The BreastBasic Science Conference

Cindy M DeutmeyerMUSC Department of Surgery

May 25th, 2010

AnatomyDevelop along paired mammary ridgesPrimary bud 15-20 secondary buds epithelial cordsMajor (lactiferous) ducts empty into shallow mammary pit mesenchyme proliferates elevation above skin nipple 4% Inverted nipples (pit not elevated above skin)Puberty: Estrogen & Progesterone proliferation of epithelial & connective tissue elementsPolymastia: accessory breastAmastia: absence of breastPoland’s Sx: hypoplasia or absence of breast w/rib, chest wall, & upper extremity defectsPolythelia: accessory nipples (1%)

Anatomy

3 tissue types: fatty, fibrous, glandular15-20 lobes composed of several Lobules Each lobe drains into Lactiferous Duct/Sinus, and eventually nippleCooper’s suspensory ligaments: fibrous connective tissue bands, perpendicular to dermis, structural support

Breast Boundaries

SuperiorClavicle, 2nd rib

InferiorInframammary Fold, 6th rib

MedialSternum (lateral border)

LateralAnterior axillary line,

Latissimus dorsiPosterior

Pectoral fascia

* Axillary tail of Spence

Blood Supply & LymphaticsInternal Mammary a. perforatorsIntercostal a.Axillary a. branches

* Lateral thoracic* Highest thoracic

Thoracoacromial a. branches

3 principal groups of veins* Internal thoracic v. perforators* Intercostal v. perforators* Axillary v. tributaries

Batson’s plexus: surrounds vertebral column

6 axillary lymph node groupsReceive 75% lymph drainage3 axillary lymph node levels* Level I: lateral to Pec minor* Level II: deep to Pec minor* Level III: medial to Pec minor

Cases

Case 1: Breast Pain

35 y.o. G1P1 presents with complaints of pain in breasts.

Pain is bilateral, diffuse. Feels swollen.

POBHx- SVD x 1

PGYNHx- regular menses

PMHx/PSHx- negative

MEDS- none

FHx- noncontributory

Breast Pain

Differential diagnosisFibrocystic changes

Mastalgia/mastodynia

Cyst

Duct obstruction

Inflammation/infection- mastitis

Trauma

Breast PainFibrocystic change

Most common of benign breast conditions

Replaces “fibrocystic disease”

Multiple tender breast masses

May be cyclic in nature

May be exaggerated response to hormones

Usually present as cyclic, bilateral pain and breast engorgement

Pain diffuse, often radiates to shoulders or upper arms

Prominent thickened plaques of breast tissue, often in upper outer quadrants

Breast PainFibrocystic change

ManagementFine-needle aspiration- diagnostic & therapeuticUltrasound w/needle biopsy if bloody fluid, residual mass, cyst recurrenceRestrict caffeine, foods containing methylxanthinesOCPsPain medications- ibuprofen, salicylates, acetaminophenDiureticsDanazolBromocriptine

Breast PainInfection/inflammation

Presents with pain, erythema, fever

Lactational mastitis- Occurs postpartum, Staph aureus or MRSA colonization

Management- ultrasound, antibiotics (PCN), continue breast feeding or pumping (if not MRSA); incision and drainage of abscess if virulent strain/nosocomial

Nonlactational abscess-Can be due to fistula, tuberculosis, fungi, carcinoma

Mammo & Ultrasound req

Zuska’s Dz: recurrent retroareolar infections

Case 2: Nipple Discharge

35 y.o. G1P1 presents with complaints of spontaneous nipple discharge.

