The Breast

Saint Agatha
 FUNCTIONAL ANATOMY
• At the fifth or sixth
week of fetal
development, two
Primitive
ventral bands of milk line

thickened ectoderm
(mammary ridges,
milk lines) are evident
in the embryo
• The breast or mammary gland (lat. mamma, grc. mastos) is the
largest skin gland.
• That is modified sweat gland.
• It exists in the male as well as in the female, but in the former only in
the rudimentary state.
• At the end of the first month of embryonic development, the
mammary gland begins to develop as a solid bud of epidermis into
the underlying mesenchyme.
• This primary bud occurs from cranial part of the mammary ridges,
thickened strips of ectoderm.
• Each primary bud give rise to several secondary buds that develop
into the lactiferous ducts and their branches that make up the
mammary gland.
• During pregnancy that the breast assumes its complete morphologic
maturation and functional activity.
• The breast remains undeveloped in the
female until puberty, when it enlarges in
response to ovarian estrogen and
progesterone, which initiate proliferation of
the epithelial and connective tissue
elements.
• However, the breasts remain incompletely
developed until pregnancy occurs.
 Developmental anomalies
• Absence of the breast (amastia) is rare and
results from an arrest in mammary ridge
development that occurs during the sixth fetal
week.
• Poland's syndrome consists of hypoplasia or
complete absence of the breast, costal cartilage
and rib defects, hypoplasia of the subcutaneous
tissues of the chest wall, and brachysyndactyly.
• Breast hypoplasia also may be iatrogenically
induced prior to puberty by trauma, infection, or
radiation therapy.
• Symmastia is a rare anomaly recognized
as webbing between the breasts across
the midline.
• .
symmastia
• Accessory nipples (polythelia) occur in
less than 1% of infants and may be
associated with abnormalities of the
urinary tract (renal agenesis and cancer),
abnormalities of the cardiovascular system
(conduction disturbances, hypertension,
congenital heart anomalies), and other
conditions (pyloric stenosis, epilepsy, ear
abnormalities, arthrogryposis).
 Polymastia
• Supernumerary breasts may occur in any
configuration along the mammary milk
line, but most frequently occur between
the normal nipple location and the
symphysis pubis
• Turner's syndrome (ovarian agenesis and
dysgenesis) and Fleischer's syndrome
(displacement of the nipples and bilateral
renal hypoplasia) may have polymastia as
a component.
• Accessory axillary breast tissue is
uncommon and usually is bilateral.
 GYNECOMASTIA
• Gynecomastia refers to an enlarged breast
in the male.
• Physiologic gynecomastia usually occurs
during three phases of life: the neonatal
period, adolescence, and senescence.
• Common to each of these phases is an
excess of circulating estrogens in relation
to circulating testosterone.
 Classification
• Grade I :Mild breast enlargement without
skin redundancy
• Grade IIa: Moderate breast enlargement
without skin redundancy
• Grade IIb: Moderate breast enlargement
with skin redundancy
• Grade III Marked breast enlargement with
skin redundancy and ptosis, which
simulates a female breast
 Estrogen excess states
A. Gonadal origin
• 1. True hermaphroditism

• 2. Gonadal stromal (nongerminal) neoplasms of the testis

– a. Leydig cell (interstitial)
– b. Sertoli cell
– c. Granulosa-theca

• 3. Germ cell tumors

– a. Choriocarcinoma
– b. Seminoma, teratoma
– c. Embryonal carcinoma
 Estrogen excess states
• B. Nontesticular tumors
– 1. Adrenal cortical neoplasms
– 2. Lung carcinoma
– 3. Hepatocellular carcinoma

• C. Endocrine disorders

• D. Diseases of the liver—nonalcoholic and

alcoholic cirrhosis

• E. Nutrition alteration states

 Androgen deficiency states
– A. Senescence

– B. Hypo-androgen states (hypogonadism)

• 1. Primary testicular failure

– a. Klinefelter's syndrome (XXY)
– b. Reifenstein's syndrome
– c. Rosewater, Gwinup, Hamwi familial gynecomastia
– d. Kallmann's syndrome
– e. Kennedy's disease with associated gynecomastia
– f. Eunuchoidal males (congenital anorchia)
– g. Hereditary defects of androgen biosynthesis
– h. ACTH deficiency

