diseases of the breast

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DISEASES OF THE BREAST
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Breast Anatomy

• Four quadrants
• Parenchyma
• Alveoli Lobules Lobes
• Three tissue types
• Glandular epithelium epithmyoep
• Fibrous stroma and supporting structures
• Fat
• Cooper ligaments
• Fibrous continuations of the superficial fascia,
  which span the parenchyma of the breast to the
  deep fascial layers

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THE BREAST

• Woman's breast is made up of glands that make
  breast milk (lobules),
• ducts (small tubes that carry milk from the
  lobules to the nipple),
• fatty and connective tissue, blood vessels, and
  lymph (pronounced limf) vessels.
• Most breast cancers begin in the cells that line
  the ducts (ductal cancer), some begin in the
  lobules (lobular cancer), and the rest in other
  tissues.

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Breast Anatomy

• Vasculature
• Arterial supply
• Internal mammary artery(60)
• Lateral thoracic artery(30)
• Venous return
• Intercostals
• Axillary vein(primary)
• Internal mammary vein
• Lymphatics

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Breast Anatomy

• Lymphatics
• Axillary chain
• Level 1 lateral to pectoralis minor muscle
• Level 2 along and under pectoralis minor
• Level 3 - medial to pectoralis minor
• Rotters nodes
• Between pectorial minor and major muscles
• Internal mammary chain (relatively minimal
  drainage)
• Parasternal
• medial

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Breast Anatomy

• Nerves
• Long thoracic nerve
• Thoracodorsal nerve
• Medial pectoral nerve
• Lateral pectoral nerve

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• The breasts can either be divided into quadrants
  or in relationship to the face of a clock for
  purposes of location of abnormalities. The Four
  Quadrants are the
• UIQ Upper Inner Quadrant
• LIQ Lower Inner Quadrant
• UOQ Upper Outer Quadrant
• LOQ Lower Outer Quadrant

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Infectious and Inflammatory Breast Disease

• Cellulitis, Acute mastitis and Abscess
• Usually associated with lactation
• Mostly pyogenic bacterial infection-
  Staphylococcus and Streptococcus
• Chronic mastitis
• May follow acute pyogenic mastitis
• Tuberculous mastitis- may reach the breast by
  haemotogenous or lymphatic or direct spread from
  the lungs or pleura
• FB mastitis

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Benign Lesions of the Breast

• Mammary duct ectasia(Plasma mastitis)
• Generally found in older women.
• Dilatation of the subareolar ducts can occur.
• A palpable retroareolar mass, nipple discharge,
  or retraction can be present.
• Periductal fibrosis and inflammation(lymphocytes,
  histiocytes, multinucleated histiocytic giant
  cells massive number of plasma cells.
• May be mistaken for carcinoma of the breast
• Fat necrosis
• Associated with trauma or radiation therapy to
  breast.
• Can simulate cancer with mass or skin retraction.
• Bx is diagnostic and generally with lipid-laden
  macrophages, scar tissue, and chronic
  inflammatory cells.

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Mammary duct ectasia. The dilated duct contains
foamy histiocytes and the periductal tissue is
infiltrated by lymphocytes
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Mammary duct ectasia. In this late stage, the
ductal lumen is filled with lipid material and
foamy histiocytes. The periductal fibrosis is
marked with collections of hemosiderin laden
macrophages
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Benign Lesions of the Breast

• Cysts
• Fluid-filled, epithelium-lined cavities
• Influenced by ovarian hormones
• Explains sudden appearance during the menstrual
  cycle, their rapid growth, and their spontaneous
  regression with completion of the menses.
• Common after age 35, and rare before 25.
  Incidence declines after menopause.
• Three colors by needle aspiration
• Simple cyst, clear or green fluid and is benign.
• Milk-filled cyst, called galactocele and is
  benign.
• Bloody cyst is a cause of concern for malignancy.

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Benign Lesions of the Breast

• Fibrocystic breasts
• Broad spectrum of clinical and histologic
  findings
• Loose association of cyst formation, breast
  nodularity, stromal proliferation, and epithelial
  hyperplasia.
• Appears to represent an exaggerated response of
  breast stroma and epithelium to hormones and
  growth factors.
• Dense, firm breast tissue with palpable lumps and
  frequently gross cysts, commonly painful and
  tender to touch.
• Commonest benign breast disease producing
  palpable lump in the breast of adult women
• No consistent association between fibrocystic
  complex and breast cancer.

