Carcinoma breastCarcinoma breastEtiologyEtiology

Commoner in westernCommoner in westernAfter middle ageAfter middle age

Familial in 5%Familial in 5%Mutation of tumour suppressor genesMutation of tumour suppressor genes

1.1. BRCA1-located in longarm of BRCA1-located in longarm of chromosome17chromosome17

2.2. BRCA2-located in longarm of BRCA2-located in longarm of chromosone13chromosone13

Li-Fraumen’s syndrome is autosomal Li-Fraumen’s syndrome is autosomal dominant condition in breast cancer dominant condition in breast cancer

inheritanceinheritanceDiet low in phytoestrogens and high alcoholDiet low in phytoestrogens and high alcohol

Commoner in nulliparous.obese women-Commoner in nulliparous.obese women-(contd)(contd)

Carcinoma breastCarcinoma breast EtiologyEtiology

Early menarchy and late menopauseEarly menarchy and late menopause Early childbearing and breastfeeding Early childbearing and breastfeeding

reducesreduces 3-5 times risk when first degree relatives 3-5 times risk when first degree relatives

havehave Benign conditons as Benign conditons as

atypia,hyperplasia,epitheliosisatypia,hyperplasia,epitheliosis

Carcinoma breastCarcinoma breast PathologyPathology Lactiferous duct-ductal ca.Lactiferous duct-ductal ca. Lobules-lobular ca.(10%)Lobules-lobular ca.(10%) Both may be of insitu or invasiveBoth may be of insitu or invasive Mainly unilateral (2-5% bilateral)Mainly unilateral (2-5% bilateral) Unifocal or multifocalUnifocal or multifocal Multifocal—tumour tissue within the same Multifocal—tumour tissue within the same

quadrant at multiple fociquadrant at multiple foci Multicentric---tumour tissue within the Multicentric---tumour tissue within the

same breast but different quadrantsame breast but different quadrant

Normal anatomyNormal anatomy

Lobular ca insituLobular ca insitu

Invasive lobularInvasive lobular

Ductal ca.in situDuctal ca.in situ

Invasive ductal ca.Invasive ductal ca.

DCISDCIS

DCISDCIS Intra-ductal ca. without any invasion into Intra-ductal ca. without any invasion into

the basement membrane is the basement membrane is 5-20% common. The histological variants 5-20% common. The histological variants

areare SolidSolid Comedo(central necrosis-fast growing)Comedo(central necrosis-fast growing) CribriformCribriform PapillaryPapillary Risk of lymphnode spread is negligible.so Risk of lymphnode spread is negligible.so

axillary dissection is not necessary.axillary dissection is not necessary.

DCISDCIS SOLIDSOLID CRIBRIFORMCRIBRIFORM

DCISDCIS

PAPILLARYPAPILLARY COMEDOCOMEDO

Invasive ca. Invasive ca. (adenocarcinoma)(adenocarcinoma)

Histological variantsHistological variants 1.infiltrating ductal (75%)1.infiltrating ductal (75%) 2.infiltrating lobular (5-10%)2.infiltrating lobular (5-10%) 3.tubular3.tubular 4.medullary4.medullary 5.mucinous or colloid5.mucinous or colloid

Panel A: Low power view of a well differentiated Panel A: Low power view of a well differentiated infiltrating ductalinfiltrating ductal carcinoma shows tumor cells carcinoma shows tumor cells which infiltrate the stroma as solid nests and which infiltrate the stroma as solid nests and glands. Panel B: High power view demonstrates glands. Panel B: High power view demonstrates relatively uniform nuclei with no evidence of relatively uniform nuclei with no evidence of mitotic activity mitotic activity

