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
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 -CNB Indice of Poliferation PCNA Apoptosis Bcl2 protein bax:bcl2 ratio (dec ratio-poor prog) Angiogenesis VGEF GF EGF,HER2/neu Steroid H.R EP,PR Dx study Hx,PE ca stage 1-4 CBC,LFT CXR,MMG ER,PR HER-2/neu
Bone scan ca stage 2-4 U/s or CT abdo
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
1°testicular failure--klinefelter synd 2°testicular 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
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
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
LCIS DCIS 1.age 44-47 54-58 yr 2.incidence 2-5 5-10% 3.clinical no mass,pain,dc 4.MMG no microcalci 5.premeno 2/3 1/3 6.synchro 5 2-46% 7.multicentric 60-90 40-80% 8.bilat 50-70 10-20% 9.axilla metas 1 1-2% 10.male - 5% 11.subsequent ca interval to dx 15-20 5-10yr
histo ductal ductal
incidence 25-35% 25-70% laterality 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
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 1.chro 17q21 13q12 2.fxn 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
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
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 number of axillary LN involve -supraclavicular LN metas--stage4 T T0-no evidence Tis-ca in situ T1-tumor <=2cm T2-tumor 2-5cm T3-tumor >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 N0-no N1+ve1-3,mobile N2+ve4-9,fix or matted N3+ve>10 or IMLN/SCLN/IFLN M M0-no M1-distant metas N0 N1 N2 N3
T1 I IIa IIIa IIIc
T2 IIa IIb IIIa IIIc
T3 IIb IIIa IIIa IIIc T4 IIIb IIIb IIIb IIIc Early breast ca--T1-2, N0-1
Locally advance--T3-4, N2-3 Stage 4,recurrent--M1 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
Isolated tumor cell or tumor cruster (pN0)
-<0.2mm
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,2b) -BCT--Tx of choice
-MRM+/-reconstruction--alternative -SLN,RT,systemic tx--if have I/C
3.locally advanced (stage 3a,3b) -metastasis w/u
-induction cmt--anthracyclin 4 cycle A.65%--reduce size--sx
-BCT vs MRM
-then PO RT, CT+/-ET B.not reduce size
-change anthracyclin--taxane -RT -if HER2+ve--Herceptin 4.stage 4/recurrent -local control--sx,RT -all--systemic 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 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 -CNTexcept 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
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 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
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
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 low ET ET
-Inter ET CT-->ET CT
or (antra) (antra/tax) CT-->ET
(CMF/antra)
high CT-->ET CT-->ET CT (antra) (antra) (tax)
E.responsive--ER/PR+ve
E.uncertain--ER/PR+ve but <10% E.non-responsive--ER/PR-ve
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
