Breast Carcinoma
Dr. Ashraf A. Fatah
Assistant professor
Faculty of medicine
Majma’ah University
Breast carcinoma-
0BJECTIVES
 The epidemiology & Impact.
 The
etiology & morphology.
 Discuss
the laboratory diagnosis.
(Robbins Basic Pathology, 8th ed. P. 743- 750).
2
What is Breast Carcinoma?

Breast ca. is groups of heterogeneous
disease with a wide array of histological
appearances, clinical characteristic , and
prognosis.
Breast ca. is most prevalent “non-skin”
malignancy, primarily affects women but
also can affect men(1%) (F>>M).
 Breast ca. is the second cause of cancer
related death among women .
 WHO 2003- >1 million diagnosed worldwide
yearly
 1 out of 9 women who live to age 90- USA.


Underlying Genetic& enviromental
Anatomic origins of common
breast lesions
Epidemiology- incidence
Incidence of old
•female become to
increase due to:
Awareness
___________
II.Mammography
I.
Small DCIS lesion.
________________
III. Apply
national
Screening
program for
early detection
•
Epidemiology- Risks (BCRAT)
• Gender (M= 1% risk)
• Age (peak75-80,46y)
• Age menarche
(early menarche & late
menopause)
• Age at First Live
Birth-1st pregnancy20
• Late menopause..
• Family hx:1st degree
• Genetic abn. BRCA1
and BRCA2 mutations
• Radiation therapy
• Race/Ethnicity
• Atypical
Hyperplasia& cancer in
other breast.
• Breast density
• Obesity in young
<40–decrease risk
• Estrogen exposure
-replacement .
• Alcohol consumptio
• Tobacco,smoking&
diet- still not clear
Epidemiology- Risks (BCRAT)
 Factors
associate with decrease risk:
 Obesity:<40y female- anovulatory cycles.
 Coffee (caffeine)-consumption.
 Breast Lactation suppresses ovulation.
 Exercise- small protective effects.
 Reducing endogenous estrogens by drug
or oophorectomy
Conclusion: what is the major risk factors?
Major risk factors for the development
of breast cancer are hormonal and
genetic
The impact of breast cancer
 Long-term
 Emotional
 Changes
 Diet
side effects of treatment
effects&Your relationships
to your body-
esp. young ladies.
and physical activity
 Practical
issues: work, money or
insurance.
 Fund-burden
for diagnosis, molecular
workup and Researches
Breast carcinoma-0BJECTIVES
 Discuss
the epidemiology &
Impact of breast cancer.
 Define
the etiology+morphology.
 Discuss
the laboratory diagnosis.
(Robbins Basic Pathology, 8th ed. P. 743- 750).
9
Breast carcinoma- Etiology
 Based
on risks factors the etiology
divided into two categories;
 1. Hereditary breast cancer- 12% of
cancer, Genetic mutation affect 1st
degree relatives in BRCA1, BRCA2,
P53, CHEK2 genes.
 2. Sporadic breast cancer duet to
Hormonal exposure- gender, age at
menarche, menopause, reproductive
hx, breastfeeding, exogenous
estrogens(play a direct role in
carcinogenesis)
BRCA1/BRCA2,P53 &CHEK2
tumor suppressor GENES
 BRCA1
(chr17): single gene hereditary
cancer risk 52%= 2% of all breast ca.poor differentiated with medullary
feature, ER negative
 BRCA2(chr13) : single gene hereditary
cancer risk 32%= 1% of all breast ca.
poor differentiated, ER positive.
 P53 (chr17): single gene hereditary
cancer risk 3%= <1% of all breast ca
 CHEK2(chr22)single gene hereditary ca= 5%
BRCA1/BRCA2, P53
tumor suppressor GENES
 These
Genes mutations are associated :
increased risk for Male breast
ca(BRCA2) Pancreatic, prostate, ovarian
ca.
 The majority of sporadic cancers
occur in postmenopausal ,hormonal
exposure and are ER positive.
 Metabolites of estrogen can cause
mutations or generate DNAdamaging free radicals in cell.
 BREAST
CARCINOMA-MORPHOLOGY
The normal breast depend on a complex interplay
between luminal cells, myoepithelial cells, stroma.









