Red Flags
- New breast lump, skin tethering, peau d'orange, nipple retraction or discharge, axillary lymphadenopathy — same-day imaging and triple assessment[1]
- Inflammatory breast cancer (rapid skin changes, oedema, erythema, peau d'orange) — emergent multidisciplinary oncology; neoadjuvant chemotherapy[1]
- BRCA1/2 or other high-penetrance mutation in patient or strong family history — clinical genetics; consider risk-reducing surgery and intensified surveillance[1]
- CDK4/6 inhibitor on advanced ER-positive — monitor neutropenia (palbociclib), diarrhoea (abemaciclib), QTc (ribociclib); cardiac and ILD review[1]
First-line treatment
Interventions
- Multidisciplinary tumour board for all[1]Surgical, medical, and radiation oncology + radiology + pathology + nuclear medicine; treatment driven by stage and molecular subtype
- Surgery — BCS or mastectomy[1]Breast-conserving surgery with whole-breast radiotherapy is equivalent to mastectomy for early-stage; sentinel lymph node biopsy for clinically node-negative; oncoplastic techniques to optimise cosmesis
- Adjuvant radiotherapy[1]Whole-breast RT after BCS (hypofractionated standard); post-mastectomy RT for ≥4 positive nodes, T3+, or close margins; nodal RT per axillary status
- Genomic risk-stratification (Oncotype DX, MammaPrint)[1]ER-positive HER2-negative N0 disease — informs decision on adjuvant chemotherapy where benefit uncertain (ESMO endorses where available)
- Advanced/metastatic ER-positive: endocrine + CDK4/6 inhibitor[1]First-line for HR+/HER2- metastatic: aromatase inhibitor + CDK4/6 inhibitor (palbociclib/ribociclib/abemaciclib); fulvestrant + CDK4/6 inhibitor for prior endocrine therapy; PIK3CA-mutant: alpelisib + fulvestrant; AKT pathway: capivasertib + fulvestrant
First-line drug therapy
| Drug | Class | Adult | Paediatric | Notes |
|---|---|---|---|---|
| Tamoxifen[1] | Selective estrogen receptor modulator | 20 mg PO daily × 5–10 years | — | Adjuvant for premenopausal ER-positive; risk of VTE and endometrial cancer; CYP2D6 interactions |
| Aromatase inhibitor (anastrozole, letrozole, exemestane)[1] | Aromatase inhibitor | Anastrozole 1 mg PO daily; letrozole 2.5 mg PO daily; exemestane 25 mg PO daily — × 5–10 years | — | Adjuvant for postmenopausal ER-positive; bone loss — DXA and calcium/vitamin D ± bisphosphonate; arthralgia |
| Trastuzumab + pertuzumab + chemotherapy[1] | Dual HER2 blockade + chemotherapy | Trastuzumab 6 mg/kg IV every 3 weeks (after loading) × 1 year; pertuzumab 420 mg every 3 weeks (after loading) | — | Neoadjuvant or adjuvant in HER2-positive; cardiotoxicity — baseline and serial echocardiogram; combine with taxane in chemotherapy phase |
| Trastuzumab deruxtecan (T-DXd)[1] | HER2-directed antibody-drug conjugate | 5.4 mg/kg IV every 3 weeks | — | HER2-positive metastatic breast cancer second-line (DESTINY-Breast03); also HER2-low metastatic (DESTINY-Breast04); pneumonitis monitoring |
| Sacituzumab govitecan[1] | Trop-2-directed antibody-drug conjugate | 10 mg/kg IV days 1, 8 every 21 days | — | Triple-negative metastatic breast cancer second-line; HR+/HER2- after endocrine + chemotherapy; neutropenia, diarrhoea |
