Anatomy
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The breast is composed of 15–20 lobes, which are each composed of several
lobules.
Each lobe of the breast terminates in a major (lactiferous) duct (2–4 mm in
diameter), which opens through a constricted orifice (0.4–0.7 mm in diameter) into the ampulla of the nipple.
Fibrous bands of connective tissue travel through the breast (suspensory
ligaments of Cooper), which insert perpendicularly into the dermis and
provide structural support.
The axillary tail of Spence extends laterally across the anterior axillary fold.
The upper outer quadrant of the breast contains a greater volume of tissue
than do the other quadrants.
BLOOD SUPPLY, INNERVATION
• Blood supply, innervation, and lymphatics. The breast receives its blood
supply from (1) perforating branches of the internal mammary artery; (2)
lateral branches of the posterior intercostal arteries; and (3) branches
from the axillary artery, including the highest thoracic, lateral thoracic, and
pectoral branches of the thoracoacromial artery.
• The veins and lymph vessels of the breast follow the course of the arteries
with venous drainage being toward the axilla. The vertebral venous plexus
of Batson, which invests the vertebrae and extends from the base of the
skull to the sacrum, can provide a
route for breast cancer metastases
to the vertebrae, skull, pelvic bones,
and central nervous system.
• Lateral cutaneous branches of the third through
sixth intercostal nerves provide sensory
innervation of the breast (lateral mammary
branches) and of the anterolateral chest wall.
• The intercostobrachial nerve is the lateral
cutaneous branch of the second intercostal nerve
and may be visualized during surgical dissection
of the axilla.
• Resection of the intercostobrachial nerve causes
loss of sensation over the medial aspect of the
upper arm.
LYMPHATICS
• The boundaries for lymph drainage of the axilla are not well
demarcated, and there is considerable variation in the position of
the axillary lymph nodes.
• The 6 axillary lymph node groups recognized by surgeons are (1) the
axillary vein group (lateral); (2) the external mammary group
(anterior or pectoral); (3) the scapular group (posterior or
subscapular); (4) the central group; (5) the subclavicular group
(apical); and (6) the interpectoral group (Rotter’s).
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The lymph node groups are assigned levels according to their relationship to the pectoralis
minor muscle.
Lymph nodes located lateral to or below the lower border of the pectoralis minor muscle are
referred to as level I lymph nodes, which include the axillary vein, external mammary, and
scapular groups.
Lymph nodes located superficial or deep to the pectoralis minor muscle are referred to as
level II lymph nodes, which include the central and interpectoral groups.
Lymph nodes located medial to or above the upper border of the pectoralis minor muscle are
referred to as level III lymph nodes, which make up the subclavicular group.
The axillary lymph nodes usually receive more than 75 percent of the lymph drainage from
the breast.
Selected Benign Breast Disorders and Diseases
CYSTS
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Cysts: In practice, the first investigation of palpable breast masses is frequently
needle biopsy, which allows for the early diagnosis of cysts. A 21-gauge needle
attached to a 10-mL syringe is placed directly into the mass. The volume of a
typical cyst is 5–10 mL, but it may be 75 mL or more.
If the fluid that is aspirated is not bloodstained, then the cyst is aspirated to
dryness, the needle is removed, and the fluid is discarded as cytologic examination
of such fluid is not cost-effective. After aspiration, the breast is carefully palpated
to exclude a residual mass. If one exists, ultrasound examination is performed to
exclude a persistent cyst, which is reaspirated if present.
If the mass is solid, a tissue specimen is obtained.
When cystic fluid is bloodstained, 2 mL of fluid are taken for cytology.
The mass is then imaged with ultrasound and any solid area on the cyst wall is
biopsied by needle.
The two cardinal rules of safe cyst aspiration are (1) the mass must disappear
completely after aspiration, and (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.
Selected Benign Breast Disorders and Diseases
FIBROADENOMAS
• 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 fibroade- nomas 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.
Selected Benign Breast Disorders and Diseases
SCLEROSING DISORDERS
• Sclerosing Disorders: The clinical significance of sclerosing
adenosis lies in its mimicry of cancer.
• It may be confused with cancer on physical exam- ination,
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, hence
biopsy is recommended.
Selected Benign Breast Disorders and Diseases
PERIDUCTAL MASTITIS
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Periductal Mastitis: Painful and tender masses behind the nipple-areola complex
are aspirated with a 21-gauge needle attached to a 10-mL syringe.
Any fluid obtained is submitted for cytology and for culture using a trans- port
medium appropriate for the detection of anaerobic organisms.
Women are started on a combination of metronidazole and dicloxacillin while
awaiting the results of culture.
A subareolar abscess usually is unilocular and often is associated with a single duct
system. Preoperative ultrasound will accurately delineate its extent
The surgeon may either undertake simple drainage with a view toward formal
surgery, should the problem recur, or proceed with definitive surgery.
In a woman of childbearing age, simple drainage is preferred, but if there is an
anaerobic infection, recurrent infection frequently develops.
Recurrent abscess with fistula is a difficult problem and may be treated by
fistulectomy or by major duct excision, depending on the circumstances.
Antibiotic therapy is useful for recurrent infection after fistula excision, and a 2–4week course is recommended prior to total duct excision.
Selected Benign Breast Disorders and Diseases
NIPPLE INVERSION
• Nipple Inversion: More women request
correction of congenital nipple inversion than
request correction for the nipple inversion that
occurs secondary to duct ectasia.
• surgical complications of altered nipple sensation,
nipple necrosis, and postoperative fibrosis with
nipple retraction.
• Because nipple inversion is a result of shortening
of the subareolar ducts, a complete division of
these ducts is necessary for permanent
correction of the disorder.
INFECTIOUS AND INFLAMMATORY DISORDERS OF THE
BREAST
Bacterial Infection
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Bacterial infection. 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.
