10/29/2011

FEMALE BREAST

BREAST
PATHOLOGY

Dr. Co-Fibra

Life Cycle Changes

Disorders of Breast Development

Milkline Remnants
Accesory Axillary Breast Tissue
Congenital Nipple Inversion

PERSISTENCE OF EPIDERMAL
Milkline Remnants THICKENINGS
MILKLINE
ALONG THE
Accessory Axillary Breast Tissue
Milklline Axilla to Perineum Supernumerary Breast
Ductal system extends into
SQ tissue of axillary Fossa
( Axillary Tail of Spence )

Undergo Lactational Change

May Develop Cancer

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Congenital Nipple Inversion

Simple Retraction to Evert Nipple Clinical Presentation

of Breast Disease

Common Clinical Symptoms of Breast

Pain
Disease
( Mastalgia / Mastodynia )
a) Common symptom
12%
Have Ca
b) Cyclic
7%
Have c) Noncyclic- Localized
Ca Pain a) Ruptured cyst
5% Have
Lumpiness b) Physical Injury
Cancer
Nipple Discharge
1% c) Infection
Palpable Mass
Have
Ca
Painfull Breast mass
95% are Benign
10% are Malignant

Discrete Palpable Mass

Lumpiness Mostly
Invasive Ca
Nodularity of the breast
Only 1% Have Cancer
Fibroadenoma
Cysts
At least 2cm in size
Incidence of Malignancy Higher
in Older Patients

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Location of Malignant Breast Mass Nipple Discharge

UOQ UIQ Less Common

Spontaneous & Unilateral Can be from Ca
50% 10% Small discharge Manipulation
20%
Central or
Milky ( galactorrhea ) High Prolactin
Subareolar Pituitary adenoma , Hypothyroidism
10% 10% Endocrine anovulatory syndromes
Oral drugs, Methydopa, Phenothiazines
LOQ LIQ

Nipple Discharge Bloody Nipple Discharge

Bloody / Serous Discharges
Commonly Benign
Duct Papilloma or Cyst
Pregnancy
Some are Malignant
Incidence Increases with Age
7% < 60y/o
30% >60y/o

Age Related Changes in Breast

Mammographic Screening

Sensitivity & Specificity

Increases with Age
Detect Average size 1.1 cm

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Principal Mammographic Signs of

Breast Cancer
Densities
Invasive Ca
Fibroadenoma
Cyst
Calcification
Form on secretions, necrosis, hyalinized stroma
Probably Malignant
Small / Irregular/ Numerous / Clustered
Cancer with Calcification only is rarely associated
with LN mets
Mammography

Carcinomas Missed by Mammography

Surrounding Radiodense Tissue
Especially in Young Women
Absence of Calcification ULTRASOUND
Small size
Diffuse Infiltrating Pattern w/ minimal Distinguish Solid vs Cystic Lesion
desmoplasia Define Border
Located close to chest wall or Periphery

MRI
Cancer cells has rapid uptake of Contrast
Media
More Vascularized INFLAMMATORY DISORDERS
Useful in screening Ca with Dense Breast
Det. Extent of Chest wall Invasion UNCOMMON
High rate of False Positive Results < 1% with Breast Symptoms
Limits its Usefulness Outside this group

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Clinical Manifestation Acute Mastitis

Erythematous Swollen Painful First Month of Breastfeeding

Breast Cracks/ Fissures
R/O Inflammatory Breast Ca Vulnerable to bacteria
Commonly Stap. aureus
in non lactating Woman Streptococci

Periductal Mastitis Periductal Mastitis

Recurrent Alveolar Abscess
Most (+) Inverted Nipple
90% are Smokers Depletes Vit A
Alter Ductal epithelial differentiation

Fat Necrosis TRAUMATIC FAT NECROSIS

History Breast Trauma / Prior Surgery
Painless Mass , Skin Thickening or
Retraction
Mammographic Density or Calcification
History Breast Trauma / Prior Surgery
Mammographic Density or Calcification
Painless Mass , Skin Thickening or Retraction
But Painful in Acute Stage
Skin Retraction Simulate Cancer
Microscopic:
Lipid Laden macrophages
Foreign body Giant cells
Fibrosis
Dystrophic calcification

