““Strength does not come from Strength does not come from winning. Struggles & Hardship winning. Struggles & Hardship develop your strength. When you go develop your strength. When you go through hardship and decide not to through hardship and decide not to surrender, that is strength”surrender, that is strength”

Arnold SchwarzeneggerArnold Schwarzenegger Bodybuilder and ActorBodybuilder and Actor

Pathology of Breast Pathology of Breast CancerCancer

Dr. Venkatesh M. ShashidharDr. Venkatesh M. ShashidharSenior Lecturer in PathologySenior Lecturer in PathologyFiji School of MedicineFiji School of Medicine

IntroductionIntroduction

Modified sweat glands.Modified sweat glands. Lobes and lobules of gland Lobes and lobules of gland in fat tissue stroma.in fat tissue stroma. Ducts emerge from acini of glandsDucts emerge from acini of glands Smaller ducts join to form lactiferous Smaller ducts join to form lactiferous

ductsducts Lactiferous ducts merge just beneath the Lactiferous ducts merge just beneath the

nipple to form a lactiferous sinus.nipple to form a lactiferous sinus. Then individually open on nipple Then individually open on nipple

Normal BreastNormal Breast

Myoepithelial Cells (ipx)Myoepithelial Cells (ipx)

DisordersDisorders CongenitalCongenital

Aplasia – turners, Juvenile hypertrophyAplasia – turners, Juvenile hypertrophy InflammatoryInflammatory

Infections acute/chronic – Trauma Fat necrosisInfections acute/chronic – Trauma Fat necrosis Duct ectasia discharge, sinusDuct ectasia discharge, sinus Fibrocystic disease – common – painful lumpsFibrocystic disease – common – painful lumps

NeoplasticNeoplastic Benign - FibroadenomaBenign - Fibroadenoma Malignant – Ca Malignant – Ca

Fibrocystic DiseaseFibrocystic Disease Fibroadenosis, Fibrocystic change, etc.Fibroadenosis, Fibrocystic change, etc. Commonest lump, 10-50% womenCommonest lump, 10-50% women ? Hormonal? Hormonal Periodic discomfort – pain.Periodic discomfort – pain. Eipethilial hyperplasia – premalignantEipethilial hyperplasia – premalignant Irregular palpable lumps – mimic ca.Irregular palpable lumps – mimic ca.

Adenosis – hyperplasia - cysts – papillomatosis – Adenosis – hyperplasia - cysts – papillomatosis – metaplasia – fibrosis.metaplasia – fibrosis.

Benign Neoplasms:Benign Neoplasms: Fibroadenoma Fibroadenoma Duct PapillomaDuct Papilloma AdenomaAdenoma Connective tissue tumorsConnective tissue tumors

Features (Fibroadenoma)Features (Fibroadenoma) Young age 3Young age 3rdrd decade. decade. Single, rounded, mobile, painless lumps. Single, rounded, mobile, painless lumps. No scarring or calcification.No scarring or calcification. Slit like glands in Fibrous stromaSlit like glands in Fibrous stroma

Breast Carcinoma Breast Carcinoma

20% of all cancers in 20% of all cancers in womenwomen

Commonest cause of death - Commonest cause of death - 35-55y35-55y

In UK 1 in 10-12 chancesIn UK 1 in 10-12 chances 1 in 8 women in US1 in 8 women in US Less incidence in AsiaLess incidence in Asia Majority of cancers arise in Majority of cancers arise in

the ducts.the ducts. Very rare before age 25Very rare before age 25

Risk Factors:Risk Factors:

Female sex..!, Age, Obesity, high fat diet Female sex..!, Age, Obesity, high fat diet Maternal relative with breast cancer. Maternal relative with breast cancer. Longer reproductive span. Longer reproductive span. Nulliparity, Oral contraceptivesNulliparity, Oral contraceptives Later age at first pregnancy. Later age at first pregnancy. Atypical epithelial hyperplasia. Atypical epithelial hyperplasia. Previous breast cancer/Endometrial Ca. Previous breast cancer/Endometrial Ca. Geographic factors - countryGeographic factors - country BRCA1 and BRCA2BRCA1 and BRCA2 genes genes

Etiology of Breast Carcinoma:Etiology of Breast Carcinoma:

Clinical Features:Clinical Features: Physiologic vs Pathologic changesPhysiologic vs Pathologic changes Lump / lumpsLump / lumps Lumps are much more common than CaLumps are much more common than Ca Characters of Characters of lumplump* and * and ageage** Discharge in many conditions.Discharge in many conditions. Hard, soft, inflammationHard, soft, inflammation Skin fixation / Skin fixation / SkinSkin retractionretraction * *

Diagnosis:Diagnosis: MammorgraphyMammorgraphy UltrasoundUltrasound Fine Needle Aspiration BiopsyFine Needle Aspiration Biopsy Core BiopsyCore Biopsy Excision BiopsyExcision Biopsy Frozen sectionFrozen section Immunoperoxidase,Immunoperoxidase, Molecular techniques – Gene detection.Molecular techniques – Gene detection.

Histological TypesHistological TypesHistologic Type Freq. (UK)

Infiltrating Duct Ca 63.6 (75)

Lobular Carcinoma 5.9 (10)

Infiltrating Ductal & Lobular Ca 1.6

Medullary Carcinoma 2.8 (3)

Mucinous (colloid) Carcinoma 2.1 (3)

Comedocarcinoma 1.4

Carcinoma-In-Situ 5%

Breast Carcinoma Breast Carcinoma

Breast Carcinoma Breast Carcinoma

Breast Carcinoma - SchirrousBreast Carcinoma - Schirrous

Infiltrating Duct Carcinoma: small hardInfiltrating Duct Carcinoma: small hard

Medullary Carcinoma: Large softMedullary Carcinoma: Large soft

Infiltrating Duct CarcinomaInfiltrating Duct Carcinoma

Infiltrating Duct CarcinomaInfiltrating Duct Carcinoma

Medullary Carcinoma: Inflammation.Medullary Carcinoma: Inflammation.

Infiltrating Duct Carcinoma: FibrosisInfiltrating Duct Carcinoma: Fibrosis

Schirrous CarcinomaSchirrous Carcinoma

Medullary CarcinomaMedullary CarcinomaSoft, inflammatory cellsSoft, inflammatory cells

Intraductal in-situ CarcinomaIntraductal in-situ Carcinoma

Lobular CarcinomaLobular Carcinoma

Intraduct Carcinoma-in-situIntraduct Carcinoma-in-situ

Intraduct CarcinomaIntraduct Carcinoma

Lymphatic spread – Peu-de Orange..Lymphatic spread – Peu-de Orange..

Spread of Breast Spread of Breast Carcinoma:Carcinoma:

Pagets DiseasePagets Disease

Pagets Disease (Epidermal invasion)Pagets Disease (Epidermal invasion)

Estrogen Receptor & Prognosis:Estrogen Receptor & Prognosis: Estrogen receptor expression is Estrogen receptor expression is

proportional to differntiation of tumorproportional to differntiation of tumor inversly proportional to prognosis and inversly proportional to prognosis and

response to tamoxifen (receptor antagonist) response to tamoxifen (receptor antagonist) therapy.therapy.

Demonstrated by Immunoperoxidase Demonstrated by Immunoperoxidase special stain.special stain.

HER2HER2 The HER2 proto-oncogene encodes a cell The HER2 proto-oncogene encodes a cell

surface receptor that is overexpressed in surface receptor that is overexpressed in approximately 25%-30% of breast cancers. approximately 25%-30% of breast cancers.

Trastuzumab (Herceptin®) is the first Trastuzumab (Herceptin®) is the first monoclonal antibody that targets the monoclonal antibody that targets the extracelluar domain of the HER2 protein, extracelluar domain of the HER2 protein, and inhibits growth of breast cancer cells and inhibits growth of breast cancer cells that over express this protein. that over express this protein.

Estrogen receptor (ER) in nucleiEstrogen receptor (ER) in nuclei

Immunoperoxidase Positivity Immunoperoxidase Positivity

Neg 1+

2+ 3+

Stag Definition 5-year

Surv (%) 7-year Surv (%)

I Tumor 2 cm or less without spread 96 92

II

Tumor 2-5cm with regional lymph node involvement but without distant metastases, OR > 5 cm in diameter without spread

81 71

III

Any size with skin/chest wall fixation, & axillary or internal mammary nodal involvement, without distant metastases

52 39

IV Tumor of any size with or without regional spread but with evidence of distant metastases

18 11