Breast cancer · House

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.

References

1.ESMO Clinical Practice Guidelines on Early and Advanced Breast Cancer (2023, Pocket 2024) (2024)