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Breast short note by S.

Wichien (SNG KKU)


Embryology 5th,6th wk -2 ventral bands of ectoderm (mammary ridge/milk line) (axilla to inguinal area) Polymastia -accessory breast Polythelia -accessory nipple -<1% of infant -asso urinary/CVT abnormality Inverted nipple -failure of pit to elevate above skin -4% infant Witch milk -maternal H.via placenta Amastia -arrest milk line develop Poland synd -hypoplasia/absence of breast -rib/costal cartilage defect -hypoplasia of subcu of chest wall -brachysyndactyly Symmastia -rare anomaly -webbing between breast across midline Supernumerary breast -along milkline -common btw nipple and symphysis -accessory axilla breast Anatomy -15-20 lobes -Cooper suspensory ligament -2nd/3rd rib--6th/7th rib -lateral sternum--ant axillary line -retromammary bursa -axillary tail of Spence -upper outer--greater volume -lactiferous sinus--stratified sq.epi major duct--2 cuboidal cell minor duct--single columnar/cuboid Nipple-areola complex -pigment -puberty--darker,elevate configuration -sebaseous gl,sweat gl,accessory gl -smooth m--cir/long--erection Alveolar epithelium -- 2 products 1.prot.component of milk -merocrine secretion -in endoplasmic reticulum 2.lipid component of milk -apocrine secretion -in cytoplasm colostrum -first few day -low lipid--hi Ab(lympho,plasma cell) Blood supply Artery -perforating br of int mam.a. -lateral br of post ICS a. -br from axillary a. :highest thoracic :lateral thoracic :pectoral br of thoraco-acroomial a Vein -perforating br of int mam.v. -perforating br of post ICS v. -tributaries of axillary v. Batson vertebral v.plexus :root of bone metas Nerve -3-6 ICS n. -cervical plexus--ant br of supraclavi n -intercostobrachial n--lat.br of 2 ICS n

Breast short note by S.Wichien (SNG KKU)


Lymph node Internal mammary node 25% Axillary node 75% Level 1 -axillary v.gr -ext.mammary gr--ant -scapular gr--post Level 2 -central gr -interpectoral gr--rotter Level 3 -subclavicular gr--apical gr Skip metastasis -25-29%--level 2,3 -3%--level 3 **SLNB can miss 3% Node metastasis 1.tumor cluster -isolated tumor cell <0.2cm 2.micrometas -0.2-2 cm 3.macrometas ->2cm Physiology Estrogen--duct development Progesterone--lobular development Prolactin--lactogenesis Pregnancy -inc ovarian/placental E&P -duct&lobular epi proliferate -prominent Montgomery gland Milk production&relaese -stimulate nerve ending (NAC) -prolactin secretion -oxytocin--contract myoepithelium Investigation MMG -detect early breast ca -true positive 90% -screen at 40 yr Ultrasound -in equivocal MMG finding ,cystic mass -uls guide bx Ductogram -nipple discharge -duct dilator-->small canular -0.1-0.2 ml contrast is injected -filling defect-->intraductal papilloma MRI -hi-sen, low spec than MRM 1.ALN+ve, unknown 1 2.promblematic MMG 3.rupture silicone Nonpalpable lesion Bx -u/s localization--have mass -stereotactic technic --no mass Palpable lesion Bx -FNA Bx -CNBx CNBx need further excision 1.ADH, ALH 2.radial scar 3.papilloma lesion 4.vascular proliferation 5.phylloides tumor Indice of Poliferation Apoptosis Angiogenesis GF Steroid H.R PCNA Bcl2 protein Bax : Bcl2 ratio (low=poor prog) VGEF EGF, HER2/neu EP, PR

Breast short note by S.Wichien (SNG KKU)


