Session 9 Breast diseases and breast feeding

• The different types of mastitis include:

  • Lactation (puerperal mastitis): most common; affects breastfeeding women.
  • Periductal (mammary duct ectasia): affects menopausal and postmenopausal women and smokers; occurs when milk ducts thicken.
• Intraductal papillomas are benign, non cancerous wart-like tumours that grow within the milk ducts of the breast.
• Fibroadenomas are common, benign breast tumours consisting of both glandular and connective tissue: most common in women in their 20s and 30s.
• Types of Breast Cancer?

  • Ductal carcinoma in-situ
  • invasive ductal carcinoma
  • Lobular carcinoma (in-situ and invasive)
• Risk factors of breast cancer?

  • Age
  • Reproductive history - early menarche, late menopause etc
  • Endogenous hormones - HRT and OCP
  • Breast density
  • Radiotherapy and radiation
  • Family history
  • Smoking
  • Alcohol
  • Obesity
• Oncotype DX test?

  • is a genomic test used for early stage, ER+, HER2- breast cancers that analyses the expression of 16 cancer related genes that can affect how an early stage breast cancer is likely to behave and respond to treatment.
  • is both a prognostic test, since it provides more information about how likely (or unlikely) the breast cancer is to come back, and a predictive test, since it predicts the likelihood of benefit from chemotherapy or radiation therapy.
• Breast cancer treatment: Hormonal therapy?

  • Blocking ovarian function - Ovarian ablation by surgery (oophorectomy) or by radiation Treatment with drugs called gonadotropin-releasing hormone (GnRH) agonists, aka luteinizing hormone-releasing hormone (LHRH) agonists.
  • Blocking oestrogen production - Aromatase inhibitors.
  • Blocking oestrogen’s effects Selective oestrogen receptor modulators (SERMs) such as tamoxifen
• Tamoxifen is metabolized via CYP2D6.
• BRCA1 and BRCA2 proteins are Caretakers of Chromosomal Stability- they promote high fidelity homologous recombination repair of double-stranded DNA (DSDNA) breaks. The processing and repair of DSBs can lead to mutations, loss of and chromosome rearrangements that result in cell death or cancer.
• Trastuzumab (Herceptin) is a humanised monoclonal antibody against HER2 receptor.
• what does Herceptin do?

  • Binding to HER2 results in inhibition of downstream pathways.
  • Binding to HER2 attracts immune cells to tumour site and promotes ADCC (antibody-dependent cellular cytotoxicity).
  • Binding to HER2 results in receptor internalisation and degradation
• Targeted therapies for breast cancer?

  • Immunotherapy
  • Herceptin
  • Pembrolizumab
• Targeted therapy for familial breast cancer - PARP inhibitor - plays a central role in DNA repair including DNA damage caused by alkylating agents and chemotherapeutic drugs.
• Alveolus – myoepithelial cells and lactocytes in breasts
• Phases of development of breasts?

  • Mammogenesis
  • Few ducts, develops at 4 wks gestation, under influence of oestrogen and progesterone
  • Lactogenesis I
  • 1st phase - proliferation - Hypertrophy of the ductal-lobular-alveolar system
  • 2nd phase - secretory - colostrum
  • Lactogenesis II
  • Day 3-8 postpartum, Onset of copious milk production, drop in progesterone, presence of Prolactin.
  • Galactopoiesis
  • autocrine, breast size decreases
  • Involution
  • Decrease in milk secretion, Apoptosis, High sodium levels
• Prolactin?

  • Initiation and maintenance of breastmilk production
  • Placenta delivers - HPL ↓
  • Prolactin ↑
  • More at night
  • Inhibitory pathway - Dopamine agonist, Prolactin-Inhibiting Factor (PIF) (antagonists)
• Oxytocin?

  • Response to suckling, and sight and smell of baby
  • Milk Ejection Reflex
  • Contraction of myoepithelial cells
  • Forces milk from the alveoli down the ducts
  • Key to lactation continuation