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Benign Epithelial Lesions

3 GROUPS
1) Nonproliferative Breast
Changes
2) Proliferative Breast Changes
3) Atypical Hyperplasia

FIBROCYSTIC CHANGE
Most Common Breast Lump in Women
< 50y/o
Reproductive period 3 Morphologic Changes
Blue Dome Cysts
Size vary with menstruation
No Malignant Potential

CYSTS & FIBROSIS ADENOSIS

Increase in
number of
acini per
Lobule

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Normal Duct vs Epithelial Hyperplasia

Proliferating breast diseases

without atypia
Proliferation of Ductal
Epithelium/Stroma

EPITHELIAL HYPERPLASIA SCLEROSING ADENOSIS

Ducts & Lobules are Estrogen Acini/ Terminal duct Proliferate in the
Lobules
Sensitive
At Least Double the Number
Cells Distends ducts/lobules Often Confused with Ductal Cancer
Irregular fenestrations in the Presentation
periphery Palpable mass
Radiologic Density
Calcification

Morphology
Acini/ Terminal duct increased in number
Acini are compressed and distorted in central
portions and dilated at the periphery
Stromal fibrosis
Create solid cords of double strands of cells
Mimic Cancer

Sclerosing Adenosis

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PAPILLOMAS PAPILLOMA
Multiple Branching fibrovascular cores
Have a connective tissue axis lined by
Luminal and Myoepithelial cells
Growth occurs w/in ducts
Large lesions > Solitary / Sinuses of the
nipple
Smaller lesions -> Multiple / Deepr within
the duct system

PAPILLOMAS
Nipple Discharge
> 80% of Large Lesions
Bloody Discharge PROLIFERATING BREAST DISEASE
Torsion in the stalk
Nonbloody Discharge WITH ATYPIA
Intermittent Blockage
With Release of Normal Breast Secretions
Small Palpable mass
Densities
Calcification

Morphology FEATURES
ATYPICAL DUCTAL ATYPICAL LOBULAR
Cellular Proliferation resemble carcinoma HYPERPLASIA W/ ATYPIA HYPERPLASIA W/ ATYPIA
in situ
But Lacking sufficient qualitative & More common in biopsy Is a common incidental
w/ calcification ( 5-17%) finding ( < 5% )
quantitative features for diagnosis of
cancer
Less frequent in biopsy
Harbor some of the same genetic losses from densities or
and gains present in Carcinoma in situ palpable mass
( CIS )

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ATYPICAL DUCTAL HYPERPLASIA Atypical Ductal Hyperplasia

Resembles DIC
Duct filled with a mixed population of cells
Oriented columnar cells at the periphery
More rounded cells w/in the central portion
Sometimes with cribriform spaces which are
round and regular
BUT Peripheral spaces are irregular & slit like
Proliferation is Limited in extent and only
partially filling the ducts

ATYPICAL LOBULAR HYPERPLASIA Atypical Lobular Hyperplasia

Proliferating of cells identical to those of
Lobular carcinom in situ (LCIS )
Population of monomorphic small, round,
loosely cohesive cells
But the cells do not fill or distend more than
50% of the acini within the lobule

FIBROADENOMA
Most Common Breast Tumor < 35y/o women
Discrete Movable
STROMAL BREAST TUMORS
Frequently Mulitple and Bilateral
Painless or Painful Mass
Arise from Intralobular Increase in size with Pregnancy
stroma Estrogen Sensitive
Rarely Becomes Malignant
Stroma proliferates Compress the ducts

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Morphology Fibroadenoma
Spherical nodules/ well-circumscribed
Rubbery, grayish white
Delicate cellular myxoid stroma
Surrounds or compress the duct