Gynecomastia -Male breast enlarge,elongate,inc epi -often unilateral -12-15 yr -at least 2 cm in diameter -usually not predispose ca Physiologic 1.neonate 2.adolescent 3.senescence--dec T,relative inc E Klinefelter synd (XXY) -hypoandrogenic state -inc risk of ca breast Classification gr1-mild enlarge,wo skin redundancy gr2a-mod enlarge,wo skin redundancy gr2b-mod enlarge,w skin redundancy gr3-mark enlarge,as female breast Cause Estrogen excess 1.testicular tumor -germ cell tumor--seminoma -gonodal tumor--leydig,sertoli cell 2.non testicular tumor -adrenal cortical tumor -lung ca -hepatoma 3.non alc/alc cirrhosis Androgen deficiency 1.senescene 2.hypogonadism 1testicular failure--klinefelter synd 2testicular failure :trauma,orchitis,cryptorchidism,XRT Tx -add testosterone Drugs reserpine,theophylline verapamil TCA,furosemide Tx -stop drugs Idiopathic -tamoxifen 40 mg/d 1-4 m ANDI Abberrant of Normal Development and Involution Early reproductive yr (15-25yr) Normal 1.lobular development 2.stromal development 3.nipple eversion Disorder 1.fibroadenoma (<3cm) 2.adolescent hypertrophy 3.nipple inversion Disease 1.giant fibroadenoma (>3cm) 2.gigantomastia 3.subareolar absecss Mammary duct fistula Later reproductive yr (25-40yr) Normal 1.cyclic change of menstruation 2.epi hyperplasia of preg Disorder 1.cyclic mastalgia and nodularity 2.bloody nipple discharge Disease 1.incapacitating mastalgia 2.Involution Normal 1.lobular involution 2.duct involution--dilatation/sclerosis 3.epi turnover Disorder 1.macrocyst/sclerosing lesion 2.duct ectasia/nipple retraction 3.epi hyperplasia Disease 1.2.periductal mastitis 3.epi hyperplasia w atypia

Breast short note by S.Wichien (SNG KKU)


Benign breast disease 1.Non-proiferative disorder no inc risk ca -fibrocystic disease (cyst & apocrine metaplasia) -duct ectasia -mild ductal epi hyperplasia -calcification -fibroadenoma and related lesion 2.proliferative disorder wo atypia no inc risk ca -sclerosing adenosis -radial & complex sclerosing lesion -ductal epi hyperplasia -intraductal papilloma 3.atypical proliferative lesion inc risk ca 4x -atypical lobular hyperplasia -atypical ductal hyperplasia Benign breast Tx Cyst -cyst aspiration Fibrocystic dz -reassure/symp Tx -danazol,nsaid,tamoxifen,bromocrip Fibroadenoma giant fibroadenoma >5cm -should r/o phyllodes tumor Sx I/C ->40yr -rapid growth>20% ->5cm Sclerosing disorder -excision bx are needed to r/o ca -stereotactic guide bx Periductal mastitis -ATB--metro+cloxa -abscess--drainage Recurrent abscess w fistula Fistulectomy Total d excision -small abscess large>50%areolar -same lesion different lesion -no N.inversion mark N.inversion -young pt old pt -no d/c pus d/c -no fistulec recur after fistulec Nipple inversion -shortening subareolar duct -sx correction--cosmetic reason -c/p--nipple sensation/necrosis, fibrosis-->nipple retraction Intraductal papilloma -microdochectomy Cyclic mastalgia 1st=Pimrose oil (Gamma Linoleic Acid) 2nd=Danazol 3rd=Bromocriptine 4th=Tamoxifen

Breast short note by S.Wichien (SNG KKU)


Infection 1.bact infection -Staph--localized,deep abscess Strep--diffuse superficial involve -breast feeding -subareolar,periduct,retromam space Tx -local w care--warm comp -iv ATB -I&D--should Bx abscess cavity Zuska disease (recurrent periductal mastitis) -recurrent retroarolar infect/abscess Tx -ATB+I&D 2.mycotic infection -blastomycosis or sporotrichosis -intra oral fungi--sucking infant -abscess close to NAC Tx -antifungal agent -+/-drainage 3.hiradenitis supparativa -axilla--sebaceous gl NAC--Montgoney gl -mimic chronic inflam,paget,ca 4.mondor s dz -variant of thrombophlebritis -superficial v of ant chest wall -lateral thoracic v,thoracoepigastric v superficial epigastric v -tender,cord like structure -benign, self limited dz--4-6 wk Tx -anti-inflam -warm compression -restrict of motion of ipsilat ext -braissiere support -not improve-->excision LCIS & DCIS 1.age 2.incidence 3.clinical 4.MMG 5.premeno 6.synchro 7.multicentric 8.bilat 9.axilla metas 10.male 11.subsequent interval to dx histo incidence laterality LCIS DCIS 44-47 54-58 yr 2-5 5-10% no mass,pain,dc no microcalci 2/3 1/3 5 2-46% 60-90 40-80% 50-70 10-20% 1 1-2% 5% ca 15-20 5-10 yr ductal ductal 25-35% 25-70% bilat ipsilat

