Week 1

• Key concerns

  Breast cancer, Family history and genetics and Metastasis
• Younger patients with breast cancer

  • Typically have a genetic link
• Expected signs & symptoms

  • Nipples not in line
  • Pain
  • Discharge
  • Lump
  • Skin is dimpled/differs from other breast
  • Spread to axillary lymph nodes
  • Metastasis to other nodes can cause lymphoedema as lymph can no longer drain (E.g. oedema of arms)
  • Chest pain and coughing
  • Metastasis to liverascitesbulging abdomen

  
• Males have mammary ducts but do not have lobules to lactate
• A history + clinical examination is not sufficient to diagnose breast cancer, need to do a triple assessment
• Nipples


  • 20 or more lactiferous sinuses or ducts
  • Keratinized stratified squamous epithelium
  • Epidermis is highly pigmented
  • Dermal papillae invade deep into surface
  • Bundles of smooth muscle fibres arranged radially + circumferencely in dense connective tissue, and longitudinally along the lactiferous ducts (contract in the cold to cause hardening of the nipple)

  
• Areola


  Contains sebaceous and sweat glands (for lubrication), Glands of Montgomery (structure between sweat gland and a mammary glands), Numerous nerve endings
• Mammary Gland Before Puberty

  • Mammary gland = lactiferous sinuses + lacterferous ducts
  • In girls at puberty increased amounts of ovarian estrogen leads to accumulation of adipose and connective tissue, increased branching and growth of the lactiferous ducts, and at the tip of the smallest ducts is the characteristic structures of the gland - the lobe
• Inactive and active mammary glands

  • Inactive mammary gland (Not pregnant): 15-20 irregular lobes separated by dense connective tissue and adipose tissue, lumen has no secretory products
  • Active mammary gland (Pregnant): Rapid proliferation with the formation of alveoli which become the actively milk secreting units, lumen contains milk secretion (lactose, fats, proteins, Ig, amino acids, vitamins)
• Epithelium in sinuses


  • Lactiferous sinus = stratified squamous epithelium, Lactiferous ducts and terminal ducts = simple cuboidal or columnar epithelium (oval nuclei and prominent nucleoli)
• Myoepithelial cells


  Surrounding the epithelium

  
• Lobule epithelium


  • Hormone sensitive - undergoes changes with menstrual cycle, pregnancy, breastfeeding, and aging
• Merocrine secretion


  Proteins synthesized in the RER, form membrane vesicles, transported via Golgi apparatus, released by fusion with plasma membrane
• Apocrine secretion


  Lipid - free droplets in cytoplasm join, move to apical region of cell, project into the lumen, envelope of plasma membrane released
• Different phases of the developing mammary glands

  • Estrogen receptor tamoxifen: Isolated estrogen receptor (ER) (protein), Immunized an animal (immune response), From animal isolate the antibodies (Ig), Incubate tissue with the Ig, Binding of receptor and Ig, To be able to see binding - signaling system, Biotin-strepavidin horse radish peroxidase, Able to identify cell with ER
• The Breast


  • Each breast is a rounded eminence lying within the superficial fascia, anterior to the upper thorax and spreading laterally to a variable extent, Position of the breast: Vertically from the 2nd /3rd rib to the 6th/7th rib, Transversely from the sternal edge(intermammary cleft) almost to the mid-axillary line, The supero-lateral quadrant is prolonged towards the axilla along the infero-lateral edge of the pectoralis major, and may extend through the deep fascia up to the apex of the axilla, 2/3 of the breast lies upon the deep pectoral fascia of the pectoralis major and 1/3 over the fascia of the seratus anterior, Retromammary space (Loose CT) allows for freedom of movement of breast, Firmly attaches to dermis by suspensory ligaments of Cooper (Retinaculae Cutis), Associated muscles: Pectoralis major, Pectoralis minor, Serratus anterior, The nipple projects centrally from the anterior aspect at the level of T4, The areola is a darkened area of skin, which encircles the base of the nipple, No adipose tissue is found immediately below the skin of the areola and papilla, however, there is a fair amount of fat deep to the skin, Made up of: Mammary gland (modified sweat gland), Fibrous connective tissue (stroma) surrounding the glandular tissue, Interlobular adipose tissue, Mammary gland consists of ± 15 to 20 lobules, each with its own lactiferous sinus and lactiferous ducts that open onto the nipple, Lobules are surrounded by connective tissue septa which condense and join to the skin and fascia, which are called retina culae cutis or Cooper's ligaments, Fat tissue fills the spaces between the septa, Areola contains sebaceous glands (Called Montgomery's tubercles), Superolateral quadrant extends upward and laterally to level of 3rd rib in axilla and is known as Tail of Spence (Found in deep fascia), Nipples have no fat, hair or sweat glands

  
• Blood supply and vessel drainage of the breast

  • Arterial supply: Medial mammary branches of perforating branches and anterior intercostal branches of the internal thoracic artery (Originating at subclavian artery), Lateral thoracic and thoracoacromial arteries (branches of axillary artery), Posterior intercostal arteries, branches of thoracic aorta in 2,3,4th ICS, Venous drainage: Mainly the axillary vein but there is some to the internal thoracic vein

  
• Innervations of the breast

  Intercostal nerve T4-6 via lateral and anterior cutaneous branches, Nipple innervated by 4th intercostal nerve

