Breast Hashmi Hormone Estrogen = Principal hormone

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Breast

• Hashmi

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Hormone

• Estrogen Principal hormone. Proliferates
  mammary epithelium. Potent mitogenic effects
• Progesterone lobular/glandular development w/in
  breast tissue. Limits estrogen binding
• Prolactin Synergistically with
  estrogen/progesterone. Stimulates
  differentiation of milk producing cells

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Breast Changes

• Puberty GnRH/LH/FSH stimulate
  estrogen/progesterone causing proliferation of
  ductal epithelium, myoepithelium, surrounding
  stroma, and glands
• Menstrual cycle increase in volume, size,
  density, nodularity, and sensitivity decreases
  w/onset of menses
• Pregnancy Prolactin increases 10-fold. Breast
  as a whole increases. Milk fats and proteins are
  produced due to prolactin
• Menopause Fibrous tissue becomes dense. Fat
  mass decreases. Lobules/ducts become atrophic

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Lymphatic Drainage

• Lateral (Ix3, II, III)
• Medial (via internal mammary vessels)
• Transpectoral (Rotter ? III)
• Retropectoral (II ? III)

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Benign Disorders

• Fibrocystic Disease
• Non-proliferative Cyst/Apocrine Metaplasia, Duct
  Ectasia, Mild Epithelial Hyperplasia,
  Calcification, Fibroadenoma
• Proliferative Sclerosing Adenosis, Radial
  Scar/Complex Sclerosing, Moderate/Florid
  Epithelial Hyperplasia, Intraductal Papilloma
• Atypical Proliferative Atypical Lobular
  Hyperplasia, Atypical Ductal Hyperplasia
• Inflammatory Abscess, Mondor Disease

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Fibrocystic Disease

• Clinically refers to presence of palpable lumps
  in the breast which fluctuate in size and
  discomfort with menstrual cycle.
• Fibrocystic changes are normal changes expected
  within the breast that become more evident with
  aging
• General term, being outdated with more specific
  terminology for specific histological pathology

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Non-proliferative Lesions

• Cysts/Apocrine Metaplasia ? Micro/Macrocyst
  secondary to ductal obstruction from sloughing
  of epithelium. Metaplasia occurs when the flat
  ductal epithelium makes a transition to tall
  columnar cells, hence causing ductal obstruction
• Duct Ectasia ? dilation, periductal inflammation,
  and fibrosis of retroareolar ducts just beneath
  the nipple. May present with nipple discharge,
  pain, subareolar abscess, mammary duct fistula,
  nipple retraction.

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Non-proliferative Lesions

• Mild Epithelia Hyperplasia ? Refers to increase
  in number of cells with relation to basement
  membrane. Normally two cell layers line the
  duct above the basement membrane. Mild
  hyperplasia refers up to 5 layers.
• Calcification ? Benign long parallel lines,
  popcorn pattern, radiolucent center,
  uniformity of size, well defined without
  spicules, branches, or comma shapes Malignant
  irregular, poorly defined, contain branches,
  spicules, or comma shapes
• Fibroadenoma ? discrete, well defined, firm,
  freely movable, and non-tender. Overgrowth of
  normal tissue

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Proliferative Lesions

• Sclerosing Adenosis ? incidental finding, or
  painful mass. Normal two cell layer and
  basement membrane is intact. Proliferation of
  terminal duct lobular unit, forming cords of
  epithelium within stromal tissue.
• Radial Scar/Complex Sclerosing Lesion ?
  Sclerosing adenosis forming a central scar
  w/proliferating epithelial elements spreading in
  a stellate fashion
• Moderate/Florid Epithelial Hyperplasia ?
  Hyperplasia from the normal two-cell layer to a
  point where nearly 70 of the lumen is filled
  with cells forming clefts, papillomas, arches,
  and bridges
• Intraductal papillomas ? Bloody nipple discharge,
  Identified by galactogram/ductogram. Neoplastic
  changes w/in the epithelium forming a polyp

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Atypical Proliferative

• Atypical Lobular Hyperplasia ? Less than ½ of
  the acinar lobular unit is filled with
  hyperplastic cells with atypia. When more than
  ½ it is considered lobular carcinoma in situ.
• Atypical Ductal Hyperplasia ? Incomplete
  expression of ductal carcinoma in situ which is
  defined as at least 2 ducts completely filled
  with uniform neoplastic appearing cells,
  causing intracellular bridges and arches

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Inflammatory Lesions

• Abscess ?
• Periareolar nonlactating breast, may lead to
  fistulas. Puerperal childbirth/breast feeding,
  major duct is obstructed with milk causing
  mastalgia, swelling, redness
• Mondor Disease ? Linear, tender, cord like mass
  due to thrombophlebitis of the thoracoepigastric
  vein as it courses the anterior/lateral aspect
  of the breast. Warm compress and aspirin is the
  treatment

