with smooth walls
and no internal echoes (Fig. 2–12). Complicated
cysts tend to have some internal echoes, wall
thickening, or other abnormalities. Complex
cysts (or complex masses) contain mixed cystic
and solid components. Whereas simple cysts are
never cancer and do not require any interven-
tion, complicated and complex cysts cannot be
written off as easily. For complicated cysts, often
the internal echoes are due to proteinaceous
debris,
hemorrhage,
or
calcium
deposits.
Depending on their appearance and the clinical
history, diagnosis by fine needle aspiration
(FNA) biopsy may be necessary. While compli-
cated cysts have a cancer risk of less than 1%,
complex cysts have a high rate of cancer, ranging
from 20% to 40%. Core needle biopsy or even
wire-localized biopsy is recommended.
Beyond solid versus cystic, the breast surgeon
must be aware of the limitations of ultrasound
in differentiating between benign and malig-
nant masses. On ultrasound, benign character-
istics include smooth lesions with few or no
lobulations, homogenous echogenicity, a paral-
lel orientation with the width greater than the
height, and mild posterior acoustic enhance-
ment. On the other hand, malignant lesions
have an irregular shape with heterogeneous
echogenicity, strong posterior shadowing, and
an echogenic rim. They may be spiculated and
may be taller than wide. When combined with
the clinical information, ultrasound can be
helpful, but one must remember that some
cancers have all the classic characteristics of a
benign lesion, and vice versa.
Local and Regional Staging
Upon the diagnosis of breast cancer, ultrasound
is becoming increasingly important in the
clinical staging of the disease. Ultrasound of
the primary mass may allow for a more accurate
measurement of the tumor size, as well as detect
additional foci of disease. This can directly
impact the decision to perform breast conserva-
tion. More important, ultrasound of the axilla
can demonstrate abnormal lymph nodes sus-
picious for metastases (see Chapter 13). This
also allows for the ultrasound-guided FNA of
these lymph nodes, which can allow patients
with documented axillary disease to bypass sen-
tinel lymph node biopsy and proceed directly
to axillary lymph node dissection (Fig. 2–13).
Guidance of Interventional Procedures
Ultrasound is often used to help guide inter-
ventions such as FNA biopsies or core needle
biopsies (see Chapter 3). If a lesion is visible on
both mammogram and ultrasound, ultrasound-
guided biopsy offers several advantages. It is
faster and requires no radiation or breast com-
pression. It is usually much more comfortable
for the patient.
The patient is positioned supine, or in some
cases depending on the position of the lesion,
obliquely on a table, with the arm raised above
Figure 2–11. Ultrasound demonstrates an irregular
hypoechoic mass with spiculated margins. Pathology
demonstrated
invasive
ductal
carcinoma.
(Image
courtesy of Dr. Alexis Nees, Department of Radiol-
ogy, University of Michigan.)
A +
+
Figure
2–12. Ultrasound
demonstrates
circum-
scribed oval anechoic lesion with posterior acoustic
enhancement. Findings are consistent with simple
cyst. (Image courtesy of Dr. Alexis Nees, Department
of Radiology, University of Michigan.)
30
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
the head. Once the lesion is identified with
the ultrasound, the skin is marked and then
prepped. After anesthetizing the skin, a num-
ber 11 scalpel is used to make a small incision
and the biopsy needle introduced. One hand
holds the transducer (and remains fixed) while
the other hand advances the needle. The nee-
dle is easily visualized on ultrasound, particu-
larly when the transducer is kept parallel to
the needle. As with stereotactic biopsy, either
a
spring-loaded
or
vacuum-assisted
needle
can be used. Once the needle is in position, it
is fired and a post-fire image is obtained. Sev-
eral specimens are obtained and a metal clip
can be placed at the site. Afterward direct pres-
sure is applied, followed by a sterile dressing
once hemostasis has been assured.
Magnetic Resonance Imaging
Technique
Advances in surface coil technology and imag-
ing sequences have allowed magnetic resonance
imaging (MRI) to emerge as a method for imag-
ing the breasts. The use of contrast attempts to
overcome one of the major limitations of other
breast
imaging
modalities
(mammography,
ultrasound), specifically the differentiation of
benign
and
malignant
lesion.
Contrast-
enhanced breast MRI (CE-MRI) takes advantage
of the production of angiogenic substances by
tumors that result in the development of new
vessels to supply the tumor. These new vessels
are abnormal, with increased capillary perme-
ability and arterial to venous shunting. This neo-
vascularity results in rapid uptake of contrast
agent to the tumor relative to the normal tissue.