LCIS -only in female breast -Terminal Duct Lobular Unit--TDLU -distort/distend TDLU -maintain normal N:C ratio -calcify in adjacent tissue -incidental finding DCIS -can seen in male breast ca -proliferation of epi in duct -papillary growth -intraductal ca 1.cribiform pattern 2.solid growth pattern 3.comedo growth pattern Classification of DCIS Histo nu.gr necrosis DCIS grade comedo hi extensive high IM IM focal/no IM noncomedo low absent low IM--intermediate

Breast short note by S.Wichien (SNG KKU)


Ca breast 1.sporadic 65-75% 2.familial 20-30% 3.hereditary 5-10% BRCA1 45% BRCA2 35% p53(Li fraumeni) 1% STK11/LKB1(Peutz Jegh) <1% PTEN(cowden) <1% BRCA1 BRCA2 17q21 13q12 Tumor suppression DNA damage repair 3.risk ca 60-80% 4.age young 50 yr 5.fam hx 52% 32% 6.ovary ca 80% 20% 7.male <20% 76% 8.ca prostate,colon,pancreas 9.diff poorly diff well diff 10.HR -ve +ve 11.bilat yes yes 1.chro 2.fxn Hereditary risk of ca breast ->=2 fam hx of ca breast/ovary -ca breast < 50yr -ca breast+ovary in same pt -male breast Cancer prevention for BRCA mutation 1.prophylactic mastectomy & recons 2.prophylactic oophorectomy & HRT 3.intensive survei for ca breast&ovary 4.chemoprevention Screening recommendation -early screen at 25 yr -clinical breast exam q 6 m -MMG q 12 m -TVS, ca-125 q 1yr Invasive breast ca 1.paget dz of nipple -chronic,eczema of nipple -weeping lesion,ulcer -extensive of DCIS -pagetoid feature -pathognomonic=paget cell in epi -DDx-superficial spreading melanoma :S-100 immunostaining--melanoma :CEA immunostaining--paget dz 2.invasive ductal ca 2.1 adenoca c productive fibrosis (scirrhous,simple,NST)--80% -60% axillary LN metas -perimenopausal,menopause -poor margin -solitary,firm mass -cut surface--stellate,chalky white or yellow streak into surrounding tissue 2.2 medullary ca--4% -special type -BRCA-1 hereditary breast ca -soft,hemorhage -often deep in breast -50%asso DCIS -5yr better than NST,invasive lobular Microscopic -dense lymphoreticular infiltrate lymp/plasma cell predominate -poorly diff,active mitosis -sheet like growth pattern 2.3 mucinous (colloid)--2% -elderly -bulky tumor -extracellular pool of mucin -glistening and gelatinous -firm consistency -5yr--73%, 10yr--59% 2.4 papillary--2% -small -fibrovascular stalk -multilayer epithelium -prognosis as mucinous 2.5 tubular--2% -perimenopausal,menopause -tubular arranged -long term survival approach 100% 3.invasive lobular ca--10% -histo--small cell c round nuclei, scant cytoplasm -special stain--intracytoplasmic mucin, displace nucleus(signet-ring cell) -poorly defined mass -multifocal,multicentric and bilat -insidious growth--difficult to detect 4.rare ca -adenoid cystic -squamous cell -apocrine

Breast short note by S.Wichien (SNG KKU)


