Schwartz: Breast

Development
 5th to 6th week of embryologic week, two bands of thickened ectodermal ridge develop
 Formation of primary buds  15-20 secondary buds  epithelial cords develop around secondary buds
and extend to surrounding mesenchyme
 Inverted nipple- develops when a pit fails to elevate into skin
 Amastia- absence of breast tissue d/t arrest in mammary ridge development durig 6th week of fetal life
 Poland’s syndrome- hypoplasia or complete absence of mammary tissue and combined with costal cartilage
and rib defects, brachysyndactily
 Polythelia- accessory nipples along ectodermal ridge
 Polymastia- extra mammary tissue
 Turner’s and Fleischer’s syndrome are associated with extra mammary tissue
o Turner (ovarian agenesis and dysgenesis
o Fleischer- nipple displacement and bilateral renal hypoplasia
Nipple areola complex
 Montgomery’s tubercles- elevations of sebaceous gland, sweat glands, accessory glands
 Cooper’s ligaments- provides attachemtn of breast to underlying muscles
 Smooth muscle fibers- erection of nipple
Inactive and active breast
 Major ducts- line with 2 layers of cuboidal cels
 Minor ducts- lined with a layer of either cuboidal or columnar cells
 Pregnancy- hypertrophy of alveolar epithelium and accumulation of secretory products
 Colostrum- milk during first few weeks, contains less lipid and high antibodies, which are from lymphocytes
Blood supply, innervation, lymphatics
Blood supply
 Perforating branches of internal mammary arteries
 Lateral branches of posterior intercostal arteries
 Branches of axillary artery
Drainage
 Perforating braches of internal thoracic vein
 Lateral branches of posterior intercostal veins
 Tributaries of axillary vein
Lymphatics
 According to pectoralis minor muscle
 Level1: lateral, contains scapular, external mammary, axillary
 Level2: deep, contains central and interpectoral group
 Level 3: medial, subclavicular
Batson’s complex- provide route for metastasis to vertebrae, skull, pelvis, central nervous system
Physiology of breast
 Estrogen- ductal development
 Progesterone- epithelial and lobular development
  Prolactin- primary stimulus for lactogenesis in late pregnancy and postpartum
 FSH and LH- regulat release of hormones mentioned above
 Oxytocin- stimulates release of milk

Gynecomastia
 Enlargement of male breast tissue
 Due to excess estrogen in relation to testosterone levels
 Occur in three phases: neonate, adolescent, scenescence
 Neonate- due to placental estrogen
 Adolescent- due to excess estradiol
 Senescence- due to decreased testosterone leading to hyperestrenism
o Occur in 50-70 years old
 Graded according to enlargement, skin involvement
o Grade 1- mild enlargement, no skin redundancy
o Grade 2a- moderate, no skin redudnacy
o Grade 2b- moderate, with skin redundancy
o Grade 3- marked, with skin redudnacy and ptosis
 Dx: in nonobese patients, mass diameter has to be 2cm
 Pharmacologic causes:
o Drugs that have estrogenic activity
o Drugs that inhibit or decrease synthesis of testosterone

Inflammatory and infectious disorders of breast

Bacterial infections
 Staphylococcus aureus
o Inoculated by suckling neonate
o Point tenderness, erythema, hyperthermia
o Affects deep, localized breast tissues
o Tx: antibiotics (initial), repeated aspiration
o Operative drainage- reserved for those not treated with antibx
 Streptococcus
o Superficial lobular infection
o Diffuse superficial involvement
o Tx: local wound care, warm compress, antibiotic
 Epidemic puerperal mastitis
o MRSA inoculated by suckling neonate
o Tx: antibiotic, stop breastfeeding
 Nonepidemic puerperal mastitis (sporadic)
o Affects interlobular connective tissue
o Causes milk stasis and retrograde infection
o Tx: empty breast with suction +antibiotic
 Zuska’s
 o Recurrent periductal mastitis
o Smoking is a risk factor
o Tx: antibiotic with incision and drainage
Mycotic infection
 Commonly sporotrichosis and blastomychosis
 Purulent fluid mixed with blood
 Candida albicans
o Affects skin and presents as erythematous scaly lesions
o Tx: removal of maceration and nystatin
Hydradenitis suppurative
 Chronic inflammatory condition of nipple areolar complex and axilla
 If near nipple-areola complex, may mimic other diseases such as paget’s disorder of the nipple or invasive
breast cancer
 Risk factor: women with chronic acne
 Tx: antibx with incision and drainage
Mondor’s disease
 Variant of thrombophlebitis usually affecting superficial veins of anterior chest wall
 Presents with pain, usually unilaterally, bilateral is rare
 Tx: inflammatory drugs
 Veins usually involved: lateral thoracic vein, thoracoepigastric, superficial epigastric vein
 Benign, self-limited disorder, not indicative of cancer

