Breast Patho Lect

BREAST PATHOLOGY

Edna May Go, MD

The Female Breast

Life Cycle Changes

Prepubertal breast

Consists of duct

system ending in

terminal ducts with

minimal lobule

Beginning of

Menarche

Terminal ducts give

rise to lobules

Interlobular stroma

increases in volume

Paucity of adipose

tissue

Life Cycle Changes

Follicular phase

Lobules are

quiescent

After ovulation

Estrogen and

progesterone

Cell proliferation

increases

Vacuolization of

epithelial cells

Intralobular stroma

becomes markedly

edematous

Life Cycle Chnages

Pregnancy Lobules increase

number and size

Reversal of stromal-epithelial relationship

End of pregnancy Breast is composed

almost entirely of lobules separated by a relatively scant amount of stroma

By third trimester, secretory vacuoles of lipid material found within epithelial cells of TDLU

After Birth Breast produces

colostrum Changes to milk (higher

fat calories) within first 10 days as progesterone drops

After cessation of lactation Lobules regress and

atrophy

Life Cycle Changes

Third decade

Lobules and stroma

start to involute

Old Age

Lobules may totally

disappear, leaving only

ducts to create a

morphologic pattern

similar to male breast

Normal breast

extreme

Terminal duct lobular unit

Normal postpubertal female breast, non-lactating. Arrow heads

delineate the lobule. The terminal ductule (short arrow) leads

from the lobule to the duct system (larger arrows). Note how the

pink fibrillar extracellular matrix material (mostly collagen) tends

to wrap concentrically around the ducts and lobules. r Figure 2.

Fine needle aspiration

cytology True-Cut biopsy

Examination of frozen section

Mammography

Diagnostic methods

woman presents at a clinic with a breast lump, a

needle can be inserted into the area and cells

aspirated without the need for even a local

anaesthetic.

After smearing and staining, the cells are

examined by a pathologist, and if the specimen

is adequate a diagnosis can be made.

Fine needle aspiration cytology

Figure 13 Quick-core cutting needle (Cook Medical Inc, Bloomington, IN, USA)

used to obtain core biopsies of soft tissue. (a) Photograph shows the needle set

that has a handle, which enables one-handed control and a spring-loaded

trigger with a rapid-firing mechanism. (b) Close-up photograph of the needle tip

shows the bevelled-point stylet that enables easy penetration into the lesion with

minimal trauma to the surrounding tissue. Firing of the sharp cutting edge of the

cannula facilitates obtaining an intact core tissue sample within the slotted

stylet.

Mammography

X-raying of the breasts is used to help in the

diagnosis of both palpable and impalpable

lesions.

the basis of screening programmes, which try to

detect impalpable small breast cancers. i.e.

early tumours.

It is important that the pathologist carefully

examines the tissue to ensure that the lesion

has been removed.

Another approach which can be used in the clinic is Tru-Cut biopsy, in which a

core of tissue is removed using a biopsy needle.

Examination of frozen section

A further approach is that of examining the breast lesion

very rapidly by frozen section at the time of surgery.

A small sample is frozen, and sections are cut, stained

and interpreted by a pathologist within a few minutes.

Tru-Cut biopsy

http://clinlabs.path.queensu.ca/kgh/pathology/process-1.jpg

http://clinlabs.path.queensu.ca/kgh/pathology/photos/frozencutting.jpg

Disorder of Development

Milkline remnants

Accessory axillary bresat tissue

Congenital nipple inversion

Spontaneously corrected during pregnancy

Macromastia

Reconstruction or augmentation

Most common complication is formation of thick

fibrous capsule causing cosmetic deformity

Site for fibroadenoma and carcinoma

http://www.brooksidepress.org/Products/Military_OBGYN/Textbook/Breast/supnipple2.jpg

http://en.wikipedia.org/wiki/Image:Invertednipple.jpg

Clinical Presentations of Breast

Disease

Mastalgia or mastodynia

Most common symptom

Palpable mass

Not become palpable until 2cm in diameter

Nipple discharge

Galactorrhea is seen in increased production of

prolactin (pituitary adenoma), hypothyroidism,

endocrine anovulatory syndromes

Mammography

Screening recommended at age 40

Principal mammographic signs of breast

cancer

Densities

Invasive carcinoma, fibroadenoma, cysts

Calcifications

Associated with secretory material, necrotic debris,

hyalinized stroma

DCIS is most common malignancy associated with

calcifications

Inflammations

Acute mastitis

During early weeks of nursing

Vulnerable to bacterial infection because of

development of cracks and fissures in the nipple

Staphylococcus aureus

Most common

Single or multiple abscesses

Streptococci

Less common

Diffuse spreading infection

INFLAMMATIONS

ACUTE MASTITIS

+ BREAST FEEDING

+ CRACKS FISSURES IN NIPPLES,

+ STAPH, STREP

+ LOCALIZED ACUTE

INFLAMMATION

Inflammations

Periductal mastitis

Recurrent subareolar abscess, squamous metaplasia of lactiferous ducts, Zuska disease