Panel A: Low power view of an Panel A: Low power view of an infiltrating infiltrating lobularlobular breast carcinoma shows small tumor breast carcinoma shows small tumor cells that infiltrate the stroma singly and in a cells that infiltrate the stroma singly and in a single file pattern. Panel B: High power view single file pattern. Panel B: High power view demonstrates that the tumor cells are relatively demonstrates that the tumor cells are relatively small and uniform in appearance small and uniform in appearance

medullarymedullary

Panel A: Low power view of a Panel A: Low power view of a medullary breast medullary breast carcinomacarcinoma shows that the tumor has a well shows that the tumor has a well circumscribed border. Panel B: High power view circumscribed border. Panel B: High power view demonstrates that the tumor cells grow in a syncytial demonstrates that the tumor cells grow in a syncytial pattern and have marked nuclear atypia. A prominent pattern and have marked nuclear atypia. A prominent lymphoplasmacytic infiltrate is also present. lymphoplasmacytic infiltrate is also present.

tubulartubular

Panel A: Low power view of a Panel A: Low power view of a tubular breast carcinomatubular breast carcinoma shows that the tumor is composed of well formed glands or shows that the tumor is composed of well formed glands or tubules that invade the mammary stroma. Panel B: High tubules that invade the mammary stroma. Panel B: High power view demonstrates that the tubules are composed of power view demonstrates that the tubules are composed of columnar cells with relatively uniform nuclei. Many of the columnar cells with relatively uniform nuclei. Many of the cells show "snouts" of eosinophilic cytoplasm at their cells show "snouts" of eosinophilic cytoplasm at their lumenal ends lumenal ends

mucinousmucinous

Panel A: Low power view of a Panel A: Low power view of a mucinous breast mucinous breast carcinomacarcinoma shows small nests of tumor cells dispersed in shows small nests of tumor cells dispersed in large pools of extracellular mucous. Panel B: High large pools of extracellular mucous. Panel B: High power view demonstrates that the nests are composed power view demonstrates that the nests are composed of cells with relatively uniform, low grade nuclei of cells with relatively uniform, low grade nuclei

Invasive ductal ca.Invasive ductal ca. Macroscopic typesMacroscopic types Scirrhous ca.60Scirrhous ca.60%-common,hard,whitish,non-%-common,hard,whitish,non-

capsulated,irregular with cartilagenous capsulated,irregular with cartilagenous consistency.it contains malignant cells with consistency.it contains malignant cells with stroma.(cuts like an unripe pear)stroma.(cuts like an unripe pear)

Medullary ca.alsoMedullary ca.also called called encephaloid(soft),contains malignant cells encephaloid(soft),contains malignant cells with dispersed lymphocyteswith dispersed lymphocytes

Inflammatory caInflammatory ca, or lactating ca,or mastitis , or lactating ca,or mastitis carcinomatosis…most malignant,2%,seen in carcinomatosis…most malignant,2%,seen in lactating or pregnant women,mimics acute lactating or pregnant women,mimics acute mastitis because of short mastitis because of short duration,pain,warmth and tendernessduration,pain,warmth and tenderness

contd.contd.

Invasive ductal ca.Invasive ductal ca. Inflam.ca. is rapidly progressive,short Inflam.ca. is rapidly progressive,short

duration,involving whole breast with Peau duration,involving whole breast with Peau d’ orange,often extending to the skin of d’ orange,often extending to the skin of chest wall alsochest wall also

Rapid metastasis to chest wall,lung,bone.Rapid metastasis to chest wall,lung,bone. It is always stage 4It is always stage 4 Total count is normalTotal count is normal Biopsy FNAC –undifferentiated cell seenBiopsy FNAC –undifferentiated cell seen Treated by external radiotherapy and Treated by external radiotherapy and

chemotherapy-worst prognosis chemotherapy-worst prognosis

Mastitis carcinomatosisMastitis carcinomatosis Mimics acute mastitisMimics acute mastitis IBC is highly IBC is highly

angiogenic and angiogenic and angioinvasive angioinvasive

Invasive ductal ca.Invasive ductal ca. Colloid ca.—produces Colloid ca.—produces

abundant mucinabundant mucin Paget’s disease of the Paget’s disease of the

nipple -superficial nipple -superficial manifestation of an manifestation of an intra-ductal intra-ductal ca.,malignancy spreads ca.,malignancy spreads within duct upto the within duct upto the skin of nipple and down skin of nipple and down into the substance of into the substance of breast,mimics eczema breast,mimics eczema of nipple and areola.of nipple and areola.