A. Breast Duct syst.
B. Lobules
C. Nipple
D. Fat + CT
E. Vessels
(Lymphatic blood)
F. Attached to Chest
Muscle & Ribs
A. Cells lining duct
B. Basement membrane
C. Open central duct
Morphologic changes displayed from left to right
according to the risk for subsequent invasive ca.
CLASSIFICATION OF BREAST CARCINOMA
 Carcinoma:

It is not one disease, but many, heterogeneous
group.
 Greater>95%
are adenocarcinoma from
ducts and lobules- classified in to:
–In-situ carcinoma (15-30%)increase with Mammography(calcification+ periductal fibrosis )
(lobular & Ductal)
–Invasive carcinoma (infiltrating)(7085%)
(lobular & Ductal)
CLASSIFICATION OF BREAST CARCINOMA
Distribution of
Histologic Types of Breast Cancer
Types
Carcinoma In-situ
Percentages
15- 30%
DCIS
80%
LCIS
20%
Invasive carcinoma
70- 85%
IDC- NOS
79%
Lobular carcinoma
10%
Tubular/cribriform carcinoma
6%
Mucinous (colloid) carcinoma
2
Medullary carcinoma
2
Papillary carcinoma
2
Metaplastic carcinoma
<1
Ductal carcinoma in-situ(DCIS)
involve Ductal System.
Vague palpable mass
* +micro-calcification
 +\-Nipple discharge
 + periductal fibrosis
 limited to BM




5 VARIANTS (Comedo,
solid, papillary,
micropapillary,
cribriform).
A. Cells lining duct
C. Intact basement
membrane
D. Open central duct
Cribriform
- Solid DCIS Comedo DCIS
Paget’s disease
DCIS-Epidermal
erythematous&scales
Mammogram; calcification
Papillary DCIS
Lobular carcinoma in situ(LCIS)









Breast Lobular system
1 to 6% of all ca.
Bilateral 20%
No calcification
A. Cells are identical
and dyscohesive
B. Cancer cells, but all
contained within the
lobules
C. BM intact
D.ER+PR positive, her2
is negative
The cells lack the cell
adhesion protein Ecadherin
Lobular carcinoma in-situ(LCIS)
Invasive ductal carcinoma IDC









A. Duct System.
B. irregular border, firm
C. Peau d'orange app
( skin changes-tethering)
D. +\- % LN metas. +
desmoplastic stroma
A. Cells lining duct
B. Extra cancer like
cells, but acontained
within duct
C. Intact basement
membrane
D. Open central duct
Invasive ductal carcinoma
tumor with irregular border + calcifiacation, margins
Invasive ductal carcinoma
Invasive Lobular carcinoma ILC
A.Involved lobular System.
B. difficult to be detected.
C. bilterality,multi-centeric, multifocality
D. irregular border, firm.
E. dyscohesive cells. Absent tubules.
F. Cells arranged in single file, loose clusters
or sheet, targetoid, occ. Signet-ring cell.G.
minimal desmoplasia
.
H. ER positive, +\- LCIS& HER2/neu
overexpression is very rare.
Graded as: well, moderate, poor
differentiation.
Metastasis : occur to the peritoneum and
retroperitoneum, the leptomeninges
Inavsive Lobular carcinoma
Vascular & lymphatic invasion(VLI)
A. Veins in breast
 B. Lymph channels

A. Cells lining duct
 B. Cancer cells,
breaking through BM.
 C. Broken BM
 D. Cancer entering a
lymph channel.
 E. Cancer entering
vein.

Medullary carcinoma
Circumscribed ,
rapid growing mass
+ pushing border
 solid, syncytiumlike cohesive cell.