Seen in smokers (90%)

Vitamin A deficiency

Toxic substances alter differentation of ductal epithelium

Recurrent disease

Fistula tract

Inverted nipple secondary to fibrosis and scarring

Keratin is trapped within ductal system causing dilation and rupture

PERIDUCTAL MASTITIS

+ SQUAMOUS METAPLASIA OF

LACTIFEROUS DUCTS

+ RECURRENT SUBAREOLAR

ABSCESS

+ MORE THAN 90% ARE SMOKERS

+ KERATINIZING SQUAMOUS

EPITHELIUM INTO THE ORIFICES

OF THE LACTIFEROUS DUCTS/

GRANULOMATOUS REACTIONS

Inflammations

Mammary duct

ectasia

Fifth-sixth decade

Multiparous women

Dilation of ducts,

inspissation of breast

secretions, marked

periductal and

interstitial chronic

granulomatous

inflammation reaction

Duct ectasia

Mamfoamy histiocytes and the periductal tissue

is infiltrated mary duct ectasia. The dilated duct

contains by lymphocytes

Inflammations

Fat necrosis

History of trauma

Hemorrhage (early stage), central liquefactive

necrosis of fat (later), pregressive fibroblastic

proliferation and increase vascularization and

lymphocytic inflitration

Foreign body giant cells, calcification,

hemosiderin

This is fat necrosis of the breast. The most common

etiology is trauma. It can be a localized, firm area with

scarring that can mimic a breast carcinoma.

Microscopically, however, fat necrosis consists of irregular

steatocytes with no peripheral nuclei and intervening pink

amorphous necrotic material and inflammatory cells,

including foreign body giant cells responding to the

necrotic fat cells.

Inflammations

Lymphocytic mastopathy

Sclerosing lymphocytic lobulitis

Collagenized stroma surrounding atrophic ducts

and lobules

Epithelial basement membrane is thickened

Prominent lymphocytic infiltrate surrounds

epithelium and blood vessels

Most common in women with type 1 diabetes or

autoimmune thyroid disease

Lymphocytic mastitis/diabetic

mastopathy characterized by keloid-like fibrosis and prominent lymphocytic infiltrate surrounding breast ducts and

lobules.

Inflammations

Granulomatous mastitis

Systemic Wegener granulomatosis, sarcoidosis

Infections Mycobacterial, fungal

Granulomatous lobular mastitis Uncommon breast-limited disease distinguished by

grnulomas involving lobular epithelium

Only affects parous women

Hypersensitivity reaction mediated by alterations in lobular epithelium during lactation

Benign Epithelial Lesions

Nonproliferative breast changes (Fibrocystic changes)

Benign morphologic changes

Cysts are most common cause of palpable mass and alarming if solitary, firm and unyielding

Patterns

Cysts

May have apocrine metaplasia

Fibrosis

Caused by cyst rupture

Adenosis

Increase in number of acini per lobule


Lactational adenoma

Palpable masses in pregnant or lactating women

Normal-appearing breast tissue with physiologic

adenosis and epithelial lactational changes

Exaggerated focal response to hormonal

influences

PROLIFERATIVE BREAST DISEASE WITHOUT

ATYPIA

+ PROLIFERATION OF DUCTAL EPITHELIUM AND / OR STROMA

WITHOUT EPITHELIAL ABNORMALITY

+ MODERATE OR FLORID EPITHELIAL HYPERPLASIA

+ SCLEROSING ADENOSIS

+ COMPLEX SCLEROSING LESIONS

+ PAPILLOMAS

+ FIBROADENOMAS WITH COMPLEX FEATURES


Epithelial

Hyperplasia

Defined as more

than two cell layers

Moderate to florid

More then four cell

layers


Sclerosing adenosis

Number of acini per terminal duct is ingreased to at least twice the number found in uninvolved lobules