Paget’s diseasePaget’s disease

Paget’s disease of the Paget’s disease of the nipplenipple Paget’sPaget’s 1.unilateral1.unilateral 2.distinct edges2.distinct edges 3.itching absent3.itching absent 4.menopausal women4.menopausal women 5.vesicles absent5.vesicles absent 6.nipple flattened or 6.nipple flattened or

destroyeddestroyed 7.firm7.firm 8.underlying lump is 8.underlying lump is

palpablepalpable

EczemaEczema BilateralBilateral IndistinctIndistinct PresentPresent Lactating womenLactating women PresentPresent Nipple usually intactNipple usually intact

SoftSoft No lumpNo lump

Clinical presentation of Clinical presentation of ca.brca.br

Lump(hard,painless),Lump(hard,painless), Ulceration fungationUlceration fungation Axillary LN ,supraclivicular LNAxillary LN ,supraclivicular LN Chest pain,haemoptysisChest pain,haemoptysis Bone pain,tenderness,pathological Bone pain,tenderness,pathological

fracturefracture Pleural effusion,ascitesPleural effusion,ascites Liver secondaries,ovarian tumoursLiver secondaries,ovarian tumours

Clinical presentation of Clinical presentation of ca.brca.br Cutaneous manifestaionsCutaneous manifestaions Peau d’ orange due to obstruction of dermal Peau d’ orange due to obstruction of dermal

lymphatics,openings of the sebaceous glands lymphatics,openings of the sebaceous glands and hair follicles get buried in the edemaand hair follicles get buried in the edema

Dimpling of skin-infiltraion of ligts.of CooperDimpling of skin-infiltraion of ligts.of Cooper Retraction of nipple due to involvement of Retraction of nipple due to involvement of

lactiferous ducts.lactiferous ducts. Ulceration,discharge from nipple,areolaUlceration,discharge from nipple,areola Cancer-en-cuirasse-skin over the chest wall Cancer-en-cuirasse-skin over the chest wall

and breast studded with cancer nodules-and breast studded with cancer nodules-armour coatarmour coat

Tethering to skinTethering to skin

Ca breastCa breastSpread to deeper planesSpread to deeper planes Pectoralis major—akimboPectoralis major—akimbo Latissmus dorsi---extending the arm against Latissmus dorsi---extending the arm against

resres Serratus anterior---pushing wall with Serratus anterior---pushing wall with

extended armsextended arms Chest wall---leaning forward,raising the armChest wall---leaning forward,raising the armLymphatic spreadLymphatic spread Sappey’s subareolar plexusSappey’s subareolar plexus Cutaneous lymphaticsCutaneous lymphatics Intramammary lymphatics-all go toIntramammary lymphatics-all go toAxillary group-75%,,,int.mamm.-25%Axillary group-75%,,,int.mamm.-25%

Ca breastCa breastAxillary groupAxillary group

Anterior or pectoral along lateral thoracic Anterior or pectoral along lateral thoracic art.art.

Posterior or subscapularPosterior or subscapular Lateral or brachialLateral or brachial Central Central ApicalApical Rotter’s interpectoralRotter’s interpectoral

Spreads by permeation,embolization and Spreads by permeation,embolization and retrograde mannerretrograde manner

Ca breastCa breast Lymphatic manifestationsLymphatic manifestations Peau d’ orangePeau d’ orange Arm oedemaArm oedema Elephantiasis chirurgensElephantiasis chirurgens Brawny oedemaBrawny oedema LymphangiosarcomaLymphangiosarcoma

Breast is in subcutaneous plane but its Breast is in subcutaneous plane but its extension,axillary tail of Spence,passes extension,axillary tail of Spence,passes through an opening in the deep fascia-through an opening in the deep fascia-foramen of Langerforamen of Langer

Independent mobility for node and along with Independent mobility for node and along with the primary tumour for extension.the primary tumour for extension.

