Pathological Investigations for Carcinoma Breast
Core needle biopsy (at least 2-3 cores) with ultrasound or stereotactic guidance is mandatory before any treatment, and must include immunohistochemistry for ER, PgR, HER2, and Ki-67 on the biopsy specimen 1.
Initial Tissue Acquisition
Biopsy Technique
- Core needle biopsy is the gold standard - obtain minimum 2-3 cores under US or stereotactic guidance 1
- Fine-needle aspiration is acceptable only if core biopsy is technically impossible 1
- Never perform excisional biopsy except in rare cases of repeatedly negative core biopsies 1
- Place a marker clip or carbon into the tumor at time of biopsy to ensure correct site resection 1
Special Situations
- Multifocal/multicentric disease: Biopsy ALL lesions separately 1
- Suspicious lymph nodes: Perform US-guided FNA or core biopsy with clip/carbon marking 1
- Preoperative systemic therapy planned: Core biopsy is absolutely mandatory (not optional) to confirm invasive disease and assess biomarkers 1
Mandatory Pathological Assessments
Histological Evaluation
The pathology report must include:
- WHO histological classification and AJCC 8th edition TNM staging 1
- Histological type (invasive carcinoma NOS 70-75%, lobular 12-15%, or one of 18 rare subtypes) 1
- Tumor grade (using standardized grading system)
- Presence/absence of ductal carcinoma in situ (DCIS) 1
- Lymphovascular invasion status
Biomarker Testing (Mandatory on Core Biopsy)
Estrogen Receptor (ER)
- Use standardized methodology: Allred score or H-score 1
- Fixation better controlled on core biopsies than surgical specimens 1
Progesterone Receptor (PgR)
- Essential for luminal subtype classification 1
HER2 Status
- Perform IHC first; if 2+ (ambiguous), reflex to ISH (FISH/CISH/SISH) 1
- Follow ASCO-CAP guidelines strictly 1
- HER2 positive defined as:
- IHC 3+ (>10% complete membrane staining), OR
- ISH: HER2 copies ≥6, OR HER2/CEP17 ratio ≥2 with HER2 copies ≥4, OR HER2/CEP17 <2 with HER2 copies ≥6 1
Ki-67 Proliferation Index
- Provides additional prognostic information, particularly if standardized 1
- Critical for distinguishing luminal A-like from luminal B-like tumors 1
Critical Pitfalls and Retesting Requirements
When to Retest on Surgical Specimen
- If ER/PgR/HER2 all negative on biopsy: Retest on surgical specimen to account for tumor heterogeneity 1
- If HER2 positive on biopsy: Mandatory retesting on surgical specimen for specific tumor types (invasive carcinoma NOS grade I that is ER/PgR-positive, tubular/mucinous/cribriform, adenoid cystic, or secretory carcinoma) 1
- In case of discrepancy between biopsy and surgical specimen, surgical specimen results are definitive 1
Quality Control Issues
- Ensure pathology-imaging concordance - if discordant, repeat imaging and/or obtain additional tissue 2
- Core needle biopsy sensitivity is 97-99% when properly performed 2
Emerging and Supplementary Markers
While not yet routine, consider in appropriate clinical contexts:
- PIK3CA and ESR1 mutations for treatment selection in advanced disease 3
- BRCA/HRD status particularly for triple-negative disease 3
- PD-L1 expression and tumor-infiltrating lymphocytes (TILs) for immunotherapy candidates 3, 4
- Multigene expression assays (Oncotype DX, MammaPrint) for prognostic stratification when indicated 3
Workflow Algorithm
- Suspicious lesion identified → Core needle biopsy (2-3 cores) with marker placement
- Concurrent lymph node assessment if suspicious → FNA or core with marking
- Immediate biomarker testing on core biopsy: ER, PgR, HER2, Ki-67
- If triple-negative on biopsy → Retest on surgical specimen
- If HER2 positive on biopsy → Selective retesting based on tumor characteristics
- Final classification using WHO classification and AJCC TNM staging with prognostic biomarkers
This approach ensures optimal tissue acquisition, accurate diagnosis, and appropriate biomarker assessment to guide treatment decisions that impact mortality and quality of life.