Normal lobular arrangement is maintained

Myoepithelial cells are prominent


Complex Sclerosing

Lesion (Radial Scar)

Stellate lesions

characterized by a

central nidus of

entrapped glands in

a hyalinized stroma

Not associated with

prior trauma or

surgery


Papillomas Composed of multiple

branching fibrovascular cores, each having a connective tissue axis lined by luminal and myoepithelial cells

Epithelial hyperplasia and apocrine metaplasia may be present

Small duct papillomas showincreased risk of subsequent carcinoma

Proliferative Breast Disease with

Atypia

Atypical ductal

hyperplasia

Histologically

resemble DCIS

Characteristically

limited in extent,

cells are not

completely

monomorphic, fail to

completely fill ductal

spaces

Atypical lobular

hyperplasia

Cells identical to LCIS

Cells do not fill or

distend more than

50% of the acini

within a lobule

May extend into ducts

Increased risk of

developing invasive

carcinoma

Breast Lesions and Relative Risk of Developing Invasive

Carcinoma

Pathologic lesion Relative risk (Absolute

lifetime risk)

Breast at risk Modifiers of risk

Nonproliferative breast changes 1.0 (3%) neither

Proliferative disease without

atypia

1.5 to 2.0

(5-7%)

both Increased risk if there is

family history

Decreased risk 10 years

after biopsy

Proliferative disease with atypia

(ADH, ALH)

4.0 to 5.0

(13-17%)

both Increased risk if there is

familty history

Increase risk if

premenopausal

Decreased risk 10 years

after biopsy for ALH

LCIS 8.0 to 10.0

(25-30%)

both Treatment

DCIS 8.0 to 10.0

(25-30%)

ipsilateral Treatment

Risk Factors in Carcinoma of the Breast

Age

Rarely found before

25y/o

77% occur in

women50 y/o up

Average age is 64

Age at menarche

Women who reach

menarche

whenyounger than

11 y/o have 20%

increased risk


First live birth

First full term

pregnancy at

younger than 20 y/o

have half the risk of

nulliparous women

or women over the

age of 35 at their

first birth

First-degree

relatives with

breast cancer

Risk of breast

cancer increase

with the number of

affected first

degree relatives

(mother, sister,

daughter)

Risk Factors in Carcinoma of the

Breast

Breast biopsies

Increased risk associated with prior breast biopsies showing atypical hyperplasia

Race

Lower in black women but presents at more advanced stage and increased mortality compared to white women

Caucasian women generally have the highest rate of breast cancer


Breast

Estrogen exposure

Postmenopausal hormone replacement therapy slightly increases the risk of breast cancer

Estrogen with progesterone increases the risk more than estrogen alone

Radiation exposure

Threapeutic radiation or radiation after atom bomb exposure increases risk


Breast

Carcinoma of the

contralateral breast

or endometrium

Increases risk

Geographic

influence

US and EU are 4x to

7x higher than other

countries


Diet

Moderate or heavy alcohol consumption increases risk

Due to higher estrogen levels and lower folate levels?

Obesity

Decreased risk in obese women younger than 40 years

Due to anovulatory cycles and lower progesterone levels

Increased risk in postmenopausal obese women

Due to synthesis of estrogen in fat


Exercise

Decreased risk of

breast cancer in

premenopausal

women who

exercise

Breast-feeding

The longer women

breast-feed, the

greater is the

reduction in the risk

of breast cancer


Environmental

toxins

Organochlorine

pesticides have

estrogenic effects

Tobacco

Not associated with

breast cancer

Etiology and Pathogenesis

The major risk factors for the development of breast cancer are hormonal and genetic (family history)

About 25% of familial cancers (or around 3%of all breast cancers) can be attributed to 2 highly penetrant autosomal dominant genes: BRCA1 and BRCA2

The general lifetime breast cancer risk for female carriers is 60% to 85%, the median age at diagnosis is about 20 years earlier compared to women without these mutations


Mutated BRCA1 also increases the risk of developing ovarian carcinoma

Male breast cancers are markedly increased only in familites carrying BRCA2 mutations

BRCA1-associated breast cancers are more commonly poorly differentiated, have a syncitial growth pattern with pushing margins, have a lymphocytic response, and do not express hormone receptors or overexpress HER2/neu epidermal growth factor receptor

Most common Single Gene Mutations Associated

with Hereditary Breast Cancer

BRCA1 (17q21)