  
• Lymphatic drainage of the breast

  • Lateral and superior breast (75% of lymph drainage): Axillary lymph nodes, Anterior (pectoral) lymph nodes, Lateral (humeral) lymph nodes, Posterior (subscapular) lymph nodes, These all drain into the other axillary lymph nodes: central lymph nodes -> apical, Which drain into clavicular nodes (supraclavicular and infraclavicular), Into subclavian trunk, Into thoracic duct (on left) or lymphatic duct (on right) subclavian vein
  • Medial breast: Parasternal lymph nodes, Into bronchomediastinal trunk, Into thoracic duct (on left) or lymphatic duct (on right) subclavian vein
  • Inferior breast: Diaphragmatic lymph nodes, Into bronchomediastinal trunk, Into thoracic duct (on left) or lymphatic duct (on right) subclavian vein
  • Deep surface: Interpectoral nodes -> apical nodes -> clavicular nodes, Into subclavian trunk, Into thoracic duct (on left) or lymphatic duct (on right) subclavian vein
  • Subareolar: Pectoral nodes following lateral and superior breast drainage

  
• Left and right breast lymphatics are linked over the midline (metastasis in breast cancer)
• Why the physiology of the breast is important for the clinician

  • The breast is an important clue to underlying disease: Genetics (Klinefelter), Drug side effects (gynacomastia in males), Liver disease, Endocrinopathy in the female (prolactinoma, hypothyroidism)

  
• Action of hormones on the breast

  • Polypeptide hormones: Prolactin (milk protein synthesis and excretion), Oxytocin (milk ejection & contraction of myoepithelialcells), Human placental lactogen (similar to prolactin)
  • Steroid hormones: Oestrogens (increase duct and breast fat growth & inhibit prolactin-induced milk secretion), Progestogens (inhibit lactation), Cortisol and androgens
• Endocrine control of the breast

  • No histologic or functional difference in the breasts of boys and girls prior to puberty, Pubertal growth of the female breast primarily dependent on the action of estradiol, To produce true alveolar development at the ends of the ducts, the synergistic action of progesterone is required, Inside the gland a variety of mediators influence cell division and differentiation such as insulin like growth factors and epidermal growth factor, and inhibitory factors such as transforming growth factor beta, Once the anatomic development of the ducts and alveoli is complete, the continued action of estrogen and progesterone is not required for lactation itself

  
• Endocrine control of milk formation

  • Complex: requires appropriate priming by estrogen and progesterone, Specific lactogenic hormones, The permissive action of glucocorticoids (cortisol), insulin, thyroxine, growth hormone, There are 2 lactogenic hormones: Human placental lactogen (secreted in large amounts by the placenta during the latter part of gestation and prepares the breast for milk production, disappears from circulation shortly after termination of pregnancy) and Prolactin (secretion rises during pregnancy and plays the critical role in the initiation and maintenance of lactation)
• Insulin like growth factors and epidermal growth factor

  • Influence cell division and differentiation
• Inhibitory factors such as transforming growth factor beta

  • Influence cell division and differentiation
• Once the anatomic development of the ducts and alveoli is complete, the continued action of estrogen and progesterone is not required for lactation itself
• Endocrine control of milk formation

  Complex: requires appropriate priming by estrogen and progesterone
• Specific lactogenic hormones


  • Human placental lactogen
  • Prolactin
• Human placental lactogen


  • Secreted in large amounts by the placenta during the latter part of gestation and prepares the breast for milk production
  • Disappears from circulation shortly after termination of pregnancy
• Prolactin


  • Secretion of pituitary prolactin rises during pregnancy
  • Plays the critical role in the initiation and maintenance of lactation in the puerperium
  • During late pregnancy and lactation 60 to 80 % of the anterior pituitary may consist of prolactin-secreting cells
  • Predominant regulation of prolactin secretion is negative—under ordinary basal conditions inhibitory hypothalamic hormones (dopamine) are delivered to the pituitary via the hypothalamic portal system and inhibit the release of prolactin
  • Most factors that influence prolactin secretion do so by affecting dopamine levels
  • Basal prolactin levels fall following delivery, but secretion is enhanced by stimulation of the breasts such as nursing the "sucking reflex"
  • Prolactin binds to a specific receptor on the cell surface of breast acinar cells to enhance the synthesis of milk via a tyrosine kinase mediated process
• A normal lactating woman forms about 1 L of milk containing: 38 g of fat, 70 g of lactose, 12 g of protein
• If woman does not nurse/empty breasts postpartum, lactation usually ceases after 2 weeks
• Galactorrhea


  • Nonpuerperalor inappropriate lactation
  • Failure of normal hypothalamic inhibition of prolactin release. Drugs, CNS disease, stalk compression
  • Enhanced prolactin release: Breast trauma, sucking reflex, hypothyroidism
  • Autonomous prolactin release. Tumours
• Gynecomastia


  • Breast tissue in adult men
  • Physiologic: Newborn, Adolescence, Aging
  • Pathologic: Drugs, Deficient production or action of testosterone, Increased estrogen production
• How does delivery stimulate breast milk production?

  1. Expulsion of the placenta at delivery causes abrupt decline in Oestrogen and progesterone levels

  2. Oestrogen antagonises prolactin; when it drops at delivery, the prolactin's milk production effect kicks in

  3. Suckling stimulates prolactin release, as well as oxytocin
• Clinical presentation of breast pathology

  • Pain
  • Lump
  • Nipple discharge
  • Age

  
• Age incidence of benign and malignant breast disease

  • Fibrocystic changes: increases with age (40-60yrs)
  • Fibro adenoma (Around 20 yrs)
  • Cancer: increases at age (60+ yrs)
• Acute mastitis


  • Caused by: Lactating breast, Staph aureus, Unilateral abscess
  • Treatment: Incision and drainage, Antibiotics
• Periductal mastitis


  • Recurrent subareolar abscess, Subareolar mass, erythematous, often recurrent, fistula may track to edge of areola, fibrosis, scarring, nipple inversion
  • Caused by: Squamous epithelium extending deep into duct, Entrapment of keratin, Duct dilatation, Rupture, 2nd infection