• 2. Secondary testicular failure

– a. Trauma
– b. Orchitis
– c. Cryptorchidism
– d. Irradiation

– C. Renal failure
– III. Drug-related
– IV. Systemic diseases with idiopathic mechanisms
• The breast is
composed of 15 to 20
lobes, which are each
composed of several
lobules.
• Fibrous bands of
connective tissue travel
through the breast
(suspensory ligaments
of Cooper), insert
perpendicularly into the
dermis, and provide
structural support.
• The mature female breast extends from the level
of the second or third rib to the inframammary
fold at the sixth or seventh rib.
• It extends transversely from the lateral border of
the sternum to the anterior axillary line.
• The deep or posterior surface of the breast rests
on the fascia of the pectoralis major, serratus
anterior, and external oblique abdominal
muscles, and the upper extent of the rectus
sheath.
 Nipple areola complex
• The epidermis of the nipple–areola complex is
pigmented and is variably corrugated.
• During puberty, the pigment becomes darker
and the nipple assumes an elevated
configuration.
• During pregnancy, the areola enlarges and
pigmentation is further enhanced.
• The areola contains sebaceous glands, sweat
glands, and accessory glands, which produce
small elevations on the surface of the areola
(Montgomery tubercles).
• Smooth-muscle bundle fibers, which lie circumferentially
in the dense connective tissue and longitudinally along
the major ducts, extend upward into the nipple where
they are responsible for the nipple erection that occurs
with various sensory stimuli.
• The dermal papilla at the tip of the nipple contains
numerous sensory nerve endings and Meissner's
corpuscles.
• This rich sensory innervation is of functional importance
as the sucking infant initiates a chain of neurohumoral
events that results in milk letdown.
 BLOOD SUPPLY
(1) perforating branches of the internal
mammary artery
(2) lateral branches of the posterior
intercostal arteries
(3) branches from the axillary artery,
including the highest thoracic, lateral
thoracic, and pectoral branches of the
thoracoacromial artery
 NERVE SUPPLY
• The second, third, and fourth anterior
intercostal perforators and branches of the
internal mammary artery arborize in the
breast as the medial mammary arteries.
 LYMPHATIC DRAINAGE
• 6 axillary lymph node groups recognized by
surgeons :
– (1) the axillary vein group (lateral) that consists of 4 to 6 lymph
nodes, which lie medial or posterior to the vein and receive most
of the lymph drainage from the upper extremity
– (2) the external mammary group (anterior or pectoral group)
that consists of 5 or 6 lymph nodes, which lie along the lower
border of the pectoralis minor muscle contiguous with the lateral
thoracic vessels and receive most of the lymph drainage from
the lateral aspect of the breast
– (3) the scapular group (posterior or subscapular) that
consists of 5 to 7 lymph nodes, which lie along the posterior wall
of the axilla at the lateral border of the scapula contiguous with
the subscapular vessels and receive lymph drainage principally
from the lower posterior neck, the posterior trunk, and the
posterior shoulder;
• (4) the central group that consists of 3 or 4 sets of
lymph nodes, which are embedded in the fat of the axilla
lying immediately posterior to the pectoralis minor
muscle and receive lymph drainage both from the
axillary vein, external mammary, and scapular groups of
lymph nodes and directly from the breast
• (5) the subclavicular group (apical) that consists of 6
to 12 sets of lymph nodes, which lie posterior and
superior to the upper border of the pectoralis minor
muscle and receive lymph drainage from all of the other
groups of axillary lymph nodes
• (6) the interpectoral group (Rotter's) that consists of 1
to 4 lymph nodes, which are interposed between the
pectoralis major and pectoralis minor muscles and
receive lymph drainage directly from the breast. The
lymph fluid that passes through the interpectoral group of
lymph nodes passes directly into the central and
subclavicular groups.
 LEVELS OF LN
• Level I - Lateral to pectoralis minor
insertion
• Level II- Behind the insertion
• Level III – Medial / Above the pectoralis
minor insertion
• Supraclavicular nodes
 Infectious and inflammatory
disorders
• Bacterial infections
– Staphylococcus aureus and Streptococcus species
are the organisms most frequently recovered from
nipple discharge from an infected breast.
– Breast abscesses are typically seen in staphylococcal
infections and present with point tenderness,
erythema, and hyperthermia.
– These abscesses are related to lactation and occur
within the first few weeks of breast-feeding.
 Bacterial infections
• They are treated with local wound care,
including warm compresses, and the
administration of intravenous antibiotics
(penicillins or cephalosporins).
• Breast infections may be chronic, possibly with
recurrent abscess formation.
• In this situation, cultures are taken to identify
acid-fast bacilli, anaerobic and aerobic bacteria,
and fungi.
• Uncommon organisms may be encountered and
long-term antibiotic therapy may be required.
 Bacterial infections
• Tuberculous infection – anti TB drugs
• Breast pump to drain the breast of milk in
the puerpueral women
 Mondor’s disease
• This variant of thrombophlebitis involves the
superficial veins of the anterior chest wall and
breast.
• In 1939, Mondor described the condition as
"string phlebitis," a thrombosed vein
presenting as a tender, cord-like structure.
• Frequently involved veins include the lateral
thoracic vein, the thoracoepigastric vein, and,
less frequently, the superficial epigastric vein.
Mondor’s disease
 Mondor’s disease
• Typically, a woman presents with acute pain in
the lateral aspect of the breast or the anterior
chest wall.
• A tender, firm cord is found to follow the
distribution of one of the major superficial veins.
• Rarely, the presentation is bilateral, and most
women have no evidence of thrombophlebitis in
other anatomic sites.
• This benign, self-limited disorder is not indicative
of a cancer.
 Mondor’s disease
• When the diagnosis is uncertain, or when a mass is
present near the tender cord, biopsy is indicated.
• Therapy for Mondor's disease includes the liberal use of
anti-inflammatory medications and warm compresses
that are applied along the symptomatic vein.
• Restriction of motion of the ipsilateral extremity and
shoulder as well as brassiere support of the breast are
important.
• The process usually resolves within 4 to 6 weeks.
• When symptoms persist or are refractory to therapy,
excision of the involved vein segment is appropriate.
BENIGN BREAST DISEASES
 Aberrations of Normal
Development and Involution
• The basic principles underlying the aberrations
of normal development and involution (ANDI)
classification of benign breast conditions are
– (1) benign breast disorders and diseases are related
to the normal processes of reproductive life and to
involution;
– (2) there is a spectrum of breast conditions that
ranges from normal to disorder to disease;
– (3) the ANDI classification encompasses all aspects
of the breast condition, including pathogenesis and
the degree of abnormality.
 Early reproductive years (age
15–25)
• Normal
– Lobular development
– Stromal development
– Nipple inversion
• Disorder
– Fibroadenoma
– Adolescent hypertrophy
– Nipple inversion
• Disease
– Giant fibroadenoma
– Gigantomastia
– Sub-areolar abscess
– Mammary duct fistula
 Later reproductive years (age
25–40)
• Normal
– Cyclical changes of menstruation
– Nodularity
– Epithelial hyperplasia of pregnancy
• Disorder
– Cyclical mastalgia
– Bloody nipple discharge
• Disease
– Incapacitating mastalgia
 Involution (age 35–55)
• Normal
– Lobular involution
– Duct involution
• Dilatation
• Sclerosis
– Epithelial turnover
• Disorder
– Duct ectasia
– Nipple retraction
– Epithelial hyperplasia
• Disease
– Periductal mastitis
– Epithelial hyperplasia with atypia.
 Classification of benign breast
disorders according to pathology
• Nonproliferative disorders of the breast
– Cysts and apocrine metaplasia
– Duct ectasia
– Calcifications
– Fibroadenoma and related lesions

• Proliferative breast disorders without atypia

– Sclerosing adenosis
– Radial and complex sclerosing lesions
– Ductal epithelial hyperplasia
– Intraductal papillomas

• Atypical proliferative lesions

– Atypical lobular hyperplasia (ALH)
– Atypical ductal hyperplasia (ADH)
 Classification of benign breast disorders
according to pathology
• Nonproliferative disorders of the breast account
for 70% of benign breast conditions and carry no
increased risk for the development of breast
cancer.