Syndrome: Familial breast and ovarian cancer

Incidence: 1 in 860

~2% of all breast cancers

Function: tumor suppressor, transcriptional

regulation, repair of double-stranded DNA breaks

Breast carcinomas are commonly poorly

differntiated and triple negative (basal-like),

and have p53 mutations



BRCA2 (13q12-13)

Syndrome: Familial breast and ovarian cancer

Incidence: 1 in 740


Function: tumor suppressor, transcriptional

regulation, repair of double-stranded DNA breaks

Biallelic germline mutations cause a rare form of

Fanconi anemia



P53 (17p13.1)

Syndrome: Li-Fraumeni

Incidence: 1 in 5000



CHEK2 (22q12.1)

Syndrome: Li-Fraumeni variant

Incidence: 1 in 100


Function: cell cycle checkpoint kinase, recognition and repair of DNA damage, activates BRCA1 and p53 by phosphorylation

May increase risk for breast cancer after radiation exposure

Also seen in cancers of prostate, thyroid, kidney, colon


In sporadic tumors, about 50% have decreased or absent expression of BRCA1

Major risk factors for sporadic breast cancer are related to hormone exposure: gender, age at menarche and menopause, reproductive history, breast feeding, and exogenous estrogens

Majority of sporadic tumors occur in postmenopausal women and overexpressed ER

Proposed precursor-carcinoma sequence in breast cancer

Ductal Carcioma in Situ

Intraductal carcinoma

5 architectural subtypes

Comedocarcinoma Solid sheets of

pleomorphic cells with high-grade nuclei and central necrosis

Necrotic cell membranes commonly calcify

Ductal Carcinoma in Situ

Noncomedo DCIS

Monomorphic population of cells with nuclear grades ranging from low to high

Cribriform DCIS Intraepithelial

spaces are evenly distributed and regular in shape (cookie cutter like)

Papillary DCIS Grows into spaces and

lines fibrovascular cores typically lacking the normal myoepithelial cell layer

Micropapillary DCIS Bulbous protrusions

without a fibrovascular core, forming complex intraductal patterns

Ductal Carcinoma in Situ

Lobular Carcinoma in Situ

Not associated with calcifications or a stromal reaction that would form a density

1-6% of all carcinomas

Bilateral in 20-40%

Cells are identical with invasive lobular carcinoma and atypical lobular hyperplasia

LCIS and ILC lack expression of e-cadherin (transmembrane protein responsible for epithelial cell adhesion)

Invasive Ductal Carcinoma

Invasive carcinoma, no special type (NST) Cannot be classified as

any other type

70-80% of all breast cancer

Gross: firm to hard, irregular border, small pinpoint foci or streaks of chalky white elastotic stroma at the center, calcifaction may be present

Microscopic: well differentiated tumors consists of tubules lined by minimally atypical cells (typically do not overexpress HER2/neu),

others are composed of anastomosing sheets of pleomorphic cells (typically overexpress HER2/neu)

Invasive Ductal Carcinoma

Invasive Lobular Carcinoma

Usually present like IDC as palpable mass or mammographic density

Reported to have greater incidence of bilaterality (biased)

Incidence increasing in postmenopausal women probably due to hormone replacement therapy

Histologic hallmark is the pattern of single infiltrating tumor cells , often only once cell width (Indian filing)

Lack hormone receptors, aneuploid, may overexpress HER2/neu

Has different metastasis pattern: peritoneum, retroperitoneum, leptomeninges, GIT, ovaries and uterus

Invasive Lobular Carcinoma

Medullary Carcinoma

Well circumscribed mass

History of rapid growth

Consists of solid synctium-like sheets (occupying more than 75% of the tumor) of large cells with vesicular, pleomorphic nuclei, containing prominent nucleoli and frequent mitoses

