Breast Cancer: General Topics & Workup
Comprehensive general breast oncology — screening (MASAI/DENSE/WISDOM), triple assessment workup, WHO classification, HER2 spectrum, pathology biomarkers (ER/PR/Ki-67/Nottingham), BRCA testing, menopausal status, ovarian escape monitoring, and bone metastasis management.
ER+ Breast Cancer
~75%
Most common subtype
BRCA1/2 Lifetime Risk
Up to 87%
BRCA1 breast cancer risk
Ki-67 Threshold
≥20%
High proliferation cutoff
Bone Mets
70%
HR+ MBC have bone involvement
How do you approach a newly diagnosed breast cancer — from epidemiology to classification?
NCCN 2026
- Average Risk: Annual mammography from age 40
- Dense Breasts (BI-RADS C/D): Supplemental US or MRI
- BRCA+: Annual MRI from age 25; mammography + MRI from age 30
- AI Integration: MASAI trial — AI-supported screening reduces interval cancers by 12%
ESMO 2026
- Average Risk: Mammography q2yr age 50–69
- Age 40–49: Individualized shared decision-making
- WISDOM trial approach — risk-stratified screening reduces overdiagnosis
- Polygenic risk scores + clinical factors for stratification
Hong Kong (BCSPP Phase II, 2025)
- High Risk (BRCA/prior chest RT): Age 35–74 — subsidized annual mammography + MRI
- Moderate Risk (1 FDR): Age 44–69 — mammography q2yr
- Average Risk: HK Breast Cancer Risk Assessment Tool to qualify for pilot
- Shifted from "not recommended" to Risk-Based Approach
| Trial | Year | Key Finding |
|---|---|---|
| MASAI (The Lancet) | Jan 2026 | AI-supported mammography reduces interval cancers by 12%; identifies aggressive cancers earlier; no increase in false positives |
| DENSE Trial (Final Update) | 2025 | Supplemental MRI in BI-RADS D women significantly reduces interval cancer vs mammography alone |
| SOUND Trial | 2023/2026 | In cT1N0 + negative axillary US: omitting SLNB is safe — does not impact survival |
| WISDOM Study | 2025 | Risk-stratified screening (PRS + clinical factors) non-inferior to annual; fewer benign biopsies |
Viva Questions & Clinical Pearls
Q: Average-risk 40yo in HK — what do you do?
A: Use HK Risk Assessment Tool. NCCN recommends annual from 40; HK CEWG less certain for average risk — shared decision-making. Discuss benefits/harms.
Q: Patient has BI-RADS D breasts. What supplemental imaging?
A: Supplemental MRI per DENSE trial. Breast density is both a masking factor AND an independent risk factor for breast cancer.
Q: BRCA1 carrier — screening protocol?
A: Age 25–29: annual MRI only. Age 30+: annual mammography + annual MRI. Discuss RRBSO by age 35–40 for ovarian cancer prevention.
Q: Examiner asks about MASAI trial — what do you say?
A: Level 1 evidence (The Lancet 2026). AI-supported screening reduces radiologist workload ~44%, reduces interval cancers by 12%. Use as triage tool, not replacement for radiologist.
| Histological Type | Key Features | Clinical Pearls |
|---|---|---|
| Invasive NST (No Special Type) | Previously IDC. Most common (70–80%). Diagnosis of exclusion. | Diverse biology — check grade, ER/PR/HER2, Ki-67 |
| Invasive Lobular Carcinoma (ILC) | Loss of E-cadherin (CDH1). Single-file discohesive cells. Multicentric, bilateral. | Metastasises to GI tract, peritoneum, ovaries. Lower FDG uptake → prefer WB-MRI staging. |
| Tubular | >90% tubules, ER+/HER2-. Excellent prognosis. | Special type — better prognosis. Chemo often omitted if N0. |
| Mucinous/Colloid | Cells floating in mucin pools. Pure = excellent prognosis. | Pure mucinous: low nodal risk. Mixed mucinous = standard treatment. |
| Metaplastic Carcinoma | Spindle/squamous/bone-forming components. Aggressive. Often TNBC. | Highly chemoresistant. Consider genomic sequencing (PIK3CA, PTEN). |
| Invasive Micropapillary | High lymphovascular invasion. High nodal involvement. | Worse prognosis despite small size — aggressive axillary management. |
| Medullary-like | TILs-rich, often BRCA1-associated. | Paradoxically better prognosis. High TILs = better pCR to NACT. |
The New HER2 Landscape (2025–2026)
| Category | Definition | Treatment Implication |
|---|---|---|
| HER2-Positive | IHC 3+ OR IHC 2+/ISH+ | Trastuzumab, pertuzumab, T-DM1, T-DXd |
| HER2-Low | IHC 1+ OR IHC 2+/ISH- | T-DXd eligible (DESTINY-Breast04) |
| HER2-Ultralow (New 2026) | IHC 0 with faint membrane staining <10% cells (>0 and <1+) | T-DXd benefit per DESTINY-Breast06 |
| HER2-Zero (Null) | Truly no staining | No ADC eligibility currently |
PAM50 Intrinsic Subtypes
- Luminal A: ER-high, PR-high, HER2-neg, Low Ki-67 — best prognosis
- Luminal B: ER-pos, Low PR, HER2-pos/neg, High Ki-67 — more aggressive
- HER2-Enriched: Most are IHC 3+
- Basal-like: Overlaps with TNBC
PD-L1 & TILs
- PD-L1: CPS ≥10 required for pembrolizumab in TNBC (KEYNOTE-355)
- TILs: Now standard reporting in TNBC and HER2+
- High TILs (>20–30%) → better chemo response and survival
- Medullary-like tumors: TILs-rich = better prognosis paradox
Viva Questions & Clinical Pearls
Q: Pathology shows ILC — what changes in your workup?
A: Confirm with E-cadherin IHC (loss = ILC). Lower threshold for bilateral MRI. Unique metastatic sites: GI tract, ovaries, peritoneum. FDG-PET may be falsely negative → prefer WB-MRI for staging.
Q: Biopsy shows TNBC IHC 0 — is T-DXd relevant?
A: Re-review slides for HER2-Ultralow: faint staining in <10% cells (>0 and <1+). DESTINY-Breast06 shows T-DXd benefit in HR+ MBC even at ultralow level.
Q: What is metaplastic carcinoma — how do you treat it?
A: Spindle + squamous = metaplastic. TNBC subtype but highly chemoresistant. Consider genomic sequencing for PIK3CA, PTEN actionable mutations. Clinical trial preferred.
Q: Grade vs Stage — patient asks which is worse: G3 1cm or G1 3cm?
A: Grade 3 1cm often carries worse prognosis — biology trumps size in early stage. Use Oncotype DX for any Grade 2–3 uncertainty in N0/N1 ER+ patients.
Clinical Decision Support
Integrated calculators to support workup and treatment decisions in breast cancer management. Use Mirels' Score for long bone fracture risk (≥9 = prophylactic fixation) and SINS Score for spinal instability (≥7 = surgical consult).
Clinical reference only. These guidelines are intended to support, not replace, clinical judgment. Treatment decisions should be individualised based on patient-specific factors, local protocols, and multidisciplinary team input. Always apply clinical judgment and consult local institutional guidelines where applicable. Data reflect published literature as of April 2026.