Progression of a staphylococcal infection may result in subcutaneous, sub- areolar, interlobular
(periductal), and retromammary abscesses (unicentric or multicentric),
necessitating operative drainage of fluctuant areas.
Preoperative ultrasonography is effective in delineating the extent of the needed drainage
procedure, which is best accomplished via circumareolar incisions or incisions paralleling Langer
lines.
Although staphylococcal infections tend to be more localized and may be located deep in the breast
tissues, streptococcal infections usually present with diffuse superficial involvement.
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.
INFECTIOUS AND INFLAMMATORY DISORDERS OF THE
BREAST
Hidradenitis Suppurativa
• Hidradenitissuppurativa. Hidradenitis suppurativa of the nippleareolacomplex or axilla is a chronic inflammatory condition that
originates within the accessory areolar glands of Montgomery or
within the axillary sebaceous glands.
• When located in and about the nipple-areola complex, this disease
may mimic other chronic inflammatory states, Paget disease of the
nipple, or invasive breast cancer.
• Involvement of the axillary skin is often multifocal and contiguous.
• Antibiotic therapy with incision and drainage of fluctuant areas is
appropriate treatment.
• Complete excision of the involved areas may be required and may
necessitate coverage with advancement flaps or split-thickness skin
grafts.
INFECTIOUS AND INFLAMMATORY DISORDERS OF THE
BREAST
Mondor's Disease
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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.
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.
Most women have no evidence of thrombophlebitis in other anatomic sites.
When the diagnosis is uncertain, or when a mass is present near the tender cord,
biopsy is indicated.
Therapy for Mondor disease includes the liberal use of antiinflammatory
medications and warm compresses that are applied along the symptomatic vein.
Restriction of motion of the ipsilateral extremity and shoulder and brassiere
support of the breast are important.
The process usually resolves within 4–6 weeks. When symptoms persist or are
refractory to therapy, excision of the involved vein segment is appropriate.
RISK FACTORS FOR BREAST
CANCER
Hormonal 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.
• 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
RISK FACTORS FOR BREAST
CANCER
• Nonhormonal Risk Factors
• Radiation (radiation therapy for Hodgkin's
lymphoma have a breast cancer risk that is 75
times greater)
• Studies also suggest that the risk of breast
cancer increases as the amount of alcohol a
woman consumes increases.
• high fat content diet
Risk Assessment
• The average lifetime risk of breast cancer for
newborn U.S. females is 12%.
• A software program incorporating the Gail
model is available from the National Cancer
Institute at http://bcra.nci.nih.gov/brc.
• Claus and colleagues
Factors Associated with Increased
Risk of Breast Cancer
• White
• Older
• Family history; Breast cancer in mother, sister, or daughter (especially
bilateral or premenopausal)
• BRCA1 or BRCA2 mutation
• Endometrial cancer
• Proliferative forms of fibrocystic disease
• Cancer in other breast
• Early menarche (under age 12)
• Late menopause (after age 50)
• Nulliparous or late first pregnancy
screening mammography
• Routine use of screening mammography in women 50 years of age
reduces mortality from breast cancer by 33%.
• This reduction comes without substantial risks and at an acceptable
economic cost.
• However, the use of screening mammography in women <50 years of age
is more controversial for several reasons: (a) breast density is greater and
screening mammography is less likely to detect early breast cancer; (b)
screening mammography results in more false-positive test findings, which
results in unnecessary biopsies; and (c) younger women are less likely to
have breast cancer, so fewer young women will benefit from screening.
• Current recommendations are that women undergo baseline
mammography at age 35 and then have annual mammographic screening
beginning at age 40.
Incidence of Sporadic, Familial, and Hereditary
Breast Cancer
• Sporadic breast cancer 65–75%
• Familial breast cancer 20–30%
• Hereditary breast cancer 5–10%
 BRCA1 a 45%
 BRCA2 35%
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p53a (Li-Fraumeni syndrome) 1%
STK11/LKB1a (Peutz-Jeghers syndrome) <1%
PTENa (Cowden disease) <1%
MSH2/MLH1a (Muir-Torre syndrome) <1%
ATMa (Ataxia-telangiectasia) <1%
Unknown 20%
 Both BRCA1 and BRCA2 function as tumor-suppressor genes, and for each gene, loss of both
alleles is required for the initiation of cancer.
BRCA Mutations
BRCA1
• Five to 10% of breast cancers are caused by inheritance of
germline mutations such as BRCA1 and BRCA2, which are
inherited in an autosomal dominant fashion with varying
penetrance
• BRCA1 is located on chromosome arm 17q, spans a genomic
region of approximately 100 kilobases (kb) of DNA, and
contains 22 coding exons
• Data accumulated since the isolation of the BRCA1 gene
suggest a role in transcription, cell-cycle control, and DNA
damage repair pathways.
• More than 500 sequence variations in BRCA1 have been
identified.
• predisposing genetic factor in as many as 45%
of hereditary breast cancers and in at least
80% of hereditary ovarian cancers.
• Female mutation carriers have up to a 90%
lifetime risk for developing breast cancer and
up to a 40% lifetime risk for developing
ovarian cancer
• Approximately 50% of children of carriers
inherit the trait.
• In general, BRCA1-associated breast cancers are
invasive ductal carcinomas, are poorly differentiated,
and are hormone receptor negative.
• BRCA1-associated breast cancers have a number of
distinguishing clinical features, such as an early age
of onset compared with sporadic cases; a higher
prevalence of bilateral breast cancer; and the
presence of associated cancers in some affected
individuals, specifically ovarian cancer and possibly
colon and prostate cancers.
BRCA2
• BRCA2 is located on chromosome arm 13q and spans
a genomic region of approximately 70 kb of DNA. The
11.2-kb coding region contains 26 coding exons
• The biologic function of BRCA2 is not well defined,
but like BRCA1, it is postulated to play a role in DNA
damage response pathways.
• BRCA2 messenger RNA also is expressed at high
levels in the late G1 and S phases of the cell cycle.