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Fibrocystic change. Multiple dilated cystic
spaces with occasional papillary projections
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Benign Lesions of the Breast

• Neoplasia
• Fibroadenoma
• Is the most common benign tumour of female breast
• Well-defined, mobile benign tumor of breast
• Composed of both stromal and epithelial elements
  in the breast
• Common in younger women, and is most common tumor
  in women younger than age 30 years
• Can be diagnosed by FNA and followed if lt 2-3 cm
  and age lt 35
• Otherwise Dx by excision.
• At operation are well-encapsulated and detach
  easily.
• Phyllodes tumors (cystosarcoma phyllodes)
• Giant fibroadenomas
• Can be classified as benign, borderline and
  malignant
• Rarely malignant

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• Phyllodes tumoronce more commonly referred to as
  cystosarcoma phyllodes (from Greek kystis "sac,
  bladder", sarkoma "fleshy tumor", and
  phyllon "leaf")
• Leaf like appearance is pathognomonic feature

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Fibroadenoma removed during breast biopsy
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Breast fibradenoma
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Benign phyllodes tumour
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Benign Lesions of the Breast

• Intraductal Papilloma
• Polyps of epithelium-lined breast ducts
• Mostly occurs in lactiferous duct or lactiferous
  sinus near the nipple
• Located under the areola in most cases
• When under the nipple and areolar complex it
  often present with a bloody nipple discharge..
• Need to rule out invasive papillary carcinoma.

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Benign Breast Disease

• Nipple discharge
• Pathologic nipple discharge is persistent and
  spontaneous and is not associated with nursing.
• Requires further evaluation
• Galactorrhea
• Bilateral, milky discharge occurs
• Obtain prolactin levels, if highly elevated,
  suspect pituitary adenoma as one of causes.

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• Bloody nipple discharge
• Most common cause is intraductal papilloma
• Cancer present 10 of time.
• Cytologic exam on discharge
• Mammogram to rule out associated mass

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Carcinoma sites in breast
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Type of breast cancer.

• Carcinoma in situ This term is used for early
  stage cancer, when it is confined to the place
  where it started.
• In breast cancer, it means that the cancer is
  confined to the ducts or the lobules.
• Ductal carcinoma in situ (DCIS)
• This is the most common type of noninvasive
  breast cancer.
• DCIS means that the cancer is confined to the
  ducts.
• Lobular carcinoma in situ (LCIS)
• This condition begins in the milk-making glands
  but does not go through the wall of the lobules.

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Type of breast cancer-cont--

• Invasive (infiltrating) ductal carcinoma (IDC)
• This is the most common breast cancer.
• It starts in a milk passage or duct, breaks
  through the wall of the duct, and invades the
  tissue of the breast.
• Invasive (infiltrating) lobular carcinoma (ILC)
  This cancer starts in the milk glands or lobules.
• It can spread to other parts of the body

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BREAST CANCER
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BREAST CANCER
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Ductal Carcinoma in Situ

• Seen as microcalcifications on mammogram
• Confined to ductal cells.
• No invasion of the underlying basement membrane.
• Chance of recurrence 25-50 in 5 years, of these
  50 will be invasive

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Ductal carcinoma in situ
Dr. Susan Loves Breast Book, 2005. S. Love
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DCIS, comedo type. Solid sheets of malignant
cells fill the Dilated ducts
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Does in situ disease become invasive disease?
Dr. Susan Loves Breast Book, 2005. S. Love
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Lobular Carcinoma in Situ

• Not detectable on mammography
• Most commonly found incidentally
• Risk of invasive breast cancer in 20 years is
  15-20 bilaterally

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Lobular carcinoma in situ
Dr. Susan Loves Breast Book, 2005. S. Love
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Non-invasive breast cancers

• 10 of all types of breast cancer
• Good prognosis
• Ductal carcinoma in situ,
• lubular carcinoma in situ, and
• pagets disease

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Favorable histologic types

• Tubular carcinoma
• 2 of all invasive breast cancers
• Generally diagnosed by mammography
• Distinctive under microscope
• Long-term survival aproaches 100
• Mucinous (colloid) carcinoma
• 3 of all invasive breast cancers
• Generally confined to elderly population
• Bulky, mucinous tumor with characteristic
  microscopic features
• 5 and 10 year survival rates are 73 and 59
  percent, respectively
• Papillary carcinoma
• lt2 of all invasive breast cancers
• Generally presents in seventh decade, and is a
  slowly progressive disease
• 5 and 10 year survival rates are 83 and 56
  percent, respectively

