Breast

• Risk factors for Breast Cancer in Men

  • >50
  • Family History
  • Increased Oestrogen -> obesity, liver disease, genetic
  • Kleinfelter Syndrome
  • Testicular Disorders
  • Radiation of the chest -> Hodgkin Lymphoma
• Mutations in Certain Oncogenes

  • Relative Risk (RR) >4 +++
  • BRCA1, BRCA2, ATM, or TP53 gene (p53) Mutation Carrier
  • Rate of developing Cancer is 50-80%
  • RR 2-3.99 ++
  • 2 or more first degree relatives with breast cancer CHEK2 mutation carrier (mum, sis, daughter)
  • RR 1.25-1.99 +
  • 1 first degree relative or multiple second degree relatives (Grandma, Aunt, Niece)
  • Decreased RR <0.8
  • reproductive: more babies/breastfeeding = less risk
  • Hormones: demoxifin/raloxifin
  • Body size/lifestyle
• Breast is modified sweat glands to produce milk.

  made up of:

  • ducts (transport milk to nipple)
  • 15-20 lobes -> multiple lobules on each (glands that secrete milk)
  • Fibrofatty Stroma
• Lobes:

  • each lobe is encapsulated by CT and Cooper's ligaments
  • Divided into lobules - terminal duct lobular unit
  • Composed of:
  • multiple glandular units
  • surrounded by stroma and are demarcated by a basement membrane
  • Encircled by myoepithelial cells that can contract under the influence of oxytocin
  • breastfeeding releases oxytocin to contract myoepithelial cells -> express milk
• Nipple is composed of:

  • dense CT
  • skin contains numerous sebaceous glands
• Breast Histology

  • myoepithelial cells
  • terminal duct lobular units -> purple
  • number and size determined by age
  • stroma -> pink
• Benign Lesions of the Breast:

  1. Fat Necrosis -> FNA
  2. Breast Abscess
  3. usually occur in lactating women -Mastitis

  • lactation not clearing fast enough -> duct gets clogged
  • responds well to antibiotics -> lump clears
  • 3. Simple Cyst usually round, dense areas on a mammogram (white)/ultrasound (black)
  • pap stain - foamy macrophages
  • apocrine cells present
  • 4. Fibroadenoma
  • 5. Atypical Ductal Hyperplasia
  • 6. Intraduct Papilloma
  • -difficult to differentiate from papillary cancer
  • -p63 stains nuclei of myoepithelial cells and is +ve in a benign papillary lesion
• Carcinomas In Situ:

  • precancerous
  • confined to Ducts or Lobules
  • no metastatic Behaviour

  Ductal Carcinoma In Situ (DCIS)

  • sent for excision
  • usually admixed with invasive component

  Lobular Carcinoma In Situ (LCIS)

  • usually watched
  • most 40-50 year olds
• Infiltrating Ductal Carcinoma

  Most common -> 75% of breast cancers

  Prognosis depends on grade

  Tends to metastasise through lymphatics (armpits)
• Types of Breast Cancer:

  Infiltrating Ductal Carcinoma

  Infiltrating Lobular Carcinoma

  Medullary Carcinoma

  Mucinous (colloid) carcinoma

  Tubular Carcinoma

  Papillary Carcinoma

  Metaplastic Breast Cancer

  Mammary Paget's Disease

   
• Proteins Expressed in Breast Cancers

  • Oestrogen receptor (ER)
  • Progesterone receptor (PR)
  • Human epidermal growth factor receptor 2 (HER2)
• Pathogenesis of BC


  Activation of steroid hormones -> Oestrogen & Progesterone activate nuclear receptors -> bind to epithelial cell receptors to promote cell growth, differentiation and survival by penetrating cell membrane and binding to nucleus -> promoter regions of E2 & PR responsive genes -> dimerisation
• Oestrogen and progesterone


  Intracellular signally molecules that activate nuclear receptors
• Oestrogen and progesterone binding


  1. Bind to breast epithelial cell receptors

  2. Promote cell growth, differentiation and survival

  3. Penetrate the cell membrane

  4. Bind to nucleus
• Dimerisation


  A change in receptor conformation which allows the receptor to associate with another Her family receptor
• Tyrosine kinases (RTKs)


  • Located on the surface of breast cells
  • Have a role in cancer development specifically ErbB family
  • Cause numerous downstream cellular signals which lead to multiple cellular effects
• ErbB family


  Responds to growth factor stimulation

  overexpression provides oncogenic signals.

  incl:

  • EGFR
  • HER2
  • ErbB3
  • ErbB4

  oncogenic signalling pathway associated with tumours -> non small cell lung cancer and breast cancer

  All 4 ErbB's contribute to pathogenesis of cancer in response to growth factor stimulation.
• Neoplasms Metastatic to Breast

  • lung
  • haematopoietic
  • Gynae
  • Melanoma
  • GI
  • Urinary
  • Misc