Fibroadenoma PHYLLODES TUMOR

May hyalinized and calcify after menopause Bulky tumor
Mimics Ca Derived from stromal cells
Increased risk for Ca is limited to Complex Often Benign
FAD Mostly 60 y/o
( Table 23-1 ) Lobulated tumor with cystic spaces
Cyst > 0.3cm May contain Leaflike Extensions
Sclerosing adenosis Sign of Malignancy
Epithelial calcification Hypercellular stroma
Papillary apocrine metaplasia Mitoses (+)

Features Features
Few cm to large bulbous lesion Treatment
Phylloides Wide Excision / Simple mastectomy
Avoid recurrence
Criteria Majority are low grade
More cellular Recur locally
Rarely metastasize
Mitosis
Rarely High grade
Nuclear pleomorphism Aggressive
Stroma overgrowth Frequent local recurrences
Infiltrative Borders 1/3 distant hematogenous metastasis
Only Stromal component metastasize

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Phylloides tumors
LOW GRADE LESION HIGH GRADE LESIONS
Resemble FAD Resemble soft tissue Gross
More cellular sarcoma
Contain mitotic figures Frequency of chromosomal Phylloides
changes increases with
grade
Majority have amplification of
EGFR
Often recurrent

Microscopic Phylloides

BREAST CANCER

EPIDEMIOLOGY
MOST COMMON CANCER IN ADULT WOMEN
MEAN AGE 64 Y/O
SECOND MOST COMMON CANCER
PRODUCING DEATH IN WOMEN
RISK FACTORS
MOST COMMON BREAST MASS IN WOMEN
OVER 50 Y/O

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1. First Generation Relatives 1. Early Menarche/Late Menopause

a. 13% Develop Ca
b. 87% Will not Develop Ca 2. Nulliparity / Infertility
2. Genetic (10% of cases ) 3. Fewer children with Late age at 1st
a) Autosomal Dominant BRCA1 and BRCA2 Delivery
b) Li-Fraumeni Multicancer Syndrome 4. Postmenopausal Obesity
o Inactivatin of TP53 Suppressor Gene
o Aromatization of Androstenedione
3. Other Genes
o RAS oncogene, ERBB2, RB suppressor gene Estrogen

1. Hormone Replacement Therapy ATYPICAL DUCTAL DYPERPLASIA

- 1.2 to 1.7 fold increase ETHNIC/ RACE
- Most are ER (+) low mortality NON HISPANIC WHITE ( HIGHEST RATE )
AFRICAN & HISPANIC ( ADVANCED STAGE )
2. Oral Contraceptive Pills DEVELOP IN YOUNGER AGE
- No convincing relation ER NEGATIVE
POORER PROGNOSIS
- Decrease risk for Endometrial & Ovarian Ca
ENDOMETRIAL CANCER
IONIZING RADIATION
SMOKING CIGARETTES

HIGHER BREAST DENSITY - Less Complete DIET

Involution of lobules at each menstruation
RADIATION EXPOSURE exposure at younger
age and high doses
CARCINOMA OF CONTRALATERAL BREAST -
Higher with Germline Mutation
BRCA1 / BRCA 2
ENDOMETRIAL Ca - R/T Estrogen
GEOGRAPHIC INFLUENCE
4x to 7x higher in USA & Europe
Modifiable risk factors
Caffeine may Decrease risk
Moderate or Heavy Alcohol Increases the Risk
OBESITY
Decreased Risk in < 40y/o anovulatory
cycles
Increased Risk for Postmenopausal Obese
Women
EXERCISE Small protective effect

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Etiology and pathogenesis

BREAST FEEDING Major Risk Factors Types
Decreased Risk for Longer Duration SPORADIC
Lactation Suppress Ovulaltion 1. HORMONAL
Trigger Terminal Differentiation Luminal Cells
HORMONAL EXPOSURE
2. GENETIC HEREDITARY
TOBACCO
No Clear Association GERMLINE MUTATION

ENVIRONMENTAL TOXINS
Organochlorine pesticides Estrogenic
Effects
No Definite Association