Has moderate to marked lymphoplasmacytic infiltrates

Has a pushing (non-infiltrative) border

All medullary carcinoma are poorly differentiated

Lymphovascular invasion is never seen

Has slightly better prognosis than IDC

Aneuploid, absence of hormone receptors, HER2/neu overexpression is not observed

13% carry BRCA1 gene but most are not associated with BRCA1 mutation

Medullary Carcinoma

Mucinous Carcinoma

1-6% of all breast

cancers

Presents as

circumscribed mass

Seen in older women

Grow slowly

Tumor cells are seen

as clusters and small

islands of cells within

large lakes of mucin

Prognosis is slightly

better than IDC

Incidence slightly

higher in women with

BRACA1 mutation

Mucinous Carcinoma

Tubular Carcinoma

2% of all breast cancers

10% of all breast cancers with less than 1cm diameter

Women in late forties

Multifocal within one breast (10-56%), bilateral in 9-38%

Axillary metastasis occur in less than 10%

Consists exclusively of well-formed tubules with absent myoeptihelial cell layer

Apocrine snouts are typical, calcifications

95% are diploid and express hormone receptors

Excellent prognosis

Tubular Carcinoma

Invasive Papillary Carcinoma

~1% of all invasive breast cancers

Invasive carcinoma with papillary

architecture

Overall prognosis is better than IDC

Invasive papillary carcinomas are usually ER

positive and have favorable prognosis

Invasive micropapillary carcinomas are more

likely ER negative and HER2 positive with

lymph node metastates and poorer prognosis

Metaplastic Carcinoma

Major Prognostic Factors

Invasive carcinoma or in situ disease

In situ by definition are confined to ductal system and cannot metastasize

Distant metastasis

Once distant metastases are present, cure is unlikely

Lymph node metastases

Axillary lymph node status is the most important prognostic factor for invasive carcinoma in the absence of distant metastases

Sentinel node is highly predictive of the status of the remaining nodes

Macrometastases (>0.2cm) are of proven prognostic importance

~10-20% without axillary lymph node metastases have a recurrence outside of breast

Metastasis occur via internal mammary lymph nodes or hematogenously

Major Prognostic Factors

Tumor size Second most important

prognostic factor and is independent from lymph node status

Women with node-negative carcinomas under 1cm in diameter have a prognosis approaching that of women without breast cancer (10 year survival rate is 90% without treatment)

Locally advance disease Tumors invading into skin

or skeletal muscle are frequently associated with concurrent or subsequent distant disease

Inflammatory carcinoma Breast cancers presenting

with breast swelling and skin thickening due to dermal lymphatic involvement have a particularly poor prognosis

Minor Prognostic Factors

Histologic subtypes Tubular, mucinous,

medullary, lobular, papillary

Tumor grade Nottingham Histologic

Score (Scarf-Bloom-Richardson)

Combines nuclear grade, tubule formation and mitotic rate

Estrogen and Progesterone receptors Hormone receptor-

positive cancers have a slightly better prognosis than hormone receptor-negative cancers

ER-positive cancers are less likely to respond to chemotherapy


HER2/neu

Human epidermal growth factor receptor 2, c-erb B2, neu)

Transmembrane glycoprotein involved in cell growth control

Overexpression is associated with amplification of the gene on 17q21

Overexpression is associated with poorer survival but its main importance is as a predictor of response to agents that target it [e.g. Trastuzumab (Herceptin) or lapatinib]

Lymphovascular invasion

Strongly associated with the presence of lymph node metastases

Poor prognostic factor in women without lymph node metastases

Risk factor for local recurrence


Proliferative rate Tumors with high

proliferation rates have a worse prognosis

Methods to asses prolifetation Mitotic count

Immunohistochemical detection of cellular proteins produced during cell cycle (cyclins, Ki-67)

Flow cytometry as the S-phase fraction

Thymidine labeling index

DNA content Determined by flow

cytometry or image tissue analysis

Tumors with a DNA index of 1 have the same total amount of DNA as normal diploid cell

Aneuploid tumors are those with abnormal DNA indices and have a slightly worse prognosis


Response to

neoadjuvant therapy

Alternative approach

wherein patient is

treated before

surgery

Most likely to respond

well are poorly

differentiated, ER

negative tumors with

necrosis

Gene expression

profiling

Can predict survival

and recurrence-free

interval

Identifies patient who

are most likely to

benefit from

particular type of

chemotherapy

Stromal Tumors

Fibroadenoma

Most common benign tumor of the female breast

Epithelium is hormonally responsive

Characteristic large lobulated (popcorn) calcifications on mammography

Well circumscribed, rubbery mass

Stroma is usually delicate, cellular and often myxoid, enclosing glandular and cystic spaces lined by epithelium

Stromal Tumors

Phyllodes Tumor Arise fromintralobular

stroma like fibroadenoma

Cystosarcoma phllodes

Phyllodes (Greek, leaflike)

Varies in size, larger lesions often have bulbous protrusions

Distinguished fromfibroadenoma on the basis of cellularity, mitotic rate, nuclear pleomorphism, stromal overgrowth and infiltrative borders