• This category includes

– cysts,
– duct ectasia,
– periductal mastitis,
– calcifications,
– fibroadenomas and related disorders.
1 CYST
2 FIBROCYSTIC CHANGE
Benign Breast Conditions

3 FIBROADENOMA

8 out of 10 breast masses are benign

breast conditions
 Fibrocystic disease
• The term fibrocystic disease is nonspecific.
• Too frequently, it is used as a diagnostic term to
describe symptoms, to rationalize the need for
breast biopsy, and to explain biopsy results.
• Synonyms include
• fibrocystic changes,
• cystic mastopathy,
• chronic cystic disease,
• chronic cystic mastitis,
• Schimmelbusch's disease,
• mazoplasia,
• Cooper's disease,
• Reclus' disease, and
• fibroadenomatosis.
• Fibrocystic disease refers to a spectrum of
histopathologic changes that are best diagnosed
and treated specifically.
 Fibradenoma
• Fibroadenomas are seen predominantly in
younger women age 15 to 25 years
• Fibroadenomas usually grow to 1 or 2 cm in
diameter and then are stable, but may grow to a
larger size.
• Small fibroadenomas (1 cm in size or less) are
considered normal, while larger fibroadenomas
(up to 3 cm) are disorders and giant
fibroadenomas (larger than 3 cm) are disease.
Fibrocystic breast change vs
Fibradenoma
 Fibroadenoma
• Similarly, multiple fibroadenomas (more
than five lesions in one breast) are very
uncommon and are considered disease.
Giant fibroadenoma
• The precise etiology of adolescent breast
hypertrophy is unknown.
• A spectrum of changes from limited to massive
stromal hyperplasia (gigantomastia) is seen.
• Nipple inversion is a disorder of development of
the major ducts, which prevents normal
protrusion of the nipple.
• Mammary duct fistulas arise when nipple
inversion predisposes to major duct obstruction,
leading to recurrent subareolar abscess and
mammary duct fistula.
 Cyclical mastalgia in later
reproductive years
• Cyclical mastalgia and nodularity are usually
associated with premenstrual enlargement of the
breast and are regarded as normal.
• Cyclical pronounced mastalgia and severe
painful nodularity are viewed differently than are
physiologic discomfort and lumpiness.
• Painful nodularity that persists for more than 1
week of the menstrual cycle is considered a
disorder.
• In epithelial hyperplasia of pregnancy, papillary
projections sometimes give rise to bilateral
bloody nipple discharge.
Pathology of Proliferative Disorders
Without Atypia
• Proliferative breast disorders without
atypia include
– sclerosing adenosis,
– radial scars,
– complex sclerosing lesions,
– ductal epithelial hyperplasia,
– intraductal papillomas.
4 INTRADUCTAL
PAPILLOMA
 Sclerosing adenosis
• Sclerosing adenosis is prevalent during the
childbearing and perimenopausal years and has
no malignant potential.
• Histologic changes are both proliferative (ductal
proliferation) and involutional (stromal fibrosis,
epithelial regression) in nature.
• Sclerosing adenosis is characterized by
distorted breast lobules and usually occurs in
the context of multiple microcysts, but
occasionally presents as a palpable mass.
 Calcification
• Benign calcifications
are often associated
with this disorder.
 Radial scars and Complex sclerosing
lesion
• Central sclerosis and varying degrees of
epithelial proliferation, apocrine
metaplasia, and papilloma formation
characterize radial scars and complex
sclerosing lesions of the breast.
• Lesions up to 1 cm in diameter are called
radial scars, while larger lesions are called
complex sclerosing lesions.
 Radial scars and Complex sclerosing
lesion
• Radial scars originate at sites of terminal duct
branching where the characteristic histologic
changes radiate from a central area of fibrosis.

• All of the histologic features of a radial scar are

seen in the larger complex sclerosing lesions,
but there is a greater disturbance of structure
with papilloma formation, apocrine metaplasia,
and, occasionally, sclerosing adenosis
 Pathology of Atypical Proliferative
Diseases
• The atypical proliferative diseases have
some of the features of carcinoma in situ
(CIS) but either lack a major defining
feature of CIS or have the features in less
than fully developed form.
• In 1978, Haagensen and colleagues
described lobular neoplasia, a spectrum of
disorders ranging from atypical lobular
hyperplasia to lobular carcinoma in situ.
 Cancer Risk Associated with Benign Breast
Disorders and In Situ Carcinoma of the Breast
Abnormality Relative Risk
Nonproliferative lesions of the breast No increased risk
Sclerosing adenosis No increased risk
Intraductal papilloma No increased risk
Florid hyperplasia 1.5 to 2-fold
Atypical lobular hyperplasia 4-fold
Atypical ductal hyperplasia 4-fold
Ductal involvement by cells of
atypical ductal hyperplasia 7-fold
Lobular carcinoma in situ 10-fold
Ductal carcinoma in situ 10-fold
 Treatment of Selected Benign
Breast Disorders and Diseases
• CYSTS
– Aspiration of the cyst
– Biopsy of aspirate

– The two cardinal rules of

safe cyst aspiration are
(1) the mass must disappear
completely after aspiration,
(2) the fluid must not be
bloodstained.