• The mutational spectrum of BRCA2 is not as well
established as that of BRCA1. To date, >250
mutations have been found
• The breast cancer risk for BRCA2 mutation carriers is close to
85%, and the lifetime ovarian cancer risk, while lower than for
BRCA1, is still estimated to be close to 20%.
• Breast cancer susceptibility in BRCA2 families is an autosomal
dominant trait and has a high penetrance.
• Approximately 50% of children of carriers inherit the trait.
• Unlike male carriers of BRCA1 mutations, men with germline
mutations in BRCA2 have an estimated breast cancer risk of
6%, which represents a 100-fold increase over the risk in the
general male population.
• BRCA2- associated breast cancers are invasive ductal carcinomas, which
are more likely to be well differentiated and to express hormone receptors
than are BRCA1-associated breast cancers.
• BRCA2-associated breast cancer has a number of distinguishing clinical
features, such as an early age of onset compared with sporadic cases, a
higher prevalence of bilateral breast cancer, and the presence of
associated cancers in some affected individuals, specifically ovarian, colon,
prostate, pancreatic, gallbladder, bile duct, and stomach cancers, as well
as melanoma.
• The 6174delT mutation is found in Ashkenazi Jews with a prevalence of
1.2%. Another BRCA2 founder mutation, 999del5, is observed in Icelandic
and Finnish populations.
CANCER PREVENTION FOR BRCA
MUTATION CARRIERS
• Risk management strategies for BRCA1 and BRCA2
mutation carriers include the following:
1. Prophylactic mastectomy and reconstruction
2. Prophylactic oophorectomy and hormone
replacement therapy
3. Intensive surveillance for breast and ovarian cancer
4. Chemoprevention
Chemoprevention
• Despite a 49% reduction in the incidence of breast cancer in high-risk
women taking tamoxifen, it is too early to recommend the use of
tamoxifen uniformly for BRCA mutation carriers.
• Cancers arising in BRCA1 mutation carriers are usually high grade and are
most often hormone receptor negative.
• Approximately 66% of BRCA1-associated DCIS lesions are estrogen
receptor negative, which suggests early acquisition of the
hormoneindependent phenotype. Tamoxifen appears to be more effective
at preventing estrogen receptor–positive breast cancers.
EPIDEMIOLOGY AND NATURAL
HISTORY OF BREAST CANCER
• Breast cancer is the most common sitespecific cancer in women and is the leading
cause of death from cancer for women aged
20 to 59 years
PRIMARY BREAST CANCER
• More than 80% of breast cancers show
productive fibrosis that involves the epithelial
and stromal tissues.
• With growth of the cancer and invasion of the surrounding
breast tissues, the accompanying desmoplastic response
entraps and shortens Cooper's suspensory ligaments 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
AXILLARY LYMPH NODE
METASTASES
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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.
the most important prognostic
correlate of disease-free and overall
survival is axillary lymph node status
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.
• Common sites of involvement, in order of frequency, are bone, lung,
pleura, soft tissues, and liver.
HISTOPATHOLOGY OF BREAST
CANCER
• Carcinoma in Situ
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2.
LOBULAR CARCINOMA IN SITU
DUCTAL CARCINOMA IN SITU
• Invasive Breast Carcinoma
1. Paget's disease of the nipple
2. Invasive ductal carcinoma
3. Adenocarcinoma with productive fibrosis (scirrhous, simplex, NST), 80% (invasive ductal
carcinoma of no special type)
4. Medullary carcinoma, 4%
5. Mucinous (colloid) carcinoma, 2%
6. Papillary carcinoma, 2%
7. Tubular carcinoma, 2%
8. Invasive lobular carcinoma, 10%
9. Rare cancers (adenoid cystic, squamous cell, apocrine)
Carcinoma in Situ
• Cancer cells are in situ or invasive depending on whether or not they
invade through the basement membrane
• Foote and Stewart published a landmark description of LCIS, which
distinguished it from DCIS
• In the late 1960s, Gallagher and Martin published their study of wholebreast sections and described a stepwise progression from benign breast
tissue to in situ cancer and subsequently to invasive cancer. They coined
the term minimal breast cancer (LCIS, DCIS, and invasive cancers smaller
than 0.5 cm in size) and stressed the importance of early detection
• It is now recognized that each type of minimal breast cancer has a distinct
clinical and biologic behavior.
Lobular Carcinoma In Situ
• LCIS originates from the terminal duct lobular units and develops
only in the female breast. It is characterized by distention and
distortion of the terminal duct lobular units
• LCIS may be observed in breast tissues that contain
microcalcifications, but the calcifications associated with LCIS
typically occur in adjacent tissues. This neighborhood calcification is
a feature that is unique to LCIS and contributes to its diagnosis.
• The frequency of LCIS in the general population cannot be reliably
determined because it usually presents as an incidental finding.
• The average age at diagnosis is 45 years, which is approximately 15
to 25 years younger than the age at diagnosis for invasive breast
cancer.
Lobular Carcinoma In Situ
• Invasive breast cancer develops in 25% to 35% of women with LCIS.
• Invasive cancer may develop in either breast, regardless of which
breast harbored the initial focus of LCIS, and is detected
synchronously with LCIS in 5% of cases.
• In women with a history of LCIS, up to 65% of subsequent invasive
cancers are ductal, not lobular, in origin. For these reasons, LCIS is
regarded as a marker of increased risk for invasive breast cancer
rather than as an anatomic precursor.
• Individuals should be counseled regarding their risk of developing
breast cancer and appropriate risk reduction strategies, including
observation with screening, chemoprevention, and risk-reducing
bilateral mastectomy.
Ductal Carcinoma In Situ.
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Published series suggest a detection frequency of 7% in all biopsy tissue
specimens.
DCIS, which carries a high risk for progression to an invasive cancer.
