Breastcancer

Epidemiology
• Most common cause of death in middle-aged women in western world.
• 1 in 8 women in the UK.
• Incidence - 120 per 100,000 women.
Aetiology
• Increasing age - by 55 yrs 85% of all lumps are malignant.
• Family history risk:
• 1 in 4 with a premenopausal first-degree relative.
• 1 in 7 if postmenopausal.
• BRCA1 (AD, Ch17) - 50-80% risk• BRCA2 (AD, Ch13) - 50% risk• p53 • Diet - possibly increased in diets low in phytoestrogens, alcohol.
• Endocrine: • Nulliparous women. • Early menarche, late menopause.
• HRT • Ionizing radiation.
• Benign breast disease - atypical hyperplasia, papilloma.
• Previous breast cancer.
Clinical features suggestive of malignancy
• Symptoms:
• New lump in at risk individuals.
• Weight loss. • Metastatic symptoms - bone pain, shortness of breath etc.
• Signs:
• Inspection - skin tethering, inverted slit nipple, Paget’s disease of the nipple (eczematous changes associated with ductal carcinoma in 50% of cases), bloody discharge, peu d’orange (dimpling arising from Cooper’s ligaments tethering skin within oedematous breast tissue). • Palpation - hard, ill-defined, irregular, non-fluctuant.
• Local invasion - fixed to underlying muscle/chest wall.
• Metastatic invasion - axillary lymphadenopathy, bone tenderness, liver enlargement, CNS • Most common location = upper outer quadrant.
Investigations
• National UK breast screening between 47 - 73 yrs (from 2012):
• Every 3 years.
• Involves two view mammography - read by two independent assessors.
• Any suspicious masses undergo - Triple Testing:
• Clinical assessment - history and examination.
• Imaging - USS, mammography.
• Pathology - FNAC, corecut.
• Ultrasound - for patients younger than 40 yrs as mammography quality poor due to • MRI - used in invasive cancer where extent of disease is unclear and where breast conserving surgery is being considered.
• Axillary ultrasound - can be used to characterise and biopsy abnormal lymph nodes.
• PET radiography - to assess metastatic spread.
• Nuclear scanning - to assess metastatic spread and treatment response.
• Affect prognosis and potential treatment modalities.
• ER - oestrogen receptor and PR - progesterone receptor - typically more indolent course and hormone therapy responsive (see later).
• HER-2 - more agressive and worse prognosis - potential response to Herceptin therapy.
Main Subtypes
Characteristics/Histology
Ductal carcinoma in
• Most common type detected on mammogram - microcalcification.
situ (DCIS)
• Malignant proliferation of epithelial cells.
• Classified according to: • Cell architecture - solid, papillary, cribiform, micropapillary.
• Grade - high, intermediate, low.
• Oestrogen receptor +ve (ER+) - decreased risk or recurrence.
• Epidermal growth factor +ve (HER-2) - increased risk of Invasive ductal
carcinoma (IDC)
• No special type (NOS), mucinous, tubular, papillary.
• Infiltration of clusters of malignant cells with dense fibrous stroma.
• Often presents with local spread.
Lobular carcinoma in
situ (LCIS)
• Few clinical features.
• Proliferation of terminal duct-lobuar unit cells.
• Typically: • Risk for invasive carcinoma (ductal or lobular) - 15% Invasive lobular
carcinoma (IDC)
• Multifocal, bilateral on presentation.
• Diffuse and not well circumscribed.
• Small, round cells which form a ‘rosary’ pattern.
Spread
• Local invasion - chest wall, skin.
• Lymphatic:
• Drain 85% of breast.
• Groups - • Central• Interpectoral• Apical - lie above pectoralis minor - drain all other groups.
1. inferolateral to pectoralis minor.
2. Posterior to pectoralis minor.
3. Superomedial to pectoralis minor.
• Internal mammary - tumours in posterior third of breast.
• Bone - lumbar vertebrae, femur, thoracic vertebrae, rib and skull.
