Breast Ca

• Breast cancer is the most common cancer in women. It is the second most common cancer worldwide
• BRCA1 and BRCA2 are anti-oncogenes that both code for tumour suppressor proteins which reduce the risk of breast cancer when functioning normally. Mutations in either of these genes, therefore, increases the risk of breast cancer as well as an increased risk of ovarian cancer
• Human epidermal growth factor receptor 2 (HER2 receptor) is a transmembrane glycoprotein that plays a key role in cell survival, proliferation and differentiation and thus is an important oncogene in breast cancer when it is overexpressed.
• BRCA1 and BRCA2 are often inherited in an autosomal dominant fashion
• Classifications of breast cancer:

  • Non-invasive breast cancer = have not invaded the basement membrane
  • Invasive breast cancer = tumour cells have invaded the basement membrane
  • Inflammatory breast cancer - presents with an erythematous oedematous breast and can often be mistaken for an infection of abscess
  • Paget's disease of the nipple - presents with rough, dry, erythematous and ulcerated skin surrounding the nipple
• Risk factors are related to increased exposure to oestrogen:

  • Nulliparity and increasing age of first childbirth
  • Early menarche (<12) and late menopause (>55)
  • Hormone replacement therapy with oestrogen and progesterone
  • Obesity
• Non oestrogen related risk factors:

  • Increased age
  • Female gender
  • Family history - first degree relative
  • Previous breast cancer
  • BRCA1 and BRCA2 mutations
  • Radiation therapy to the chest
  • Not having breastfed
  • Excessive alcohol and fat intake
• Breastfeeding is a protective factor against breast cancer
• History:

  • Most patients present with a painless lump in the breast or axilla
  • May have noticed nipple discharge
  • If the nipple discharge is unilateral or bloody this is abnormal and needs investigating for breast cancer.
  • If patients present late, they may have more systemic symptoms suggesting the disease has metastasised. These include weight loss, anorexia, bone pain, jaundice, fatigue and breathlessness.
• Features of breast lumps associated with cancer:

  • Hard with a gritty texture
  • Ill-defined, irregular margins
  • Tethered or fixed
  • Lump in the upper outer quadrant of the breast
  • A suspicious lump felt in the axilla may indicate metastasis to the lymph nodes
• Nipple changes associated with breast cancer:

  • Bleeding, discharge, inversion or deviation of the nipple
  • Unilateral more suspicious
  • Paget's disease - rough, try, erythematous and ulcerated skin surrounding the nipple
• Skin changes associated with breast cancer:

  • Rough, dry, erythematous, and ulcerated skin surrounding the nipple can be caused by Paget's Disease
  • A cancerous breast lump beneath the skin can cause dimpling or puckering of the skin.
  • Peau d’orange: the skin looks like the surface of an orange. This occurs when the lymphatic system that drains the skin is blocked by cancer cells causing the skin to become oedematous.
• Investigation with triple assessment:

  1. Clinical history and examination by a breast surgeon
  2. Radiological imaging
  3. Core biopsy or fine-needle aspiration
• Ultrasound imaging is typically used for younger women, usually under the age of 40 to investigate a breast lump. This is because younger women tend to have denser breast tissue, this makes mammography less sensitive for detecting breast cancers, so ultrasound is used instead.
• There is a breast cancer screening program in the UK for women aged 50 to 70 in which a two-view mammogram is performed every 3 years.
• Receptor status:

  • Whether the cancer is positive for progesterone receptors (PR+) and oestrogen receptors (ER+)
  • Targeted treatment that act on these receptors
  • Triple negative breast Ca = negative for oestrogen, progesterone and HER2 receptors - limited treatment options
• Endocrine therapy:

  • Tamoxifen: used in premenopausal women with ER+ cancer, works by blocking oestrogen receptors
  • Aromatase inhibitors (Letrozole, Anastrozole, Exemestane): only used in postmenopausal women with ER+ cancer. They work by blocking the enzyme aromatase which converts androgens into oestrogen.
• Biologics:

  • For cancers that express HER2, a drug called trastuzumab (also called Herceptin) is used, which is a monoclonal antibody that targets HER2.
• Common sites of metastasis - lungs, bone, liver and brain
• A complication of surgery is damage to the brachial plexus and due to the removal of lymphatics, there is a risk of developing lymphoedema in the arm of the operated side