CE-MRI uses magnetic and radiofrequency fields
to visualize the uptake of an MRI-specific con-
trast agent (gadolinium-DTPA). Breast CE-MRI
involves evaluation of the breasts before and
after the administration of the intravenous gado-
linium-DTPA. Images of the breasts are obtained
immediately after the administration of the con-
trast bolus and are repeated three to five times
over several minutes. This results in multiple
images of each slice of breast tissue, demonstrat-
ing the change in contrast enhancement over
time. Suspicious lesions are then evaluated based
on both their morphology and the kinetics of
contrast enhancement (Fig. 2–14).
Without the contrast agent, MRI is not terri-
bly useful. However, the time course of the
contrast helps differentiate benign from malig-
nant lesions. Cancers show a sharp increase in
signal intensity due to rapid contrast enhance-
ment, followed by a plateau, and early wash-
out. Benign lesions show a slower, more
gradual rise in enhancement. CE-MRI appears
to be the most sensitive modality to detect
invasive breast cancer, ranging from 88% to
100%. The sensitivity is not dependent upon
Figure
2–14. Sagittal
MR
image
demonstrates
enhancing retroareolar mass with ill-defined margins
and area of central hypoenhancement. Pathology
demonstrated
invasive
ductal
carcinoma.
(Image
courtesy of Dr. Alexis Nees, Department of Radiol-
ogy, University of Michigan.)
Figure 2–13. Image demonstrates a spinal needle
with tip in thickened cortex of abnormal axillary
lymph node in a woman newly diagnosed with
breast cancer. Cytology demonstrated metastatic
disease. (Image courtesy of Dr. Alexis Nees, Depart-
ment of Radiology, University of Michigan.)
31
2—PRINCIPLES OF BREAST CANCER SCREENING
the density of the breast, unlike mammogra-
phy. Also unlike mammography, MRI does
not use ionizing radiation. Thus MRI should
be the optimal examination for the breast.
However, CE-MRI has several drawbacks.
Although it is extremely sensitive (approach-
ing 100% for invasive cancer), the foremost
drawback is the specificity. The specificity of
MRI ranges from 37% to 96% depending on the
indication, and this variable specificity greatly
limits its use. Particularly in young women,
MRI has difficulty discriminating between can-
cers and benign lesions such as fibroadenomas,
adenosis, or even hormone-induced enhance-
ment of normal parenchyma. As of yet, there is
a lack of standardized protocol interpretation
guidelines, so there can be great variations in
interpretation between radiologists and between
institutions. This makes it challenging for a
radiologist to offer a second opinion on an MRI
from an outside institution.
Another challenge for incorporating MRI
into clinical use is the ability to obtain histo-
pathologic
proof
of
suspicious
lesions.
Abnormalities
seen
on
mammography
or
ultrasonography can easily be targeted for an
image-guided biopsy. However, abnormalities
seen only on MRI may present a challenge. If
a targeted second-look ultrasound can identify
a lesion in the area, this may be an option for
biopsy. However, if the lesion is not visualized
on
mammogram
or
ultrasound,
the
only
option is an MRI-guided biopsy. As of now,
these
are
only
available
at
a
handful
of institutions and they are limited in their
ability to biopsy lesions less than 1 cm in diame-
ter. Some institutions can do MRI-guided wire
localization, but this may lead to an excessive
use of excisional biopsies for benign lesions.
Hospitals and physicians that use MRI but do
not have the capability to biopsy MRI-only
visible lesions can put their patients in a diffi-
cult position, knowing there is a suspicious
lesion but being unable to identify it.
MRI
has
several
additional
drawbacks.
Although it has a high sensitivity for invasive
cancer, the sensitivity for DCIS is inferior to
that of mammography, possibly as low as
50%. The high cost of MRI is a notable problem.
Hormone-induced
enhancement
can
be
a
problem in premenopausal women, so it is
best to perform the examination during the
second week of the cycle. Patients with pace-
makers or aneurysm clips cannot undergo
MRI, and a reasonable percentage of patients
are bothered by claustrophobia and have dif-
ficulty with the examination.
Indications and Uses
Imaging of Silicone Breast Implants
One of the first accepted uses of breast MRI
was the imaging of silicone breast implants
when a rupture was suspected. Implants may
be placed either beneath the gland or beneath
the
pectoralis
major
muscle.