Differential Diagnosis of Differential Diagnosis of br.cabr.ca

FibroadenosisFibroadenosis Traumatic fat necrosisTraumatic fat necrosis TuberculosisTuberculosis Bloodgood cystBloodgood cyst FilariasisFilariasis MastitisMastitis AntibiomaAntibioma GalactocoeleGalactocoele Mondor’s diseaseMondor’s disease Phyloides tumourPhyloides tumour

Breast cancer-diagnosisBreast cancer-diagnosis 1.BSE.over 60% of cases are discovered.1.BSE.over 60% of cases are discovered. 2.physical examination—by physician2.physical examination—by physician 3.mammography—reveals architexture.. 3.mammography—reveals architexture..

a.suspicious signs are asymmetry,skin a.suspicious signs are asymmetry,skin thickening,irregular masses,architectural thickening,irregular masses,architectural distorsion and clustered irregular distorsion and clustered irregular microcalcifications(most important) microcalcifications(most important) b.to support the clinical impression of no b.to support the clinical impression of no evidence of malignancy in the follow up evidence of malignancy in the follow up and to screen for subclincal tumours. and to screen for subclincal tumours. c.current recommendation is a baseline c.current recommendation is a baseline mgm.at the age of 35 then annual mgm.at the age of 35 then annual screening in high riskscreening in high risk

Breast cancer-diagnosisBreast cancer-diagnosis 4.ultrasound—if the breast mass is 4.ultrasound—if the breast mass is

(palpable or not) solid or cystic(palpable or not) solid or cystic 5.needle aspiration for cytology5.needle aspiration for cytology 6.excisional biopsy..a.for HP,b.ER or PR 6.excisional biopsy..a.for HP,b.ER or PR

status(+more responsive than –ve status(+more responsive than –ve trs.,c.flow cytometry to determine if the trs.,c.flow cytometry to determine if the tr.is diploid or aneuploid and to determine tr.is diploid or aneuploid and to determine the S-phase fraction(aneuploid trs.with a the S-phase fraction(aneuploid trs.with a high S-phase fraction have poor high S-phase fraction have poor prognosis)prognosis)

Staging-ManchesterStaging-Manchester Stage OneStage One The growth is confined to The growth is confined to

breast, and is not adherent to pectoral breast, and is not adherent to pectoral muscles or to chest wall. There are no muscles or to chest wall. There are no enlarged nodes in axilla. Adherence to enlarged nodes in axilla. Adherence to the skin, or ulceration through it, does the skin, or ulceration through it, does not affect staging, if it is smaller than the not affect staging, if it is smaller than the tumour. 68% of all patients survive 5 tumour. 68% of all patients survive 5 years, and 54% 10 years.years, and 54% 10 years.

Stage TwoStage Two As for stage One, but there are As for stage One, but there are now mobile nodes in axilla. 60% of now mobile nodes in axilla. 60% of patients survive 5 years and 40% 10 patients survive 5 years and 40% 10 years.years.

Staging-ManchesterStaging-Manchester Stage ThreeStage Three There is skin involvement which is There is skin involvement which is

larger than the tumour, but it is still limited to larger than the tumour, but it is still limited to breast. If any axillary nodes are palpable, they breast. If any axillary nodes are palpable, they are still mobile. Or the tumour is fixed to are still mobile. Or the tumour is fixed to pectoral muscle, but not to chest wall. Or it is pectoral muscle, but not to chest wall. Or it is fixed to both. 15% of patients survive 5 years fixed to both. 15% of patients survive 5 years and 4% 10 years.and 4% 10 years.

Stage FourStage Four has distant metastases, either has distant metastases, either lymphatic, or blood-borne. These include lymphatic, or blood-borne. These include infiltration of the skin beyond breast, fixed infiltration of the skin beyond breast, fixed nodes in axilla, palpable nodes in supraclavicular nodes in axilla, palpable nodes in supraclavicular fossae, involvement of other breast; or deposits fossae, involvement of other breast; or deposits in bones, liver, or lungs (unusual). 4% of patients in bones, liver, or lungs (unusual). 4% of patients survive 5 years and 4% 10 years.survive 5 years and 4% 10 years.