– If either of these conditions

is not met, then ultrasound,
needle biopsy, and
perhaps excisional biopsy
are recommended.
 Management of fibroadenomas
• Removal of all fibroadenomas has been advocated
irrespective of patient age or other considerations, and
solitary fibroadenomas in young women are frequently
removed to alleviate patient concern.
• Yet most fibroadenomas are self-limiting and many go
undiagnosed, so a more conservative approach is
reasonable.
• Careful ultrasound examination with core-needle biopsy
will provide for an accurate diagnosis.
• Subsequently, the patient is counseled concerning the
biopsy results, and excision of the fibroadenoma may be
avoided.
 Management for sclerosing
adenosis
• The clinical significance of sclerosing adenosis lies in its
mimicry of cancer.
• It may be confused with cancer on physical examination,
by mammography, and at gross pathologic examination.
• Excisional biopsy and histologic examination are
frequently necessary to exclude the diagnosis of cancer.
• The diagnostic work-up for radial scars and complex
sclerosing lesions frequently involves stereoscopic
biopsy.
• It is usually not possible to differentiate these lesions
with certainty from cancer by mammography features, so
biopsy is recommended
Benign sclerosing adenosis
BREAST CANCER
 RISK FACTORS
• HORMONE ASSOCIATED RISK FACTORS
– Increased exposure to estrogen is associated with an
increased risk for developing breast cancer, whereas
reducing exposure is thought to be protective.
– Correspondingly, factors that increase the number of
menstrual cycles, such as early menarche, nulliparity,
and late menopause, are associated with increased
risk.
– Moderate levels of exercise and a longer lactation
period, factors that decrease the total number of
menstrual cycles, are protective.
 RISK FACTORS
– The terminal differentiation of breast epithelium
associated with a full-term pregnancy is also
protective, so older age at first live birth is associated
with an increased risk of breast cancer.
– Finally, there is an association between obesity and
increased breast cancer risk.
– Because the major source of estrogen in
postmenopausal women is the conversion of
androstenedione to estrone by adipose tissue, obesity
is associated with a long-term increase in estrogen
exposure
 RISK FACTORS
• Nonhormonal risk factors
– radiation exposure.
• Young women who receive mantle radiation therapy for
Hodgkin's lymphoma have a breast cancer risk that is 75
times greater than that of age-matched control subjects.
• Survivors of the atomic bomb blasts in Japan during World
War II have a very high incidence of breast cancer, likely
because of somatic mutations induced by the radiation
exposure.
• In both circumstances, radiation exposure during
adolescence, a period of active breast development,
magnifies the deleterious effect.
 RISK FACTORS
– Studies also suggest that the amount and
duration of alcohol consumption are
associated with an increased breast cancer
risk.
• Alcohol consumption is known to increase serum
levels of estradiol.
– Finally, evidence suggests that chronic
consumption of foods with a high fat content
contributes to an increased risk of breast
cancer by increasing serum estrogen levels
 Dietary Influences
• Committee on Diet, Nutrition, and Cancer
of the National Academy of Sciences –
concluded—causal relationship exists bet
dietary mammalian fat and breast cancer.
• Fried, high fat foods –inc CA 2-fold
• 5 ethnic Hawaii-strong relationship
between breast CA and total fat, saturated
fat, animal fat, unsat fat
• NCI – beef or pork –2.7 times higher
• Japanese, Eskimo—low incidence despite
large consumption of fat ( omega 3 FA)
• Obesity – 1.5-2 x higher than non-obese
• Child bearing and fertility—nulliparity and
infertility- higher prob 30-70%
women –first preg after 35- even greater
risk than nullipara
70% – 80% of breast cancer cases have
no identifiable risk factors other than
being a woman and growing older

Majority are sporadic or index cases and

have no family history of breast cancer.
 Breast cancer risk assessment
model
• Gail Model (see table 16-7 schwartz)
– Age at menarche (years)
– Number of biopsies/history of benign
breast disease, age <50 y
– Number of biopsies/history of benign
breast disease, age 50 y
– Age at first live birth (years)
 Percent Incidence of Sporadic, Familial, and Hereditary
Breast Cancer

• Sporadic breast cancer 65–75%

• Familial breast cancer 20–30%
• Hereditary breast cancer 5–10%

– BRCA-1 45%
– BRCA-2 35%
– p53 (Li-Fraumeni syndrome) 1%
– STK11/LKB1 (Peutz-Jeghers syndrome) <1%
– PTEN (Cowden disease) <1%
– MSH2/MLH1 (Muir-Torre syndrome) <1%
– ATM (Ataxia-telangiectasia) <1%
– Unknown 20%
 Cancer Prevention for BRCA
Mutation Carriers

• Risk management strategies for BRCA-1 and

BRCA-2 carriers include:

– Prophylactic mastectomy and reconstruction;

– Prophylactic oophorectomy and hormone
replacement therapy;
– Intensive surveillance for breast and ovarian
cancer
– Chemoprevention.- Tamoxifen
 EPIDEMIOLOGY
Number one cancer in women

Breast cancer is the most common site-

specific cancer in women and is the
leading cause of death from cancer for
women age 40 to 44 years.

It accounts for 33% of all female cancers

and is responsible for 20% of the cancer-
related deaths in women.
 Incidence of CA of Breast
• England and Wales – highest age-
adjusted mortality for breast CA
27/100,000
• USA-13th (22/
• South Korea – lowest (2.6/100K)
• Mormon, Seventh-day Adventists,
Alaskan, American Indian, Eskimo,
Mexican-American, Japanese and Filipino
women living in Hawaii – lower per capita
incidence other Americans
• Nuns, Jewish women – higher than
average.
• Women in less-industrialized nations-
lower rates than industrialized EXCEPT
Japan.
The incidence of breast cancer is
increasing in many countries at a
mean rate of 1% to 2% annually
and it is estimated that during the
first decade of the third
millennium nearly 1 million women
will develop this disease yearly
throughout the world.