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Less Favorable Histologic Types

• Medullary carcinoma
• 4 of all invasive breast cancers
• Soft, hemorrhagic bulky presentation
• Diagnosed microscopically (lymphocytic
  infiltration)
• Metastases to axillary nodes in 44
• 5 and 10 year survival rates are 63 and 50
  percent respectively
• Invasive ductal carcinoma
• Most common and occurs in 78 of all invasive
  breast cancers.
• Metastases to axillary nodes in 60
• 5 and 10 year survival rates are 54 and 38
  percent respectively
• Invasive lobular carcinoma
• 9 of all invasive breast cancers
• Metastases to axillary nodes in 60
• 5 and 10 year survival rates are 50 and 32
  percent respectively
• Higher incidence of bilaterality

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Least favorable type

• Inflammatory breast cancer is a rare and very
  aggressive disease in which cancer cells block
  lymph vessels in the skin of the breast.
• This type of breast cancer is called
  inflammatory because the breast often looks
  swollen and red, or inflamed post blockade.

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Pagets Disease

• Uncommon
• Usually involves the nipple
• Histologically
• vacuolated cells are seen in the epidermis of
  the nipple and result in an eczematous dermatitis
  of the nipple.
• It is generally associated with an underlying
  intraductal or invasive carcinoma.
• Mammography should be performed
• About 30 of patients have axillary node
  metastasis at diagnosis.
• Mastectomy is the standard of treatment
• 80 have a 10 year survival rate if there is no
  mass present and no axillary nodes are involved.

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Paget's disease of the nipple
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Paget's disease of the nipple
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Paget's disease of the nipple
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Paget's disease of nipple. Paget's cells have
pale, vacuolated cytoplasm and large nuclei and
migrate through the epidermis from parabasal cell
layers upward. Notice the highes concentration in
the deep layers of epidermis
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Invasive ductal carcinoma of the breast
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Breast invasive scirrhous carcinoma
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A well-differentiated ductal carcinoma made up of
small acini and glands.
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Medullary Carcinoma of the Breast, Mastectomy
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MEDULLARY CARCINOMA, BREAST
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Tumor cells in a medullary carcinoma have
anaplastic nuclei, prominent nucleoli, and
ill-defined cell borders giving the appearance of
a syncytial pattern.
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Breast invasive lobular carcinoma
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Infiltrating Lobular Carcinoma of Breast -The
linear pattern of infiltration is also known as
"indian filing".
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COLLOID(MUCINOUS) CARCINOMA, BREAST
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Mucinous carcinoma is characterized by tumor
cells surrounded by abundant extracellular mucin
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PAPILLARY CARCINOMA, BREAST
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Papillary carcinoma with stromal invasion.

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Inflammatory carcinoma

• 1.5-3 of breast cancers
• Characteristic clinical features of erythema,
  peau dorange, and skin ridging with or without a
  palpable mass.
• Commonly mistaken for cellulitis.
• Will generally fail antibiotics before being
  diagnosed
• Disease progresses rapidly, and more than 75 of
  patients present with palpable axillary nodes.
• Distant metastatic disease also at much higher
  frequency than the more common breast cancers.
• 30 5 year survival rate
• Requires chemotherapy treatment immediately

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Inflammatory carcinoma with malignant cells in
the dermal lymphatics, which are associated with
lymphocytic infiltration and stromal edema.

• .

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BREAST CANCER RISK FACTORS

• There are a variety of risk factors that may
  contribute to the development of breast cancer.
• Risk factors can be categorized as major, minor
  and inconclusive.
• The major risk factors for developing breast
  cancer include
• gender,
• age,
• genetics,
• family history and personal history of breast
  cancer.
• The first two risk factors are the most
  important.
• It is important to emphasize prior to reviewing
  the major risk factors that 85 of women who
  develop breast cancer have no other risk factors
  than being female and aging.

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GENDER

• The biggest risk factor for developing breast
  cancer is gender.
• The lifetime risk for women developing breast
  cancer is 1 in 8.
• Approximately half of all women who develop
  breast cancer have no identifiable risk factor
  other than being female.

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AGE

• Besides being female,
• the second greatest risk factor for developing
  breast cancer is age.
• Older women are much more likely to get breast
  cancer.
• Breast cancer is much less frequent among younger
  women, with the earliest diagnoses usually being
  made at around 25 years.

