Breast Carcinoma

A malignant tumour of breast epithelial cells

Aetiology

Risk factors

  • Female sex and age are the most signigicant risk factors
  • Mutations to certain genes are well-documented risk factors, most importantly the tumour suppressor genes BRCA1 and BRCA2
  • Family history in a first degree relative
  • Previous benign disease
  • Geographic variation (more common in developed countries)
  • Degree of exposure to unopposed oestrogen has also been well-documented to cause an increase in risk to develop breast cancer
    • Early menarche
    • Late menopause
    • Nulliparous women
    • First pregnancy after 30 years of age
    • Oral contraceptives or HRT use
  • Lifestyle factors:
    • Obesity
    • Physical activity is protective
    • Alcohol consumption
    • Diet
    • NSAID lower risk
    • Smoking

Pathophysiology

  • Arises in the glandular epithelium of the terminal duct lobular unit (TDLU)
  • It is an adenocarcinoma but is usually just referred to as ‘breast carcinoma’

Histological classification

Invasive cacinoma of the breast can be classified into:
  • Invasive ductal carcinoma (75-85%)
    • Can be further classified into tubular, cribriform, papillary, mucinous (/colloid), or medullary carcinomas, all showing distinct patterns of growth
  • Invasive lobular carcinoma (10%)
    • Characterised by a diffuse (stromal) pattern of spread that makes detection more difficult
  • Other subtypes (5%), such as medullary carcinoma or colloid carcinoma
  • Other factors used in classification:
    • Gene expression profiling
    • Hormone receptor expression - oestrogen receptor, progesterone receptor, HER2

Spread

  • Local invasion - stroma of breast skin, muscles of chest wall
  • Lymphatics - axillary, sentinel, apical, infraclavicular, supraclavicular, cervical, internal mammary, inframammary
  • Metastasises - bone, liver, brain, lungs, abdominal viscera, female genital tract

Clinical presentation

  • Patients can present symptomatically or asymptomatically via screening (particularly for ILC)
  • Clinical features may include breast lump(s), asymmetry, or swelling (all or part of breast), abnormal nipple discharge, nipple retraction, skin changes (dimpling/peau d’orange, or Paget’s-like changes), mastalgia, or with a palpable lump in the axilla

Investigations

Triple assessment:
  • Clinical assessment - history and breast exam
  • Imaging - mammogram, breast USS
  • Histology - FNA cystology C1-5 (now rarely done), core biopsy B1-5, vaccum assisted biopsy (large volume), skin biopsy, incisional biopsy of mass (now rare)
    • Grading - tubular differentiation, nuclear pleomorphism, mitotic activity
    • Staging - TNM

Management

Breast conserving surgery

  • Breast conserving surgery is the preferred treatment - wide local excision with or without an oncoplastic procedure to shape the breast

Modified radical mastectomy

  • Removes the entire breast, including the overlying skin and axillary lymph nodes
  • Pectoralis major muscle is preserved - facilitates wound healing and potentially allows for reconstruction
  • Most women who require or request mastectomy are candidates for breast reconsturction - prosthetic or autologous tissue

Axillary surgery

  • Axillary surgery is most commonly performed alongside wide local excision and mastectomies, in order to assess nodal status (SNB) and remove any nodal disease
  • Axillary node clearance involves removing all nodes in the axilla - common complications include paraesthesia, seroma formation, and lymphedema in the upper limb

Radiation therapy

  • Essential component of breast-conserving surgery
  • Indications for post-mastectomy RT include involvement of more than three nodes, positive surgical margins and/or tumors larger than 5 cm

Adjuvant systemic therapy

  • Chemotherapy
  • Hormonal therapy
    • Tamoxifen used typically in pre-menopausal patients
    • Aromatase inhibitors are advised for post-menopausal patients as adjuvant therapy
  • Immunotherapy may be used in patients whose cancers express specific growth factor receptors
    • Herceptin for HER-2
    • Bevacizuman for VEGF
    • Lapatibin for EGFR and HER-2