Ca breast staging -palpate axillary LN--ccuracy only 33% -axillary LN dissect >=10 node -tumor size correlate c axillary metas -single most predictor of survival is -supraclavicular LN metas--stage4 T T1-<=2cm T1mi-<=1mm T1a->1, <=5mm T1b->5, <=10mm T1c->10, <=20 T2->2, <=5cm T3->5cm T4-any size c extend chest wall,skin T4a--chest wall,not pectoralis m. T4b--edema,peau d orange,ulcer T4c--both a+b T4d--inflam ca N N1-1-3, mobile N1mic->0.2-<2mm/>200cell N2-4-9, fix or matted N3->=10 or IMLN/SCLN/IFLN M M0-no M1-distant metas Sentinel LN bx -T1,2,3 , No C/I -palpable lymphadenopathy -prior sx,CMT,XRT -multifocal breast ca Agent 1.radioactive colloid -intraop gamma probe -radioactivity count 2.isosulfan blue dyle (Lymphazurin) -intraop visualization *combine 1+2=more accurate Procedure -4ml of isosulfan blue dye is inject -1ml inject between ca site and skin -nonpalpate--u/s guide,wire localize -3-4 cm incision curved transverse -lower axilla just below hairline -identify lateral of pectoralis m -divided clavipectoral fascia -exposed axilla content Tx -false+ve--3% (3% skip to level 3) Macrometas(pN1) ->2mm Tx--must ALND Micrometas(pN1mic) -0.2-2mm Tx--should ALND Early breast castage1, 2a Locally advancestage2b,3a,3b,3c (T3/N2) Isolated tumor cell or tumor cruster (pN0) -<0.2mm Tx--ALND=controversy

number of axillary LN involve

Breast short note by S.Wichien (SNG KKU)


Ca breast Tx 1.in situ 1.1 LCIS--risk ca 15-20 yr A.close f/u -CBE q 6-12mo -mammogram,US q 1yr B.tamoxifen C.prophylactic bilat.mastectomy -in BRCA1 +ve -not ALND 1.2 DCIS--premalignant A.local excision -size<0.5 cm -low grade B.local excision + RT ->0.5 cm C/I as BCT -prior RT -can't free margin :multicentric/diffuse calcify :persist +ve margin >=2 C.simple mastectomy -can't b D.chemoprevention -not tamoxifen except -DCIS in premenopause E.SLNB -not done--risk +ve <1% Van nuy prognostic index 2.Early breast ca (stage1,2a) -BCT--Tx of choice -MRM+/-reconstruction--alternative -SLN,RT,systemic tx--if have I/C 3.locally advanced (stage 2b,3a,3b,3c) -metastasis w/u -neoadjuvant CMTanthracyclin 4 cycle A.65%reduce sizeSx 1.BCT vs MRM 2.ALND vs SLNBx -FNA -ve before adjuvant CMTcan SLNBx 3.PO RT, CT+/-ET B.not reduce size -change anthracyclintaxane -RT -if HER2+veHerceptin 4.stage 4/recurrent -local controlSx/RT -ALNDnot improve overall survival rate -allsystemic tx Metas breast cainduction CMT 3 mo 1.disease response -pt resectableSx +/- PORT -pt unresectableRT 2.disease progression -2 line CMT +/- targeted Tx Local recurrent A.prior BCT -total mastectomy +CT+/-ET -not RT B.prior MRM -wide local excision +/- RT or -RT alone then CT +/- ET Tx for metastasis Bone -bone pain--RT -patho.fx--ORIF -biphosphonate--all bone metas -ER+ve--ET -ER-ve--CT up 1 grade Brain -localize--sx -multiple,can't sx--steroid+/-RT SC compression -can sx--laminectomy -unresectable--steroid+/-RT Liver -can sx--sx -CT up 1 grade Lungs -isolated should sx > RT

Breast short note by S.Wichien (SNG KKU)


Breast Sx 1.BCT -wide local excision -margin 1cm -label margin 3,6,9,12 o clock Absolute C/I -multicentric, >1quadrant -persistence +ve margin (2 time) -prior RT -1st trimester pregnancy Relative C/I -multifocal but in same quadrant -large and pendulum breast -large tumor to breast ratio -medial quadrant lesion -CNT except RA -BRCA1,2 mutation -nipple areola complex excision 2.MRM -dissect breast, nipple -ALND (at least10) level 1,2 3.SLNB -if -ve ---not ALND indication -clinical -ve node -T<5cm -no prior systemic tx C/I -palpable node -T>5cm---often metas -T1---rare to +ve -inflam ca -metastasis -previous sx -previous neoadjuvant CMT -multifocal Mastectomy Simple mastectomy -all breast tissue -nipple-areolar complex -1cm of skin around excised scar Extend simple mastectomy -above + level 1 node Modified radical mastectomy -above + level 1,2 node -if palpate level 3--remove The Halstead radical mastectomy -above + pectoralis major/minor + level 1,2,3 nodes Nipple sparing mastectomy ->nipple 2cm+frozen Skin sparing mastectomy -early ca, preserve native skin Axillary node dissection -for staging, control regional ds -10-15 node 1,2 level