Benign breast disorders and diseases

Early reproductive years- 15 -25 years old
normal disorder disease
 Lobular development  Fibroadenoma  Giant fibroadenoma
 Nipple eversion  Nipple inversion  Gigantomastia
 Stromal development  Adolescent hypertrophy  Subareolar abscesses
 Mammary duct fistula
Fibroadenoma- <1cm is still normal, <3cm fibroadenoma, >3 giant fibroadenoma

Nonproliferative breast diseases:

Calcification
 Calcium deposits due to trauma or inflammation
Fibroadenoma
 Abundant stroma, well circumscribed tumor, hormonal dependent
Adenoma of the breasts
 Similar to fibroadenoma but sparse stroma
 Lactating adenoma- for pregnant or postpartum women
 Tubular adenoma- nonpregnant women
Hamartoma- 2-4cm discrete breast tumor
Adenolipoma- sharply demarcated fatty tumor
Proliferative disorders without atypia
Sclerosing adenosis
 No malignant potential
 Can be managed with observation as long as imaging features are normal
Radial scars- up to 1cm lesions
Complex sclerosing lesions- larger lesions
Mild ductal hyperplasia- 3-4 layers above basement membrane
Moderate ductal hyperplasia- 5 or more layers
Florid- up to 70% of minor duct lumen is involved
Intraductal papilloma- bloody, serous nipple discharge

Atypical proliferative disorders

Atypical ductal hyperplasia- lesions 2-3mm, higher risk of invasive breast cancer
Ductal carcinoma in situ- tumor >3mm
Ductal lesions- have e-cadherin activity
Atypical lobular hyperplasia- minimal distention
LCIS- distention but maintained architecture
Lobular lesions- no e-cadherin activity

Treatment:
Cysts- needle biopsy, 21 gauge needle inserted to aspirate cysts, aspirate to dryness if not bloodstained
 If mass remains or if bloodstained, core needle biopsy for further diagnosis
Fibroadenoma- usually self-limited, if <2mm surgical excision not necessary, pathognomic is younger than 25 year
old women
Sclerosing adenosis- imitates cancer
 Stereotactic biopsy- to differentiate between slceoring adenosis and cancer
Periductal mastitis- women who presents with tender masses behind nipple-areolar complex is managed by inserting
21-gauge needle to aspirate fluid and sent out for culture to identify organism
 Antibiotic with wide coverage and continued when culture results are in
Nipple inversion- due to shorterning of subareolar ducts
 Tx: division of these ducts

Risk factors of breast cancers:

Those that increase exposure to estrogen:
 Early menarche <12
 Older age at first pregnancy >30 years old
 OCP use- higher for those >4 years of use, estrogen+progesterone use also has higher risk
 Obesity
 High fat diet
Other risk factors
 Mantle radiation at early age for hodgkin’s lymphoma
 Smoking
 Alcohol
Screening for high risk
High risk- known mutation, radiation at young age, personal history of breast ca,
55-75 years old- biennial screening
40-54- annual screening
<40- ultrasound
MRI- for those high risk with BRCA mutation

Chemoprevention
Tamoxifen- selective estrogen receptor modulator
 Side effect: endometrial cancer
Aromatase inhibitor- lesser risk for endometrial cancer, side effect: arthritis

Primary breast cancer

 Skin retraction- d/t shortening of cooper’s
 Peau d’orange- d/t blockage of lymph drainage
Axillary lymph node metastase- most important prognostic indicator
 The larger the size, the more cancer cells that are shed into cellular spaces and spread to lymph circulation
 At 20th cell doubling- cancer cells have their own neovascularization and may seed into systemic circulation
 Cancer cells that grow >0.5mm can metastasize usually at the 27th cell doubling time
 Mets in order of frequency: bone, lung, liver