Veronesi U, Sacchini V, Colleoni M, Goldhirsch A. Breast

cancer. In: Pollock RE, ed. Manual of Clinical Oncology, 7th
ed. UICC 1999: 491-514
We don’t want this!
In the Philippines, the
incidence of breast cancer is
30.2/100,000.
It is considered one of the
highest in Asia.

Breast Cancer Working Group. Breast cancer. In: Arcellana-

Nuquid EY, ed. The Handbook of Clinical Oncology, 2nd ed.
2001: 135
 NATURAL HISTORY
• PRIMARY DISEASE
– Starts from mutation in a single cell
– Doubling time
– More than 80% of breast cancers show
productive fibrosis that involves the epithelial
and stromal tissues. (schirrous type).
 PRIMARY DISEASE
• With growth of the cancer and
invasion of the surrounding
breast tissues, the
accompanying desmoplastic
response entraps and shortens
the suspensory ligaments of
Cooper to produce a
characteristic skin retraction.

• Localized edema (peau

d'orange) develops when
drainage of lymph fluid from
the skin is disrupted.
• With continued
growth, cancer cells
invade the skin and
eventually ulceration
occurs.
• As new areas of skin
are invaded, small
satellite nodules
appear near the
primary ulceration.
• The size of the primary breast cancer
correlates with disease-free and overall
survival, but there is a close association
between cancer size and axillary lymph
node involvement.
• In general, up to 20% of breast cancer
recurrences are locoregional, more than
60% are distant, and 20% are both
locoregional and distant
Breast Cancer Stages: Natural
History
 Axillary Lymph Node Metastases
• As the size of the primary breast cancer
increases, some cancer cells are shed into
cellular spaces and transported via the
lymphatic network of the breast to the regional
lymph nodes, especially the axillary lymph
nodes.
• Lymph nodes that contain metastatic cancer are
at first ill-defined and soft, but become firm or
hard with continued growth of the metastatic
cancer.
 Axillary Lymph Node
Metastases
• Eventually the lymph nodes adhere to each
other and form a conglomerate mass.
• Cancer cells may grow through the lymph node
capsule and fix to contiguous structures in the
axilla including the chest wall.
• Typically, axillary lymph nodes are involved
sequentially from the low (level I) to the central
(level II) to the apical (level III) lymph node
groups.
 Importance of lymph node status
• While more than 95% of the women who
die of breast cancer have distant
metastases, the most important prognostic
correlate for disease-free and overall
survival is axillary lymph node status.
• Node-negative women have less than a
30% risk of recurrence, compared to as
much as a 75% risk for node-positive
 Distant Metastases
• At approximately the twentieth cell doubling,
breast cancers acquire their own blood supply
(neovascularization).
• Thereafter, cancer cells may be shed directly
into the systemic venous blood to seed the
pulmonary circulation via the axillary and
intercostal veins or the vertebral column via
Batson's plexus of veins, which courses the
length of the vertebral column.
• These cells are scavenged by natural killer
lymphocytes and macrophages.
• Successful implantation of metastatic foci
from breast cancer predictably occurs after
the primary cancer exceeds 0.5 cm in
diameter, which corresponds to the
twenty-seventh cell doubling.
• For 10 years following initial treatment,
distant metastases are the most common
cause of death in breast cancer patients.
• While 60% of the women who develop
distant metastases will do so within 24
months of treatment, metastases may
become evident as late as 20 to 30 years
after treatment of the primary cancer.
• Common sites of involvement, in order of
frequency, are
– bone, lung, pleura, soft tissues, and liver.
 PATHOLOGY
• Lobular carcinoma in situ
• Ductal carcinoma in situ
• Invasive breast carcinoma
– Invasive ductal – 70 % of cases
– Invasice lobular carcinoma
– Other special types
 DIAGNOSIS
• History
• Physical examination
– Inspection
• Assymetry
• Dimpling
• Retraction
• Ulcers
– Palpation
• Mass
• Nipple discharge
 Histologic classification
I. Paget's disease of the nipple
II. Invasive ductal carcinoma
A. Adenocarcinoma with productive fibrosis (scirrhous,
simplex, NST) 80%
B. Medullary carcinoma 4%
C. Mucinous (colloid) carcinoma 2%
D. Papillary carcinoma 2%
E. Tubular carcinoma (and ICC) 2%
III. Invasive lobular carcinoma 10%
IV. Rare cancers (adenoid cystic, squamous cell,
apocrine)
 Paget’s disease
• a chronic, eczematous
eruption of the nipple,
which may be subtle, but
may progress to an
ulcerated, weeping
lesion.
• Paget's disease is usually
associated with extensive
DCIS and may be
associated with an
invasive cancer.
• A palpable mass may or
may not be present.
• Biopsy of the nipple will
show a population of cells
that are identical to the
underlying DCIS cells
(pagetoid features or
pagetoid change).
• Pathognomonic of this
cancer is the presence of
large, pale, vacuolated
cells (Paget's cells) in the
rete pegs of the
epithelium.
Warning Signals
 Imaging techniques
• Mammography
– Recommended:
• Annually starting at age 40
• Earlier for those with strong family history
Mammogram
Stellate lesion with malignant
calcification. In addition there is
inversion of the nipple and adjacent skin
thickening.
• Ultrasound
– Solid
– Cystic
– Borders
• Ductography
• MRI
Breast Ultrasound): Poorly circumscribed region of increased echogenicity on

ultrasound consistent with Breast cancer.