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GENETICS

• About 5-10 of breast cancer cases are
  hereditary, the third greatest risk factor.
• This is thought to be because of the cyclical
  changes that occur in the breast during a woman?s
  lifetime, thus linked to be due to the influence
  of reproductive hormones (estrogen and
  progesterone), breast cells are constantly going
  through rapid cell growth and division.
• This raises the odds that mutations in DNA are
  the origin of breast cancer in women.
• .

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GENETICS-cont--

• Women with a hereditary risk for factor for
  breast cancer carry the BRCA 1 or BRCA 2 genes.
• The identified breast cancer genes (BRCA 1 and
  BRCA 2) are located on Chromosome 17.
• Women who carry the BRCA 1 and BRCA2 have up to
  an 85 chance of developing breast cancer in
  their lifetime.
• These mutations are present in far less than 1
  of the general population.

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Hereditary breast cancers

• Hereditary breast cancers 5-15 of breast cancers
• BRCA1 mutation-
• chromosome 17q21,
• thought to be tumor suppressor gene
• lifetime risk of breast cancer 82,
• lifetime risk of ovarian cancer 44
• BRCA2 mutation-
• chromosome 13q12,
• early age of onset,
• male breast cancer
• lifetime risk of breast cancer is 70,
• lifetime risk of ovarian cancer 17

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FAMILY HISTORY

• The fourth major risk factor for developing
  breast cancer is family history.
• Breast cancer risk is higher among women whose
  close blood relatives have this disease (mother,
  sister or daughter).
• A blood relative can be from either the mother?s
  or the father?s side of the family,
• But the closer the relative, the higher the risk
  factor.
• The more first-degree relatives a person has with
  the disease, the greater the risk.
• Women are also at a higher risk if the breast
  cancer occurs in a relative before age 50.

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PERSONAL HISTORY

• The last major risk factor for developing breast
  cancer is having a personal history of the
  disease.
• A woman with cancer in one breast has a greater
  risk of developing a new cancer in the other
  breast.
• Having a history of the following types of
  cancers may also increase the risk of developing
  breast cancer colon, uterine, salivary gland and
  Hodgkin?s disease

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MINOR RISK FACTORS

• Many minor risk factors for developing breast
  cancer are associated with hormonal changes in
  the woman?s body.
• Reproductive hormones (estrogen / progesterone)
  are thought to influence breast cancer risk
  through their effects on cell proliferation and
  DNA damage, as well as promotion of cancer
  growth.

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MINOR RISK FACTORS

• The minor risk factors related to hormonal
  factors include
• Childbearing Age
• Menstrual History
• Use of Hormone Replacement Therapy (HRT)

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MINOR RISK FACTORS-cont--

• CHILDBEARING
• Never having children increases the risk of
  breast cancer twice over women who have had at
  least one baby.
• Also, having children later in life (over the age
  of 30) increases the risk of developing breast
  cancer.
• Also breast feeding has consistently been shown
  to decrease a woman?s risk of breast cancer
  slightly, with greater benefit associated with
  longer duration

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MINOR RISK FACTORS-cont--

• MENSTRUAL HISTORY
• Women who start menstruating at an early age
  (early menarche - before age 12) or
• who went through menopause at a late age (after
  age 55) are at an increased risk for breast
  cancer.
• As long as a woman is menstruating, there is a
  greater risk of mutating genetic material.
• The greater the number of menstrual cycles in the
  woman?s lifetime, the greater the risk of breast
  cancer

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MINOR RISK FACTORS-cont--

• HORMONE REPLACEMENT THERAPY
• Estrogen and progesterone, produced in the
  ovaries are important hormones used to regulate
  the menstrual cycle and pregnancy.
• As a woman ages, the ovaries begin to shrink and
  the levels of estrogen and progesterone in the
  body fluctuate ? called peri-menopause, which can
  last for many years.
• HRT was approved in 1945 to relieve the symptoms
  caused by peri-menopause

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HORMONE REPLACEMENT THERAPY

• A study in the summer of 2002 found increased
  risk of developing breast cancer in women taking
  HRT.
• An added disadvantage to the use of HRT is that
  its use increases the proliferation of dense
  glandular tissue in the breast, which reduces the
  effectiveness

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INCONCLUSIVE RISK FACTORS

• There are a number of inconclusive risk factors
  for developing breast cancer which include the
  following
• Obesity
• Alcohol consumption
• Higher Socioeconomic Status
• Cultural Origin

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INCONCLUSIVE RISK FACTORS

• OBESITY
• Some studies suggest that obesity increases the
  risk for postmenopausal, but not pre-menopausal,
  breast cancer.
• In postmenopausal women, circulating estrogen is
  primarily produced in adipose tissue.
• Thus, having more adipose tissue can increase
  estrogen levels and the likelihood of developing
  breast cancer

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INCONCLUSIVE RISK FACTORS

• ALCOHOL CONSUMPTION
• Alcohol is consistently associated with increased
  breast cancer risk (the equivalent of two drinks
  a day may increase breast cancer risk by 21).
• A recent review concluded that the most likely
  mechanism by which alcohol increases risk of
  breast cancer is by increasing estrogen and
  androgen levels.

