CHAPTER 23: The Breast

Breast uniqueness to other organs:

1. major function is the nutritional support of infant
2. structure of the organ undergoes changes during adulthood, particularly during
pregancy, before involuting with age
3. breasts are visible and, have a social, cultural, and personal significance not shared by
other organs

 ONLY in pregnancy does the breast become completely mature and functional
 By the end of the pregnancy the breast is composed almost entirely of lobules
 Milk is produced in lobules
 permanent changes produced by pregnancy may explain the reduction in breast cancer
risk that is observed in women who give birth to children at young ages.
 cessation of lactation, epithelial cells undergo apoptosis and lobules regress
 permanent increase in the size and number of lobules post pregnancy
 3rd decade - interlobular stroma converts from radiodense fibrous stroma to radiolucent
adipose tissue

Disorders of Development of Breast

A. Milk Line Remnants

 Supernumerary nipples - epidermal thickenings along the milk line from the axilla to the
perineum
 heterotopic, hormoneresponsive foci
 painful premenstrual enlargements
B. Accessory Axillary Breast Tissue

 axillary tail of Spence - extends into the subcutaneous tissue of the chest wall or the
axillary fossa
 prophylactic mastectomy
C. Congenital Nipple Inversion

 failure of the nipple to evert during development; unilateral

 Acquired nipple retraction – sign of invasive cancer or an inflammatory nipple disease
 Clinical Presentations of Breast Disease
1. mastalgia or mastodynia

 cyclic with menses or noncyclic

 Diffuse cyclic pain in premenstrual edema
 Noncyclic pain in ruptured cysts, physical injury, and infections
2. Palpable masses

 most common are cysts, fibroadenomas, and invasive carcinomas

 benign in premenstrual women
 50% of carcinomas are located in the upper outer quadrant
3. Nipple discharge

 Worrisome if spontaneous and unilateral

 Galactorrhea
o elevated prolactin levels (e.g., by a pituitary adenoma)
o hypothyroidism
o endocrine anovulatory syndromes
o oral contraceptives
o tricyclic antidepressants
o methyldopa
o phenothiazines
o NOT associated with malignancy
 Bloody or serous discharges - from large duct papillomas and cysts
 Bloody discharge in pregnancy can be normal

 Mammographic screening
o most common means to detect breast cancer
o sensitivity and specificity of mammography increase with age
o Age of 40 – only 10% cancer probability
o Age of >50 - >25%
Principal mammographic signs of breast carcinoma

a. Densities

 Rounded densities are most commonly benign

b. Calcifications

 benign lesions; malignant if small and irregular

 apocrine cysts, hyalinized fibroadenomas, and sclerosing adenosis
 ductal carcinoma in situ (DCIS) - most commonly detected as mammographic
calcifications

 inability to image a palpable mass does NOT indicate that it is benign

Inflammatory Disorders of Breast

A. Acute Mastitis

 first month of breastfeeding ; usually bacterial (Staphylococcus aureus)

 Only one duct system or sector of the breast is involved
 Staphylococcal abscesses may be single or multiple
 Streptococci cause spreading infection in the form of cellulitis
B. Squamous Metaplasia of Lactiferous Ducts

 A.k.a subareolar abscess, periductal mastitis, and Zuska disease

 painful erythematous subareolar mass
 inverted nipple as secondary effect of inflammation
 deficiency of vitamin A associated with smoking
 keratinizing squamous metaplasia
 chronic granulomatous inflammation
 en bloc surgical removal of the involved duct and contiguous fistula tract is curative
C. Duct Ectasia

 palpable periareolar mass

 thick, white nipple secretions
 Pain and erythema are UNCOMMON
 fifth or sixth decade of life, usually in multiparous women
 NOT associated with cigarette smoking
 Ectatic dilated ducts are filled with inspissated secretions
 numerous lipid-laden macrophages
 Granulomas may form around cholesterol deposits and secretions
 Mimics invasive carcinoma
D. Fat Necrosis

 fat necrosis are protean and can closely mimic cancer

 painless palpable mass, skin thickening or retraction, or mammographic densities or
calcifications
 history of breast trauma or prior surgery
 central areas of  liquefactive  fat  necrosis  with  neutrophils  and 
macrophages
 Grossly;  Ill-defined, firm, graywhite  nodules containing  small  chalky-
white  foci
E. Lymphocytic Mastopathy

