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Breast cancer

Definition
  • Malignant neoplastic growth of breast tissue
    • Ductal
    • Lobular
    • (Connective)
Risk Factors
  • (Unopposed ) oestrogen
    • HRT?
    • Early menarche
    • Late age at child-birth
    • No breastfeeding
  • Age
  • Endogenous hormone levels
  • High breast density
  • Obesity
  • Physical activity
  • Alcohol
  • Shift work?
  • Family history
  • Genetic
    • BRCA1/2
Differential diagnosis
  • (Sebaceous) cyst
  • Fat necrosis
  • Benign hyperplasia
    • Fibroadenosis
    • Fibroma
    • Hemartoma (1/3 go on to cancer)
  • Mastitis
  • Galactocele
  • Malignant 
    • DCIS/LCIS
    • IDC/ILC (invasive)
    • Sarcoma (rare - after initial radiation)
    • Medullary carcinoma
Epidemiology
  • 1/11 women
  • 1% (of breast cancers) are in men
  • Lower Africa/Asia
  • Higher social class more likely to present
  • Japan --
    • But immigrants catch up within 2 generations
  • Black women < white
Aetiology
  • DNA damage / inherited defects
  • Leading to unregulated growth
  • Further mutations => invasion, metastasis
Clinical features
  • Malignant lump
    • Invasive
    • Non-motile
    • Vascularised
    • Irregular edges/spiculated/craggy
    • +/- ill-defined edges
    • Peau d'orange?
    • Pitting?
    • Nipple inversion?
    • Discharge?
    • Non-fluctuating?
    • Not transilluminable
    • Pain?
    • Lymph node involvement?
    • Metastatic features
      • Bone > Liver > Lungs > Brain
    • Cachexia (definition: >5% weight loss in 6 months)
    • Tiredness, fatigue, anorexia
Pathophysiology
  • 6 steps
    • Growth factor self-sufficiency
      • Factor, receptor, pathway 
    • Lack of negative control
    • Apoptosis evasion
    • Endless replicative potential
    • Angiogenesis
    • Metastasis
Investigations
  • Triple test:
    • Clinical
    • Radiological
      • Xray (only >35)
      • Ultrasound
      • MRI 
        • for metastases?
        • and screening? (3-yearly)
    • Biopsy
      • FNA
      • Core biopsy
  • Genetic screening
    • PR
    • OR
    • HER-2
Management
  • Chemo
    • Chemical
      • Narrow therapeutic index
      • Primary / combined / adjuvant / neoadjuvant
      • NB only 3% of cells are mitotic => need multi-dose regime
      • Side effects
        • Epithelial damage (nausea, vomiting, dry mouth)
        • Infertility
        • Secondary cancers
        • PSN (peripheral sensory neuropathy)
        • Bone marrow suppression
          • => Neutropenic sepsis
    • Hormonal
      • Lower oestrogen levels
        • Post-menopausal => use aromatase inhibitors => androgen - => estrone -
        • Pre-menopausal
          • oophorectomy 
          • GnRH => hypothalamus GnRH receptor downregulation => LH/FSH --
      • Lower oestrogen response
        • SERMs (e.g. Tamoxifen)
        • ERDs (oestrogen receptor downregulators)
    • Biological
      • Antibodies vs growth factor receptors
  • Radiotherapy
    • Direct
      • Heavy particles
      • Bragg peak effect
    • Indirect
      • Relies on ROS generation
      • cf hypoxic tumours
    • Brachytherapy
  • Surgical
    • 1 cm margin if possible
    • Palliative surgery?
    • Preserve lymph nodes if possible to avoid lymphoedema
Prognosis
  • Depends on stage and grade
  • 50% chance of recurrence in opposite breast
  • HER2 receptor is a bad sign
  • Nottingham Prognostic Index => 10-year survival rate
    • 0.2 (size in mm + nodal status + grade (1-9))

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