Laboratory and Diagnostic Testing for Newly Diagnosed Breast Cancer
For newly diagnosed breast cancer, order complete blood count, comprehensive metabolic panel (including liver and renal function, alkaline phosphatase, calcium), bilateral mammography with breast ultrasound, and core needle biopsy with biomarker assessment (ER, PR, HER2, Ki67), but do not routinely order metastatic imaging unless the patient has high tumor burden, aggressive biology, or symptoms suggesting distant disease. 1
Essential Laboratory Studies
Baseline blood work should include: 2
- Complete blood count 2, 1
- Liver function tests 2
- Renal function tests 2
- Alkaline phosphatase 2
- Calcium levels 2
Menopausal status verification is mandatory if uncertain, measured by serum estradiol and follicle-stimulating hormone levels 2, 1. This determination is critical for treatment planning, particularly for endocrine therapy decisions 2.
Important Caveat About Routine Labs
Multiple high-quality studies demonstrate that routine preoperative CBC and liver function tests have extremely low yield in early-stage, clinically node-negative breast cancer 3, 4. In one study of 1,082 patients with stage I/II disease, abnormal LFTs prompted 84 additional imaging studies but detected zero cases of metastatic disease 4. The positive predictive value for occult metastasis is only 1.1% for LFTs and 1.3% for CBC 3. However, these tests remain recommended by ESMO guidelines before surgery and systemic therapy 2, likely because they establish baseline values for monitoring treatment toxicity rather than detecting metastases.
Pathological Tissue Assessment
Core needle biopsy is mandatory before any treatment and must include: 2, 1
- Estrogen receptor (ER) status by immunohistochemistry 2, 1
- Progesterone receptor (PR) status by immunohistochemistry 2, 1
- HER2 status by immunohistochemistry and/or in situ hybridization 2, 1
- Histological type and grade per WHO classification 1
- Ki67 proliferation index 2, 1
HER2 testing requires specific attention: If IHC shows 2+ (equivocal), confirm with FISH or other in situ hybridization 2. The updated ASCO-CAP guidelines define HER2 positivity as IHC 3+ when >10% of cells show complete membrane staining (previously 30%), or FISH positive if HER2 gene copies ≥6 or HER2/chromosome 17 ratio ≥2 2.
Imaging Studies
Bilateral mammography with breast ultrasound is essential 2, 1. The added value of ultrasound is well-proven for diagnostic workup 2.
Breast MRI is not routinely recommended but may be considered in specific situations: 2
- Familial breast cancer with BRCA mutations 2
- Breast implants 2
- Lobular cancers 2
- Before neoadjuvant chemotherapy 2
- When conventional imaging findings are inconclusive 2
Metastatic Staging: When to Order Additional Imaging
Do NOT routinely order metastatic workup for early-stage disease 2. In asymptomatic patients, there is Level I evidence that routine chest X-rays, bone scans, liver ultrasound, CT scans, or PET/CT do not produce survival benefit 2.
Order metastatic imaging (chest CT, abdominal CT/ultrasound, bone scintigraphy) ONLY for: 2
- Clinically positive axillary nodes 2
- Large tumors (≥5 cm) 2
- Aggressive tumor biology 2, 1
- Clinical signs or symptoms suggesting metastases 2
- Abnormal laboratory values suggesting metastases 2
PET-CT may be useful when conventional methods are inconclusive and can replace traditional imaging for staging in high-risk patients, particularly those with locally advanced or inflammatory disease 2. However, PET-CT has limited specificity for locoregional staging compared to sentinel lymph node biopsy 2.
Critical Pitfall About Chest X-rays
Chest X-rays are no longer recommended in current NCCN guidelines for early-stage breast cancer 3, 4. One study found that routine chest X-rays in clinically node-negative patients had a positive predictive value of only 1.5% for occult metastasis 3. Despite this, many centers continue ordering them unnecessarily, adding cost without clinical benefit 4.
Tumor Markers: Not Recommended at Diagnosis
Do NOT order serum tumor markers (CA 15-3, CEA, CA 27-29) for initial diagnosis or staging 2, 5. These markers lack sensitivity for early disease and specificity for breast cancer 6, 5. CA 15-3 and CEA are only useful for monitoring treatment response in metastatic disease that cannot be assessed by conventional imaging 5.
Additional Genetic Testing
Consider germline BRCA1/2 testing for: 1
- Triple-negative breast cancer 1
- Young age at diagnosis 1
- Family history of breast, ovarian, or related cancers 1
Gene expression profiles (Oncotype DX, MammaPrint, Prosigna, Breast Cancer Index) may provide prognostic and predictive information for ER-positive disease to guide chemotherapy decisions 2, 1. These are not part of initial diagnostic workup but are ordered after pathology confirms hormone receptor-positive disease to aid treatment planning 2.
Clinical Assessment Requirements
Complete medical history must document: 1