Key Facts

Breast cancer management has been revolutionised by screening, molecular subtyping, and targeted therapies. The multidisciplinary approach ensures individualised treatment.

Epidemiology

~55,000 new cases/year in UK (most common cancer overall). ~400 cases in men annually. Lifetime risk: ~1 in 7 (women). Peak incidence 55-65 years (second peak >70). 5-year survival: ~87% overall.

Aetiology

Risk factors:

• Non-modifiable: Female sex, age, family history, BRCA1/2 mutations (~5-10% of cases), early menarche, late menopause, nulliparity, previous breast cancer, atypical ductal hyperplasia, LCIS
• Modifiable: HRT (combined — increases risk), alcohol, obesity (post-menopausal), OCP (slight increase), physical inactivity
• BRCA1: ~60-80% lifetime risk of breast cancer; also ovarian cancer (~40%)
• BRCA2: ~45-55% lifetime risk of breast cancer; also ovarian, prostate, pancreatic

Pathophysiology

• Normal breast epithelium → atypical hyperplasia → DCIS (non-invasive) → invasive carcinoma
• Invasive ductal carcinoma (no special type — NST): ~70-80% of breast cancers
• Invasive lobular carcinoma: ~10-15%; diffuse growth pattern, often bilateral
• DCIS: Pre-invasive; ~25% progress to invasive cancer over 10 years if untreated
• Molecular subtypes: Luminal A (ER+/HER2−, low Ki-67), Luminal B (ER+/HER2+, high Ki-67), HER2-enriched, Basal-like (triple-negative)

Common Presentations

• Painless breast lump: Usually hard, irregular, fixed
• Screen-detected: Mammographic abnormality (microcalcifications, spiculated mass)
• Nipple changes: Retraction, Paget's disease (eczematous nipple — underlying DCIS/invasive cancer)
• Skin changes: Peau d'orange (lymphatic invasion), dimpling, tethering
• Axillary lymphadenopathy: May be the presenting feature
• Inflammatory breast cancer: Diffuse erythema, oedema, peau d'orange — rapidly progressive; poor prognosis

Red Flags (2WW Referral — NICE NG12)

• Unexplained breast lump in women ≥30
• Breast lump with other features (skin/nipple changes) at any age
• Unilateral nipple changes at ≥50 (discharge, retraction)
• Axillary lump in women ≥30
• Skin changes suggestive of breast cancer at any age

Triple Assessment (One-Stop Breast Clinic)

1. Clinical examination: Inspection and palpation of breast and axillae

2. Imaging:

• Mammography: Women ≥40 (microcalcifications, spiculated masses, architectural distortion)
• Ultrasound: Women <40 (dense breast tissue); also guides biopsy and assesses cysts
• MRI breast: BRCA carriers, lobular cancer (multifocality), pre-operative planning

3. Tissue diagnosis:

• Core biopsy (14G needle): Preferred — provides histological architecture
• FNA: Cytology only; used for lymph nodes

Staging

• CT chest/abdomen/pelvis: For locally advanced or suspected metastatic disease
• Bone scan/PET-CT: If bone/distant metastases suspected
• Sentinel lymph node biopsy (SLNB): Intraoperative staging — identifies first draining node(s)

Pathology

• Histological type, grade (Nottingham — tubule formation, nuclear pleomorphism, mitotic count)
• Receptor status: ER, PR, HER2 (IHC/FISH), Ki-67
• Oncotype DX: 21-gene recurrence score for ER+/HER2−/node-negative — guides adjuvant chemotherapy decision

Surgery

• Wide local excision (WLE/lumpectomy): Breast-conserving surgery + adjuvant radiotherapy — equivalent survival to mastectomy (NSABP B-06, EORTC trials)
• Mastectomy: If multifocal, large tumour:breast ratio, patient preference, BRCA carrier, inflammatory cancer
• Immediate or delayed reconstruction: Implant-based or autologous tissue (DIEP flap, LD flap)
• SLNB: Standard for clinically node-negative patients; if positive → axillary treatment (ANC or radiotherapy per AMAROS trial)
• Axillary node clearance (ANC): If >2 positive sentinel nodes or preoperative FNA-confirmed node involvement

Adjuvant Therapy

Radiotherapy:

• After WLE: Whole breast radiotherapy (reduces local recurrence from ~30% to ~10%)
• After mastectomy: If T3/T4, ≥4 positive nodes, positive margin

Endocrine therapy (ER+):

• Pre-menopausal: Tamoxifen 20mg OD for 5-10 years (± ovarian suppression)
• Post-menopausal: Aromatase inhibitor (anastrozole 1mg, letrozole 2.5mg) for 5-10 years
• Side effects: Tamoxifen — VTE, endometrial cancer; AIs — arthralgia, osteoporosis

Chemotherapy:

• ER−, HER2−, node-positive, high-risk: Anthracycline + taxane regimen (e.g., EC-T)
• Oncotype DX guides decision for ER+/HER2−/N0 patients

Targeted therapy:

• Trastuzumab (Herceptin): HER2+ disease — 1 year adjuvant; reduces recurrence ~50% (HERA trial)
• Pertuzumab: Added to trastuzumab for high-risk HER2+ (APHINITY trial)
• CDK4/6 inhibitors (ribociclib, abemaciclib): ER+/HER2− advanced disease

Referral Criteria

• Any breast lump meeting 2WW criteria — urgent referral to breast clinic
• BRCA carriers — specialist genetics and risk-reducing surgery discussion
• Metastatic disease — oncology

• Overall 5-year survival: ~87%
• Stage I: >95% 5-year survival
• Stage IV (metastatic): Median survival ~2-3 years; ~25% 5-year survival
• ER+ disease: Better prognosis than ER−; but late recurrence (>5 years) more common
• HER2+ with trastuzumab: Excellent outcomes; survival improved by ~30%
• Triple-negative: Poorer prognosis; higher recurrence rate but often occurs early (<3 years)
• Male breast cancer: Same stage-for-stage prognosis as female; often diagnosed later

Receptor Status and Treatment

Key Trials