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Breast Cancer

Breast Cancer

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Published by: sarguss14 on Dec 05, 2008
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07/13/2014

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Pathology (Dra. Sionzon)
Breast Carcinoma
Hindi ni lecture!
Case
49 F
Firm, non-tender lump
Irregular, firm fixed mass, right breast
Rough, reddened overlying skin
Mammography: irregular
 The irregular mass lesion seen here is aninfiltrating ductal carcinoma of breast. Thecenter is very firm (scirrhous) and whitebecause of the desmoplasia. There are areasof yellowish necrosis in the portions of neoplasm infiltrating into the surroundingbreast. Such tumors appear very firm andnon-mobile on physical exam.
 This breast biopsy demonstrates a carcinoma.Note the irregular margins and varied cutsurface. This small cancer was found bymammography. The margins of the specimenhave been inked with green dye followingremoval to assist in determining whethercancer extends to the margins oncehistologic sections are made.
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?
Male breast cancer is 100x less common thanbreast cancer in women
Histologically, it has the same features as themore common cancer of the female breast
50% of tumors have already metastasize atthe time of diagnosis
Risk Factors
1.Country of birth2.Family Hx – 1st degree relative, affected at anearly age, bilateral
chrom 17q- BRCA1 ~ ovarian CA
chrom 13q12-13- BRCA23.Menstrual & Reproductive Hx – late parity
low risk for post-oophorectomy4.Fibrocystic Dse & Epithelial Hyperplasia5.Exogenous Estrogens6.Contraceptive Agents7.Ionizing Radiation8.Breast Augmentation9.Meningioma; Ataxia-Telangiectasia
Location
 
Farsi
1 of 6
BREAST CARCINOMAOVERVIEW OF BREAST CARCINOMA
 
Pathology –
Breast Carcinoma
by 
 Dra. Sionzon
Page
2
of 6
Multicentricity
(+) of CA in a breast quadrant other the 1containing the dominant mass
more in lobular than duct CA
Bilaterality
5X for invasive CA, more so for (+) Family Hx
more in lobular
can be synchronous or metachronous
intramammary or independent spread
MammographyFine Needle Aspiration BiopsyMicroscopic Grading of Breast Carcinoma:Nottingham Modification of the BloomRichardson SystemTubuleFormation
 1 point Tubular formation in >75% of thetumor2 points Tubular formation in 10% to 75%of the tumor3 points Tubular formation in <10% of thetumor
NuclearMorphism
 1 pointNuclei with minimal variation insize and shape2 pointsNuclei with moderate variation insize and shape3 pointsNuclei with marked variation insize and shape
Rosai, J. Ackerman’s Surgical Pathology 
Grade I3-5 points
Grade II6-7 points
Grade III8-9 points
What are the prognostic factors in breastcancer?CATEGORY I
Proven Prognostic or Predictive
 Tumor stage using AJCC\UICC TNMsystem
 Tumor size
Nodal status
Histologic grade and type
Hormone receptor status
CATEGORY II
Promising Prognostic or Predictive
HER-2/
neu
p53
Vascular invasion
Cell proliferation
 Tumor angiogenesis
Epidermal growth factor receptor(EGFR)
CATEGORY III
Factors needing further evaluation
bcl-2
 TGF-a
 Thrombomodulin
BRCA1 and 2
Cathepsin D
Hormone Receptor Status
Correlates well with response to hormonetherapy and chemotherapy
Can be done by:
Biochemical method
Immunohistochemical stains
In situ hybridization
Associated with:
High nuclear & low histologic grades
Absence of tumor necrosis
Absence of p53 mutations
Bcl2 immunoreactivityextremely smalltumors (1-2 mm)calcificationCA --- 50-60%benign --- 20%
 
Pathology –
Breast Carcinoma
by 
 Dra. Sionzon
Page
3
of 6
Progesterone receptor (PR) positivity in abreast carcinoma. The usefulness of thisdetermination is not as well established as forestrogen receptors. Carcinomas that are PRpositive, but not ER positive, may have aworse prognosis.
Estrogen receptor (ER) positivity in a breastcarcinoma. The use of the immunoperoxidasetechnique allows determination of ERpositivity within just the nuclei of theneoplastic cells, without interference fromother cells.
HER-2/
neu
Gene
HER-2/
neu
is a gene which belongs to afamilyof genes that produce humanepidermal growth factor receptors.
It is called HER-2 because it was the secondgene of that gene family identified.
It is called neu because it was first identifiedin tumors of the neurological system.
 The gene was studied by 2 different groups of researchers. The second group called it cerbB-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 bymutation/amplification and which promotescancer development
It is localized to chromosome 17q
Encodes for a transmembrane growth factorreceptor
Has tyrosine kinase activity
HER-2/
neu
Protein
HER-2/
neu
gene produces a transmembrane185-kDa protein which is expressed in normalsecretory 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 thecell surface that receives signals whichregulate cell growth.
In a normal cell there are 2 copies of theHER-2/
neu
gene in the nucleus andapproximately 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 toadverse outcome in 1986
>100 studies of gene amplification andprotein overexpression published by late1997
>85% of studies have associated increasedHER-2/
neu
activity with poor prognosis inlymph node negative disease
Expression of c-erbB-2 is significantly relatedto positive lymph nodes, poor nuclear grade,and lack of steroid receptors and highproliferative activity.
Patients expressing this antigen have a poorprognosis. Anthracyclin adjuvant therapy ismore beneficial to patients expressing thisantigen.
HER-2/
neu
Staining Intensity CB11, BreastCarcinomaWhat is the significance of HER-2/neupositivity in breast carcinoma?HER-2/
neu
as Target of Therapy
Anti-HER-2/
neu
therapeutic antibodies(Herceptin®)
HER-2/
ne
u
 
antibody directed therapy
IN SITU CARCINOMA

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