Pathology (Dra.

Sionzon)
Breast Carcinoma
Hindi ni lecture!

BREAST CARCINOMA have been inked with green dye following

removal to assist in determining whether
Case cancer extends to the margins once
 49 F histologic sections are made.
 Firm, non-tender lump
 Irregular, firm fixed mass, right breast
 Rough, reddened overlying skin
 Mammography: irregular

OVERVIEW OF BREAST CARCINOMA

Incidence
 most common malignancy & leading cause of
CA death in females
 more common in Europeans & Americans
 localized
 less than 2 cm in diameter or in situ

What about cancer of the male breast?

 The irregular mass lesion seen here is an  Male breast cancer is 100x less common than
infiltrating ductal carcinoma of breast. The breast cancer in women
center is very firm (scirrhous) and white  Histologically, it has the same features as the
because of the desmoplasia. There are areas more common cancer of the female breast
of yellowish necrosis in the portions of  50% of tumors have already metastasize at
neoplasm infiltrating into the surrounding the time of diagnosis
breast. Such tumors appear very firm and
non-mobile on physical exam. Risk Factors
1. Country of birth
2. Family Hx – 1st degree relative, affected at an
early age, bilateral
• chrom 17q - BRCA1 ~ ovarian CA
• chrom 13q12-13 - BRCA2
3. Menstrual & Reproductive Hx – late parity
• low risk for post-oophorectomy
4. Fibrocystic Dse & Epithelial Hyperplasia
5. Exogenous Estrogens
6. Contraceptive Agents
7. Ionizing Radiation
8. Breast Augmentation
 This breast biopsy demonstrates a carcinoma. 9. Meningioma; Ataxia-Telangiectasia
Note the irregular margins and varied cut
surface. This small cancer was found by Location
mammography. The margins of the specimen
Farsi 1 of 6
 Pathology – Breast Carcinoma by Dra. Sionzon Page 2 of 6

size and shape

Nuclei with moderate variation in
2 points size and shape
Nuclei with marked variation in
3 points size and shape
Rosai, J. Ackerman’s Surgical Pathology
 Grade I 3-5 points
 Grade II 6-7 points
 Grade III 8-9 points

What are the prognostic factors in breast

Multicentricity cancer?
 (+) of CA in a breast quadrant other the 1
containing the dominant mass CATEGORY I
 more in lobular than duct CA  Proven Prognostic or Predictive
 Tumor stage using AJCC\UICC TNM
Bilaterality system
 5X for invasive CA, more so for (+) Family Hx  Tumor size
 more in lobular  Nodal status
 can be synchronous or metachronous  Histologic grade and type
 intramammary or independent spread  Hormone receptor status
Mammography CATEGORY II
extremely small  Promising Prognostic or Predictive
tumors (1-2 mm)  HER-2/neu
 p53
calcification
 Vascular invasion
CA --- 50-60%  Cell proliferation
 Tumor angiogenesis
benign --- 20%  Epidermal growth factor receptor
(EGFR)

Fine Needle Aspiration Biopsy CATEGORY III

 Factors needing further evaluation
 bcl-2
 TGF-a
 Thrombomodulin
 BRCA1 and 2
 Cathepsin D

Hormone Receptor Status

 Correlates well with response to hormone
Microscopic Grading of Breast Carcinoma: therapy and chemotherapy
Nottingham Modification of the Bloom  Can be done by:
Richardson System  Biochemical method
Tubule  Immunohistochemical stains
Formation  In situ hybridization
Tubular formation in >75% of the  Associated with:
1 point tumor  High nuclear & low histologic grades
Tubular formation in 10% to 75%  Absence of tumor necrosis
2 points of the tumor  Absence of p53 mutations
Tubular formation in <10% of the  Bcl2 immunoreactivity
3 points tumor
Nuclear
Morphism
1 point Nuclei with minimal variation in
 Pathology – Breast Carcinoma by Dra. Sionzon
 Progesterone receptor (PR) positivity in a
breast carcinoma. The usefulness of this
determination is not as well established as for
estrogen receptors. Carcinomas that are PR
positive, but not ER positive, may have a
worse prognosis.
 Estrogen receptor (ER) positivity in a breast
carcinoma. The use of the immunoperoxidase
technique allows determination of ER
positivity within just the nuclei of the
neoplastic cells, without interference from
other cells.
HER-2/neu Gene
 HER-2/neu is a gene which belongs to a
“family” of genes that produce human
epidermal growth factor receptors.
 It is called HER-2 because it was the second
gene of that gene family identified.
 It is called neu because it was first identified
in tumors of the neurological system.
 The gene was studied by 2 different groups of
researchers. The second group called it c
erbB-2.
The HER-2/neu Gene
(oo ganon talaga, iba to sa HER-2 kse meron to THE
HER-2 hehe. Copy paste lang gnagawa ko e.)
 HER-2/neu gene is an oncogene
 An oncogene is a gene activated by
mutation/amplification and which promotes
cancer development
 It is localized to chromosome 17q
 Encodes for a transmembrane growth factor
receptor
 Has tyrosine kinase activity
Page 3 of 6
HER-2/neu Protein
 HER-2/neu gene produces a transmembrane
185-kDa protein which is expressed in normal
secretory epithelial cells (including breast,
pancreas, intestine and salivary gland).
 It is also known as neu, c-neu, p185, c-erbB-2
 The HER-2/neu protein is a receptor on the
cell surface that receives signals which
regulate cell growth.
 In a normal cell there are 2 copies of the
HER-2/neu gene in the nucleus and
approximately 50,000 copies of the HER-
2/neu protein on the cell surface.
HER-2/neu and Breast Cancer
 HER-2/neu gene amplification was linked to
adverse outcome in 1986
 >100 studies of gene amplification and
protein overexpression published by late
1997
 >85% of studies have associated increased
IN SITU CARCINOMA
HER-2/neu activity with poor prognosis in
lymph node negative disease
 Expression of c-erbB-2 is significantly related
to positive lymph nodes, poor nuclear grade,
and lack of steroid receptors and high
proliferative activity.
 Patients expressing this antigen have a poor
prognosis. Anthracyclin adjuvant therapy is
more beneficial to patients expressing this
antigen.
HER-2/neu Staining Intensity CB11, Breast
Carcinoma
What is the significance of HER-2/neu
positivity in breast carcinoma?
HER-2/neu as Target of Therapy
 Anti-HER-2/neu therapeutic antibodies
(Herceptin®)
 HER-2/neu antibody directed therapy
 Pathology – Breast Carcinoma by Dra. Sionzon Page 4 of 6