TNM STAGINGTNM STAGING

Breast Cancer T, N, and M Categories Breast Cancer T, N, and M Categories Primary tumor (T):Primary tumor (T):

TX:TX: Primary tumor cannot be assessed. Primary tumor cannot be assessed. T0:T0: No evidence of primary tumor. No evidence of primary tumor. Tis:Tis: Carcinoma in situ (DCIS, LCIS, or Paget Carcinoma in situ (DCIS, LCIS, or Paget disease of the nipple with no associated tumor disease of the nipple with no associated tumor mass)mass)T1:T1: Tumor is 2 cm (3/4 of an inch) or less across. Tumor is 2 cm (3/4 of an inch) or less across.T2: T2: Tumor is more than 2 cm but not more than Tumor is more than 2 cm but not more than 5 cm (2 inches) across. 5 cm (2 inches) across. T3:T3: Tumor is more than 5 cm across. Tumor is more than 5 cm across. T4: T4: Tumor of any size growing into the chest Tumor of any size growing into the chest wall or skin. This includes inflammatory breast wall or skin. This includes inflammatory breast cancer. cancer.

Regional lymph nodes (N): Regional lymph nodes (N): – NX: Regional lymph nodes cannot be NX: Regional lymph nodes cannot be

assessed (e.g., previously removed) assessed (e.g., previously removed) N0: No regional lymph node metastasis N0: No regional lymph node metastasis N1: Metastasis to movable ipsilateral axillary N1: Metastasis to movable ipsilateral axillary lymph node(s) lymph node(s) N2: Metastasis to ipsilateral axillary lymph N2: Metastasis to ipsilateral axillary lymph node(s) fixed to each other or node(s) fixed to each other or to other structuresto other structures

N3: Metastasis to ipsilateral internal mammary N3: Metastasis to ipsilateral internal mammary lymph node(s) lymph node(s)

Distant metastasis (M): Distant metastasis (M): – MX: Presence of distant metastasis cannot be MX: Presence of distant metastasis cannot be

assessed assessed M0: No distant metastasis M0: No distant metastasis M1: Distant metastasis present (includes M1: Distant metastasis present (includes metastasis to ipsilateral supraclavicular metastasis to ipsilateral supraclavicular lymph nodes) lymph nodes)

–

T0T0 T1T1 T2T2 T3T3 T4T4

N0N0 ONEONE

N1 TWON1 TWO

N2 THREE-AN2 THREE-A

N3 THREE-BN3 THREE-B

M1 FOURM1 FOUR

TREATMENT PROTOCOLTREATMENT PROTOCOLBIOPSY & WORK UP

STAGE I STAGE II STAGE III

CT

STAGE IV

LUMPECTOMYAX. DISS.

RTMRM

OR MRM

ORLUMPECTOMY

AX. DISS.RT

SURGERY

& / OR RT

CT

Treatment protocolTreatment protocol For stage 2 and stage 3 disease along For stage 2 and stage 3 disease along

with the above, with the above, adjuvant chemotherapyadjuvant chemotherapy is used for node-positive cases, and high is used for node-positive cases, and high risk node-negative pts.risk node-negative pts.

Adjuvant hormone therapyAdjuvant hormone therapy is used for is used for those patients with hormone-sensitive those patients with hormone-sensitive tumors.tumors.

chemotherapychemotherapy IndicationsIndications Advanced ca. as a palliative procedureAdvanced ca. as a palliative procedure After simple mastectomy,in stage 3 with After simple mastectomy,in stage 3 with

fixed axil.LNfixed axil.LN In inflammatory ca.In inflammatory ca. In stage 4 with secondaries in In stage 4 with secondaries in

bone,lungs,liverbone,lungs,liver Premenopausal age with poorly Premenopausal age with poorly

differentiated trs.differentiated trs.

chemotherapychemotherapy Toxic effects---alopecia,bone marrow Toxic effects---alopecia,bone marrow

depression,cystitis,nephritis,megaloblastidepression,cystitis,nephritis,megaloblastic anemia..c anemia..