| Pembrolizumab + chemotherapy (TNBC)[1] | Anti-PD-1 + chemotherapy | Pembrolizumab 200 mg IV every 3 weeks + chemotherapy backbone | — | Neoadjuvant TNBC stage II–III (KEYNOTE-522); first-line PD-L1-positive metastatic TNBC; immune-related adverse events |
| Olaparib or talazoparib (BRCA-mutated)[1] | PARP inhibitor | Olaparib 300 mg PO BD; talazoparib 1 mg PO daily | — | BRCA-mutated metastatic and selected adjuvant high-risk early-stage (OlympiA); haematological monitoring |
Tamoxifen[1]
Selective estrogen receptor modulator
- Adult
- 20 mg PO daily × 5–10 years
- Paediatric
- —
Adjuvant for premenopausal ER-positive; risk of VTE and endometrial cancer; CYP2D6 interactions
Aromatase inhibitor (anastrozole, letrozole, exemestane)[1]
Aromatase inhibitor
- Adult
- Anastrozole 1 mg PO daily; letrozole 2.5 mg PO daily; exemestane 25 mg PO daily — × 5–10 years
- Paediatric
- —
Adjuvant for postmenopausal ER-positive; bone loss — DXA and calcium/vitamin D ± bisphosphonate; arthralgia
Trastuzumab + pertuzumab + chemotherapy[1]
Dual HER2 blockade + chemotherapy
- Adult
- Trastuzumab 6 mg/kg IV every 3 weeks (after loading) × 1 year; pertuzumab 420 mg every 3 weeks (after loading)
- Paediatric
- —
Neoadjuvant or adjuvant in HER2-positive; cardiotoxicity — baseline and serial echocardiogram; combine with taxane in chemotherapy phase
Trastuzumab deruxtecan (T-DXd)[1]
HER2-directed antibody-drug conjugate
- Adult
- 5.4 mg/kg IV every 3 weeks
- Paediatric
- —
HER2-positive metastatic breast cancer second-line (DESTINY-Breast03); also HER2-low metastatic (DESTINY-Breast04); pneumonitis monitoring
Sacituzumab govitecan[1]
Trop-2-directed antibody-drug conjugate
- Adult
- 10 mg/kg IV days 1, 8 every 21 days
- Paediatric
- —
Triple-negative metastatic breast cancer second-line; HR+/HER2- after endocrine + chemotherapy; neutropenia, diarrhoea
Pembrolizumab + chemotherapy (TNBC)[1]
Anti-PD-1 + chemotherapy
- Adult
- Pembrolizumab 200 mg IV every 3 weeks + chemotherapy backbone
- Paediatric
- —
Neoadjuvant TNBC stage II–III (KEYNOTE-522); first-line PD-L1-positive metastatic TNBC; immune-related adverse events
Olaparib or talazoparib (BRCA-mutated)[1]
PARP inhibitor
- Adult
- Olaparib 300 mg PO BD; talazoparib 1 mg PO daily
- Paediatric
- —
BRCA-mutated metastatic and selected adjuvant high-risk early-stage (OlympiA); haematological monitoring
Safety-net
- Be breast-aware: know what is normal for you and report any new lump, nipple change, skin change, or unexplained pain[1]
- Attend recommended mammography appointments — most early breast cancers are detected on screening before symptoms appear[1]
- Adjuvant therapy can last 5–10 years — adherence is the single biggest determinant of long-term survival[1]
Referral criteria
- Suspicious clinical lesion, abnormal mammogram, or biopsy-proven cancerBreast cancer multidisciplinary clinic[1]
- Inflammatory breast cancer or rapidly progressive diseaseTertiary breast oncology same-week[1]
- BRCA1/2 mutation or strong family historyClinical genetics; consider risk-reducing mastectomy and salpingo-oophorectomy[1]
- Pregnancy with newly diagnosed breast cancerJoint oncology and obstetric clinic[1]
Clinical summary
Risk-stratified screening, triple-assessment diagnosis, and stage- and subtype-driven treatment of breast cancer per ESMO 2024 guidance.