• Liver• Lungs• Brain• Adrenals• Ovaries Staging
• Follows the TNM staging system:
• Tis - in situ - TDCIS, TLCIS, TPagets• T1 - less than 20 mm - further divided between <1 mm, 1-5 mm, 5-10 mm, 10-20 mm.
• T2 - 20-50 mm• T3 - > 50 mm• T4 - Any size which is invading chest wall or skin.
• N0 - no lymph node involvement.
• N1 - Clinically detectable, mobile level I or II axillary nodes on ipsilateral side.
• N2 - Immobile, fixed ipsilateral axillary nodes or internal mammary nodes.
• N3 - N3a - infraclavicular nodes, N3b - both axillary and internal mammary nodes, N3c - • M0 - no detectable metastases.
• cM0 - no clinically detectable metastases but tumour cells in blood, bone marrow or non- • M1 - clinically detectable metastases.
Treatment
• Non-surgical
• Chemotherapy - can be adjuvant or neo-adjuvant (if large/ inflammatory tumour), may reduce recurrence and risk of death. e.g. cyclophosphamide and docetaxyl (if lymph node +ve).
• Selective oestrogen receptor modulators -SERMs - Tamoxifen, Raloxifine can be given prophylactically in high risk individuals. Given for 5 years typically.
• Aromatase inhibitors - Anastrazole/Arimidex reduce systemic oestrogen levels. • Antibody therapy - Herceptin or Trastuzumab a monoclonal antibody which on binding to HER-2 receptors promotes cell destruction.
• Advocated in intermediate/high risk carcinoma following surgical treatment.
• Nodal radiotherapy in nodal disease.
• Indicated in DCIS, early unifocal invasive carcinoma and early Paget’s disease.
• Margin of at least 2mm.
• If incomplete resection margin then re-excision of mastectomy.
• Higher rate of recurrence but better cosmesis.
• Simple - excision of breast tissue, sparing axilla.
• Modified Radical (‘Patey’) - breast tissue, pectoralis minor and axillary contents • ‘Halstead’ Radical - breast tissue, pectoralis minor and major plus axillary • Prophylactic mastectomy may be offered in high risk individuals - BRCA1/BRCA2. • Involves injecting local breast tissue (usually peri-areolar) with blue dye and • The node that first takes up both visible dye and the isotope is the sentinel node i.e the first node to receive lymphatic drainage from the tumour site. • This is then excised and examined histologically. If negative for metastases then full axillary clearance not justified.
• Not indicated in palpable nodes.
• Axillary clearance - excision of all nodes below the axillary vein - Level I to III.
• Can be performed immediately on day of resection or after.
• Implant reconstruction - may involve a tissue expander.
• TRAM (transverse rectus abdominus muscle) flap - • Pedicled - flap involving skin, superficial fascia and rectus abdominus is made and tunneled to the anterior chest - supplied by deep superior epigastric artery.
• Free - flap from lower rectus abdominus is mobilised with inferior epigastric vessel which is anastomosed with thoracodorsal or internal mammary vessels. • DIEP (deep inferior epigastric perforator) flap - spares rectus abdominus.
• Latissimus dorsi flap - tunneled through axilla to anterior chest wall.
Complications of surgery
• Mastectomy:
• Bleeding, haematoma, damage to adjacent structures.
• Infection, abscess, haematoma, excess skin at corners (‘dog ears’), seroma, damage to long thoracic nerve causing winging of scapula (due to serratus anterior paralysis), damage to thoracodorsal nerve causing weakness in abduction against resistance (due to paralysis of latissimus dorsi).
• Infection, abscess, haematoma, seroma, reduced upper limb mobility and intercostal • Lymphoedema, infection, tumour recurrence.
Prognosis
• Based on stage, grade, hormone receptor status, presence of oncogenes and growth factor
• Nottingham prognostic index (NPI) incorporates some of these aspects: • NPI = [0.2 x S] + N + G• S is the size of the index lesion in centimetres• N is the number of lymph nodes involved: 0 =1, 1-3 = 2, >3 = 3• G is the grade of tumour: Grade I =1, Grade II =2, Grade III =3 5-year survival

Source: http://mrcsrevise.com/breastcancer.pdf