When
the
implant ruptures, the silicone may still be
contained by the fibrous capsule surrounding
the implant. This is known as an intracapsular
rupture. An extracapsular rupture occurs when
the silicone escapes beyond the fibrous cap-
sule. The “linguine sign,” the appearance of
curvilinear lines representing the collapsed
elastomer shell, is a highly reliable sign of
intracapsular rupture. When the rupture is
extracapsular, the high-signal silicone can be
seen outside of the fibrous capsule.
The Occult Primary Breast Cancer
Occasionally, breast cancer patients present
with axillary metastasis without clinical or
radiographic evidence of the primary tumor.
In most cases in which the primary tumor
cannot be found, modified radical mastectomy
is recommended. MRI is being used increas-
ingly to identify a primary tumor when mam-
mography
and
whole-breast
ultrasound
is
negative. Several small studies have demon-
strated that with the use of contrast-enhanced
breast MRI, more than 70% of primary tumors
can be identified. If a primary tumor is identi-
fied, the patient can undergo breast conserva-
tion therapy. If the MRI is negative, treatment
options include a modified radical mastectomy
or an axillary lymph node dissection followed
by whole breast irradiation.
The low specificity of MRI must be consid-
ered when a lesion is discovered, because
false-positive results can occur. Repeat mam-
mograms and ultrasounds should be obtained,
directed at the area suggested by the MRI. If a
lesion is seen, than a stereotactic or ultra-
sound-guided biopsy should be performed. If
ultrasound fails to identify a lesion, MRI-
directed biopsy can be performed at facilities
with the appropriate equipment.
Assessing Candidacy for Breast
Conservation
Although breast conservation has radically
changed the surgical treatment of breast can-
cer, allowing many women to avoid mastec-
tomy,
it
often
requires
more
than
one
operation to achieve negative margins and
some
women
who
initially
pursue
32
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
lumpectomy are found to have more extensive
disease
requiring
mastectomy.
MRI
has
emerged as a possibly improved method of
staging the local extent of the tumor and iden-
tifying women who might not be suitable can-
didates for breast conservation due to either
the extent of the primary or multicentric
disease.
Indeed, MRI has been shown to detect both
additional foci of disease within the ipsilateral
breast and undiagnosed contralateral cancers.
The majority of the data are from single insti-
tutions, showing the increased detection of
unrecognized foci of disease from between
10% and 30%. The impact on surgical therapy
is significant. Several authors have described
MRI prompting wider excisions in 3% to 13%
of women and mastectomies in 7% to 25% of
women otherwise planning on lumpectomy.
Based on these studies, many surgeons and
radiologists have initiated the routine use of
MRI in the preoperative staging of breast
cancer.
These data, however, must be interpreted
carefully. In series of patients treated by breast
conservation without preoperative MRI, the
conversion to mastectomy and the local recur-
rence rates are not nearly as high as the series
of MRI would suggest they should be. Even
lobular carcinomas, whose size is notoriously
underestimated by mammography and ultra-
sound, do not seem to fail breast conservation
therapy (BCT) or locally recur to the degree
that the MRI studies might imply.
Taken together, this suggests that MRI is
detecting multifocal or multicentric foci of dis-
ease that might not have led to local recur-
rence
after
lumpectomy,
radiation,
and
systemic therapy. Many studies using serial
subgross sectioning to evaluate the breasts of
women with known cancers have shown addi-
tional foci of disease in 20% to 60% of
patients. These data were often used to argue
against breast conservation, but 30 years of
experience have clearly demonstrated that
local recurrence rates are acceptably low after
lumpectomy, whole breast irradiation, and
when indicated systemic therapy. There is no
evidence that the use of MRI for patient selec-
tion improves local control. There is also no
evidence that it decreases the reexcision rate.
It thus seems possible that the use of MRI in
this setting may be leading to women under-
going more extensive surgery than necessary.
When staging a woman with breast cancer
(see Chapter 10), the use of MRI should not
be performed routinely, even in women with
lobular carcinoma. A balanced discussion must
be held with the woman about the potential
benefits and risks of undergoing an MRI before
surgery, how this information might alter the
surgery, and whether this is worthwhile. It is
also important that MRI only be done at insti-
tutions that also have the capability to per-
form
MRI-guided
biopsy
of
any
newly
identified lesions. If that capability is not pres-
ent and the MRI-detected lesion cannot be
found on a directed mammogram or ultra-
sound, the woman may be facing an awkward
decision of undergoing mastectomy for what
might be a benign lesion versus ignoring a
possible second cancer in pursuit of breast
conservation.