BRCA 1
Inactivated in 50% by methylation
Marked Increase risk for Ovarian Ca ( 20- 40% of
Hereditary Breast carriers )
Poorly Differentiated (Medulary or

Cancer Metaplastic)
Triple Negative
(-) Hormone Receptors or OverExpress HER2/Neu
Loss of Inactive X chromosome and Reduplication of
Active X
Result to Absence of Barr Body

BRCA2 Hereditary Breast Cancer

GENE BREAST CANCER RISK BY AGE 70
BRCA1 and BRCA2 BRCA1 40-90%
Relatively Poorly Differentiated Tumor Suppressor Gene BRCA2 30-90%
Often ER (+) Transcriptional regulation
Repair of Double stranded
Germline Mutation DNA breaks
Mutation Major
Smaller Risk for Ovarian Ca (10-20% )
P53 >90%
Higher than BRCA1 for Male Breast Cancer Tumor suppressor
Critical in cell cycle control
DNA replication/repair
Apoptosis
CHEK2 10-20 %
Cell cylce check point kinase
DNA repair
Acitvates

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Sporadic Breast Cancer

Postmenopausal
Are ER (+)
Major Risk Factors
Hormone Exposure
Clinical Manifestation


Gender
Age at Menarche of Breast Cancer
Menopause
Reproductive History
Breastfeeding
Exogenous estrogen

Frequency of Symptoms PAINLESS BREAST MASS

LUMP 60-70 % LEFT BREAST > RIGHT BREAST
Ratio 1.07: 1
PAIN 14-18% Palpable Mass
>50% have (+) Axillary LN
NIPPLE PROBLEMS 7-9%
1. LUOQ
DEFORMITY 1% 40-50%
2. Central
INFLAMMATION 1% 3. Upper
FAMILY HISTORY 3-14% 4. Inner
5. Lower Outer
6. Lower Inner

NIPPLE RETRACTION
Mass is Located Centrally PAINLESS AXILLARY
LYMPHADENOPATHY

Positive in >50% when mass is

Palpable

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Peau dorange
Lymphedema

MAMMOGRAPHY

Mammographic Appearance A SCREENING TEST

STELLATE AND 64% DETECTS NONPALPABLE BREAST MASS
CIRCULAR W/O Half the size of a palpable breast mass
CALCIFICATION < 20% has
DOES NOT DISTINGUISH BENIGN FROM MALIGNANT
STELLATE AND 17%
STARTS ANNUALLY AT 40 y/o
CIRCULAR W/
CALCIFICATION IDENTIFIES MICROCALCIFICATION
OFTEN (+)
a) DUCTAL Ca IN SITU
CALCIFACTION 19% b) SCLEROSING ADENOSIS

NATURAL HISTORY STAGING

LYMPHATIC SPREAD HEMATOGENOUS
OUTER QUADRANT AXILLARY NODES SIGNIFICANCE :
INNER QUADRANT INTERNAL MAMMARY NODES
EXTRANODAL SPREAD
COMMON SITES
LUNGS, BONES, LIVER, BRAIN, OVARIES
MOST COMMON CANCER METASTATIC TO LUNGS &
BONE
PAIN IN BONE METS
RELIEVED WITH RADIATION
EXTRANODAL METASTASIS > NODAL METS
SENTINEL NODE BIOPSY
SAMPLING OF INITIAL NODE THAT DRAINS THE
TUMOR
IF (-) MOST LIKELY NODAL GROUP IS ALSO
NEGATIVE
IF (+) 1/3 CHANCE OTHER NODES IN THAT
GROUP IS (+)

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ESTROGEN AND PROGESTERONE OTHER TEST

RECEPTOR ASSAYS S PHASE FRACTION
> 5% POOR PROGNOSIS
OFTEN (+) IN POSTMENOPAUSAL WOMEN
DNA PLOIDY
SIGNIFICANCE
Diploid Tumor is BETTER than Aneuploid
a) CONFERS OVERALL BETTER PORGNOSIS Tumor
b) CANDIDATE FOR ANTIESTROGEN THERAPY ERBB2 ONCOGENE STATUS
( TAMOXIFEN )
Poor Prognosis if Amplification is Present

