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The Breast
Saint Agatha
FUNCTIONAL ANATOMY
• At the fifth or sixth
week of fetal
development, two
ventral bands of
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
Oh yes!!!
• 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
• 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
• II. Androgen deficiency states
– A. Senescence
– B. Hypoandrogen 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.
• 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.
• 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.
• 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.
• 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)
Clinical Significance
• 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.
1CYST
FIBROCYSTIC CHANGE
2
Benign Breast Conditions
3FIBROADENOMA
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.
• 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.
II. 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 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.
• Benign calcifications
are often associated
with this disorder.
• 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 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
III. 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.
– The terminal differentiation of breast epithelium
associated with a full-term pregnancy is also
protective
– older age at first live birth is associated with an
increased risk of breast cancer.
– 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
• 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.
– 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
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%
• a Affected gene.
• SOURCE: Adapted with permission from Martin AM et al. 47
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.
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).
• 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.
• 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.
• 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
1Fine Needle Aspiration Biopsy
2Open 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
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

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THE BREAST

  • 2.
  • 4.
  • 5. FUNCTIONAL ANATOMY • At the fifth or sixth week of fetal development, two ventral bands of thickened ectoderm (mammary ridges, milk lines) are evident in the embryo
  • 6. • 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.
  • 7. • 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.
  • 8. 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.
  • 9. • Symmastia is a rare anomaly recognized as webbing between the breasts across the midline.
  • 11. • 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).
  • 12. 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
  • 14.
  • 15.
  • 16. • 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.
  • 17.
  • 18. 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.
  • 19.
  • 20. 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
  • 21. • 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
  • 22. • 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
  • 23. • II. Androgen deficiency states – A. Senescence – B. Hypoandrogen 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
  • 24. • 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.
  • 25.
  • 26. • 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.
  • 27.
  • 28. 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).
  • 29.
  • 30. • 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.
  • 31. 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
  • 32. 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.
  • 33. 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;
  • 34.
  • 35. • (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.
  • 36.
  • 37. 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
  • 38. 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.
  • 39.
  • 40. • 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.
  • 41. • Tuberculous infection – anti TB drugs • Breast pump to drain the breast of milk in the puerpueral women
  • 42. 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.
  • 43.
  • 44. • 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.
  • 45. • 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.
  • 47. 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.
  • 48. 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
  • 49. 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
  • 50. 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.
  • 51. 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)
  • 52. Clinical Significance • 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.
  • 53.
  • 55. Benign Breast Conditions 3FIBROADENOMA 8 out of 10 breast masses are benign breast conditions
  • 56. 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.
  • 57. 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.
  • 58.
  • 59. • Similarly, multiple fibroadenomas (more than five lesions in one breast) are very uncommon and are considered disease.
  • 61. • 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.
  • 62. 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.
  • 63. II. Pathology of Proliferative Disorders Without Atypia • Proliferative breast disorders without atypia include – sclerosing adenosis, – radial scars, – complex sclerosing lesions, – ductal epithelial hyperplasia, – intraductal papillomas.
  • 65. • 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.
  • 66. • Benign calcifications are often associated with this disorder.
  • 67. • 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.
  • 68. • 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
  • 69.
  • 70. III. 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.
  • 71. 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
  • 72. 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.
  • 73. 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.
  • 74. 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
  • 77. 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.
  • 78. – The terminal differentiation of breast epithelium associated with a full-term pregnancy is also protective – older age at first live birth is associated with an increased risk of breast cancer. – 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
  • 79. • 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.
  • 80. – 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
  • 81. 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.
  • 82. 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)
  • 83. 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% • a Affected gene. • SOURCE: Adapted with permission from Martin AM et al. 47
  • 84. 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
  • 85. 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.
  • 86. 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
  • 88. 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
  • 89. 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).
  • 90. • 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.
  • 91.
  • 92. • 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.
  • 93. • 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.
  • 94. • In general, up to 20% of breast cancer recurrences are locoregional, more than 60% are distant, and 20% are both locoregional and distant
  • 95. Breast Cancer Stages: Natural History
  • 96. 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.
  • 97. • 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.
  • 98. 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
  • 99. 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.
  • 100. • 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.
  • 101. • 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.
  • 102. PATHOLOGY • Lobular carcinoma in situ • Ductal carcinoma in situ • Invasive breast carcinoma – Invasive ductal – 70 % of cases – Invasice lobular carcinoma – Other special types
  • 103. DIAGNOSIS • History • Physical examination – Inspection • Assymetry • Dimpling • Retraction • Ulcers – Palpation • Mass • Nipple discharge
  • 104. 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)
  • 105. 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.
  • 106. • 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.
  • 108. Imaging techniques • Mammography – Recommended: • Annually starting at age 40 • Earlier for those with strong family history
  • 110. Stellate lesion with malignant calcification. In addition there is inversion of the nipple and adjacent skin thickening.
  • 111. • Ultrasound – Solid – Cystic – Borders • Ductography • MRI
  • 112. Breast Ultrasound): Poorly circumscribed region of increased echogenicity on ultrasound consistent with Breast cancer.
  • 113. (Breast MRI): MRI images depicting a breast cancer
  • 114. Definitive diagnosis • FNAB • CORE NEEDLE BIOPSY • OPEN BIOPSY
  • 115. Diagnosis of Breast Cancer 1Fine Needle Aspiration Biopsy 2Open Biopsy
  • 116. STAGING • T – tumor size • N- Nodal status – Sentinel lymph node • M – Distant metastasis – Lungs – Liver – Bones
  • 117. Breast Cancer Stages Please refer to your text book for further detail Table 16-11
  • 118. 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
  • 119. 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
  • 120.
  • 121. Adjuvant therapy • Chemotherapy – For tumors more than 2 cms – Positive lymph nodes • Radiation therapy – For DCIS – For breast conservation – For advance staged disease
  • 122. Hormonal therapy • SERMS: Selective estrogen modulators – Tamoxifen – 5 years – Aromatase inhibitors • Ablative endocrine therapy – Oophorectomy • Given to ER / PR positive tumors
  • 123. Immune / antibody therapy • Traztuzumab – For her2/neu positive tumors
  • 124. 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%.
  • 125. 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.
  • 126. Can be benign or malignant
  • 127. Please read on the following topics • Inflammatory breast cancer • Male breast cancer
  • 128. Breast cancer screening and prevention methods Early detection is the key to cure
  • 129. Early Detection Measures • MONTHLY breast self examination by age 20 • YEARLY health worker breast examination by age 30 • YEARLY mammogram by age 40