Screening
Mammography remains the standard of care
for breast cancer screening. However, there
has
been
great
hope
that
MRI,
with
its
increased sensitivity even in the face of dense
breast tissue, could help increase early detec-
tion, especially among younger women. The
detection of cancer with MRI is dependent
upon the increased vascularity of cancer. This
results in enhancement of the lesion after the
injection of contrast material. As opposed to
mammographic detection, MRI detection is
not limited by the density of the breast. How-
ever, because benign lesions may also enhance
with contrast material, enhancement alone is
not diagnostic. Thus distinguishing between
benign and malignant lesions requires evalua-
tion of the kinetics of the enhancement as
well as the morphology of the lesion.
Initial trials of MRI screening focused on
women with a high risk of developing breast
cancers. In women with known BRCA1/2
mutations,
MRI
screening
was
shown
to
decrease the stage (tumor size, nodal status)
at which cancer is detected. Eventually, several
single and multi-institutional trials demon-
strated the superiority of MRI screening as
compared to mammography and ultrasound.
This led to five prospective randomized trials
comparing the use of mammography and
MRI in high-risk women. All but one demon-
strated an increased sensitivity of MRI for the
detection of cancer.
Based on these results, screening with MRI is
recommended for women at particularly high
risk of developing breast cancer (Table 2–6).
However, there are still several issues that need
to be addressed. First, no studies have been
done on other groups of high-risk women,
33
2—PRINCIPLES OF BREAST CANCER SCREENING
such as those with LCIS, ALH, or ADH (see
Chapter 8). Retrospective studies in this popu-
lation have shown minimal benefit but a
high number of biopsies secondary to MRI’s
decreased specificity. In the five randomized
trials in high-risk women, the specificity was
lower than that of mammography, and MRI
will lead to an increased number of follow-up
studies and biopsies. This will further increase
the costs of screening with MRI, which is
already significantly higher than that of mam-
mography alone.
It is important to note that MRI is an
adjunct to mammography, not a replacement.
As many cancers detected by MRI and missed
on mammography are found on mammogra-
phy and missed on MRI. MRI is also not used
to determine whether a suspicious lesion on
mammography should be biopsied. It is also
worth noting that the data to date suggest
the usefulness of MRI screening is in high-risk
individuals. When screening is applied to a
low or intermediate risk population, the utility
drops
because
this
population
has
fewer
cancers. The positive predictive value (PPV) is
the percentage of abnormal lesions that turn
out to be cancer. This is extremely variable
with MRI depending on the method of imag-
ing, how an abnormal lesion is defined, and
the incidence of cancer within the population
being screened. Therefore it is difficult to
assess whether MRI is cost-effective outside of
the highest risk populations, and at this time
cannot be recommended.
Response to Neoadjuvant Therapy
Neoadjuvant chemotherapy as a method of
downstaging primary tumors and evaluating
response to chemotherapy is becoming increas-
ingly popular (see Chapter 18). Throughout
the course of chemotherapy, the response is
monitored by physical examination, mam-
mography, and ultrasound, and after treatment
these modalities are used to determine whether
BCT is appropriate. Several investigators have
examined the use of MRI in this regard. How-
ever, the data from these studies have been var-
iable and MRI can neither accurately predict
complete response (women with no residual
disease on MRI still have pathologic disease)
nor incomplete response (women with a resid-
ual lesion have no disease on pathology). MRI
can be very helpful in the determination of
eligibility for BCT after neoadjuvant chemo-
therapy, but it cannot be used to identify
women who may not require surgery at all.
Follow-up of Breast Cancer Patients
The increased sensitivity of MRI has also raised
the question of whether it might be appropri-
ate for the surveillance of patients after breast
conservation surgery. However, it is unclear
whether the earlier identification of local
recurrence impacts outcome or would change
treatment. There are also few data on the abil-
ity of MRI to detect recurrences any earlier
than
mammography
in
breasts
that
have
undergone surgery and radiation. Therefore,
at this time, MRI should not be used as a sur-
veillance tool.