Breast short note by S.Wichien (SNG KKU)


MRM -preserve pectoralis m. -removed axillary LN level 1,2 -preserve medial pectoral n. :penetrate pectoralis minor :supply pectoralis major -skin flap 7-8 mm -fascia of pec.major m.and overlying breast tissue are elevated off -->complete removal of breast Boundary lateral--ant margin of latissimus dorsi medial--midline of sternum seperior--subclavius inferior--2-3cm inf to inframam.fold Axillary LN dissection Preserve -thoracodorsal n -long thoracic n--wing scapular If palpate LN at apex of axilla -divided pectoral minor :near insertion--coracoid process -dissect axilla v.medial to costoclavicular (Halsted) ligament Seroma -30%of case -use closed system suction drainage -until <30ml/d Infection -2nd to skin flap necrosis -debridement,ATB Lymphedema -10% Predisposing f. -extensive axillary LN dissection -obesity -radiation therapy -presence of pathologic LN Rx -fitted compressive sleeves -intermittent compressive device **Patey modification -remove pectoralis minor -complete dissect level 3 nodes MRM C/p 1.wound infection -staph 2.flap necrosis -minor <2cm2--conservative -major--graft/flap 3.hematoma 4.pneumothorax -Halsted sx 5.seroma -most common c/p -off when<20 ml 2d 6.lymphedema -ALND--25-30% -ALND+RT--50-60% -SLNB--2-4% 7.lymphagiosarcoma -Stewart Treves synd -chronic lymphedema -s/p MRM >10yr -poor prognosis -WLE or RT+CMT 8.nerve inj -long thorasic n--wing scapula -thoracodorsal n--int rotate,abduct -med pectoral n--m atrophy -intercostobrachial n--sensory 9.chronic pain synd -s/p intercostobrachial inj -neuroma 10.axillary v/A inj 11.frozen shoulder 12.c/p asso SLNBx -allergic rxn/shock -not use in pregnancy

Breast short note by S.Wichien (SNG KKU)


Breast reconstruction -defect can't cover c skin graft -->myocutaneous flap Immediate after sx -after mastectomy for early inva ca Delayed 6mo after complete adju Tx -for advanced breast ca -ensure locoregional control of ds Myocutaneous flap 1.latissimus dorsi flap -skin paddle--latissimus dorsi m. -thoracodorsal a.--from post ICS a 2.rectus abdominis flap -Transverse Rectus Abdominis Myocutaneous flap (TRAM) -skin paddle--rectus abdominis m. -inf epigastric a -free TRAM--microvascu.anastomosis Chest wall defect -ca involved chest wall -1,2 rib -- ok ->2 rib--Marlex mesh -then cove by flap Breast RT I/C -BCT--aftet sx 2-3 wk, not>6 wk -T3,4 -inflam breast -skin,fascia,pectoralis involve -lymphovascular invasion -close margin,free margin <1mm -axilla LN status :+ve>4node :>2cm :matted node>3 nodes :gross extracapsular invasion -palliative tx for stage 4/recurrent Endocrine Tx -all in HR+ve -premense--tamoxifen > AI :20mg/d *5yr :stop if AUB,thromboembolic -postmense--AI > Tamoxifen :upfront--tamoxifen 5yr :switching--tamoxifen 2yr--AI 3yr :extended AI--tamoxifen 5yr--AI 3yr Determining menopause -prior bilat oophorectomy ->=60yr, <=60yr+no mens >=12mo Drugs 1.antiestrogen -tamoxifen,toremifene,fulvestrant Tamoxifen s/e -DVT,pulmo.emboli -endometrial ca -hot flush--most common -thrombocytopenia,leukopenia 2.AI -anastrozol--arimidex -letrozole--femara AI s/e -osteoporosis 3.LHRH -goserelin,leuprolide,buserelin Chemotherapy I/C -T>1cm -all in node +ve -ER,PR -ve -lymphovascular invasion -hi nuclear grade -HER2/neu overexpression 3 groups 1.non-anthracyclin based regimen--CMF -low risk of recurrent 2.anthracycline based regimen -FAC*6, CAF*6 -<35yr, node+ve, HER2+ve 3.taxane based regimen -pacitaxel,docetaxel -failure from 2 -hi risk of recurrent :<35yr, poorly diff tumor, HR-ve, HER2+ve 3.Target tx -HER2/neu overexpression + metas -early case--trial -Herceptin(Trastuzumab) iv q3wk--1yr