SURGICAL PROCEDURES SURGICAL PROCEDURES

A. MODIFIED RADICAL MASTECTOMY B. BREAST CONSERVATION THERAPY
1. Nipple Arelar Complex a. Lumpectomy with Microscopic Free Margins
2. Beast Tissue b. Removal of Level I & II axillary LN
3. Pectoralis minor c. Breast Radiation
4. Axillary Nodes
Damage Long Thoracic Nerve
Winged Scapula
Lymphedema

PROGNOSIS

OVERALL 25% OF WOMEN DIE FROM

THEIR DISEASE
GYNECOMASTIA

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DESCRIPTION CLINICAL FEATURES

NON-NEOPLASTIC GENERALLY BILATERAL DISTINCT IN ONE
OFTEN REVERSIBLE BREAST ENLARGEMENT NIPPLE SECRETION IS RARE
ENLARGEMENT OF RUDIMENTARY DUCT SYSTEM PALPABLE RETROAREOLAR NODULE OR PLAQUE LIKE
PROLIFERATION INDURATION
GLANDULAR OCCASIONAL ACHING PAIN
MESENCHYMAL
DUE TO ESTROGEN

MORPHOLOGY TYPES :GYNECOMASTIA

GROSS PHYSIOLOGIC PATHOLOGIC
CIRCUMSCRIBED ENLARGEMENT NORMAL IN RELATED TO:
FIRM , GREY WHITE NEWBORN, 1. CIRRHOSIS
PUBERTY,ELDERLY INABILITY TO
MICROSCOPIC METABOLIZE ESTROGEN
INCREASED NUMBER OF DUCTS SURGERY NOT 2. KLINEFELTERS
INDICATED SYNDROME
MYXOID STROMA W/ FIBROBLASTS
3. ENDOCRINE TUMORS
CHRONIC INFLAMMATION 4. DRUGS
SPIRONOLACTONE BLOCKS
ANDROGEN RECEPTORS

FEATURES
EXTREMELY RARE
< 1%
BREAST CANCER RISK FACTORS:
HIGH SOCIO-ECONOMIC CLASS

IN MEN NEVER MARRIED

FAMILY HISTORY
HIGH BODY MASS INDEX
PREVIOUS BREAST/TESTICULAR DISEASE/ GYNECOMASTIA

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FEATURES RISK FACTORS

RISK FACTORS:
KLINEFELTER SYNDROME BRCA2 SUPPRESSOR GENE
INFERTILITY / LOW FERTILITY KLINEFELTERS SYNDROME
HYPERESTRINISM USUALLY HAVE POOR PROGNOSIS
CIRRHOSIS
DIABETES MELLITUS
LIMITED PHYSICAL ACTIVITY
HIGH RED MEAT

CARCINOGENESIS AND TUMOR PROGRESSION BREAST MALIGNANCY

> 95% ARE ADENOCARCINOMA
TYPES
1. CARCINOMA IN SITU [ CIS ]
- Neoplastic Proliferation limited to ducts & lobules
by basement membrane
2. INVASIVE CARCINOMAS
- Penetration of the basement membrane
into stroma
- Spread into vasculature and reach regional
lymph nodes and distant mets

DUCTAL CARCINOMA DEFINITION DCIS

IN SITU NEOPLASTIC INTRADUCTAL LESION
INTRADUCTAL CARCINOMA LIMITED TO DUCTS BY BASEMENT
DCIS MEMBRANE
MYOEPITHELIAL CELLS PRESERVED
INCREASED EPITHELIAL PROLIFERATION
CELLULAR ATYPIA
PRECURSOR LESION
INHERENT BUT NOT OBLIGATE TENDENCY
FOR PROGRESSION TO INVASIVE BREAST
CANCER