Right breast, bloody discharge

POBHx- SVD x 1

PGYNHx- benign

PMHx/PSHx- negative

MEDS- OCPs

FHx- noncontributory

Nipple discharge

Differential diagnosisBreast lesions-

intraductal papilloma, ductal ectasia, fibrocystic changes, breast abscess

Drug induced-

phenothiazines, reserpine, methyldopa, imipramine, amphetamine, OCPs

CNS lesions-

pituitary adenoma, empty sella, hypothalamic tumor

Medical conditions-

Cushings, hypothyroid, chronic renal failure

Carcinoma

Idiopathic

Nipple discharge

WorkupExam

Labs- Prolactin, TSH

Mammogram

Cytologic evaluation of discharge- not very useful

Ductography

Nipple Discharge Intraductal papilloma

Epithelial tumors arising in ducts of breast

Main cause of nipple discharge in nonpregnant or nonlactating women

Usually women age 40-45

Benign, extremely small increased cancer risk

Size 2-5 mm, usually not palpable

Present with spontaneous, bloody, serous or cloudy nipple discharge

Management- excisional biopsy

Nipple DischargeDuctal ectasia

Second most common cause of nipple discharge

Older patients

Increase in glandular secretion

Discharge thick, gray/black color

Can lead to nipple retraction and breast mass

Management- medical, icepacks, anti-inflammatory agents, broad spectrum antibiotics, surgery if abscess or mass present

Nipple discharge

*Bad signsSerous, serosanguinous, or watery discharge

Associated with mass

Unilateral

Single duct

Positive cytology

Positive mammography

Age >50 yrs old

Case 3: Breast Lump

45 y.o. G2P2 presents with complaints of mass in left breast. Noticed on self exam.

Breast Lump

HistoryLength of time present

Presence of pain

Change in size or texture

Relationship to menstrual cycle

Nipple discharge

Family history of breast or ovarian cancer and ages

Age at first live birth, menarche, menopause

Breast Lump

Differential diagnosisFibroadenoma

Macrocysts

Galactoceles

Lipoma

Abscess

Rare causes- sclerosing adenosis, cystosarcoma phyllodes

Malignancy

Breast Lump

Work up

Exam

Imaging- Diagnostic mammogram- less sensitive in younger women due to breast density

Ultrasound- can distinguish cystic lesions from solid masses (require further evaluation)

Biopsy- GET A TISSUE DIAGNOSIS!!Fine needle aspiration, Core needle biopsy, Open biopsy

Breast MassFibroadenoma

Second most common benign breast disease, most common benign solid tumor

Firm, painless, mobile breast mass, 2-3 cm, commonly in upper outer quadrants

Usually women aged 20-40

Multiple in 15-20% of patients

Slow growing, do not regress spontaneously

Can be stimulated by exogenous estrogen, progesterone, lactation, pregnancy

Management- watch & wait, biopsy, or excision

Breast MassMacrocysts

Most often women age 35-50Fluid-filled sacOften solitary but can be multipleCan have associated nipple dischargeAspiration for diagnosis and therapy

GalactocoeleMilk-filled cystUsually follows lactationFirm, tender massUsually in upper quadrantsDiagnostic aspiration often curative

LipomaNontenderNo associated skin or nipple changesUsually postmenopausal womenManagement- biopsy or excision

Breast cancer>180,000 new cases per year (estimated from 2008)80% in women >50 yrs old, 20% in women <50 yrs old>40,000 deaths per year (estimated from 2008)Second leading cause of cancer-related death in womenLifetime risk of breast cancer 12%One in eight women will develop breast cancerIncreasing incidence but decreasing mortalityLower incidence in Asian/Pacific Islanders, Hispanic/Latina, American Indian/Alaska nativesHigher mortality in African Americans (though lower lifetime risk)Incidence & Mortality lowest in Asia/Africa, underdeveloped nations, those who have not adopted the Westernized reproductive & dietary patterns

Breast cancer

Risk factors (21% of cases)

Factor Relative Risk

+ FHx 1.2-3.0

Menstrual Hx (menarche <12, >40 yrs total) 1.3-2.0

OCP use No effect

Estrogen replacement <10 yrs No effect

Pregnancy (1st >35 y.o., nulliparous) 2.0-3.0

Contralateral breast cancer 5.0

Ovarian/uterine cancer 2.0

Breast cancer

Classification

Ductal carcinoma (>80% of cancers)

In situ: progresses to invasive cancer; cribiform, solid, comedo types; classified by nuclear grade & necrosis; calcifications on mammo