Positron Emission Tomography
Technique
The above described modalities are anatomic in
nature. Positron emission tomography (PET)
scanning demonstrates physiologic changes,
based
on
the
uptake
of
neutron-deficient
radionuclides (positron emitters) tagged to a
metabolic tracer. 18F-FDG (fluorodeoxyglucose
labeled with fluorine-18) is the most com-
monly used agent and is transported across
TABLE 2–6 American Cancer Society
Guidelines for Screening with MRI
Recommended Annually Based on Evidence
BRCA Mutation Carriers
Untested first-degree relative of BRCA carrier
Lifetime risk >20% to 25% defined by BRCAPRO or
other family history model
Recommended Based on Expert Consensus
Opinion
Radiation to chest from age 10 to 30
Li-Fraumeni syndrome and first-degree relatives
Cowden syndrome (and variants) and first-degree
relatives
Insufficient Evidence to Recommend For or
Against
Lifetime risk 15% to 20%
LCIS
ALH or ADH
Dense breasts on mammography
Personal history of intraductal or invasive breast
cancer
Recommend Against Based on Expert
Consensus
Lifetime risk <15%
34
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
the cell membrane through glucose pathways.
As most tumors have a high aerobic glycolytic
rate than normal tissue, there is increased
uptake of the FDG. The emitter decays, releas-
ing a positron, which then interacts with an
electron, ultimately releasing two photons in
opposite directions. The PET scanner detects
these
photons
with
detectors
placed
180
degrees apart (Fig. 2–15).
Indications and Uses
At this time, the use of PET scanning offers lit-
tle assistance in the identification of a primary
tumor. Although early, small studies suggested
that PET might be very accurate, subsequent
larger studies failed to confirm these findings.
This is primarily because the sensitivity of
PET drops significantly as the tumor gets smal-
ler, with a sensitivity of less than 25% for
tumors less than 1 cm. PET scan adds very lit-
tle to present imaging studies of the breast,
such as mammography or ultrasound. It also
has not been demonstrated to be very helpful
in those situations in which mammography
is limited, such as the identification of multi-
focal disease that might preclude breast con-
serving
surgery
or
in
identifying
lobular
carcinomas. However, a promising technology
is that of PET-mammography (PEM), which
may prove to be a useful adjunct in the
identification and staging of primary breast
cancers. At this time, PET-mammography is
experimental.
PET scanning has also been examined as a
method of detecting metastases in the axillary
lymph nodes. If accurate, this might preclude
the need to perform sentinel lymph node
biopsy in clinically node-negative patients.
However,
when
compared
with
sentinel
lymph node biopsy, the sensitivity of PET was
quite low and often missed small volume
disease. One promising area for PET might be
the identification of disease in the internal
mammary
lymph
nodes,
although
more
studies are necessary.
Perhaps the best use of PET scans in breast
cancer is for the detection of distant disease.
One significant advantage is that, as compared
to a CT of the chest, abdomen, and pelvis and
a bone scan, PET allows for a one-step proce-
dure
with
a
minimal
radiation
exposure.
When compared with CT or MRI, PET does
appear to be equally sensitive and specific in
identifying distant disease. Although PET is
not typically used as the first modality for
identifying metastases, it is often used when
a CT scan shows a borderline suspicious lesion,
especially when biopsy of this lesion would be
difficult. It can also be used to differentiate
scar tissue or radiation-induced fibrosis from
recurrent tumor. This is particularly true in
patients with brachial plexopathy.
Principles of Breast Cancer
Screening
The decision to recommend screening an
asymptomatic population for cancer must be
based
on
several
well-established
criteria
(Boxes 2–1 and 2–2). First, the disease needs
to be prevalent and serious enough to justify
the cost and effort of screening. Screening
large populations for a rare disease would not
be appropriate from a cost-analysis standpoint.
Of course, this partly depends upon the cost of
Figure 2–15. PET scan showing metastatic disease
in a patient with a history of breast cancer. The PET
scan shows multiple metabolic foci involving the
suprahilar, supraclavicular, and axillary regions on
the right. Small nodes are also seen along paratra-
cheal region bilaterally, extending into the supracla-
vicular on the left. Metabolic foci are also seen along
the periaortic nodes bilaterally.