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FEATURES COMEDOCARCINOMA
MAMMOGRAPHY
SOLID SHEETS OF PLEOMORPHIC
DX OF DCIS INCREASES 5% 15%-30%
ALMOST 50% ARE DCIS CELLS WITH HIGH GRADE
DETECTED AS CALCIFICATION HYPERCHROMATIC NUCLEI
LESS COMMONLY AS DENSITY
CENTRAL NECROSIS
HISTOLOGIC SUBTYPES
MAY CALCIFY
1. COMEDOCARCINOMA
2. NONCOMEDO DCIS PERIDUCTAL FIBROSIS
1. SOLID CREATE AVGUE NODULARITY
2. CRIBRIFORM
3. PAPILLARY
3. PAGETS DISEASE

COMEDOCARCINOMA NONCOMEDO DCIS

CONSIST OF MONOMORPHIC
POPLATION OF CELLS WITH
NUCLEAR GRADES LOW TO HIGH
a. CRIBRIFORM DCIS
b. SOLID DCIS
c. PAPILLARY DCIS
d. MICROPAPILLARY

CRIBRIFORM SOLID VARIANT

INTRAEPITHELIAL SPACES ARE

EVENLY DISTRIBUTED AND
REGULAR IN SHAPE
( COOKIE CUTTER-LLIKE )

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PAPILLARY / MICROPAPILLARY
DCIS WITH MICROINVASION
DCIS
INVASION TO STROMA IS NO MORE
THAN 0.1CM,
MOST COMMONLY ASSOCIATED
WITH COMEDOCa
FEW FOCI OF INVASION
PROGNOSIS IS SIMILAR TO DCIS

PAGETS DISEASE OF THE NIPPLE CLLINICAL- PAGETS

RARE MANIFESTATION OF BREAST
CANCER
1% - 4%
UNILATERAL ERTHEMATOUS
ERUPTION WITH SCALE CRUST
PRURITUS IS COMMON

DIAGRAM PAGETS DSE MORPHOLOGY OF PAGETS

MALIGNANT CELLS EXTEND FROM
DCIS LACTIFEROUS SINUSES
NIPPLE SKIN
DOES NOT CROSS THE BASEMENT
MEMBRANE
DISRUPTS THE NORMAL EPITHELIAL
BARRIER NIPPLE DISCHARGE
TUMORS CELLS (+) IN DISCHARGE

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LOBULAR
CARCINOMA
IN SITU (LCIS)

FEATURES FEATURES
MORE COMMON IN YOUNGER PROGRESSION TO INVASIVE LOBULAR
WOMEN CARCINOMA
80%-90% OCCUR BEFORE MENOPAUSE 1% per year
ALMOST ALWAYS AN INCDENTAL Both Breast are increased risk
FINDING
Slightly higher in ipsilateral breast
NOT ASSOCIATED WITH:
CALCIFICATION
STROMAL REACTION
20%-40% BILATERAL
MUCH HIGHER IN DCIS ( 10%-20% )

MORPHOLOGY MORPHOLOGY
CELLS ARE SIMILAR TO INVASIVE
LOBULAR Ca
SHARE GENETIC ABNORMALLITIES
LOSS OF EXPRESSION OF E-cadherin
E-cadherin adhesion protein
DYSCOHESIVE ROUND CELLS
DUE TO LOSS OF E-cadherin
OVAL TO ROUND NUCLEI AND SMALL
NUCLEOLI
ALMOST ALWAYS EXPRESS ER AND PR
(-) HER2/NEU OVEREXPRESSION

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MONOMORPHIC
POPULATION OF
DYSCOHESIVE
SMALL ROUND
CELLS EXPANDS
ACINI IN A LOBULE
INVASIVE
CARCINOMA

NOS TYPE ( NST )INVASIVE

DUCTAL CARCINOMA
MOST COMMON TYPE
70% - 80%
INVASIVE DUCTAL
3 TYPES
CARCINOMA
1. WELL-DIFFERENTIATED
2. MODERATELY DIFFERENTIATED
3. POORLY DIFFERENTIATED

