Overview
Breast Cancer
1. Clinical Overview
Summary
Breast cancer is the most common cancer in women (1 in 8 lifetime risk) and the second most common cancer overall. It is a heterogeneous disease classified by receptor status (ER, PR, HER2) which determines treatment. Triple assessment (clinical examination, imaging, histopathology) is the diagnostic standard. Treatment is multimodal including surgery (breast-conserving or mastectomy), radiotherapy, and systemic therapy (chemotherapy, endocrine therapy, targeted therapy). Screening mammography (NHS Breast Screening Programme) reduces mortality. Advances in targeted therapy (trastuzumab, CDK4/6 inhibitors) and immunotherapy have improved outcomes, particularly in HER2+ and triple-negative subtypes.
Key Facts
- Incidence: Most common cancer in women; 1 in 8 lifetime risk
- Screening: NHS mammography ages 50-70 (every 3 years)
- Subtypes: ER+/PR+ (70%), HER2+ (15-20%), Triple-negative (15%)
- Triple Assessment: Clinical exam + Imaging + Histopathology
- Surgery: Wide local excision (WLE) vs Mastectomy
- Prognosis: 5-year survival ~90% (early), ~25% (metastatic)
Clinical Pearls
"Receptor Status Drives Treatment": ER/PR positive = Endocrine therapy. HER2+ = Trastuzumab. Triple-negative = Chemotherapy. Always know the receptor status.
"Triple Assessment is Non-Negotiable": Any breast lump requires clinical examination + imaging + pathology. Don't skip steps.
"Skin Changes = Red Flag": Peau d'orange, skin dimpling, nipple retraction or inversion are concerning for malignancy or inflammation.
"CDK4/6 Inhibitors Transform ER+ Disease": Palbociclib, ribociclib added to endocrine therapy nearly double progression-free survival in metastatic ER+ disease.
2. Epidemiology
Incidence
- Most common cancer in women (55,000 new cases/year UK)
- 1 in 8 lifetime risk
- Rare in men (<1%)
Demographics
- Peak incidence: 55-65 years (post-menopause)
- Rare <30 years
- Increasing incidence but decreasing mortality
Risk Factors
| High Risk | Moderate Risk |
|---|---|
| BRCA1/BRCA2 mutation | Early menarche (<12) |
| Previous breast cancer | Late menopause (>5) |
| Chest radiotherapy | Nulliparity |
| Atypical hyperplasia | First pregnancy >0 |
| Strong family history | HRT use |
| Obesity (post-menopausal) | |
| Alcohol |
Genetic Predisposition
- BRCA1 mutation: 55-65% lifetime risk (also ovarian)
- BRCA2 mutation: 45% lifetime risk
- TP53 (Li-Fraumeni), CHEK2, ATM
3. Pathophysiology
Cell of Origin
- Most arise from terminal duct lobular unit (TDLU)
- Ductal carcinoma (75-80%)
- Lobular carcinoma (10-15%)
Molecular Subtypes
| Subtype | Receptors | Prognosis | Treatment |
|---|---|---|---|
| Luminal A | ER+, PR+, HER2-, Ki67 low | Best | Endocrine alone |
| Luminal B | ER+, PR±, HER2±, Ki67 high | Intermediate | Endocrine + Chemo |
| HER2-enriched | ER-, PR-, HER2+ | Poor untreated | Trastuzumab + Chemo |
| Triple-negative (Basal) | ER-, PR-, HER2- | Poor | Chemotherapy (± Immunotherapy) |
Spread
- Local: Skin, chest wall, pectoralis muscle
- Lymphatic: Axillary nodes (most common), internal mammary, supraclavicular
- Haematogenous: Bone (most common), Liver, Lung, Brain
4. Clinical Presentation
Symptoms
| Feature | Notes |
|---|---|
| Lump | Most common presentation (painless, hard, irregular) |
| Nipple discharge | Bloody or clear; single duct |
| Nipple change | Inversion, eczematous (Paget's) |
| Skin changes | Dimpling, peau d'orange, ulceration |
| Breast asymmetry | New change in shape |
| Axillary lump | Nodal metastasis |
Inflammatory Breast Cancer (Emergency)
Presentation by Stage
Erythema, oedema, peau d'orange
Common presentation.
Warm breast
Common presentation.
May mimic mastitis
Common presentation.
Aggressive; requires urgent treatment
Common presentation.