Histologically, DCIS is characterized by a proliferation of the epithelium that
lines the minor ducts, resulting in papillary growths within the duct lumina.
papillary growth pattern, cribriform growth pattern, solid growth pattern,
comedo growth pattern,
Calcium deposition occurs in the areas of necrosis and is a common feature
seen on mammography.
*Figure From: The Breast. Schwartz's Principles of Surgery, 10e, 2014
Ductal Carcinoma In Situ.
• The risk for invasive breast cancer is increased
nearly fivefold in women with DCIS
• The invasive cancers are observed in the
ipsilateral breast, usually in the same quadrant
as the DCIS that was originally detected, which
suggests that DCIS is an anatomic precursor of
invasive ductal carcinoma
• DCIS is now frequently classified based on
nuclear grade and the presence of necrosis
Invasive Breast Carcinoma
• Invasive breast cancers have been described as lobular or ductal in
origin
• About 80% of invasive breast cancers are described as invasive
ductal carcinoma of no special type (NST). These cancers generally
have a worse prognosis than special-type cancers.
• Foote and Stewart originally proposed the following classification for
invasive breast cancer.
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Paget’s disease of the nipple
Invasive ductal carcinoma—Adenocarcinoma with productive fibrosis (scirrhous, simplex, NST), 80%
Medullary carcinoma, 4%
Mucinous (colloid) carcinoma, 2%
Papillary carcinoma, 2%
Tubular carcinoma, 2%
Invasive lobular carcinoma, 10%
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Rare cancers (adenoid cystic, squamous cell, apocrine)
Paget’s disease of the nipple
• Paget’s disease of the nipple was described in 1874.
• It frequently presents as a chronic, eczematous eruption of the nipple, which
may be subtle but may progress to an ulcerated, weeping lesion.
• Paget’s disease usually is associated with extensive DCIS and may be
associated with an invasive cancer.
• A palpable mass may or may not be present.
• A nipple biopsy specimen 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 cells) in the rete pegs of the epithelium. Paget’s disease may be
confused with superficial spreading melanoma. Differentiation from
pagetoid intraepithelial melanoma is based on the presence of S-100 antigen
immunostaining in melanoma and carcinoembryonic antigen
immunostaining in Paget’s disease.
• Surgical therapy for Paget’s disease may involve lumpectomy or mastectomy,
depending on the extent of involvement of the nipple-areolar complex and
the presence of DCIS or invasive cancer in the underlying breast
parenchyma.
Invasive ductal carcinoma
• Invasive ductal carcinoma of the breast with productive fibrosis
(scirrhous, simplex, NST) accounts for 80% of breast cancers and
presents with macroscopic or microscopic axillary lymph node
metastases in up to 25% of screen-detected cases and up to 60% of
symptomatic cases.
• This cancer occurs most frequently in perimenopausal or
postmenopausal women in the fifth to sixth decades of life as a
solitary, firm mass.
• It has poorly defined margins and its cut surfaces show a central
stellate configuration with chalky white or yellow streaks extending
into surrounding breast tissues.
• In a large patient series, 75% of ductal cancers showed estrogen
receptor expression.
Invasive lobular carcinoma
• Invasive lobular carcinoma accounts for 10% of breast cancers.
• Special stains may confirm the presence of intracytoplasmic mucin,
which may displace the nucleus (signet-ring cell carcinoma).
• At presentation, invasive lobular carcinoma varies from clinically
inapparent carcinomas to those that replace the entire breast with a
poorly defined mass.
• It is frequently multifocal, multicentric, and bilateral. Because of its
insidious growth pattern and subtle mammographic features,
invasive lobular carcinoma may be difficult to detect.
• Over 90% of lobular cancers express estrogen receptor.
DIAGNOSIS OF BREAST CANCER
• In~30% of cases, the woman discovers a lump in her breast. Other
less frequent presenting signs and symptoms of breast cancer
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(a) breast enlargement or asymmetry;
(b) nipple changes, retraction, or discharge;
(c) ulceration or erythema of the skin of the breast;
(d) an axillary mass; and
(e) musculoskeletal discomfort.
• Breast pain usually is associated with benign disease.
• Diagnosis of breast cancer;
• Examination
• Imaging Techniques; Mammography, Ductography, Ultrasonography, Magnetic Resonance
Imaging
• Breast Biopsy;
Examination
• Symmetry, size, and shape of the breast are
recorded, as well as any evidence of edema
(peaud’orange), nipple or skin retraction, or
erythema.
• Careful palpation of supraclavicular and
parasternal sites also is performed.
• A diagram of the chest and contiguous lymph
node sites is useful for recording location, size,
consistency, shape, mobility, fixation, and other
characteristics of any palpable breast mass or
lymphadenopathy
Imaging Techniques;
Mammography
• Mammography has been used in North America since the 1960s
• Conventional mammography delivers a radiation dose of 0.1 cGy per study.
By comparison, chest radiography delivers 25% of this dose. However, there
is no increased breast cancer risk associated with the radiation dose
delivered with screening mammography.
• Screening mammography is used to detect unexpected breast cancer in
asymptomatic women. In this regard, it supplements history taking and
physical examination.
• With screening mammography, two views of the breast are obtained, the
craniocaudal (CC) view and the mediolateral oblique (MLO) view. The MLO
view images the greatest volume of breast tissue, including the upper outer
quadrant and the axillary tail of Spence.
• Compared with the MLO view, the CC view provides better visualization of
the medial aspect of the breast and permits greater breast compression.
• Diagnostic mammography is used to evaluate women with abnormal
findings such as a breast mass or nipple discharge.
Imaging Techniques;
Mammography
• Spot compression may be done in any projection by using a small
compression device, which is placed directly over a mammographic
abnormality that is obscured by overlying tissues.
• The compression device minimizes motion artifact, improves
definition, separates overlying tissues, and decreases the radiation
dose needed to penetrate the breast.
• Magnification techniques (×1.5) often are combined with spot
compression to better resolve calcifications and the margins of
masses.
