Key Facts

Breast cancer is the most common cancer in the UK and a leading cause of cancer mortality in women. Treatment is increasingly personalised based on molecular subtype, stage, and genomic profiling.

Epidemiology

• UK incidence: approximately 56,000 new cases per year (most common cancer overall)
• Mortality: approximately 11,500 deaths per year
• Lifetime risk: 1 in 7 women; 1 in 870 men
• Peak incidence: 60-64 years
• 5-year survival: approximately 85-90% (improvement due to screening and better treatments)

Aetiology

• Hormonal factors: early menarche, late menopause, nulliparity, late first pregnancy (>30), HRT (combined > oestrogen-only), OCP (small increased risk while taking)
• Genetic: BRCA1 (60-80% lifetime risk, typically TNBC), BRCA2 (40-60%, typically ER+), TP53 (Li-Fraumeni), PALB2, CHEK2, ATM
• Lifestyle: obesity (postmenopausal), alcohol (dose-dependent, 7% increase per unit/day), physical inactivity
• Previous: previous breast cancer, atypical ductal hyperplasia, LCIS, chest wall irradiation
• Protective: breastfeeding, multiparity, physical activity, late menarche

Pathophysiology

• Ductal carcinoma in situ (DCIS): pre-invasive; proliferation within ducts; 30-50% progress to invasive cancer over 10-20 years
• Invasive ductal carcinoma (NST): 75-80% of invasive cancers
• Invasive lobular carcinoma: 10-15%; diffuse infiltration pattern; may be bilateral
• Special types: mucinous, tubular, medullary, papillary (generally better prognosis)
• Spread: local invasion → axillary lymph nodes → systemic (bone, liver, lung, brain)

Typical Presentation

• Painless breast lump (most common)
• Detected on screening mammography (20-30% of diagnoses)
• Breast skin changes: peau d'orange, dimpling, tethering
• Nipple changes: inversion, discharge (bloody), Paget's disease (eczematous change over nipple/areola)
• Axillary lump (lymphadenopathy)

Advanced Disease

• Bone pain (most common site of metastasis)
• Dyspnoea (pleural effusion, lung metastases)
• Jaundice, abdominal pain (liver metastases)
• Headache, neurological symptoms (brain metastases)

Red Flags

• Hard, irregular, fixed breast lump
• Bloody nipple discharge (unilateral)
• Skin tethering or peau d'orange
• Axillary lymphadenopathy
• Inflammatory breast cancer (rapidly enlarging, erythematous, warm breast)
• Male breast lump

Bedside

• Triple assessment (NICE NG101):
  1. Clinical examination
  2. Imaging (mammography ± USS)
  3. Core biopsy (14G needle)
• Examine both breasts, axillae, supraclavicular fossae

Bloods

• FBC, U&Es, LFTs, calcium, ALP (baseline; staging if advanced)
• Tumour markers: CA 15-3 (monitoring, not diagnosis)

Imaging

• Mammography: first-line for women ≥40; screening detects 6-8 cancers per 1,000 women screened
• Breast USS: first-line for women <40 (dense breast tissue); USS-guided core biopsy
• MRI breast: for lobular carcinoma, BRCA carriers, implants, neoadjuvant response assessment
• CT chest/abdomen/pelvis + bone scan or PET-CT: for staging in advanced/symptomatic disease

Special Tests

• Core biopsy (14G): histological diagnosis, ER/PR status, HER2 status (IHC/FISH), Ki67
• Oncotype DX / EndoPredict / Prosigna: genomic assays for ER+/HER2-/node-negative to guide adjuvant chemotherapy benefit
• Sentinel lymph node biopsy: staging of axilla (avoids full clearance if negative)
• BRCA testing: all <50, TNBC, bilateral, male, or family history meeting criteria

Non-pharmacological

• MDT discussion
• Psychological support and breast care nurse specialist
• Fertility preservation counselling (before chemotherapy)
• Genetic counselling for BRCA carriers

Pharmacological

• Endocrine therapy (ER+):
  • Premenopausal: tamoxifen 20mg OD for 5-10 years (± GnRH agonist)
  • Postmenopausal: aromatase inhibitor (anastrozole 1mg, letrozole 2.5mg, or exemestane 25mg) for 5-10 years
  • CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) added for metastatic HR+/HER2-
• Anti-HER2 therapy (HER2+):
  • Adjuvant: trastuzumab 6mg/kg IV 3-weekly for 1 year + chemotherapy (docetaxel + carboplatin)
  • Neoadjuvant: trastuzumab + pertuzumab + chemotherapy (NeoSphere, PEONY trials)
  • Metastatic: trastuzumab deruxtecan (T-DXd) (DESTINY-Breast03)
• Chemotherapy:
  • Neoadjuvant or adjuvant: FEC-D (fluorouracil, epirubicin, cyclophosphamide → docetaxel) or dose-dense AC-T
  • Guided by genomic assays in ER+/HER2-/node-negative (TAILORx, RxPONDER trials)
• TNBC:
  • Neoadjuvant: pembrolizumab + chemotherapy (KEYNOTE-522)
  • BRCA-mutated: olaparib (OlympiAD) or talazoparib
  • Metastatic: sacituzumab govitecan (ASCENT trial)
• Bisphosphonates: zoledronic acid adjuvant in postmenopausal (AZURE, ABCSG-12) - reduces bone recurrence

Surgical/Interventional

• Breast-conserving surgery (wide local excision) + adjuvant radiotherapy: preferred for early-stage (equivalent survival to mastectomy)
• Mastectomy ± immediate reconstruction: for multicentric disease, large tumour:breast ratio, patient preference
• Sentinel lymph node biopsy (SLNB): staging; if positive → axillary clearance or axillary radiotherapy
• Neoadjuvant chemotherapy: to downstage tumour enabling BCS
• Risk-reducing mastectomy: for BRCA carriers (reduces risk by 90%)
• Adjuvant radiotherapy: whole breast after BCS; chest wall after mastectomy if high risk; boost to tumour bed

Referral Criteria

• Breast lump in woman ≥30: urgent 2-week wait referral (NICE NG12)
• Breast lump in woman <30 with concerning features: urgent referral
• Skin changes, nipple changes: urgent referral
• Family history meeting criteria: genetics referral (NICE CG164)

• Overall 5-year survival: 85-90%
• Stage I: >95% 5-year survival
• Stage II: 80-90%
• Stage III: 50-70%
• Stage IV: 25% (improving with modern therapies)
• ER+ tumours: better short-term prognosis but can recur late (up to 20 years)
• HER2+ with trastuzumab: significantly improved (50% reduction in recurrence)
• TNBC: worst short-term prognosis; lower rate of late recurrence
• Oncotype DX low recurrence score: excellent prognosis with endocrine therapy alone (no chemotherapy benefit)

Molecular Subtypes and Treatment

Key Breast Cancer Trials