POSITIVE MAMMOGRAPHY
Mammographic Appearance
FINDING
STELLATE AND 64% RADIODENSE MASS
CIRCULAR W/O MOST COMMON FINDING
CALCIFICATION CALCIFICATION W/O DENSITY
STELLATE AND 17% ARE VERY SMALL IN SIZE
CIRCULAR W/ METASTASIS ARE UNUSUAL
CALCIFICATION
WHEN NEGATIVE PALPABLE MASS
< 20% HAVE NODAL METS
CALCIFACTION 19%

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GROSS NST
FIRM TO HARD
IRRREGULAR BORDERS
CHALKY WHITE
ELASTOSIS
GRATING SOUND ON
CUTTING

DISTRIBUTION OF HISTOLOGIC MOLECULAR CLASSES OF

TYPES OF INVASIVE INVASIVE DUCTAL Ca
CARCINOMA A. LUMINAL A ( 40% - 55% OF NST )
Largest group
ER (+) and HER2/neu (-)
Respond to anti-estrogen Tamoxifen
Majority are well to moderately diff
Mostly postmenopausal women
Slow growing
Small fraction respond to chemotherapy

MOLECULAR CLASSES OF MOLECULAR CLASSES OF

INVASIVE BREAST Ca INVASIVE BREAST Ca
B. LUMINAL B ( 15% - 20% ) D. BASAL LIKE ( 13% - 25% NST )
Express ER but higher LN mets Absence of ER, PR and HER2/neu markers
Generally : Triple Negative
Higher grade Eg . Medullary, Metaplastic Ca
Higher mitosis
High Grade & prolliferation rate
Often express HER2/neu
Referred as triple positive Aggressive
Responds to Chemotherapy Frequent mets to brain and viscera
C. NORMAL BREAST LIKE ( 6% - 10% NST ) Poor prognosis
Usually Well-Diff (+) Basal keratins marker for myoepithelial cells
ER (+) (+) Cytokeratin 5 & 6 marker for progenitor
HER2/neu (-) cells

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MOLECULAR CLASSES OF
INVASIVE BREAST Ca
E. HER2 POSITIVE ( 7% - 12% NST )
ER NEGATIVE
> 90% amplification of DNA segement on
17q21 which include HER2/neu gene
Usually Poorly differentiated
High proliferation rate
High frequency of Brain Metastasis
Trastuzumab ( humanized monoclonal Ab ) +
Chemotx Highly effective for this lesion
But not penetrate thee brain barrier

FEATURES
FINDING:
PALPABLE MASS + DENSITY WITH IRREGULAR
BORDERS
NO PALPABLE MASS + SUBTLE CHANGES
INVASIVE LOBULAR DIFFUSELY INFILTRATIVE WITH LITTLE DESMOPLASIA
CARCINOMA GREATER INCIDENCE OF BILATERALITY
METASTASIS IS UNIQUE
PERITONEUM - RETROPERITONEUM
OVARIES - LEPTOMENINGES
UTERUS - GIT ( mistaken for signet
ring Ca )

FEATURES
GENETIC MUTATION IN CDH1
GENE THAT ENCODES FOR E-cadherin
SEEN IN OTHER LESIONS:
MEDULLARY
ATYPICAL LOBULAR HYPERPLASIA
LCIS CARCINOMA
GASTRIC SIGNET RING Ca

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FEATURES GROSS
6TH DECADE
SOFT FLESHY
WELL CIRCUMSCRIBED MASS WELL-
CIRCUMSCRIBED
ALL ARE POORLY DIFFERENTIATED
SLIGHT BETTER PROGNOSIS THAN NST
DESPITE HIGH NUCLEAR GRADE, (-) ER
HER2/neu OVEREXPRESSION IS NOT
OBSERVED

SOLID SYNCYTIUM
PLEOMORPHIC LARGE CELLS
LN METS ARE INFREQUENT FREQ MITOTIC FIGURES
MODERATE LYMPHOOPLASCYTIC
HAVE BASAL GENE EXPRESSION INFILTRATES
PUSHING NONINFILTRATIVE BORDERS