5. Clinical Examination
Inspection
- Skin changes: Dimpling, peau d'orange, erythema
- Nipple: Deviation, retraction, eczema (Paget's)
- Asymmetry
Palpation
- Systematic examination of all quadrants
- Lump characteristics: Size, shape, texture, mobility, fixity
- Axillary and supraclavicular lymph nodes
Features Suggesting Malignancy
| Feature | Notes |
|---|---|
| Hard, irregular lump | vs Smooth, mobile (benign) |
| Fixed to skin/chest wall | Invasion |
| Skin tethering | Cooper's ligament involvement |
| Palpable axillary nodes | Hard, matted |
| Satellite nodules | Local spread |
6. Investigations
Triple Assessment
- Clinical Examination: As above
- Imaging:
- <40 years: Ultrasound (dense breasts)
- ≥40 years: Mammography ± Ultrasound
- MRI: High-risk patients, lobular cancer, breast implants
- Pathology:
- Core needle biopsy (gold standard)
- Fine needle aspiration (cytology only)
Imaging Findings
| Modality | Malignant Features |
|---|---|
| Mammography | Spiculated mass, microcalcifications, architectural distortion |
| Ultrasound | Irregular hypoechoic mass, posterior shadowing |
| MRI | Irregular enhancing mass, washout kinetics |
Staging Investigations (Confirmed Cancer)
- CT chest/abdomen/pelvis (if >4 nodes or T3+)
- Bone scan or PET-CT (metastatic workup)
- Blood tests: FBC, LFTs, Ca2+
7. Management
Staging (TNM)
| Stage | Description | 5-Year Survival |
|---|---|---|
| 0 | DCIS | ~100% |
| I | T1N0 (≤2cm, no nodes) | ~95% |
| II | T2 or N1 | ~85% |
| III | T3+ or N2+ | ~55% |
| IV | Metastatic | ~25% |
Surgical Options
┌──────────────────────────────────────────────────────────┐
│ BREAST SURGERY │
├──────────────────────────────────────────────────────────┤
│ │
│ BREAST-CONSERVING SURGERY (WLE/LUMPECTOMY): │
│ • Tumour ≤5cm with adequate margin │
│ • Requires adjuvant radiotherapy │
│ • Equivalent survival to mastectomy │
│ │
│ MASTECTOMY: │
│ • Multicentric disease │
│ • Large tumour:breast ratio │
│ • Patient preference │
│ • Contraindication to radiotherapy │
│ • Immediate or delayed reconstruction offered │
│ │
│ AXILLARY STAGING: │
│ • Sentinel lymph node biopsy (SLNB) standard │
│ • Axillary clearance if positive SLNB │
│ │
└──────────────────────────────────────────────────────────┘
Systemic Therapy by Subtype
| Subtype | Treatment |
|---|---|
| ER+, HER2- | Endocrine (Tamoxifen/AI) ± CDK4/6i ± Chemo |
| ER+, HER2+ | Endocrine + Trastuzumab + Pertuzumab + Chemo |
| ER-, HER2+ | Trastuzumab + Pertuzumab + Chemo |
| Triple-negative | Chemotherapy ± Pembrolizumab (if PD-L1+) |
Radiotherapy
- After BCS: Whole breast RT ± Boost
- After mastectomy: If ≥4 positive nodes or high-risk features
- Hypofractionation now standard (15-16 fractions)
8. Complications
Of Disease
- Lymphoedema (post-axillary surgery/RT)
- Metastatic disease (bone, liver, lung, brain)
- Local recurrence
- Oncological emergencies (cord compression, hypercalcaemia)
Of Treatment
- Surgical: Seroma, infection, lymphoedema
- Radiotherapy: Skin changes, pneumon, cardiac (left breast)
- Chemotherapy: Neutropenia, alopecia, neuropathy
- Endocrine: Hot flushes, VTE, bone loss
9. Prognosis & Outcomes
Survival by Stage
| Stage | 5-Year Survival |
|---|---|
| I | 95-100% |
| II | 75-90% |
| III | 50-70% |
| IV | 20-25% |
Prognostic Factors
| Good | Poor |
|---|---|
| Small tumour (<2cm) | Large tumour |
| Node negative | Node positive |
| ER/PR positive | Triple-negative |
| Low grade (G1) | High grade (G3) |
| HER2+ (with treatment) | Lymphovascular invasion |
Gene Expression Profiling
- Oncotype DX, MammaPrint: Guide chemotherapy decisions in ER+ early disease
- Predict recurrence risk and chemotherapy benefit
10. Evidence & Guidelines
Key Guidelines
- NICE NG101: Early and Locally Advanced Breast Cancer (2018)
- NICE NG187: Advanced Breast Cancer (2017, updated)
- ESMO Breast Cancer Guidelines (2024)
- ABS Guidelines
Key Evidence
CDK4/6 Inhibitors
- PALOMA-3: Palbociclib + Fulvestrant doubles PFS in metastatic ER+ disease
- MONARCH-2, MONALEESA-2: Similar findings
Immunotherapy in Triple-Negative
- KEYNOTE-355: Pembrolizumab + Chemo improves PFS in PD-L1+ metastatic TNBC
HER2 Targeted Therapy
- CLEOPATRA: Pertuzumab + Trastuzumab + Docetaxel = 56 months median OS (metastatic HER2+)
11. Patient/Layperson Explanation
What is Breast Cancer?
Breast cancer is when cells in the breast grow abnormally and form a tumour. It's the most common cancer in women, affecting about 1 in 8 over a lifetime.
What Are the Symptoms?
- A new lump in the breast or armpit
- Change in breast size or shape
- Skin changes (dimpling, puckering, redness)
- Nipple changes (inversion, discharge, rash)
- Pain in the breast that doesn't go away
How is it Diagnosed?
"Triple assessment" is used:
- Clinical examination by a doctor
- Imaging (mammogram or ultrasound)
- Biopsy (taking a small sample to look at under the microscope)
How is it Treated?
Treatment depends on the type and stage:
- Surgery: Removing the tumour (lumpectomy) or entire breast (mastectomy)
- Radiotherapy: Targeting remaining cancer cells with radiation
- Drug treatment: Chemotherapy, hormone therapy (tamoxifen), or targeted therapy (Herceptin)
Screening
The NHS invites women aged 50-70 for a mammogram every 3 years. This can detect cancer early, often before any symptoms appear.
What Can I Do?
- Attend screening appointments
- Be breast aware - know what's normal for you
- Report any changes to your GP promptly
- Maintain a healthy weight and limit alcohol
12. References
Primary Guidelines
- NICE. Early and locally advanced breast cancer: diagnosis and management (NG101). 2018, updated 2023. nice.org.uk/guidance/ng101
- NICE. Advanced breast cancer: diagnosis and treatment (NG187). 2017, updated 2022.
Key Studies
- Swain SM, et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer (CLEOPATRA). N Engl J Med. 2015;372(8):724-734. PMID: 25693012
- Finn RS, et al. Palbociclib and Letrozole in Advanced Breast Cancer (PALOMA-2). N Engl J Med. 2016;375(20):1925-1936. PMID: 27959613