(Breast MRI): MRI images depicting a breast cancer
 Definitive diagnosis
• FNAB
• CORE NEEDLE BIOPSY
• OPEN BIOPSY
Diagnosis of Breast Cancer
1 Fine Needle Aspiration Biopsy

2 Open Biopsy
 STAGING
• T – tumor size
• N- Nodal status
– Sentinel lymph node
• M – Distant metastasis
– Lungs
– Liver
– Bones
Breast Cancer Stages

Please refer to your text book for further detail

Table 16-11
 Diagnostic Studies for Breast Cancer Patients

History & physical

CBC, platelets
Liver function tests
Chest x-ray
Bilateral mammogram
Hormone-receptor status
HER2/neu expression
Bone scan
Abdominal CT scan or ultrasound or MRI
 TREATMENT
• SURGERY
1. Mastectomy with axillary lymph node
dissection
1. Sentinel lymph node
2. Breast conservation surgery with radiation
1. Lumpectomy
2. Quadrantectomy (QUART)
3. Simple mastectomy (toilet)
– Consider objective of treatment whether
curative of palliative
 Adjuvant therapy
• Chemotherapy
– For tumors more than 2 cms
– Positive lymph nodes

• Radiation therapy
– For DCIS
– For breast conservation
– For advance staged disease
 Hormonal therapy
• SERMS: Selective estrogen modulators
– Tamoxifen – 5 years
– Aromatase inhibitors
• Ablative endocrine therapy
– Oophorectomy
• Given to ER / PR positive tumors
 Immune / antibody therapy
• Traztuzumab
– For her2/neu positive tumors
Her2/neu
 Prognosis
• The 5-year survival rate
– stage I patients is 94%
– stage IIa patients, 85%
– stage IIb patients, 70%
– stage IIIa patients, 52%
– stage IIIb patients, 48%
– stage IV patients, 18%.
 Phylloides tumor
• Phyllodes tumors also known
cystosarcoma phyllodes, cystosarcoma
phylloides and phylloides tumor, are
typically large, fast growing masses that
form from the periductal stromal cells of
the breast.
• They account for less than 1% of all breast
neoplasms.
Can be benign or malignant
Please read on the following topics
• Inflammatory breast
cancer

• Male breast cancer

 Breast cancer screening and
prevention methods
Early detection is the key to cure
Early Detection Measures
• MONTHLY breast self examination by age
20