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• Invasive Ductal ? 85 of breast cancer.
• Infiltrating Lobular ? 10 of breast cancer.
  Bilateral in 33. Increase in multicentricity
  w/in same breast
• Medullary ? 6 of breast cancer. Bilateral in
  20. Soft, distinct capsule fastest growing
  breast cancer.
• Pagets ? 2 of breast cancer. Crusting erosion
  of nipple, itching, burning. Pagetoid cells in
  epithelium.
• Colloid/Muscinous ? 2 of breast cancer.
  Gelatinous feel secondary to production of large
  quantities of mucin
• Tubular ? lt2 of breast cancer. Haphazard array
  of tubular structures. One cell layer w/out
  basement membrane.
• Papillary ? lt2 of breast cancer. Distinctive
  fibrovascular stalk covered with multilayered
  epithelium
• Adenoid ? lt0.1 of breast cancer. Microscopic
  features similar to salivary gland cancer
• Apocrine ? lt0.1 of breast cancer. Rare and
  aggressive. Resembles apocrine glands found in
  axilla, anogenital, and groin regions
• Secretory ? lt0.1 of breast cancer. Most common
  breast cancer in children

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Differentiation

• Well ? small, uniform, round nuclei with few
  nucleoli and mitosis. Prominent tubular pattern
• Moderate ? increase in nuclear size,
  pleomorphism, and chromatin variability,
  frequent mitosis, large and irregular nucleoli.
  Tubular structures arranged in groups, nests, or
  cords.
• Poorly ? large nuclei with variable chromatin
  pattern, prominent nucleoli and frequent,
  bizarre, mitotic figures. Absence of tubular
  structures.

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• TX Primary tumor cannot be assessed.
• T0 No evidence of primary tumor.
• Tis Carcinoma in situ
• DCIS, LCIS, or Paget disease of the nipple
• T1 Tumor is 2 cm
• T2 Tumor is more than 2 cm but not more than 5
  cm
• T3 Tumor is more than 5 cm across.
• T4 Tumor of any size growing into the chest
  wall or skin
• This includes inflammatory breast cancer

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• NX Nearby lymph nodes cannot be assessed
• N0 Cancer has not spread to nearby lymph nodes.
  
• N1 Cancer has spread to 1 to 3 axillary lymph
  nodes
• movable nodes
• N2 Cancer has spread to 4 to 9 axillary lymph
  nodes
• fixed/matted nodes
• N3 Cancer has spread to 10 or more axillary
  lymph nodes 
• Cancer has spread to the lymph nodes above the
  clavicle 
• Cancer involves internal mammary lymph nodes

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• MX Presence of distant spread cannot be
  assessed
• M0 No distant spread
• M1 Spread to distant organs is present

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• Stage 0 Tis N0 M0
• Stage I T1 N0 M0
• Stage IIa T0 N1 M0
• T1 N1 M0
• T2 N0 M0
• Stage IIb T2 N1 M0
• T3 N0 M0
• Stage IIIa T0 N2 M0
• T1 N2 M0
• T2 N2 M0
• T3 N1 M0
• T3 N2 M0
• Stage IIIb T4 Any N M0
• Any T N3 M0

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• Stage 0 This stage describes noninvasive (in
  situ) breast cancer
• DCIS/LCIS
• Stage I This stage is an early stage of invasive
  breast cancer
• The tumor measures no more than 2cm
• No lymph nodes are involved
• Stage II This stage, subdivided into IIA and
  IIB, describes invasive breast cancers
• The tumor measures less than 2 cm but has
  spread to lymph nodes
• No tumor is found in the breast but cancer is
  found in the axillary lymph nodes
• The tumor is between 2 cm and 5 cm and may have
  spread to lymph nodes
• The tumor is larger than 5 cm but hasn't spread
  to any lymph nodes

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• Stage IIIStage III breast cancers are subdivided
  into three categories IIIA, IIIB, IIIC
• Stage IIIA
• tumor is larger than 5 cm and has spread to one
  to three lymph nodes
• tumors may be any size and have spread into
  multiple lymph nodes
• lymph nodes clump together and attach to one
  another
• Stage IIIB
• any size tumor has spread to tissues nearby and
  may have spread to nodes
• inflammatory breast cancer
• Stage IIIC
• cancer is a tumor of any size that has spread
• To 10 or more lymph nodes under the arm
• To lymph nodes above or beneath the collarbone
  and near the neck
• Stage IV Spread to other, distant parts of the
  body