• Mammography also is used to guide interventional procedures,
including needle localization and needle biopsy.
• Specific mammographic features that suggest a diagnosis of breast
cancer include a solid mass with or without stellate features,
asymmetric thickening of breast tissues, and clustered
microcalcifications
Imaging Techniques;
Mammography
• These microcalcifications are an especially important sign of cancer in
younger women, in whom it may be the only mammographic
abnormality.
• The clinical impetus for screening mammography came from the
Health Insurance Plan study and the Breast Cancer Detection
Demonstration Project, which demonstrated a 33% reduction in
mortality for women after screening mammography.
• Current guidelines of the National Comprehensive Cancer Network
suggest that normal-risk women ≥20 years of age should have a
breast examination at least every 3 years.
• Starting at age 40 years, breast examinations should be performed
yearly and a yearly mammogram should be taken.
• The benefits from screening mammography in women ≥50 years of
age has been noted above to be between 20% and 25% reduction in
breast cancer mortality
Imaging Techniques;
Mammography
• The use of screening mammography in women <50 years of age is
more controversial again for reasons noted above: (a) reduced
sensitivity; (b) reduced specificity; and (c) lower incidence of breast
cancer.
• For the combination of these three reasons targeting mammography
screening to women <50 years at higher risk of breast cancer
improves the balance of risks and benefits and is the approach some
health care systems have taken.
Imaging Techniques;
Ductography
• The primary indication for ductography is nipple discharge,
particularly when the fluid contains blood.
• Radiopaque contrast media is injected into one or more of the major
ducts and mammography is performed.
• A duct is gently enlarged with a dilator and then a small, blunt
cannula is inserted under sterile conditions into the nipple ampulla.
• With the patient in a supine position, 0.1 to 0.2 mL of dilute contrast
media is injected and CC and MLO mammographic views are
obtained without compression.
• Intraductal papillomas are seen as small filling defects surrounded by
contrast media.
• Cancers may appear as irregular masses or as multiple intraluminal
filling defects.
Imaging Techniques;
Ultrasonography
• Second only to mammography in frequency of use for breast imaging,
ultrasonography is an important method of resolving equivocal
mammographic findings, defining cystic masses, and demonstrating
the echogenic qualities of specific solid abnormalities.
• Benign breast masses usually show smooth contours, round or oval
shapes, weak internal echoes, and well-defined anterior and
posterior margins. Breast cancer characteristically has irregular walls
but may have smooth margins with acoustic enhancement.
• Ultrasonography is used to guide fine-needle aspiration biopsy, coreneedle biopsy, and needle localization of breast lesions.
• Ultrasonography can also be utilized to image the regional lymph
nodes in patients with breast cancer.
Imaging Techniques;
Magnetic Resonance Imaging
• In the process of evaluating magnetic resonance imaging (MRI) as a means
of characterizing mammographic abnormalities, additional breast lesions
have been detected. However, in the circumstance of negative findings on
both mammography and physical examination, the probability of a breast
cancer being diagnosed by MRI is extremely low.
• There is current interest in the use of MRI to screen the breasts of high-risk
women and of women with a newly diagnosed breast cancer. 1) women who
have a strong family history of breast cancer or who carry known genetic
mutations require screening at an early age, because mammographic
evaluation is limited due to the increased breast density in younger women.
2) an MRI study of the contralateral breast in women with a known breast
cancer has shown a contralateral breast cancer in 5.7% of these women.
• MRI can also detect additional tumors in the index breast (multifocal or
multicentric disease) that may be missed on routine breast imaging and this
may alter surgical decision making. In fact, MRI has been advocated by some
for routine use in surgical treatment planning based on the fact that
additional disease can be identified with this advanced imaging modality and
the extent of disease may be more accurately assessed.
Breast Biopsy, Nonpalpable Lesions.
• Image-guided breast biopsy specimens are frequently required to
diagnose nonpalpable lesions.
• Ultrasound localization techniques are used when a mass is present,
whereas stereotactic techniques are used when no mass is present
(microcalcifications or architectural distortion only).
• The combination of diagnostic mammography, ultrasound or
stereotactic localization, and fine-needle aspiration (FNA) biopsy
achieves almost 100% accuracy in the preoperative diagnosis of
breast cancer.
• The advantages of core-needle biopsy include a low complication
rate, minimal scarring, and a lower cost compared with excisional
breast biopsy.
Breast Biopsy, Palpable Lesions.
• FNA or core biopsy of a palpable breast mass can usually be performed in an
outpatient setting.
• A 1.5-in, 22-gauge needle attached to a 10-mL syringe or a 14 gauge core
biopsy needle is used.
• The cellular material is then expressed onto microscope slides. Both airdried and 95% ethanol–fixed microscopic sections are prepared for analysis
• Automated devices also are available. Vacuum assisted core biopsy devices
(with 8–10 gauge needles) are commonly utilized with image guidance
where between 4 and 12 samples can be acquired at different positions
within a mass, area of architectural distortion or microcalcifications. If the
target lesion was microcalcifications, the specimen should be radiographed
to confirm appropriate sampling. A radiopaque marker should be placed at
the site of the biopsy to mark the area for future intervention
• Tissue specimens are placed in formalin and then processed to paraffin
blocks
Examination
• INSPECTION
• PALPATION
BREAST CANCER STAGING
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The clinical stage of breast cancer is determined primarily through physical
examination of the skin, breast tissue, and regional lymph nodes (axillary,
supraclavicular, and cervical).
Mammography, chest radiography, and intraoperative findings (primary tumor size,
chest wall invasion) also provide necessary staging information.
Pathologic stage combines the findings from pathologic examination of the
resected primary breast cancer and axillary or other regional lymph nodes.
A frequently used staging system is the TNM (tumor, nodes, and metastasis)
system.
The single most important predictor of 10- and 20-year survival rates in breast
cancer is the number of axillary lymph nodes involved with metastatic disease.