 chemotherapy delivery (adriamycin)  Atypia, polymorphism, mitotic activity and

 radioisotope delivery necrosis are minimal or absent.
 HER-2/neu mediated immunocytotoxicity
 HER-2/neu vaccination
 HER-2/neu gene therapy (antisense
oligonucleotides; promoter gene inactivation

Fig. 8 Lobular carcinoma in situ

Minor Morphologic Variations

 Moderate nuclear pleomorphism
 Large nuclear size
 This is positive immunoperoxidase staining  Loss of cohesiveness
for C-erb B-2 (C-neu) in a breast carcinoma.  Appreciable mitotic activity
Note the membranous staining of the
 Scattered signet ring cells
neoplastic cells. There is a correlation
 Apocrine changes
between C-erb B-2 positivity and high nuclear
grade and aneuploidy.  Focal necrosis
 Variation in shape of the involved lobule
DUCTAL CARCINOMA IN-SITU
Morphologic variants: DUCTAL CHANGES IN LCIS
 Papillary  The neighboring terminal ducts may exhibit
 Comedocarcinoma proliferation of cells similar to those involving
the lobules.
 Solid
 May form a mural/ pagetoid pattern
 Cribriform
 Can also grow in solid cribrifrom or
 Micropapillary
micropapillary
 Clinging
 Cystic hypersecretory

EVOLUTION
 The transformation into an invasive
phenotype does not occur in all cases.
 When such transformation occurs, the
process usually evolves over years or
decades.
 There is a substantial difference in the
frequency w/ which this phenomenon occurs
depending on the type of DCIS. The risk for
dev’t of invasive CA is directly proportional to Fig. 9 Involvement of duct by lobular CA In situ
the cytologic grade of the tumor.
 There is a definite relation ship between LCIS
microscopic type of DCIS and the invasive  May also be found in found in fibroadenomas
component. and in foci of sclerosing adenosis
 Not all invasive breast CA go through the  To establish diagnosis from these, cellular
sequence just described proliferation must have resulted in the
formation of solid nests that have expanded
LOBULAR CA IN SITU the lobules.
Microscopic
 The lobules are distended and completely Lobular CA In Situ
filled by relatively uniform, round, small to Special stains:
medium size cells with round normochromatic  Mucin – positive in scattered tumor cells in ¾
(or mildly hyperchromatic) nuclei. of cases.
 Pathology – Breast Carcinoma by Dra. Sionzon Page 5 of 6

 Laminin & collagen type IV can be

demonstrated in underlying basement
membrane

Immunohistochemically:
 (+) keratin,
 (+) EMA
 (+) Milk fat globule antigen
 (+) S-100 in 60% of cases

EVOLUTION
 20%-30% of px will develop Invasive CA, (a
risk about 8-10x higher)
 The risk seems greater in well developed LCIS
than in atypical lobular hyperplasia.
 The increase risk applies to both breasts,
although it is greater on the side of the  This high power microscopic view
biopsy. demonstrates intraductal carcinoma.
 The invasive CA may be of either lobular or Neoplastic cells are still within the ductules
ductal type. and have not broken through into the stroma.
Note that the two large lobules in the center
 The amount of LCIS or its morphologic
contain microcalcifications. Such
variations bears little or no relation to the
microcalcifications can appear on
magnitude of the risk.
mammography.
 If a patient with a biopsy diagnosis of LCIS is
examined periodically, the chances of her
dying as a result of breast CA are minimal.
 “ Careful life long follow up”
 Simple mastectomy can be considered in the
presence of strong family history of CA,
extensive FCC or excessive apprehension in
part of the patient, ….. Or if prolong follow-up
evaluation cannot be assured.

 Lobular carcinoma in situ is seen here.

Lobular CIS consists of a neoplastic
proliferation of cells in the terminal breast
ducts and acini. The cells are small and
round. Though these lesions are low grade,
there is a 30% risk for development of
invasive carcinoma in the same or the
opposite breast.

 Invasive lobular carcinoma of the breast is

shown here. This neoplasm arises in the
 Pathology – Breast Carcinoma by Dra. Sionzon Page 6 of 6

terminal ductules of the breast. About 5 to

10% of breast cancers are of this type. There
is about a 20% chance that the opposite
breast will also be involved, and many of
them arise multicentrically in the same
breast.

 "Indian file" strands of infiltrating lobular

carcinoma cells are seen in the fibrous
stroma. Pleomorphism is not great.

Brim! E2 na kapalit ng CNS 1 na hiningi ko sayo. Sabi

ko after ng micro exams. Ayan ha, wala na kong
utang. Kng may typo d2 hnd ko na kasalanan yon,
copy paste lang talaga ginawa ko.

Last trans ko na to for this A.Y. Y-E-H-E-Y! Excited na

ko, sa kng saan, akin na lang yon. yihee