35
2—PRINCIPLES OF BREAST CANCER SCREENING
the examination. The screening test must have
acceptable levels of both sensitivity and speci-
ficity (Fig. 2–16). If a test accurately detects
the disease, but also prompts needless workups
because it also picks up many false-positive
results, then it is not a suitable screening
examination. Finally, the disease has to have
an asymptomatic phase when it is detectable
(sojourn time) and intervention must offer a
better outcome than if treatment is initiated
when the disease is symptomatic. Assume that
the average tumor size found by a screening
test is 1 cm. If you wait for symptoms, or for
the tumor to be detectable by physical exami-
nation, the average size is 3 cm. If there is a
25% improvement in survival between treat-
ing a 1-cm tumor and a 3-cm tumor, then
screening would be worthwhile. However, if
the improvement in survival is only 1% to
2%, then this does not justify the cost and
effort involved in screening the population.
So does breast cancer meet these criteria?
There is no doubt that the disease is prevalent.
Breast cancer is the most common cancer in
women in the United States and the second
most common cause of cancer death among
women. Approximately 1 in 8 women will
be diagnosed with breast cancer and 1 in 33
will die of their disease. The sensitivity and
specificity of mammography is reasonable,
although this is dependent upon how aggres-
sive we are in recommending biopsies. If the
bar is set low, so that any mildly suspicious
lesion is recommended for a biopsy, then very
few cancers will be missed but many addi-
tional biopsies will be performed. On the other
hand, if the bar is set high, so that only the
most suspicious lesions are referred for biopsy,
then fewer unnecessary procedures will be per-
formed but more cancers will go undiagnosed
for another 6 months to 1 year.
What
about
the
sojourn
time
and
the
impact of initiating treatment at an earlier
time point? There is little doubt that the ear-
lier you treat breast cancer, the better the
survival. Consistently, across all age groups,
there exists an inverse relationship between
the size of the tumor and long-term survival.
The sojourn time, the time between when a
tumor is detected by screening and when it
would be detected by symptoms, will vary
greatly among individuals. For example, youn-
ger women will have a smaller sojourn time
because mammography is less sensitive. It has
been estimated that for women between 60
and 69 years of age, the sojourn time for
mammographic screening of breast cancer is
4.2 years (Box 2–3). This means that screening
will find the cancer 4 years earlier than if we
wait for the patient (or their doctor) to detect
it on examination. The sojourn time will also
be quite variable depending upon the body
habitus of the patient and the histology.
BOX 2–1 TERMS RELEVANT TO
SCREENING EXAMINATIONS
Incidence: The number of new cases
diagnosed during a fixed time period
divided by the total population at risk.
Prevalence: The number of people living
with the disease during a fixed time
period divided by the total population at
risk.
Sojourn time: The time between when a
cancer is detectable on a screening test
and when it would be clinically
detectable.
Interval cancers: Cancers that are
diagnosed between scheduled screening
examinations.
Lead time bias: The appearance that
screening impacted survival when in fact
it did not because survival is measured
from the time of diagnosis and not from
the time screening is initiated.
Length time bias: The appearance that
screening impacted survival when in fact
it did not because screening tended to
detect a higher percentage of slower-
growing, more biologically favorable
cancers.
Selection bias: The appearance that
screening impacted survival when in fact
it did not because the women who opted
to undergo screening have a different
probability of developing cancer (or
dying from it) than those who refused to
undergo screening.
BOX 2–2 PRINCIPLES OF
APPROPRIATE CANCER SCREENING
The disease needs to be prevalent
and serious enough to justify the
cost and effort of screening.
The screening test must have acceptable
levels of both sensitivity and specificity.
The disease has to have an asymptomatic
phase where it is detectable (sojourn
time)
Intervention offers a better outcome than
if treatment is initiated when the disease
is symptomatic.
36
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
It is important to remember that the impact
of screening on a population will be variable
over time as screening tests and treatments
improve. If screening tests become better at
detecting cancers at earlier time points, the
sojourn time will increase. On the other hand,
if treatments improve to the point that the sur-
vival of a 3-cm tumor is not much worse than
that of a 1-cm tumor, then the impact of
screening will decrease. For this reason, the
impact of screening needs to be constantly
reassessed.
Based on what we know about breast cancer
and the criteria for an ideal screening test,
breast cancer seems to be an ideal cancer for
screening. However, the only way to know this
for sure is the performance of randomized con-
trolled trials (RCTs). Retrospective studies of
screening
tests
are
often
misinterpreted
because of several biases (Box 2–1). Lead time
bias refers to the calculation of survival from
the point of diagnosis to the time of death.