Routine biopsy of internal mammary lymph nodes is not generally performed;
however, with the advent of sentinel lymph node dissection and the use of
preoperative lymphoscintigraphy for localization of the sentinel nodes, surgeons
have begun to biopsy the internal mammary nodes in some cases
SURGICAL TECHNIQUES IN BREAST
CANCER THERAPY
• Breast Conservation
• Mastectomy and Axillary Dissection
• MODIFIED RADICAL MASTECTOMY
Breast Conservation
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Breast conservation involves resection of the primary breast cancer with a margin
of normal-appearing breast tissue, adjuvant radiation therapy, and assessment of
regional lymph node status.
Resection of the primary breast cancer is alternatively called segmental
mastectomy, lumpectomy, partial mastectomy, wide local excision, and tylectomy.
For many women with stage I or II breast cancer, breast-conserving therapy (BCT)
is preferable to total mastectomy because BCT produces survival rates equivalent
to those after total mastectomy while preserving the breast
BCT allows for preservation of breast shape and skin as well as preservation of
sensation, and provides an overall psychologic advantage associated with breast
preservation.
Breast conservation surgery is currently the standard treatment for women with
stage 0, I, or II invasive breast cancer. Women with DCIS require only resection of
the primary cancer and adjuvant radiation therapy without assessment of regional
lymph nodes.
Sentinel lymph node dissection is now the preferred staging procedure with a
clinically node-negative axilla
Oncoplastic techniques are of
prime consideration when
(a) a significant area of breast skin will need to be resected with
the specimen to achieve negative margins;
(b) a large volume of
breast parenchyma will be resected resulting in a significant
defect;
(c) the tumor is located between the nipple and the
inframammary fold, an area often associated with unfavorable
cosmetic outcomes; or
(d) excision of the tumor and closure of the breast may result in
malpositioning of the nipple.
Mastectomy and Axillary
Dissection
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A skin-sparing mastectomy removes all breast tissue, the nipple-areola complex,
and scars from any prior biopsy procedures. There is a recurrence rate of less than
6 to 8%, comparable to the long-term recurrence rates reported with standard
mastectomy, when skin-sparing mastectomy is used for patients with T1 to T3
cancers.
A total (simple) mastectomy without skin sparing removes all breast tissue, the
nipple-areola complex, and skin.
An extended simple mastectomy removes all breast tissue, the nipple-areola
complex, skin, and the level I axillary lymph nodes.
The Halsted radical mastectomy removes all breast tissue and skin, the nippleareola complex, the pectoralis major and pectoralis minor muscles, and the level I,
II, and III axillary lymph nodes.
The use of systemic chemotherapy and hormonal therapy as well as adjuvant
radiation therapy for breast cancer have nearly eliminated the need for the radical
mastectomy.
MODIFIED RADICAL MASTECTOMY
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A modified radical mastectomy preserves both the pectoralis major and pectoralis
minor muscles, allowing removal of level I and level II axillary lymph nodes but not
the level III (apical) axillary lymph nodes
Anatomic boundaries of the modified radical mastectomy are the anterior margin
of the latissimus dorsi muscle laterally, the midline of the sternum medially, the
subclavius muscle superiorly, and the caudal extension of the breast 2 to 3 cm
inferior to the inframammary fold inferiorly
• The most lateral extent of the axillary vein is identified and
the areolar tissue of the lateral axillary space is elevated as
the vein is cleared on its anterior and inferior surfaces.
• The long thoracic nerve of Bell is identified and preserved as it
travels in the investing fascia of the serratus anterior muscle.
Every effort is made to preserve this nerve, because
permanent disability with a winged scapula and shoulder
weakness will follow denervation of the serratus anterior
muscle.
• Care is taken to preserve the thoracodorsal neurovascular
bundle.
In Situ Breast Cancer (Stage 0)
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Both LCIS and DCIS may be difficult to distinguish from atypical hyperplasia or from
cancers with early invasion. Expert pathologic review is required in all cases.
Bilateral mammography is performed to determine the extent of the in situ cancer
and to exclude a second cancer. Because LCIS is considered a marker for increased
risk rather than an inevitable precursor of invasive disease, the current treatment
options for LCIS include observation, chemoprevention with tamoxifen, and
bilateral total mastectomy.
There is no benefit to excising LCIS, because the disease diffusely involves both
breasts
in many cases and the risk of invasive cancer is equal for both breasts. The use of
tamoxifen as a risk reduction strategy should
be considered in women with a diagnosis of LCIS.
In Situ Breast Cancer (Stage 0)
• Women with DCIS and evidence of extensive disease (>4 cm of disease or
disease in more than one quadrant) usually require mastectomy.
• For women with limited disease, lumpectomy and radiation therapy are
recommended.
• For nonpalpable DCIS, needle localization techniques are used to guide the
surgical resection. Specimen mammography is performed to ensure that
all visible evidence of cancer is excised
• The gold standard against which breast conservation therapy for DCIS is
evaluated is mastectomy. Women treated with mastectomy have local
recurrence and mortality rates of <2%. Women treated with lumpectomy
and adjuvant radiation therapy have a similar mortality rate, but the local
recurrence rate increases to 9%.
• Forty-five percent of these recurrences will be invasive cancer when
radiation therapy is not used.
Early Invasive Breast Cancer
(Stage I, IIA, or IIB)
• the disease-free, distant disease-free, and overall
survival rates for lumpectomy with or without
radiation therapy were similar to those observed
after total mastectomy.
• However, the incidence of ipsilateral breast cancer
recurrence (in-breast recurrence) was higher in the
lumpectomy group not receiving radiation therapy.
(39.2% & 14.3%)
• These findings supported the use of lumpectomy and
radiation therapy in the treatment of stage I and II
breast cancer.