The cells are highly
pleomorphic with
frequent mitoses
Poorly differentiated
lymphoplasmacytic
infiltrate is
prominent
Mucinous (colloid) carcinoma.
Soft and Rubbery
consistency+
border pushing.
 tumor cells are
present as small
clusters within
large pools of
mucin.
 The borders are
typically well
circumscribed,
 Often good
prognosis

Tubular carcinoma
completely
composed of wellformed tubules
lined by a single
layer of welldifferentiated cells
 Myoepithelial
absent.
 Cribriform+
apocrine snout +
calcification.
 ER+VE, Her2 -ve

Metastatic breast cancer-IDC
Breast carcinoma-0BJECTIVES
 Discuss
the epidemiology &
Impact of breast cancer.
 Define
the etiology +
morphology.
 Discuss
the laboratory diagnosis.
(Robbins Basic Pathology, 8th ed. P. 743- 750).
34
Signs and Symptoms
lump or mass
Often
painless
Discharg
e or
bleeding
Change in size or
contours of
breast
35
Redness or pitting of
skin over the breast,
like the skin of an
orange
Change in color
or of areola
apperance
Symptoms
 In
early breast ca
–Easily self palpated
–Nipple discharge
–May accompanied with axillary LN
 Late
breast ca
–Local usually symptomatic
–Depends on metastatic sites
Diagnostic tools
 Breast
sonography & guided BIOPSY
– Superior in dense breast, young age
 Mammography
– Superior in loose(fatty) breast, elder
 Cytology
– Fine-needle aspiration (FNA)
 Biopsy-
histopathology
– Incision– Excision- MASTECTOMY\lump
– Immunohistochemical studies- receptor
CYTOLOGY&CORE ASSESSMENT
Macroscopic finding-Mastectomy
specimen
Receptor status
 Hormone
receptor
– Estrogen receptor (%)-diagnostic,
therapeutic & prognostic
– Progesterone receptor (%)
>10% predict response to hormone tx
 Lobular,
tubular, mucinous usually positiv
 Her2/neu
– Associate with invasion, metastasis…
– Predict poor prognosis
– IHC stain, FISH
Breast carcinoma
Her2\neu +ve
ER postive
Ideal Histopathology diagnosis
Size of tumor (TNM-STAGING)
 Grade
– Tubule Formation (Grading system)
– Nuclear Pleomorphism (Grading system)
– Mitotic Count (Grading system)
 Vascular lymphatic invasion(VLI)
 Perineural invasion(PNI)
 Nipple involvement- Paget’s disease
 Skin involvement
 Lymph node metastasis (TNM-STAGING)
 Homonal receptors status (ER, PR,Her2)

Bloom& Richardson grading system
The UICC\TNM classification
Molecular diagnosis of breast ca.
These tumors tend to be*
Luminal A
ER+ and/or PR+, HER2-, low Ki67
Luminal B
ER+ and/or PR+, HER2+ (or HER2- with
high Ki67)
Prevalence
(approximate)
40%
best prognosis.
20%
Triple
ER-, PR-, HER2negative/basal-like
15-20%
HER2 type
10-15%
ER-, PR-, HER2+
*These are the most common profiles for each subtype. However, not all tumors
within each subtype will have all these features.
ER = estrogen receptor
PR = progestrogne receptor
PROGNOSTIC AND PREDICTIVE FACTORS
 Invasive
carcinoma versus in situ
disease.
 Distant
metastases.
 Lymph
node metastases.
 Tumor
size.
 Locally
advanced disease.
 Inflammatory
carcinoma
Overview
What is breast cancer?
 What are Causes and risks?
 How about some Epidemiology?
 What’s the deal with BRCA1 and BRCA2?
 What’s are the main type of breast
carcinoma? How you described different
morphological pattern?
 How we usually diagnosed breast mass\
tumor specially if it is suspicious?
 What’s the ideal histopathology report and
how its is significant in our clinical life?
