Malignant Breast Tumors

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

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