• Currently, mastectomy with assessment of axillary
lymph node status and breast conserving surgery
with assessment of axillary lymph node status and
radiation therapy are considered equivalent
treatments for patients with stage I and II breast
cancer.
• Axillary lymphadenopathy confirmed to be
metastatic disease or metastatic disease in a sentinel
lymph node necessitates an axillary lymph node
dissection.
Relative contraindications to breast
conservation therapy
• (a) prior radiation therapy to the breast or
chest wall,
• (b) involved surgical margins or unknown
margin status after re-excision,
• (c) multicentric disease, and
• (d) scleroderma or lupus erythematosus.
• Traditionally, dissection of the level I and II axillary lymph
nodes has been performed in early invasive breast cancer.
• Sentinel lymph node dissection is now considered the
standard for evaluation of the axillary lymph node status in
women who have clinically negative lymph nodes.
• Candidates for this procedure have clinically uninvolved
axillary lymph nodes with a T1 or T2 primary breast cancer.
Controversy remains about the suitability of sentinel node
dissection in women with larger primary tumors (T3) and
those treated with neoadjuvant chemotherapy
Advanced Local-Regional Breast
Cancer (Stage IIIA or IIIB)
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Women with stage IIIA and IIIB breast cancer have
advanced local-regional breast cancer but have no
clinically detected distant metastases.
surgery is integrated with radiation therapy and
chemotherapy
Surgical therapy for women with stage III disease is
usually a modified radical mastectomy, followed by
adjuvant radiation therapy. Chemotherapy is used to
maximize distant disease-free survival, whereas
radiation therapy is used to maximize local-regional
disease-free survival. In selected patients with stage
IIIA cancer, neoadjuvant (preoperative)
chemotherapy can reduce the size of the primary
cancer and permit breast-conserving surgery.
Distant Metastases (Stage IV)
• Treatment for stage IV breast cancer is not curative but may prolong
survival and enhance a woman's quality of life
• Hormonal therapies that are associated with minimal toxicity are
preferred to cytotoxic chemotherapy.
• Appropriate candidates for initial hormonal therapy include women with
hormone receptor–positive cancers; women with bone or soft tissue
metastases only; and women with limited and asymptomatic visceral
metastases.
• Systemic chemotherapy is indicated for women with hormone receptor–
negative cancers, symptomatic visceral metastases, and hormonerefractory metastases.
SPECIAL CLINICAL SITUATIONS
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Nipple Discharge
 UNILATERAL NIPPLE DISCHARGE
 BILATERAL NIPPLE DISCHARGE
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Axillary Lymph Node Metastases in the Setting of an Unknown Primary Cancer
Breast Cancer during Pregnancy
Male Breast Cancer
Phyllodes Tumors
Inflammatory Breast Carcinoma
Rare Breast Cancers
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SQUAMOUS CELL (EPIDERMOID) CARCINOMA
ADENOID CYSTIC CARCINOMA
APOCRINE CARCINOMA
SARCOMAS
LYMPHOMAS
Nipple Discharge
UNILATERAL NIPPLE DISCHARGE
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Nipple discharge is a finding that can be seen in a number of clinical situations.
It may be suggestive of cancer if it is spontaneous, unilateral, localized to a single
duct, present in women 40 years of age, bloody, or associated with a mass
mammography and ultrasound are indicated for further evaluation.
A ductogram also can be useful and is performed by cannulating a single
discharging duct with a small nylon catheter or needle and injecting 1.0 mL of
watersoluble contrast solution.
Nipple discharge associated with a cancer may be clear, bloody, or serous. Testing
for the presence of hemoglobin is helpful, but hemoglobin may also be detected
when nipple discharge is secondary to an intraductal papilloma or duct ectasia.
Definitive diagnosis depends on excisional biopsy of the offending duct and any
associated mass lesion
Another approach is to inject methylene blue dye within the duct after
ductography.
Needle localization biopsy is performed when there is an associated mass that lies
>2.0 to 3.0 cm from the nipple.
Nipple Discharge
BILATERAL NIPPLE DISCHARGE
• Nipple discharge is suggestive of a benign condition if it is
bilateral and multiductal in origin, occurs in women 39 years
of age, or is milky or blue-green.
• Prolactin-secreting pituitary adenomas are responsible for
bilateral nipple discharge in <2% of cases.
• If serum prolactin levels are repeatedly elevated, plain
radiographs of the sella turcica are indicated and thin section
CT scan is required.
• Optical nerve compression, visual field loss, and infertility are
associated with large pituitary adenomas.
Axillary Lymph Node Metastases in the Setting of an
Unknown Primary Cancer
• A woman who presents with an axillary lymph node metastasis that is
consistent with a breast cancer metastasis has a 90% probability of
harboring an occult breast cancer
• However, axillary lymphadenopathy is the initial presenting sign in only 1%
of breast cancer patients.
• Fine-needle aspiration biopsy, core-needle biopsy, or open biopsy of an
enlarged axillary lymph node is performed to confirm metastatic disease.
• When metastatic cancer is found, immunohistochemical analysis may
classify the cancer as epithelial, melanocytic, or lymphoid in origin.
• The presence of hormone receptors (estrogen or progesterone receptors)
suggests metastasis from a breast cancer but is not diagnostic.
Axillary Lymph Node Metastases in the Setting of an
Unknown Primary Cancer
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The search for a primary cancer includes careful examination of the thyroid,
breast, and pelvis, including the rectum.
The breast should be examined with diagnostic mammography, ultrasonography,
and MRI to evaluate for an occult primary lesion.
Further radiologic and laboratory studies should include chest radiography and
liver function studies. Chest, abdominal, and pelvic CT scans also are indicated, as
is a bone scan to rule out distant metastasis.
Suspicious findings on mammography, ultrasonography, or MRI necessitate breast
biopsy.
When a breast cancer is found, treatment consists of an axillary lymph node
dissection with a mastectomy or preservation of the breast followed by wholebreast radiation therapy.
Chemotherapy and endocrine therapy should be considered.
