Malignant Breast Tumours

Epidemiology

• Most common in developed western countries
• More aggressive in African-American women
• More common in nulliparous women, women who attain early menarche and late menopause

Etiology

• Occurs due to mutation of tumour suppressor genes BRCA1/BRA2 on long arm of C17 + 13 respectively
• Occasionally associated with mutation of BRCA3 and p53
• Li-Fraumeni syndrome (LFS) – autosomal dominant condition with breast cancer inheritance (90%)
  • With sarcoma, leukaemia, brain tumours, adrenocortical tumours
• Higher risk in 1^st degree relatives
• Some benign breast diseases increase the risk
  • E.g. fibrocystic disease of the breast with atypical hyperplasia
• Previous therapeutic radiation can be predisposing factor
• More common in women on oral contraceptive pill and hormone replacement therapy

Pathology

• Ductal carcinoma – breast carcinoma arising from lactiferous ducts
• Lobular carcinoma – breast ca arising from lobules
• In situ carcinoma – pre-invasive ca which has not breached the epithelial basement membrane
  • Ductal carcinoma in situ – DCIS
  • Lobular carcinoma in situ – LCIS

Classification of primary breast cancer

Noninvasive epithelial

• LCIS
• DCIS – papillary, solid, cribiform, comedo

Invasive epithelial

• Invasive lobular
• Invasive ductal
  • NOS (not otherwise specified) – schirrous
  • Medullary
  • Medullary variant
  • Tubular
  • Colloid
  • Invasive cribriform
  • Invasive papillary

Mixed connective tissue and epithelial

• Phyllodes, angiosarcoma, carcinosarcoma

Ductal carcinoma in situ

• Intraductal carcinoma (proliferation of malignant mammary ductal epithelial cells) without any invasion into the basement membrane
• Low grade – papillary, cribriform
• High grade – solid and comedo
• Associated with high expression of C-erb2 gene
• Untreated DCIS becomes invasive in over half cases – DCIS is an anatomical precursor of ductal carcinoma
• 5% of male breast cancers are DCIS
• Clinical features – nipple discharge, small swelling
• Investigations – ultrasound assisted FNAC and mammography
• Treatment
  • Breast conservative surgery with radiotherapy
  • Hormone therapy with tamoxifen – to prevent recurrence

Lobular carcinoma in situ

• Originates in terminal duct lobular unit in female breast
• Most common in peri-menopausal and Caucasian women
• High chance to predispose to invasive cancer
  • It is a predictor of increased risk of invasive caner, not an anatomical precursor like DCIS
• Doesn’t form lump, normally an incidental finding

Other types

Scirrhous carcinoma – subtype of invasive ductal ca NOS; hard, whitish, non-capsulated, irregular, cartilaginous consistency

Medullary carcinoma – also known as encephaloid type due to its brain-like consistency. Contains malignant cells with dispersed lymphocytes

• Medullary variant – has some features of the pure form; shows high grade aggressive tumour cells with negative ER (oestrogen receptor), negative PR (progesterone receptor) and negative HER₂ protein
  • Called ‘triple negative’ breast cancer – worse prognosis

Inflammatory/lactating carcinoma

• Most aggressive type of breast cancer; most common in lactating women or pregnancy
• Mimics acute mastitis – short duration, pain, warmth, tenderness
• Clinical features – rapidly progressive, diffuse, painful, warm, involves whole breast tissue, diffuse lymphoedema due to tumour emboli
• Rapidly metastasises to chest wall, bones, lung
• Always stage IIIB carcinoma
• Investigations – FNAC to confirms diagnosis, shows undifferentiated cells
• Treatment – external radio/chemo-therapy. Worst prognosis

Colloid ca

• Produces abundant mucin
• Better prognosis

Paget’s disease of the nipple

• Superficial manifestation of an intraductal ca
• Malignancy spreads within the duct up to the skin of the nipple
• Clinical features – hard nodule just underneath areola, later ulcerates and causes destruction of nipple
• Differential diagnosis – eczema of the nipple
• Histology – large, ovoid, clear Paget’s cells with malignant features
• Treatment – radical mastectomy

Grading of tumour

• Grade I – well differentiated
• Grade II – moderately differentiated
• Grade III – poorly differentiated

Clinical features

• Most common site is upper quadrant
• Cutaneous manifestations
  • Peau d’orange – obstruction of dermal lymphatics, opening of sebaceous glands and hair follicles get buried in the oedema. Looks like orange peel
  • Dimpling of skin – infiltration of lactiferous duct
  • Retraction of nipple
  • Ulceration and discharge from nipple and areola

Spread

• Local – directly into surrounding tissue
• Lymph nodes – axillary nodes and peri-clavicular nodes
  • Sentinel node biopsy – 1^st axillary node along the lymphatic chain
  • Inject radioactive isotope technetium and blue dye around nipple and areola
    • Look for which node turns blue and remove
• Haematogenous – bone, lung, liver, brain, adrenal, other breast

Investigations

• Triple investigations
  • Physical exam
  • FNAC
  • Mammograph/ultrasound

TNM Staging

Treatment

• Surgery – see table

• Complications of mastectomy – NISE
  • Nerve injury – nerve to serratus anterior (winging of scapula on affected side)
  • Infection
  • Seroma – most common complication, accumulation of sterile fluid within a restricted dead location
  • Edema – lymphoedema
• Radiation therapy
• Chemotherapy
  • Neo-adjuvant – sandwich therapy (Chemo, then surgery, then chemo)
  • Adjuvant chemo – after definitive surgery
  • Palliative chemo – non-curative. To improve quality of life
• Hormonal therapy
  • Antioestrogen – tamoxifen 20mg
  • Aromatase inhibitor – Letrozole 2.5mg