This can easily give the appearance that sub-
jects live longer when the disease is diagnosed
early, but survival should be measured from
the beginning of screening, not from the diag-
nosis of cancer (Fig. 2–17). Otherwise the only
thing that has been lengthened is the time the
patient knows he or she has the cancer, while
death occurs at the same point in the natural
history of the disease. Another type of bias is
True-positive rate (sensitivity)
False-negative rate
True-negative rate (specificity)
False-positive rate
Positive predictive value
Negative predictive value
Accuracy
People with positive test and disease
All people with disease
People with negative test and disease
All people with disease
People with negative test and no disease
All people without disease
People with positive test and no disease
All people without disease
People with positive test and disease
All people with positive test
People with negative test and no disease
All people with negative test
All true test
All tests
A
A + C
C
A + C
D
B + D
B
B + D
A
A + B
D
C + D
A + D
A + B + C + D
True disease status
Patient has
disease
Patient does not
have disease
True positive
False negative
False positive
True negative
Positive
Negative
Test result
A
B
C
D
Figure 2–16. Measures of the accuracy of diagnostic and screening tests.
BOX 2–3
Age
Sojourn
Time
40 to 49
2.4 years
50 to 59
3.7 years
60 to 69
4.2 years
Tabar L. The swedish two-county trial twenty years
later: Updated mortality results and new insights from
long-term follow-up. Radiol Clin North Am 2000;
38(4): 625–651.
37
2—PRINCIPLES OF BREAST CANCER SCREENING
length time bias. This refers to the tendency of
screening to detect the slower growing and less
aggressive tumors. In this case, the screening
test may only identify those tumors with a bet-
ter prognosis, those that do just as well if ther-
apy is initiated in another year or 2. Thus it
appears that screening is improving survival
(because
the
patients
with
cancer
in
the
screening group do better), but in reality the
survival is the same as if screening had not
been performed. Finally, these studies often suf-
fer from a selection bias, because patients who
are more health-conscious or those with fewer
comorbidities, undergo the screening. Again,
this leads to the false assumption that the
group undergoing the screening lived longer
because of the screening, when in reality they
lived longer because they were healthier.
In a population-based RCT, these biases are
eliminated because the analysis is based on
mortality differences between the two groups
from the beginning of the screening period,
and because the randomization should equally
distribute
any
confounding
factors.
How-
ever,
even
RCTs
can
suffer
from
bias
or
misinterpretation.
Screening for Breast Cancer
There are several methods by which patients and
physicians screen for breast cancer (Box 2–4).
Besides mammography, women are encour-
aged to perform self-breast examinations on
a monthly basis and to undergo a clinical
examination by a physician at least once a
year. Given the improved survival associated
with finding breast cancer at an earlier stage,
particularly when it is noninvasive, there is
a strong motivation to develop new, more
sensitive screening examinations.
The evidence for mammographic screening
is strong, although it has come under fire
recently. There have been several RCTs exam-
ining the benefits of breast cancer screening.
These trials demonstrated a benefit in women
ages 50 years and older, with an approxi-
mate 34% reduction in the risk of dying from
breast cancer at 7 years. A follow-up analysis
of four randomized trials in Sweden, with a
median follow-up of 15.8 years, demonstrated
a 21% reduction in the risk of breast cancer
mortality.
The benefit of mammography came into
question when a Cochrane review questioned
whether five of the eight studies were appropri-
ately designed and concluded that the effective-
ness of screening mammography, based on the
remaining three studies, was not evident. How-
ever, many reviewers subsequently questioned
the Cochrane review itself, and most experts
believe that the evidence that mammography
decreases breast cancer mortality is solid.
This is not to say that there are not still
questions regarding the use of mammography,
H and P,
screening
test
H and P
alone
H and P
alone
H and P
alone
Disease
detected
Screening
is initiated
Patient
dies of
disease
Disease
detected
H and P,
screening
test
H and P,
screening
test
A
B
Figure 2–17. Lead time bias
occurs when the survival is
measured from the point where
disease is detected to when
the
patient
dies.
This
gives
the appearance that screening
lengthened the survival. How-
ever, if survival is measured
from the point that screening
was
started
to
the
moment
the patient dies, one sees that
screening had no impact on
survival.
BOX 2–4 BREAST CANCER
SCREENING RECOMMENDATIONS
American College of Surgeons:
Begin self-examinations and every
3 years clinical breast examination
at age 20.
Begin annual mammograms and yearly
clinical breast examination at age 40.
American College of Radiology
Begin annual mammograms and yearly
clinical breast examination at age 40.
National Cancer Institute
Begin every 1- to 2-year mammograms at
age 40.