Breast Cancer during Pregnancy
• Breast cancer occurs in 1 of every 3000 pregnant women, and axillary
lymph node metastases are present in up to 75% of these women
• The average age of the pregnant woman with breast cancer is 34 years.
• Fewer than 25% of the breast nodules developing during pregnancy and
lactation will be cancerous.
• Ultrasonography and needle biopsy are used in the diagnosis of these
nodules.
• Open biopsy may be required.
• Mammography is rarely indicated because of its decreased sensitivity
during pregnancy and lactation; however, the fetus can be shielded if
mammography is needed.
Breast Cancer during Pregnancy
• Approximately 30% of the benign conditions
encountered will be unique to pregnancy and
lactation (galactoceles, lobular hyperplasia,
lactating adenoma, and mastitis or abscess).
• Once a breast cancer is diagnosed, complete
blood count, chest radiography (with shielding
of the abdomen), and liver function studies
are performed.
Breast Cancer during Pregnancy
• Because of the potential deleterious effects of radiation
therapy on the fetus, radiation cannot be considered until the
fetus is delivered.
• A modified radical mastectomy can be performed during the
first and second trimesters of pregnancy, even though there is
an increased risk of spontaneous abortion after first-trimester
anesthesia.
• During the third trimester, lumpectomy with axillary node
dissection can be considered if adjuvant radiation therapy is
deferred until after delivery.
• Lactation is suppressed.
Breast Cancer during Pregnancy
• Chemotherapy administered during the first trimester carries a risk of
spontaneous abortion and a 12% risk of birth defects.
• There is no evidence of teratogenicity resulting from administration of
chemotherapeutic agents in the second and third trimesters.
• For this reason, many clinicians now consider the optimal strategy to be
delivery of chemotherapy in the second and third trimesters as a
neoadjuvant approach, which allows local therapy decisions to be made
after the delivery of the baby.
• Pregnant women with breast cancer often present at a later stage of
disease because breast tissue changes that occur in the hormone-rich
environment of pregnancy obscure early cancers.
• However, pregnant women with breast cancer have a prognosis, stage by
stage, that is similar to that of nonpregnant women with breast cancer.
Male Breast Cancer
• Fewer than 1% of all breast cancers occur in men.
• Breast cancer is rarely seen in young males and has a peak
incidence in the sixth decade of life.
• A firm, nontender mass in the male breast requires
investigation. Skin or chest wall fixation is particularly
worrisome.
• It is associated with radiation exposure, estrogen therapy,
testicular feminizing syndromes, and Klinefelter's syndrome
(XXY ).
• DCIS makes up <15% of male breast cancer, whereas
infiltrating ductal carcinoma makes up >85%.
Male Breast Cancer
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Male breast cancer is staged in the same way as female breast cancer, and stage by
stage, men with breast cancer have the same survival rate as women.
Overall, men do worse because of the advanced stage of their cancer (stage III or
IV) at the time of diagnosis.
The treatment of male breast cancer is surgical, with the most common procedure
being a modified radical mastectomy.
Sentinel node dissection has been shown to be feasible and accurate for nodal
assessment in men presenting with a clinically node-negative axillary nodal basin.
Adjuvant radiation therapy is appropriate in cases in which there is a high risk for
local-regional recurrence.
Eighty percent of male breast cancers are hormone receptor positive, and adjuvant
tamoxifen is considered.
Systemic chemotherapy is considered for men with hormone receptor–negative
cancers and for men with large primary tumors, multiple positive nodes, and
locally advanced disease.
Phyllodes Tumors
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These tumors are classified as
benign, borderline, or malignant.
Borderline tumors have a greater
potential for local recurrence.
Phyllodes tumors are usually sharply
demarcated from the surrounding
breast tissue, which is compressed
and distorted.
The stroma of a phyllodes tumor
generally has greater cellular activity
than that of a fibroadenoma.
Evaluation of the number of mitoses
and the presence or absence of
invasive foci at the tumor margins
may help to identify a malignant
tumor
Phyllodes Tumors
• Small phyllodes tumors are excised with a margin of
normal-appearing breast tissue. When the diagnosis
of a phyllodes tumor with suspicious malignant
elements is made, re-excision of the biopsy site to
ensure complete excision of the tumor with a 1-cm
margin of normal-appearing breast tissue is indicated
• Large phyllodes tumors may require mastectomy.
• Axillary dissection is not recommended because
axillary lymph node metastases rarely occur.
Inflammatory Breast Carcinoma
• Inflammatory breast carcinoma
(stage IIIB) accounts for <3% of
breast cancers.
• This cancer is characterized by
the skin changes of brawny
induration, erythema with a
raised edge, and edema (peau
d'orange)
• Permeation of the dermal lymph
vessels by cancer cells is seen in
skin biopsy specimens.
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The clinical differentiation of inflammatory breast cancer may be extremely
difficult, especially when a locally advanced scirrhous carcinoma invades dermal
lymph vessels in the skin to produce peau d'orange and lymphangitis
Inflammatory breast cancer also may be mistaken for a bacterial infection of the
breast. More than 75% of women who have inflammatory breast cancer present
with palpable axillary lymphadenopathy, and distant metastases also are
frequently present.
Surgery alone and surgery with adjuvant radiation therapy have produced
disappointing results in women with inflammatory breast cancer.
However, neoadjuvant chemotherapy with a doxorubicin-containing regimen may
effect dramatic regressions in up to 75% of cases. In this setting, modified radical
mastectomy is performed to remove residual cancer from the chest wall and axilla.
Adjuvant chemotherapy may be indicated depending on final pathologic
assessment of the breast and regional nodes.
Evaluation of breast masses in
premenopausal women
Evaluation of breast masses in
postmenopausal women
The simplest biopsy methods
• Needle biopsy (FNA cytology, Large-needle
(core needle) biopsy )
• Open biopsy
Incisional
Excisional