Stromal Tumors

Benign stromal lesions

Pseudoangiomatous stromal hyperplasia

Fibrous tumors

Myofibroblastoma

Lipoma

Hamartoma

Fibromatosis

Clonal proliferation of fibroblasts and myofibroblasts

Locally aggressive but do not metastasize

Sarcomas

Malignant tumors of the extrinsic connective tissue of the breast

Angiosarcoma, rhabdomyosarcoma, liposarcoma, leiomyosarcoma, chondrosarcoma, osteosarcoma

Sarcomatous differentiation is seen in phyllodes tumor and metaplastic carcinomas

Other malignant tumors

Lymphomas

Mostly of large cell type of B-cell origin

Young women with Burkitt lymphoma may present with massive bilateral breast involvement and are often pregnant or lactating

Metastases

Most frequent nonmammary metastases are melanomas and lung cancer

Male Breast

Gynecomastia Enlargement of male

breast Proliferation of dense

collagenous connective tissue

Marked micropapillary hyperplasia of ductal linings

Seen in puberty, very aged, hyperestrinism (esp. in liver cirrhosis), Klinefelter syndrome (XXY), functioning testicular neoplasms

Male Breast Cancer

Frequency ratio to female breast cancer is less than 1:100

Risk factors similar to those in women

First degree relatives with breast cancer, decreased testicular function, exposure to exogenous estrogens, increasing age, infertility, obesity, prior benign breast disease, exposure to ionizing radiation, residency in Western countries

Gynecomastia is not a risk factor

4-14% are attributed to germ line BRCA2 mutations

ER positivity is more common in male breast cancer (81%)

Because breast epithelium in men is limited to large ducts near the nipple, cancer usually present as a palpable subareolar mass, 2-3cm in diameter

Prognostic factor are similar in men and women

Molecular classification

Studies of breast cancers using gene

expression profiling have identified several

major breast cancer subtypes

.The best characterized of these have been

designated :

luminal A, luminal B, HER2 and basal-like

basal-like breast cancers as a distinct group.

These tumors are invasive ductal carcinomas

that feature high-histologic grade,

solid architecture,

absence of tubule formation,

high mitotic rate,

a stromal lymphocytic infiltrate,

a pushing border,

geographic zones of necrosis

and/or a central fibrotic focus, and little or

no associated DCIS

-these tumors are typically ER-, PR-, and HER2-

negative (triple negative)

and show expression of basal cytokeratins,

EGFR, and other basal-related genes

-approximately 80% of BRCA1-associated breast

cancers cluster with the basal-like group

Luminal HER2 Basal

Gene Expression Patterns High expression of hormone receptors

and associated genes (luminal A>

luminal B)

High expression of HER2 and other

genes in amplicon

Low expression of ER and associated

genes

High expression of basal epithelial genes,

basal cytokeratins

Low expression of ER and associated

genes

Low expression of HER2

Clinical Features ~70% of invasive breast cancers

ER/PR positive

Luminal B tend to be higher-histologic

grade than luminal A

Some overexpress com-HER2 (luminal

B)

~15% of invasive breast cancers

ER/PR negative

More likely to be high grade and node-

positive HER2 overexpression and gene

amplification

~15% of invasive breast cancers

ER/PR/HER2 negative

BRCA1-associated cancers

Particularly common in African

American women

Treatment Response and Outcome Respond to endocrine therapy (response

may be different for luminal A and

luminal B)

Response to chemotherapy variable

(luminal B> luminal A)

Favorable prognosis

Respond to trastuzumab (Herceptin)

Respond to anthracycline-based

chemotherapy

Poor prognosis

No response to endocrine therapy or

trastuzumab (Herceptin)

?Response to platinum-based

chemotherapy

Poor prognosis

Table 10.6 Major Molecular Categories of Breast Cancer Determined by

Gene Expression Profiling

At the present time, the clinical value of characterizing invasive breast

cancers beyond routine histopathologic type and ER, PR, and HER2

status has not been established.

Molecular Category

Luminal A Luminal B HER2 Basal-like*

ER + + - -

PR + + - -

HER2 - + + -

*Additionally performing immunostains for cytokeratin (CK)5/6 and epidermal growth factor receptor (EGFR) helps to

define more precisely tumors in the basal-like group which in addition to being ER-, PR-, and HER2-negative are positive

for CK5/6 and/or EGFR.

Table 10.7 Immunophenotyping as a Surrogate for Molecular

Category Using Estrogen Receptor, Progesterone Receptor

and HER2 Status

Thank you.

Breast Patho Lect

Documents

Transcript of Breast Patho Lect