Updated: 2/2/2019

Malignant Breast Tumors

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Introduction
  • Epidemiology
    • breast cancer is the most common cancer and second most common cause of death in adult women
  • Risk factors
    • BRCA1 and BRCA2 mutations
      • associated with multiple / early onset breast and ovarian cancer
      • other genetic relationships
        • RAS oncogene gain of function
        • overexpression of estrogen/progesterone receptors
        • overexpression of erb-B2 (HER-2, an EGF receptor)
        • Li-Fraumeni associated TP53 loss
    • increasing age
    • smoking
    • breast cancer in first degree relatives or mother with breast cancer
    • history of contralateral breast cancer
    • history of endometrial cancer
      • also an estrogen induced cancer
    • increased exposure to estrogen
      • obesity
      • nulliparity
      • early menarche (<11 y.o.)
      • late menopause (>50 y.o.)
      • late first pregnancy (>30 y.o.)
    • atypical ductal hyperplasia
Classification
  • Ductal carcinoma in situ (DCIS)
    • arises from progression of ductal hyperplasia
    • non-palpable mass 
      • seen most often on mammography due to microcalcifications
    • histology shows filled ductal lumen without basement membrane penetration
    • subtypes
      • comedocarcinoma
        • ductal carcinoma with caseous necrosis at the mass center 
  • Paget's disease
    • extension of DCIS into lactiferous ducts and skin of nipple
      • eczematous patches on nipple 
    • histology shows Paget cells 
      • large cells in epidermis with clear halo
      • also seen on vulva
  • Invasive/infiltrating ductal carcinoma
    • worst and most invasive
    • most common type
    • firm, fibrous, "rock-hard" mass
    • histology shows small, glandular, duct-like cells with stellate morphology
    • subtypes
      • tubular carcinoma
        • histology
          • well-differentiated tubules that lack myoepithelial cells
      • mucinous carcinoma
        • histology
          • carcinoma with abundant extracellular mucin
  • Lobular carcinoma in situ (LCIS)
    • non-palpable mass
    • often bilateral
    • histology shows distended lobules with neoplastic cells without BM penetration
  • Invasive lobular
    • often multiple and bilateral
    • histology shows orderly row of cells
  • Medullary
    • associated with BRCA1 and ER/PR negativity
    • histology shows fleshy, cellular, lymphatic infiltrate
  • Inflammatory 
    • poor prognosis (50% survival at 5 years)
    • histology shows dermal lymphatic invasion by tumor
    • peau d'orange seen on exam
      • see below
Presentation
  • Symptoms
    • often asymptomatic
    • breast lump
      • most commonly in upper-outer quadrant
    • nipple discharge
  • Physical exam
    • firm immobile, painless lump
    • some skin changes 
      • redness, ulcerations, edema, and nodularity
    • axillary lymphadenopathy
      • in more advanced cases
    • breast skin edema with dimpling (peau d' orange)
      • represents obstruction of the lymphatics by cancer  
Evaluation
  • Fine needle aspiration
    • can identify whether mass is solid or cystic
    • can also retrieve sample for cancer diagnosis
  • Estrogen/Progesterone receptor assays
    • most often positive in post-menopausal cancers
      • low estrogen state after menopause results in upregulation of receptors
    • positivity confers better prognosis with more effective therapeutics
  • Sentinel lymph node biopsy
    • if negative high likelihood no other nodes in group are involved
    • if positive there is 1/3 chance other nodes in group are involved
Treatment
  • Surgery
    • breast conservation resection
      • resection of tumor with margins
      • sentinel node biopsy
      • radiation
    • modified radical mastectomy
      • resection of nipple, entire breast, pectoralis minor, and level I-II axillary nodes
      • level III axillary nodes removed if involved
      • complications
        • long thoracic nerve damage
          • results in winged scapula 
        • lymphedema
Prognosis, Prevention, and Complications
  • Prognosis
    • lymph node involvement is the single most important prognostic factor
    • TNM staging
      • extranodal metastases has more significance than lymph node metastasis
  • Prevention
    • mammography
      • effective screening tool except in young woman
        • dense breast tissue in young woman interferes with specificity and sensitivity
        • most effective in postmenopausal patients because of less glandular breast
      • identifies microcalcifications or moderate sized masses
      • all woman > 40 should have mammograms
 

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Questions (4)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.ON.1) A 52-year-old female was found upon mammography to have branching calcifications in the right lower breast. Physical exam revealed a palpable nodularity in the same location. A tissue biopsy was taken from the lesion, and the pathology report diagnosed the lesion as comedocarcinoma. Which of the following histological findings is most likely present in the lesion? Review Topic

QID: 101662
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1

Orderly rows of cells surrounding lobules

25%

(5/20)

2

Disordered glandular cells invading the ductal basement membrane

10%

(2/20)

3

Extensive lymphocytic infiltrate

0%

(0/20)

4

Halo cells in epidermal tissue

5%

(1/20)

5

Pleomorphic cells surrounding areas of caseous necrosis

55%

(11/20)

M1

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