38
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
specifically when mammographic screening
should begin and when it should end. Even
though there is a clear benefit for women older
than 50, the benefits are less clear for women
in their 40s. Initially, a 1993 meta-analysis
showed no benefit to women in their 40s after
7 years of follow-up. However, subsequent
meta-analyses, which included more recent
results and longer follow-up, demonstrated
an approximate 15% reduction in breast can-
cer mortality among women in their 40s.
Even though the evidence suggests there is a
benefit to women in their 40s, the cost effec-
tiveness of screening this age group remains
in question. Similar to the number needed to
treat (NNT) as a way of evaluating the clinical
benefit of therapeutic interventions, the num-
ber needed to screen (NNS) can help put into
perspective the benefit of screening examina-
tions. When one looks at mammography,
between 1500 and 2500 women in their 40s
need to be screened regularly for 10 years to pre-
vent 1 breast cancer death. In addition, of all
these women undergoing screening, mammog-
raphy will reveal abnormalities resulting in
call-backs, short-term follow-up, and biopsies.
When one takes this into account, the cost of
screening mammography for women in their
40s can be almost 5 times that of older women.
These questions apply to the general popula-
tion, but most physicians recommend that
mammographic screening should be started
at a younger age in women with a strong fam-
ily history of breast cancer. In women with a
first-degree relative with breast cancer, particu-
larly if that cancer was premenopausal, screen-
ing should begin 5 to 10 years earlier than the
age of the family member. However, for many
women, this will mean screening begins in
their 20s and 30s, when the sensitivity of
mammography is relatively low. This fact,
along with the lack of data regarding the
impact on mortality of screening high-risk
patients earlier, makes it difficult to know the
true benefit of these recommendations.
Another question is when to discontinue
screening.
The
randomized
trials
included
almost no women over the age of 70. Case con-
trol studies of mammographic screening in
older women have failed to demonstrate an
impact on mortality in women older than 75.
This is secondary to both the lower incidence
of DCIS in this population and the reduced life
expectancy among this population. Thus the
cost effectiveness and efficacy of continuing
screening past age 70 is unclear. The decision
to continue screening should be decided on an
individual basis, based on the woman’s health
and life expectancy, breast cancer risk, and
other factors.
When screening is performed separate from
diagnostic procedures, approximately 5% to
10% of women will be called back for addi-
tional images because of a concern on the
screening mammograms. Approximately 40%
of these women will have nothing that requires
further intervention; there may be overlapping
tissue that disappeared on subsequent images
or the finding is clearly benign, such as a
cyst or benign calcifications. Of the remaining
women, they will have abnormalities that
require either short-interval follow-up images
(less suspicious lesions) or biopsy (more suspi-
cious lesions). Where to set that threshold
remains a question. Setting that threshold low,
meaning biopsy is recommended for a large
percentage of atypical lesions, results in very
few missed cancers but a large number of
benign biopsies. Setting that threshold high
will minimize the number of biopsies but delay
the diagnosis of several cancers for several
months. The impact this has on survival is
unclear. Most breast imagers strive for a 20%
to 25% cancer detection rate, meaning one fifth
to one fourth of patients referred for biopsy
have cancer.
While mammography remains the standard
of care for breast cancer screening, MRI has
emerged as a useful adjunct in appropriate
patients. In very high-risk women, such as
those with documented BRCA mutations, MRI
screening has been shown to increase the detec-
tion of cancer and decrease the stage (tumor
size, nodal status) at which cancer is detected.
Yearly screening with MRI in addition to clinical
examination and mammography is recom-
mended for women at particularly high risk of
developing breast cancer. It is not, however,
recommended for women at lower risks of
developing breast cancer.
Suggested Reading
1. Bevers
TB,
Anderson
BO,
Bonaccio
E,
et
al.
National Comprehensive Cancer Network. Breast
cancer screening and diagnosis. J NCCN 2006;4(5):
480–508.
2. Bartella L, Smith CS, Dershaw DD, et al. Imaging
breast cancer. Radiol Clin North Am 2007;45(1):
45–67.
3. Dershaw
DD.
Film
or
digital
mammographic
screening? N Engl J Med 2005;353:1846–1847.
4. Humphrey L, Helfand M, Chan B, et al. Breast can-
cer screening: A summary of the evidence. In
U.S. Preventive Services Task Force, 2002, Vol 2003.
39
2—PRINCIPLES OF BREAST CANCER SCREENING