Breast cancer

Definition

• • Malignant neoplastic growth of breast tissue

    • Ductal

    • Lobular

    • (Connective)

Risk Factors

• • (Unopposed ) oestrogen

    • HRT?

    • Early menarche

    • Late age at child-birth

    • No breastfeeding

  • Age

  • Endogenous hormone levels

  • High breast density

  • Obesity

  • Physical activity

  • Alcohol

  • Shift work?

  • Family history

  • Genetic

    • BRCA1/2

Differential diagnosis

• • (Sebaceous) cyst

  • Fat necrosis

  • Benign hyperplasia

    • Fibroadenosis

    • Fibroma

    • Hemartoma (1/3 go on to cancer)

  • Mastitis

  • Galactocele

  • Malignant

    • DCIS/LCIS

    • IDC/ILC (invasive)

    • Sarcoma (rare - after initial radiation)

    • Medullary carcinoma

Epidemiology

• • 1/11 women

  • 1% (of breast cancers) are in men

  • Lower Africa/Asia

  • Higher social class more likely to present

  • Japan --

    • But immigrants catch up within 2 generations

  • Black women < white

Aetiology

• • DNA damage / inherited defects

  • Leading to unregulated growth

  • Further mutations => invasion, metastasis

Clinical features

• • Malignant lump

    • Invasive

    • Non-motile

    • Vascularised

    • Irregular edges/spiculated/craggy

    • +/- ill-defined edges

    • Peau d'orange?

    • Pitting?

    • Nipple inversion?

    • Discharge?

    • Non-fluctuating?

    • Not transilluminable

    • Pain?

    • Lymph node involvement?

    • Metastatic features

      • Bone > Liver > Lungs > Brain

    • Cachexia (definition: >5% weight loss in 6 months)

    • Tiredness, fatigue, anorexia

Pathophysiology

• • 6 steps

    • Growth factor self-sufficiency

      • Factor, receptor, pathway

    • Lack of negative control

    • Apoptosis evasion

    • Endless replicative potential

    • Angiogenesis

    • Metastasis

Investigations

• • Triple test:

    • Clinical

    • Radiological

      • Xray (only >35)

      • Ultrasound

      • MRI

        • for metastases?

        • and screening? (3-yearly)

    • Biopsy

      • FNA

      • Core biopsy

  • Genetic screening

    • PR

    • OR

    • HER-2

Management

• Chemo

  • Chemical

    • Narrow therapeutic index

    • Primary / combined / adjuvant / neoadjuvant

    • NB only 3% of cells are mitotic => need multi-dose regime

    • Side effects

      • Epithelial damage (nausea, vomiting, dry mouth)

      • Infertility

      • Secondary cancers

      • PSN (peripheral sensory neuropathy)

      • Bone marrow suppression

        • => Neutropenic sepsis

  • Hormonal

    • Lower oestrogen levels

      • Post-menopausal => use aromatase inhibitors => androgen - => estrone -

      • Pre-menopausal

        • oophorectomy

        • GnRH => hypothalamus GnRH receptor downregulation => LH/FSH --

    • Lower oestrogen response

      • SERMs (e.g. Tamoxifen)

      • ERDs (oestrogen receptor downregulators)

  • Biological

    • Antibodies vs growth factor receptors

  • Radiotherapy

    • Direct

      • Heavy particles

      • Bragg peak effect

    • Indirect

      • Relies on ROS generation

      • cf hypoxic tumours

    • Brachytherapy

  • Surgical

    • 1 cm margin if possible

    • Palliative surgery?

    • Preserve lymph nodes if possible to avoid lymphoedema

Prognosis

• • Depends on stage and grade

  • 50% chance of recurrence in opposite breast

  • HER2 receptor is a bad sign

  • Nottingham Prognostic Index => 10-year survival rate

    • 0.2 (size in mm + nodal status + grade (1-9))