Medullary carcinoma: soft, hemorrhagic, BRCA1

Colloid/Mucinous carcinoma: elderly, bulky, gelatinous

Tubular: peri- early menopausal, rarely metastasizes

Papillary: 7th decade, nonwhite women, small, rarely metastasize

Inflammatory: dermal lymphatics invaded, erythema & warmth

Paget’s disease: eczematous lesion on nipple, usu assoc w/underlying malignancy,

Apocrine duct

Breast Cancer

Lobular carcinoma

In situ: only in female breast; calcifications on mammo in adjacent tissue; 12x more common in white women; not premalignant lesion, but marker for future development of invasive cancer

Infiltrative- multifocal, multicentric, bilateral; no distinct mass; signet-ring cell variant

Rare variants

Juvenile, epidermoid, carcinoid, squamous cell, spindle cell

Sarcoma and carcinosarcoma

Cystosarcoma phyllodes, angiosarcoma, malignant lymphoma

Breast cancer

Symptoms33% discovered by self-examBreast enlargement or asymmetryNipple changes, retraction, or dischargeUlceration or erythema of skinAxillary massMusculoskeletal complaintsEarly- mammo abnormality, painless, mobile tumor

Breast cancer

Screening Mammogram Annually every year >age 40, before age 40 in selected high-risk patients, w/annual clinical breast examStart 5-10 yrs before age of affected family memberDecreases mortality by up to 33% (not proven in women age 40-49)10% False-positive rate7% False-negative rateClustered microcalcifications, fine/stippled calcium around a lesion, solid mass, & asymmetric tissue thickening are suspicious for cancerIf equivocal findings on mammo, get ultrasound

Hereditary breast cancersHereditary breast cancers 5-10% of breast cancersAppropriate counseling must be provided to patient and family before testing for BRCA mutationsBRCA1 mutation (Breast & Ovary; some colon & prostate)

AD inheritance, chromosome 17q21, thought to be tumor suppressor genelifetime risk of breast cancer 90%, lifetime risk of ovarian cancer 40%Early age onset breast cancerBilateralUsu invasive ductal CA, poorly differentiated, hormone receptor (-)

BRCA2 mutation (Breast, less Ovary; some GI, Prostate, Melanoma, & Pancreas)chromosome 13q12, early age of onset, male breast cancerlifetime risk of breast cancer is 85%, lifetime risk of ovarian cancer 20%Well differentiated, hormone receptor (+)Ashkenazi Jews, Icelandic & Finnish populations

Clinical breast exam Q6 mo, w/yearly mammo (MRI) & transvaginal ultrasound w/CA-125 level starting at age 25 (if options below not excercised)Prophylactic mastectomy after child-bearingProphylactic oophorectomy after age 40

Breast Cancer Staging

Clinical staging based on physical examPathological staging more accurateTNM Staging systemT1:<2cm, T2:>2cm, T3:>5, T4: any size + involvement of chest wall or skinN0:0 nodes, N1:movable, N2:fixed, N3:infraclavicular, supraclavicular, internal mammary M0:no mets, M1:metsMost important predictor of survival is…

Breast Cancer Treatment

In Situ (Stage 0)LCIS:observation, chemoprevention w/Tamoxifen, & bilateral total mastectomyDCIS: >4 cm disease or disease in >1quadrant = mastectomyLow-grade DCIS <0.5cm: Needle-localized Lumpectomy alone if margins are widely free of diseaseHigh-grade DCIS or larger size: Lumpectomy w/Adjuvant radiation tx, or MastectomyRecurrence rate greater (9%) w/Lumpectomy + Rad, but mortality rate similar to mastectomyRisk for recurrence increases with: >2.5 cm size, comedo type, close margins