Breast short note by S.Wichien (SNG KKU)


Other Ca 1.axillary LN metas + unknown 1 -1% presentimg sign of ca breast -HR suggest ca breast but not dx -thyroid--breast--pelvis/rectum -breast--MMG/us/MRI 2.ca breast during pregnancy -bigger breast--delay in dx -MRM>BCT -should not SLNB -if need RT--after delivery :if must--2nd,3rd trimester -CMT/HT--2nd,3rtrimester -not tamoxifen,metrotrexate -abortion,suppress lactation :not improve prognosis Benign breast in pregnancy :galactocele,lobular hyperplasia lactating adenoma,abscess 3.male breast ca -<1% ca breast -rare in young -peak incidence--60yr -20% is preceded by gynecomastia -asso RTX,estrogen Tx Klinefelter,testicular feminize synd -same staging -poor prog than women (advance stage when dx) Tx -as female -advance--orchidectomy 4.phyllodes tumor -cut surface--classical leaf like appear -stromal cell--always monoclonal -need CNBx (FNA--not adequate) 1.benign -mitotic <2/10 2.low gr malignant -mitotic 2-5/10, stromal invade 3.hi gr malignant -mitotic >5/10, stromal invade Tx -wide excision 1cm free margin -not ALND I/C mastectomy -large size to breast ratio -skin ulceration 5.inflam breast ca -stage 3b -<3% of ca breast -75%--LN metas 25%--distant metas -dermal lymph vv invasion -indurate,erythema,raise edge, edema(peau d orange) Tx -neoadjuvant w doxorubicin -MRM remove residual ca 6.Bilateral breast ca -breast ca---risk 5x -metachronous(>3mo) > synchronous Hi-risk -<45yr -familial,hereditary -LCIS,invasive lobular ca Rx Synchronous -tx higher stage tumor Metachronous -tx as recurrent ca 7.rare ca Squamous (epidermoid) cell -rare, from metaplasia in duct Adenoid cystic ca -rare -indistinguish from adenoid cystic ca arising in salivary gland -rare node metas Apocrine ca -well diff ca -round vesicular nuclei, prominent nucleoli -low mitotic rate Sarcoma -fibrosarcoma,MFH,liposarcoma leiomyosarcoma,rhabdomyosarc chrondosarc,malig schwannoma -large,painless mass,rapid growth Tx -wide local excision -may need mastectomy -ALND not indicate, unless palpable Angiosarcoma (lymphangiosarcoma -post mastec lymphedema /post XRT -p/o 10.5 yr Tx--Forequarter ampu in palliative Tx

Breast short note by S.Wichien (SNG KKU)


St gallen Low risk -node -ve and all of -T<2cm -gr1 -no perivascular invasion -ER,PR +ve -HER2 -ve ->35yr Intermediate risk Node -ve and at least one of -T>2cm -gr2,3 -perivascular invasion -ER,PR -ve -HER2 +ve -<35yr Node +ve (1-3) and -ER,PR +ve -HER2 -ve High risk Node +ve (1-3) and -ER,PR -ve -HER2 +ve Node +ve (>4) E.rxn E.uncertain E.nonrxn ET ET ET CT-->ET CT or (antra) (antra/tax) CT-->ET (CMF/antra) CT-->ET CT-->ET CT (antra) (antra) (tax) Van Nuy prognostic index (DCIS) 1 2 3 size <=15 16-40 >=41 margin >=10 1-9 <=1 patho -hi gr no no yes -necrosis no yes y/n -nuclear gr 1,2 1,2 3 age >60 40-60 <40 4-6=excision/lumpectomy only 7-9=add XRT 10-12=mastectomy BIRADs Breast Imaging Reporting And Data S. 0=incomplete--additional imaging 1=neg--routine screening 2=benign--routine screening 3=probably benign-->98% :microcalcify--f/u 6 mo :mass--f/u 4 mo 4=suspicious abnormality--5-95%--bx 4a=low probability 4b=intermediate probability 4c=intermediate but not typical 5=highly suspicious-->=95%--bx/sx 6=known bx proven malignancy

low Inter

high

E.responsive--ER/PR+ve E.uncertain--ER/PR+ve but <10% E.non-responsive--ER/PR-ve

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