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5-year Survival Rate

• Stage
• 0 ? 100
• I ? 100
• IIA ? 92
• IIB ? 81
• IIIA ? 67
• IIIB ? 54
• IV ? 20

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• Tamoxifen
• antiestrogen medication
• antagonist, blocking the estrogen receptors
• depriving breast cancer cells of estrogen
• pre/postmenopausal patients with hormone-receptor
  positive breast cancers
• decreases short-term risk of breast cancer by 45
• 1 risk of blood clots
• 1 risk of endometrial cancer

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• aromatase inhibitors
• antihormonal agents
• postmenopausal women
• adrenal adrostenedione to estrone by aromatase
• blocking aromatase activity reduces estrogen
• increase the risk of osteoporosis
• bone density monitored
• calcium with vitamin D
• bisphosphonates

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• Trastuzumab
• monoclonal antibody
• cells with HER2/neu overexpression
• binding to the HER2 receptors
• slowing the growth of these cells
• infusion administered over 30 minutes
• weekly for 1 year

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• Nodes
• Chemo
• postmenopausal women with ER ? tamoxifen
• - Nodes
• gt1cm
• Chemo
• ER ? tamoxifen
• lt1cm
• No further treatment

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• Breast conservation
• resection of the primary breast cancer with a
  margin of normal-appearing breast tissue
• adjuvant radiation therapy
• assessment of axillary lymph node status
• Relative contraindications to breast conservation
  therapy
• prior radiation therapy to the breast or chest
  wall
• involved surgical margins or unknown margin
  status following re-excision
• multicentric disease
• scleroderma or other connective-tissue disease

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• Sentinal LN
• Clinically uninvolved axillary lymph nodes
• T1 or T2 primary breast cancer
• not had neoadjuvant chemotherapy
• Contraindications
• palpable lymphadenopathy
• prior axillary surgery
• chemotherapy or radiation therapy
• multifocal breast cancers

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• intraoperative gamma probe detection of
  radioactive colloid
• 0.5 mCi of 0.2-micron technetium-99 sulfur
  colloid in a volume of 0.2 to 0.5 mL is injected
  (three to four separate injections) at the cancer
  site or subdermally
• Subdermal injections are given in proximity to
  the cancer site or subareolar
• intraoperative visualization of isosulfan blue
  dye (Lymphazurin)
• in the operating room, 4 mL of isosulfan blue dye
  (Lymphazurin) is injected in a similar fashion
• additional 1 mL injected between the cancer site
  and the overlying skin

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• A 3- to 4-cm incision is made in line with that
  used for an axillary dissection, which is a
  curved transverse incision in the lower axilla
  just below the hairline
• After dissecting through the subcutaneous tissue
  and identifying the lateral border of the
  pectoralis muscles, the clavipectoral fascia is
  divided to gain exposure to the axillary contents
• Dissection continues, the signal from the probe
  increases in intensity as the sentinel lymph node
  is approached
• The sentinel lymph node also is identified by
  visualization of isosulfan blue dye in the
  afferent lymph vessel and in the lymph node
  itself
• Before removing the sentinel lymph node, a
  10-second in vivo radioactivity count is
  obtained. After removal of the sentinel lymph
  node, a 10-second ex vivo radioactive count is
  obtained
• Remove all visualized blue nodes AND all nodes
  within 10 of sentinel node radioactivity count

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Stage 0

• LCIS ? observation /- tamoxifen
• DCIS ? lumpectomy and radiation therapy
• Low-grade DCIS
• solid, cribriform, or papillary subtype, which is
  less than 0.5 cm in diameter
• managed by lumpectomy alone
• Tamoxifen is considered for all DCIS

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Early Invasive (I, IIa, IIb)

• mastectomy axillary lymph node status
• breast conservation
• Lumpectomy
• Axillary lymph node status
• Radiation therapy
• Adjuvant chemotherapy
• all node-positive cancers
• larger than 1 cm in size
• Tamoxifen therapy
• hormone receptorpositive women with cancers that
  are larger than 1 cm in size

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Locoregional (IIIa, IIIb)

• operable stage IIIa
• modified radical mastectomy
• followed by adjuvant chemotherapy
• followed by adjuvant radiation therapy
• inoperable stage IIIa and for stage IIIb
• neoadjuvant chemotherapy
• subsequent modified radical mastectomy
• adjuvant chemotherapy
• adjuvant radiation therapy

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Distant Mets (IV)

• Hormonal therapy
• hormone receptorpositive cancers
• bone or soft tissue metastases only
• limited and asymptomatic visceral metastases
• Systemic chemotherapy
• hormone receptornegative cancers
• symptomatic visceral metastases
• hormone refractory metastases
• Bisphosphonates
• in addition to chemotherapy or hormone therapy,
  should be considered in women with bone
  metastases