Breast Cancer TreatmentEarly Invasive (Stage I, IIA, or IIB)Mastectomy with assessment of axillary lymph node status Breast conserving surgery with assessment of axillary lymph node status + radiation (standard of care)Sentinel lymph node bx is now standard care for women with clinically negative nodes; metastatic disease in an axillary or sentinel lymph node requires full axillary dissectionContraindications to sentinel node bx: T3/T4, Inflammatory CA, palpable axillary nodes, pregnancy, DCIS without mastectomy, prior axillary surgery, after neoadjuvant chemo, prior nononcologic breast surgeryRelative contraindications to breast conserving tx: prior radiation, positive surgical margins after re-excision, multicentric disease, scleroderma, lupusChemo tx: for all node (+), cancers >1cm,and cancers >0.5cm with adverse prognostic features (BV or lymph invasion, high nuclear or histological grade, HER-2-neu amplification, & (-) hormone receptorsTamoxifen: for hormone receptor (+), >1cm; 5yr tx if premenopausal; 1-2 yr tx then aromatase inhibitor if menopausalHerceptin: for HER-2-neu (+) cancers

Breast Cancer TreatmentAdvanced Local-Regional (Stage IIIA or IIIB)No clinically detected distant metsNeoadjuvant chemo to shrink tumor & allow for breast conservation tx w/radiation (doxorubicin or taxane regiminMost get Mastectomy with evaluation of axillary status followed by radiation, +/- chemoSLNBx acceptable after neoadjuvant tx if no clinical nodes prior to chemo (need axillary dissection then)Distant Metastases (Stage IV)Tx mostly aimed at enhancing quality of lifeHormonal therapy: bone or soft tissue mets only and receptor (+)Cytotoxic chemo: hormone receptor (-) or refractory, or symptomatic visceral metsBisphosphonates: bony mets

Radiation Therapy

Can be used for all stages of Breast cancerReduces risk of local recurrenceStandard in breast conservation txNot needed for low-grade DCIS of the solid, cribiform, or papillary subtypes that is <0.5 cm & excised widely w/negative margins Mastectomy radiation: positive margins, 4 or more lymph nodes positive (or 3 or more in premenopausal woman)Chest wall & supraclavicular lymph nodes are radiated

Surgical Approach- Breast Conservation

Resection of primary cancer with a 2mm margin of normal-appearing tissue + assessment of regional node status + radiation txSegmental mastectomy, lumpectomy, partial mastectomy, wide local excisionUse areolar incision when possibleShould be able to encompass in mastectomy incision if completion mastectomy neededUpper breast lesion: follow lines of ZahnLower breast lesion: radial incisionOncoplastic techniques if possible

Surgical Approach- MastectomySkin sparing: removes all breast tissue, NAC, & prev biopsy scars (recurrence rate 6-8%)Total (simple): all breast tissue, NAC, skinModified radical: all breast tissue, NAC, skin & Level I & II axillary lymph nodesHalstead radical: same as modified, with pectoralis major & minor removed & Level III nodesPatey modification of MRM: removes pectoralis minor for dissection of Level III nodesSkin flap thickness usu 7-8 mmComplications: seroma (30%), hematoma, wound infection, skin flap necrosisLymphedema w/MRM: 10-20% (tx w/compression sleeve)

Breast Reconstruction

Immediate for prophylactic mastectomy or early invasive cancer

Delayed for advanced cancer (radiation needed)

Immediate: Expander/Implant, or Autologous tissue (latissimus dorsi myocutaneous flap; abdominal TRAM or DIEP flap)

If 2 or less ribs resected, no recon needed (scar tissue provides stabilization)

Special SituationsBreast CA in Pregnancy: usu present w/advanced disease; MRM in 1st & 2nd trimesters; lumpectomy w/axillary node dissection,radiation after delivery; chemo acceptable in 2nd & 3rd trimesters onlyMale Breast CA: <1% of all breast CA; usu invasive ductal; highest in Jewish & African-Americans; preceded by gynecomastia in 20%; similar survival rates as women; tx similar to womenPhyllodes tumor: benign, borderline, or malignant; mammo findings cannot distinguish type; sharp demarcation from normal breast tissue; Tx w/lumpectomy or mastectomy; no axillary dissection neededInflammatory Breast CA: induration, erythema, & edema; invasion of dermal lymphatics classic finding; 75% have palpable lymph nodes;Tx is neoadjuvant chemo w/MRM, radiation, +/- adjuvant chemo; poor prognosis