Carcinoma in situ- has not invaded basement membrane

Lobular CIS- multicentricity, lower risk of proceeding to invasive breast cancer, risk factor to IBC, bilateral location of
subsequent cancer, calcification in neighboring location, terminal lobules, only seen in women
Ductal CIS- high risk of proceeding to invasive, precursor to IBC, unilateral usually in the same quadrant as the
primary tumor, epithelial proliferation, calcification at areas of necrosis, account for 5% of breast cancer in men

Invasive breast carcinoma

 Invaded basement membrane
 Invasive lobular- those that originate from lobular CIS, the rest are ductal
 Invasive ductal carcinoma of no special type- common
o To be diagnosed as specific, it should contain at least 90% of the defining histologic feature
o Pagets of the nipple
o Invasive ductal carcinoma- 80%
o Medullary- BRCA1 mutation
o Mucinous colloid- seen in older population, bulky breast tumor
o Tubular- good prognosis, early menopausal
o Papillary carcinoma- 7th decade of life, small barely exceeds 3cm
o Invasive lobular- multicentric, multifocal, bilateral
Paget’s disease of the nipple
 Presents as eczematous, scaly lesions of the nipple
 Often confused with superficial spreading melanoma; differentiated by
o + CEA- pagets
 o + s-100 = melanoma
 Associated with extensive DCIS
 Pathognomic- large vacuolated cells in rete pegs of epithelium

Invasive ductal carcinoma- accounts for 80% of cases

 Common in perimenopausal women in their 5th to 6th decade of life
 Poorly circumscribed lesions
 60% axillary lymph node metastasis
Medullary carcinoma
 Common in BRCA1 mutation
 4% of all IBC
 Bulky in nature
Mucinous (colloid)
 Common in older population
 Pools of mucin
Papillary
 Common in 7th decade of life
 Papillae formation with fibrovascular stalks
Tubular
 Haphazard array of small tubular elements

Diagnosis:
History and physical examination
Imaging techniques
Mammography
 Annually in women >40 years
 Biennual in women aged 55-74 years and continuous for those with life expectancy >10 years
 Screening mammography- done for asymptomatic women with 2 views:
o Cephalocaudal view- greater breast compression
o Mediolateral oblique- greater breast tissue, including upper outer quadrant and tail of spence
 Diagnostic mammography- evaluate women with abnormal findings like nipple discharge
o Specific features that suggest cancer
 Clustered microcalficiations
 Asymmetric thickening of tissues
 Solid mass with or without stellate configurations
Ductography
 Done in women with bloody serous nipple discharges
 Contrast media injected into nipple ducts
 Intraductal papilloma- small filling defects
 Cancer- irregular masses or multiple intraluminal defects
Ultrasound
 Secondary to mammogram
  Breast cysts- circumscribed, smooth margins
 Benign breast mass- smooth contour, defined anterior and posterior margin
 Cancer- irregular walls
 Cannot detect lesions <1 cm in diameter
 Done in women <40 years old
 Features of a lymph node involved in cancer
o Cortical thickening
o Size larger than 10mm
o Hypoechoic internal echoes
o Change in shape into circular
o Absence of fatty hilum
MRI
 Done for those with BRCA mutations
 Also done for
o Assess response to therapy
o Select patients for partial irradiation technique
o Evaluate treated breast for recurrence
o Evaluate patients with nodal metastasis but undetectable primary tumor

Biopsy
Fine needle- requires 3-4 passes in the tumor
 Fixed with 95% alcohol and stained with papanicolau technique
 Allow cytologic evaluation
Core needle biopsy- gold standard
 allow analysis of breast tissue architecture

staging
 tumor, nodes, metastasis
 tumor size correlates with axillary lymph node metastasis
o the greater the size, the more metastatic cancer cells being shed at cellular spaces and
transported to lymph nodes

Diagnostic workup
For stages II, III, IV- CBC, liver function tests, chest xray
For stages III, IV- bone scan, abdominal ultrasound