CyclophosphamideCyclophosphamide MethorexateMethorexate 5-fluorouracil CMF5-fluorouracil CMF In monthly cycles for 6 months.In monthly cycles for 6 months.

Hormone therapy -Hormone therapy -includesincludes

Oestrogen receptor antagonists-tamoxifenOestrogen receptor antagonists-tamoxifen Surgical ovarian ablation-bilateral Surgical ovarian ablation-bilateral

oophorectomy or by radiationoophorectomy or by radiation LHRH agonists(medical oophorectomy)LHRH agonists(medical oophorectomy) Oral aromatase inhibitors for post Oral aromatase inhibitors for post

menopausalmenopausal Adrenalectomy or pituitory ablationAdrenalectomy or pituitory ablation Progesterone receptor antagonistProgesterone receptor antagonist Androgens.Androgens. Aminoglutethimide(medical adrenalectomy)Aminoglutethimide(medical adrenalectomy) progesteroneprogesterone

Hormone therapyHormone therapy TamoxifenTamoxifen It is antioestrogen and blocks the It is antioestrogen and blocks the

oestrogen receptors..oestrogen receptors.. 10mg.bd of 5 years10mg.bd of 5 years It is also used in BBD,infertility in It is also used in BBD,infertility in

males,desmoid tumourmales,desmoid tumour

radiotherapyradiotherapy After conservative breast surgery.breast is After conservative breast surgery.breast is

irradiated using brachytherapy.irradiated using brachytherapy. After total mastectomy,external irradiation is After total mastectomy,external irradiation is

given to axillagiven to axilla Patients with high risk of local relapse after Patients with high risk of local relapse after

surgery,a.invasive ca.,extensive insitu ca, under surgery,a.invasive ca.,extensive insitu ca, under 35 years age,multifocal disease35 years age,multifocal disease

In bone secondaries,to palliate pain and swellingIn bone secondaries,to palliate pain and swelling Inflammatory ca.,scirrhous ca,positive surgical Inflammatory ca.,scirrhous ca,positive surgical

margins..margins.. As preoperative radiotherapy,to reduce the As preoperative radiotherapy,to reduce the

tr.size and downstage the tr.so that the tr.size and downstage the tr.so that the operability is good.operability is good.

Operations for breast Operations for breast ca.ca.

1.total or simple mastectomy1.total or simple mastectomy —tr.+entire —tr.+entire breast+nipple areolar complex +skin over the breast+nipple areolar complex +skin over the tumour+axillary tail.(no axillary dissection but tumour+axillary tail.(no axillary dissection but post op.radiotherapy given to axilla)post op.radiotherapy given to axilla)

2.total mastectomy with axillary clearance2.total mastectomy with axillary clearance — —TM+removal of axil.fat fascia and TM+removal of axil.fat fascia and lymphnodeslymphnodes

3.MRM-Patey’s operation3.MRM-Patey’s operation —here 2 +removal —here 2 +removal of pectoralis minor muscle so as to have good of pectoralis minor muscle so as to have good access to upper part of axilla and to clear access to upper part of axilla and to clear interpectoral (Rotter’s) nodes.pectoralis major interpectoral (Rotter’s) nodes.pectoralis major is retained.is retained.

Patey’s operationPatey’s operation

Structures to Structures to be retainedbe retained

1.Axillary 1.Axillary veinvein

2.Bell’s nerve2.Bell’s nerve 3.Cephalic 3.Cephalic

veinvein 4.Dorsal 4.Dorsal

nervenerve

N.to ser.anteriorN.to ser.anterior

Breast conservative Breast conservative surgerysurgery

In stage 1 and2 BCS can be considered In stage 1 and2 BCS can be considered which includeswhich includes

LumpectomyLumpectomy Wide excisionWide excision QUART.(quadrantectomy+axillary QUART.(quadrantectomy+axillary

dissection +radiotherapy to the bed of dissection +radiotherapy to the bed of tr.and rest of breast.)tr.and rest of breast.)