• YEARLY health worker breast

examination by age
30

• YEARLY mammogram by age

40
Pink october
 Infiltrating malignancies
• Pagets Disease of the nipple- Sir James
Paget 1874.-chr eczematoid eruption of
the nipple (2%) of histo type
• Almost always asso with intraductal or
invasive CA
• Encrusted scaly, hyperemic and enlarged
tumor occupies nipple areola complex
• SX- tenderness, itching, burning,
intermittent hemorrhage.
 Paget’s Disease
• ¼ to 1/3- axillary node mets at time of DX
• Better PX- bec early detection
• Microscopically-intraepithelial tumor with
single or small groups of clear cells with
large vesicular and prominent nuclei.
• Pathognomonic – Paget’s cells (very large,
pale, vacuolated cells in the rete pegs of
epithelium.
 Paget’s
• Confused with superf. Melanoma
• Demo of S-100 protein or melanoma
specific Ag (MSA) immunoreactivity in
malignant melanoma
• Immunohistochemisty- CEA – present in
Paget’s absent in melanoma
• Origin of Paget’s 1. epidermotrophism of
underlying tumor cells. 2. intraepithelial
carcinomatous metaplasia
 Infiltrating ductal CA with
productive fibrosis
• 78% ( scirrhous simplex)
• Solitary, nontender, firm, ill-defined mass
• Perimenopausal or post m in 60s
• PE- ill defined border
• Cut – central radiating stellate with chalky
white or yellow streak extending to
parenchyma
• HISTO- variable cellular and nuclear grade
• Small clusters or stacked in single rows
―Indian filling‖
• Skin dimpling- Cooper’s ligament shorten
as a result of tumor infiltration and fibrosis
• Peau d’ orange-progressive diffuse skin
infiltration in the subdermal plexus and
Cooper’s lig involvement, extensive
edema of skin
 Medullary CA
• 2-15%
• Origin: large ducts
• Gross: large, soft, hemorrhagic, bulky
• Positioned deep and mobile
• Skin stretched over the mass > 3cm
• Bilateral-<20%
• ER or PR + < 10%
 Medullary
• Micro: 1. dense lymphoreticular infiltrate
composed mainly of lympho and plasma
cells. 2. large pleomorphic nuclei, poorly
diff and active cellular mitosis 3. syncytial
sheetlike growth pattern w or w/
tubuloacinar differentiation.
• 50% asso w intraductal ca component in
periphery of tumor.
• >40% axillary LN mets
• Better 5 yr PX
 Mucinous CA ( colloid)
• 2%
• Origin: ductal
• Bulky, mucinous
• Elderly
• Cut: gelatinous, glistening glaring
• Fibrosis – variable
• Axillary mets – 30%
• 5 yr surv – 73%
• 10 yr -59%
 Mucinous
• Histopath: mucin surround tumor cells
• Signet cells – absent
• 2/3 of pure mucin- contain ER
• Multiple sections – to dx CA
• Frozen section – nondiagnostic,not
advisable
• To be diff – with benign granular cell
myoblastoma
 Tubular CA
• 2%
• Single small randomly arranged tubular
cells
• The small tubular pattern and single-cell
lining of neoplastic tubules—impt histo
char of tumor.
• Premenopausal or early menopausal
• Mammo—when < 1 cm max dimension
 Tubular CA
• 10% dev axillary mets
• Survival almost 100% if CA contains 90%
or > tubular components
• Mets confined to Level I LN
 Papillary carcinoma
• <2%
• 7th decade
• Small, rarely attains >2-3 cm
• Non-Caucasian pts
• Morpho: well circumscribed; papillary,
papillae, well defined fibrovascular stalks
and multilayered epithelium, mod
pleomorphic cells.
• LOWEST freq of nodal mets
 Adenoid cystic carcinoma
• Very rare <0.1%
• Indistinguishable from adenoid cystic CA
of salivary glands
• Small 1-3 cm dia, well circumscribed, well
defined
• Dense mucoid within glandular spaces
and mimics lamina densa of basement
membrane
• Axillary mets --RARE
 Adenoid cystic carcinoma
• ONLY 7 DEATHS from pulmonary mets
 Apocrine carcinoma
• Presents as ductal or acinar growth
• With unusual tendency to involve the
lobular epithelium. Well differentiated with
rounded vesicular nuclei and prominent
nucleoli
• Very low mitotic rate, little cytomorphologic
features.
• These lesions- potentially aggressive biol
behavior
• Low to absent ER , PR –frequent
 CARCINOMA of lobular origin
• Small cells, rounded nuclei, inconspicuous
nucleoli, scant, indistinct cytoplasm.
• ―Indian filing‖- uniform small tumor cells of
arranged in a single-file orientation.
• Special stains – infrequent mucin in
cytoplasm.
• Similar to colloid ca- mucin displaces
nucleus resembling signet ring of GI CA
• ORIGIN: terminal ductules of lobules
• Non-invasive is called LCIS
• Packed with small uniform hyperplastic
cells arranged in rows or beads with few
mitosis
• Hyperchromatism, nuclear anaplasia, etc
• LCIS – 3%
• Infiltrating lobular CA – 10%
 Infiltrating lobular CA
• 10%
• Bilaterality
• Multicentricity
• multifocality
 Squamous cell
(epidermoid) carcinoma
• Infrequent
• Epithelial – result from metaplasia within
lactiferous duct system.
• Devoid of clinical or radiolographic chars
• Similar to epidermoid ca of skin—mets
exclusively thro lymphatics (1/4 of pts)
 sarcomas
• Heterogenous group of lesions
• Fibromatosis(low gr fibrosarcoma or
desmoid tumor)
• Fibrosarcoma
• Malignant fibrous histiocytoma
• Liposarcoma
• Leiomyosarcoma
• Osteogenic sarcoma
• Chondrosarcoma
• Stromal sarcoma
 sarcomas
• Large painless mass, rapid growth
• Routine mammo-not useful, false – high
 angiosarcoma
• 1948 Stewart and Treves-
lymphangiosarcoma in pt with ipsilat
lymphedema ff radical Mast
• Ave interval 10.5 yrs in 60% hx of irradia
• Overall lymphedema incidence ff RAD
MAST -15-25%,, MRM 5.5%
• Exuberant mitosis, nec, he – high grad
tumors
• Factor VIII related antigen—tumor marker
for angiosarcoma (from epith)—reliable
marker
• Px- dismal 19 months survival
• No correlation bet histo and survival
 Lymphomas
• Primary lymphoma-rare
• Large 4 cm mean
• Postmenopausal
• Tumor + axill nodes
• Similar to other lymphomas
• Total mast + LN dissection
 Inflammatory breast cancer
• Inflammatory breast cancer is a rare and
very aggressive disease with symptoms
that include redness, swelling, tenderness,
and warmth in the breast.
• Treatment for inflammatory breast cancer
is usually more aggressive than treatment
for most other types of breast cancer.
• People with inflammatory breast cancer
are encouraged to enroll in clinical trials
that are testing new treatments.
 Inflammatory Breast Cancer
• Rare and very aggressive
• Cancer cells block the lymph vessels in
the skin of the breast
• 1-5 % of all the breast cancers
• Most --invasive ductal carcinomas, --cells
that line the milk ducts of the breast and
then spread beyond the ducts
 Cont’d IBC
• progresses rapidly, --weeks or months.
• stage III or IV at diagnosis,
• younger ages (median age of 57 years,
median age of 62 years other types of
breast cancer).
• African American women is 54 years, compared
with a median age of 58 years in white women.
• frequently hormone receptor negative
• more common in obese women than in women
of normal weight. Like other types of breast
cancer, inflammatory breast cancer can occur in
men, but usually at an older age (median age at
diagnosis of 66.5 years) than in women.
 Symptoms of inflammatory breast
cancer
• swelling (edema) redness (erythema) that affect a third
or more of the breast. The skin of the breast may also
appear pink, reddish purple, or bruised.
• In addition, the skin may have ridges or appear pitted,
like the skin of an orange (called peau d'orange). These
symptoms are caused by the buildup of fluid (lymph) in
the skin of the breast. This fluid buildup occurs because
cancer cells have blocked lymph vessels in the skin,
preventing the normal flow of lymph through the tissue.
Sometimes, the breast may contain a solid tumor that
can be felt during a physical exam, but, more often, a
tumor cannot be felt
 Diagnosis of IBC
• Difficult
• No lump on PE or mammography
• Non fatty dense breast tissue—difficult in
screening mammogram
• Diff: mastitis: locally adv breast CA
 International Panel of Experts
• Minimum criteria for a diagnosis of inflammatory
breast cancer include the following:
– A rapid onset of erythema (redness), edema
(swelling), and a peau d’orange appearance
and/or abnormal breast warmth, with or
without a lump that can be felt.
– The above-mentioned symptoms have been
present for less than 6 months.
– The erythema covers at least a third of the
breast.
• Initial biopsy samples from the affected breast
show invasive carcinoma
• (estrogen and progesterone receptors)
• greater than normal amounts of the HER2
protein (HER2-positive breast cancer).
• Imaging and staging tests should include
the following
– A diagnostic mammogram and
an ultrasound of the breast and regional
(nearby) lymph nodes.
– A PET scan or a CT scan and a bone scan to
see if the cancer has spread to other parts of
the body.
 How is inflammatory breast
cancer treated?
Multi-modal therapy
1. Systemic chemotherapy -6 cycles (4-6
months) neoadjuvant chemotherapy
--Anthracycline, taxane
2. Surgery
3. Targeted Therapy—HER2 protein
trastuzumab—Herceptin—targets this
protein =
-part of neoadjuvant, adjuvant
• Studies have shown that women with
inflammatory breast cancer who received
trastuzumab in addition to chemotherapy have
better responses to treatment and better
survival.
• ER + = tamoxifen
• Aromatase inhibitors – letrozole
• Surgery – MRM
• radiation
• Adjuvant systemic therapy
• Supportive/Palliative
 Adjuvant therapy:
• Adjuvant systemic therapy may be given
after surgery to reduce the chance of
cancer recurrence.
• This therapy may include additional
chemotherapy,
• antihormonal therapy,
• targeted therapy (such as trastuzumab), or
some combination of these treatments
 Prognosis of IBC
• Because inflammatory breast cancer usually develops
quickly and spreads aggressively to other parts of the
body, women diagnosed with this disease, in general, do
not survive as long as women diagnosed with other
types of breast cancer.
• According to statistics from NCI’s Surveillance,
Epidemiology, and End Results (SEER) program, the 5-
year relative survival for women diagnosed with
inflammatory breast cancer during the period from 1988
through 2001 was 34 percent, compared with a 5-year
relative survival of up to 87 percent among women
diagnosed with other stages of invasive breast cancers.
 Prognosis
• Stage of disease:
• stage III disease have a better prognosis than
women with stage IV disease.
• stage III inflammatory breast cancer, - 40%
survive at least 5 years after their diagnosis,
• stage IV, -- 11 % survive
 Tumor grade
• Tumor grade: Women with grade I or grade II -
better prognosis than those with grade III
tumors.
• Tumor grade --cancer cells look like under a
microscope, with a higher grade indicating a
more abnormal appearance and a more
aggressive cancer that is likely to grow and
spread.
• grade I or grade II inflammatory breast
cancer, --77 % survived at least 2 years
after their diagnosis,
• grade III inflammatory breast cancer, 65 %
survived at least 2 years after their
diagnosis.
 Ethnicity
• African American women --inflammatory
breast cancer generally -- worse prognosis
than women of other racial and ethnic
groups.
• Studies --53 % of African American
women who are diagnosed with
inflammatory breast cancer survive at
least 2 years after diagnosis,
• 69 % of women from other racial and
ethnic groups
 ER
• Estrogen receptor status: Women with
inflammatory breast whose cancer cells
have estrogen receptors have a better
prognosis than those whose cancer cells
are estrogen receptor negative
• ER (-)--2 yrs median survival rate
• ER + --4 yrs median survival rate
 Multimodal therapy of IBC
• Neoadjuvant chemotherapy, mastectomy,
adjuvant chemotherapy, and radiation therapy,
their 5-year disease-free survival ranges from 24
to 49 percent.
• One long-term study found that 28 percent of
women with inflammatory breast cancer survived
15 years or longer after they were treated with
multimodal therapy.
• Historically, among women who had only
surgery, radiation therapy, or surgery and
radiation therapy, fewer than 5 percent survived
longer than 5 years
 New clinical trials for IBC
• Discuss with MD regarding new clinical
trials
 BREAST CA in males
• Breast cancer may occur in men. Men at
any age may develop breast cancer, but it
is usually detected (found) in men
between 60 and 70 years of age. Male
breast cancer makes up less than 1% of
all cases of breast cancer.
 types of breast cancer are found in men:

• Infiltrating ductal carcinoma: Cancer that

has spread beyond the cells lining ducts in
the breast. Most men with breast cancer
have this type of cancer.
• Ductal carcinoma in situ: Abnormal cells
that are found in the lining of a duct; also
called intraductal carcinoma.
• Inflammatory breast cancer: A type of
cancer in which the breast looks red and
swollen and feels warm.
 Cont’d male breast CA
• Paget disease of the nipple: A tumor that
has grown from ducts beneath
the nipple onto the surface of the nipple.
• Lobular carcinoma in situ (abnormal cells
found in one of the lobes or sections of the
breast), which sometimes occurs in
women, has not been seen in men.
• Being exposed to radiation.
• Having a disease related to high levels
of estrogen in the body, such
as cirrhosis (liver disease) or Klinefelter
syndrome (a genetic disorder.)
• Having several female relatives who have
had breast cancer, especially relatives
who have an alteration of
the BRCA2 gene.
 DX and TX
• Same
 TNM
• TX – T cannot be assessed
• T0 – No evidence of tumor
• Tis—ca in situ; intraductal, lobular, or
Paget’s
• Tumor 2 cm or less in greatest dimension
T1a 0.5 cm or less
T1b >0.5 cm but not > 1cm
T1c > 1 cm but not > 2 cm
• T2 > 2 cm but not> 5cm
• T3 > 5 cm greatest dimension
• T4 any size- chest wall or skin
T4a chest wall
T4b edema(peau d’ orange), ulceration of
skin of breast, satellite nodules same
breast
T4c T4a and T4b
 Regional lymph nodes
• NX cannot be assessed (prev removed)
• N0 no regional LN mets
• N1 met to movable ipsilat ALN
• N2 met to movable ipsilat ALN fixed to one
another or other struct
N3 met to ipsilat internal mammary LN(s)
 Distant Metastasis
• MX – cannot be assessed
• M0 –no mets
• M1 distant metastasis including ipsilateral
supraclavicular lymph node(s)
 Stage grouping
• Stage 0 Tis N0 M0
• Stage I T1 N0 M0
• Stage IIA T0 N1 M0
T1 N1 M0
T2 N0 M0
Stage IIB T2 N1 M0
T3 N0 M0
• Stage IIIA T0 N2 M0
• T1 N2 M0
• T2 N2 M0
• T3 N1 M0
• T3 N2 M0
• Stage IIIB T4 any N M0
• any T N3 M0
• Stage IV any T any N M1