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INCONCLUSIVE RISK FACTORS

• HIGHER SOCIOECONOIC STATUS
• Women with incomes in the upper 2/3rds of the
  U.S. population get breast cancer more often than
  those in the lower 1/3rd income bracket.
• The theories behind this statistic is that women
  with higher incomes have greater access of health
  care than those of lower socioeconomic status.

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The Male Breast

• Gynecomastia
• Prepubertal gynecomastia
• Rare, adrenal carcinoma and testicular tumor can
  cause this.
• Pubertal gynecomastia
• Occurs in 60-70 of pubertal boys.
• Senescent gynecomastia
• 40 of aging men have this to some degree.
• Drugs, such as steroids, digitalis, hormones,
  spironolactone, and antidepressants can cause
  this.
• .

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The Male Breast-cont---

• Male breast carcinoma
• 0.7 of all breast cancers
• lt1 of male cancers
• Average age of diagnosis is 63.6 years old
• Painless unilateral mass that is usually
  subareolar with skin fixation, chest wall
  fixation,, and ulceration.
• Mostly ductal carcinoma
• Males generally present at later stage than woman
• Overall survival worse in men,

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Symptoms of breast cancer

• The most common sign of breast cancer is a new
  lump or mass.
• A lump that is painless, hard, and has uneven
  edges is more likely to be cancer.
• But some cancers are tender, soft, and rounded.
• So it's important to have anything unusual
  checked by your doctor.
• Other signs of breast cancer include the
  following
• a swelling of part of the breast
• skin irritation or dimpling
• nipple pain or the nipple turning inward
• redness or scaliness of the nipple or breast skin
  
• a nipple discharge other than breast milk
• a lump in the underarm area

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Staging of breast cancer.

• Staging
• Staging is important to determine if the patient
  is potentially in a curable early stage or
  otherwise
• Stage 0 - Cancer in Situ
• Stage I - Cancer is less than 2 cm.
• Stage II - Cancer is between 2 to 5 cm with or
  without involvement of the glands in the armpit
• Stage III - Cancer is larger than 5 cm or there
  is extensive involvement of the glands in the
  armpit
• Stage IV - Cancer has spread outside the breast
  and involves other organs in the body
• Stage I II are considered early and curable.
• Stage IV disease is not curable.

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Diagnosis

• Fine-needle aspiration
• Sensitivity is 80-98, specificity 100
• False negatives are 2-10
• Core-needle biopsy
• More tissue, however still possibility of false
  negative and could represent sampling error
• Incisional biopsy
• For large (gt4 cm) lesions for whom pre-op
  chemotherapy or radiation will be desirable.
• Excisional biopsy
• Removal of entire lesion and a margin of normal
  breast parenchyma

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Prognostic Features

• Tumor size important prognostic factor
• Poor prognostic features of tumor
• Presence of edema or ulceration of skin, mass
  fixed to chest wall or skin, satellite skin
  nodules, peau dorange (dermal lymphatic
  invasion), skin retraction and dimpling, and
  involvement of medial portion of inner lower
  quadrant involved.
• Axillary node status
• Best source of predicting survival or outcome
• N0 has 10 year survival rate of 60
• N1 has 10 year survival rate of 50
• N2 has 10 year survival rate of 20
• If 10 or more nodes are diseased (N3) 10 yr surv.
  Rate is 14
• Poor prognostic feature of nodes
• Capsular invasion, extranodal spread, and edema
  of arm

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Prognostic Features

• Distant metastases- is very poor prognostic
  indicator
• Postive estrogen and progesterone receptor
  indicates likely response to hormonal treatment
  and is a positive prognostic indicator
• HER2 expression

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Treatment

• Modalities (palliative vs. curative)
• Surgery
• Local treatment
• Radiation
• Local treatment
• Chemotherapy and hormonal therapy
• Systemic treatment