FEATURES
OLDER WOMEN
MEDIAN AGE 71 y/o
MUCINOUS (COLLOID) SLOW GROWING

CARCINOMA WELL-MODERATE DIFF

LN METS UNCOMMON
PROGNOSIS SLIGHTLY BETTER THAN
NST

MORPHOLOGY MORPHOLOGY

SOFT OR RUBBERY
PALE GRAY-BLUE
CELLS ARRANGED IN
GELATIN
CLUSTERS AND
BORDERS ARE
SMALL ISLANDS
PUSHING OR
WITHIN LAKES OF
CIRCUMSCRIBED
MUCIN

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FEATURES
LATE 40S
SMALL IRREGULAR DENSITIES
TUBULAR CARCINOMA < 1 CM
RARE 10%
WELL-DIFF
EXCELLENT PROGNOSIS

MAJOR PROGNOSTIC
TUBULAR
BREAST CANCER
INVASIVE VS CIS
DISTANT METS
LN METS
MOST IMPT IN ABSENCE OF DISTANT METS
TEN YEAR SURVIVAL
NEGATIVE 70-80% survival
(+) 1-3nodes 35%-40%
(+) > 10 Nodes 10%-15%
TUMOR SIZE
SECOND MOST IMPORTANT
LN METS RISK INCREASES WITH SIZE

MAJOR PROGNOSTIC MINOR PROGNOSTIC FACTORS

BREAST CANCER BREAST CANCER
LOCALLY ADVANCE DISEASE HISTOLOGIC TYPE ( 30 YEAR SURVIVAL
USUALLY SEEN IN LARGE LESION )
INVADE SKIN, SKELETAL MUSCLE > 60%
INFLAMMATORY Ca TUBULAR
MUCNOUS
POOR PROGNOSIS
MEDULLARY
PRESENTATION DUE TO DERMAL
LOBULAR
LYMPHATIC INVOLVEMENT
PAPILLARY
BREAST SWELLING
< 20%
SKIN THICKENING
NST

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MINOR PROGNOSTIC FACTORS MINOR PROGNOSTIC FACTORS

BREAST CANCER BREAST CANCER
HISTOLOGIC GRADE LYMPHOVASCULAR INVASION
ER / PR POOR PROGNOSTIC FACTOR
BETTER OUTCOME WITH HORMONAL PROLIFERATIVER RATE
TX POOR PROGNOSIS WHEN HIGH
80% (+) ERPR DNA CONTENT
40% ER or PR positive USE FLOW CYTOMETRY
HER2/neu DA INDEX OF 1 = NORMAL DIPLOID
CELL
POORER SURVIVAL WHRN (+)
ANUEPLOID = ABNORMAL DNA INDICES
RESPONSIVE TO TRASTUZUMAB AGENTS SLIGHT POOR PROGNOSIS

MINOR PROGNOSTIC FACTORS

AJCC STAGING
BREAST CANCER STAGE T: PRIMARY LYMPH M: DISTANT 5 YEAR

NEOADJUVANT THERAPY CANCER NODES

(LNs)
METASTASIS SURVIVAL
(%)

PATIENT IS TREATED BEFORE SURGERY

0 DCIS or LCIS No Mets Absent 92%
RESPONSIVE ARE POORLY DIFF, ER (-) I Invasive Ca < 2 cm No Mets Absent 87%
GENE EXPRESSION II Invasive Ca > 2 cm No mets Absent 75%

PREDICT SURVIVAL A ND RECURRENCE Invasive Ca < 5 cm 1-3 positive LN Absent

III Invasive Ca >5 cm 1-3 positive LN Absent 46%
FREE INTERVAL
Any size invasive > 4 positive LN Absent
IDENTIFIES THOSE WHO WILL BENEFIT TO Invasive Ca with skin or 0 to > 10 Absent
TYPES OF CHEMOTX chest wall involved,
Inflammatory type
positive LN

IV Any size invasive Ca Negative or Present 13%

Positive LN

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