 A.k.a Sclerosing Lymphocytic Lobulitis

 single or multiple hard palpable masses
 mammographic densities
 Atrophic ducts and lobules have thickened basement membranes
 prominent lymphocytic infiltrate
 type 1 (insulindependent) diabetes or autoimmune thyroid disease
F. Granulomatous Mastitis

 can be a manifestation of systemic granulomatous diseases

 parous women
 associated with lobules, suggesting that the disease may be caused by a
hypersensitivity reaction to antigens expressed during lactation
 Similar to cystic neutrophilic granulomatous mastitis caused by Corynebacteria
 Benign Epithelial Lesions of Breast

Risk of developing breast cancer

1. nonproliferative breast changes
2. proliferative breast disease
3. atypical hyperplasia

A. Fibrocystic Changes

 A.k.a Nonproliferative Breast Changes

 “lumpy bumpy” breasts on palpation
 dense breast with cysts
 benign
 three principal morphologic changes: (1) cystic change, often with apocrine metaplasia,
(2) fibrosis, and (3) adenosis
 Unopened cysts - turbid, semi-translucent fluid of a brown or blue 
color (bluedome cysts) 
 lined either by a flattened  atrophic  epithelium  or  by  metaplastic 
apocrine  cells
  granular, eosinophilic cytoplasm  and round nuclei
 Calcifications are  common 
 diagnosis is confirmed by the disappearance  of  the  mass  after 
fine-needle  aspiration
 Cysts frequently rupture, releasing secretory material that leads to chronic
inflammation
 Adenosis is defined as an increase in the number  of acini per 
lobule
 Adenosis is normal feature of pregnancy
 acini are lined by columnar cells, which may appear  benign  or 
show  nuclear  atypia  (“flat epithelial atypia”)
 Flat epithelial atypia is a clonal proliferation associated with 
deletions of chromosome 16q ; low-grade  breast  cancers
 Lactational adenomas - palpable masses in pregnant  or  lactating  women
and NON neoplastic
B. Proliferative Breast Disease Without Atypia

 proliferation of epithelial cells, without atypia

 associated with a small increase in the risk of subsequent carcinoma
 detected as mammographic densities or calcifications
 NON clonal and are NOT commonly found to have genetic changes
 increased  numbers  of  both luminal and myoepithelial cell types fill 
and distend ducts  and lobules
 increased number of  acini that are compressed
 distorted in the central portion  of the lesion
 Complex Sclerosing Lesion - “radial scar”, has an irregular shape and can 
closely mimic  invasive carcinoma
 Papillomas  grow  WITHIN  a  dilated  duct
 Large duct papillomas - situated in the lactiferous sinuses of the 
nipple; solitary; with nipple discharge
 Small duct  papillomas – multiple and located deeper within the ductal system

C. Gynecomastia

 ONLY benign lesion seen with any frequency in the male breast
 buttonlike subareolar enlargement
 unilateral or bilateral
 increase in dense collagenous connective tissue
 epithelial hyperplasia of the duct lining
 tapering micropapillae
 Lobule formation is almost NEVER observed
 imbalance between estrogens and androgens
 hyperestrinism
 cirrhosis of the liver, since this organ is responsible for metabolizing estrogen
 In older males due to androgen production falls
 alcohol, marijuana, heroin, antiretroviral therapy, and anabolic steroids
 Klinefelter syndrome (XXY karyotype)
 Leydig cell or Sertoli cell tumors
 small increased risk of breast cancer

D. Proliferative Breast Disease with Atypia

  Atypical hyperplasia is a clonal proliferation
 moderately increased risk of carcinoma
 two forms: atypical ductal hyperplasia and atypical lobular hyperplasia
 atypical ductal hyperplasia – seen as ductal carcinoma in situ; distinguished from
DCIS by only partially fills involved ducts
 Atypical lobular hyperplasia - cells  do NOT fill or distend more than 
50% of the acini within a lobule
 BOTH may have loss of 16q or gain of 17p
 Atypical lobular hyperplasia also shows loss of Ecadherin expression
 intraepithelial spread is called “pagetoid” because of its resemblance to Paget disease

D. Clinical Significance of Benign Epithelial Changes

 Nonproliferative changes do NOT increase the risk of cancer

 Proliferative disease is associated with a 1.5 to twofold increased risk
 proliferative disease with atypia confers a four to fivefold increased risk

Carcinoma of the Breast

 most common non-skin malignancy in women

 second only to lung cancer as a cause of cancer deaths
 90 years old has a one in eight chance of developing breast cancer
 Almost all breast malignancies are adenocarcinomas
Three major biologic subgroups
1. estrogen receptor (ER)-positive and HER2-negative – most common
2. ERpositive or ERnegative
3. ER-negative and HER2-negative

Incidence and Epidemiology

