What are the recommended staging investigations for Carcinoma (Ca) of the breast?

Staging Investigations for Breast Cancer

For early-stage breast cancer (Stage I-II with ≤3 positive nodes), routine distant metastasis staging with CT scans and bone scans is not recommended, as these patients should only undergo clinical examination, laboratory tests, and bilateral breast imaging. 1

Essential Baseline Workup for All Patients

All newly diagnosed breast cancer patients require the following core investigations:

• Complete history and physical examination including assessment of menopausal status, family history, and clinical signs of metastatic disease 1
• Laboratory tests including complete blood count, liver function tests, renal function tests, alkaline phosphatase, and calcium levels 1
• Bilateral mammography and ultrasound of both breasts and regional lymph nodes 1
• Core needle biopsy (ultrasound or stereotactic-guided preferred) to confirm invasive disease and obtain tissue for biomarker analysis 1, 2
• Biomarker assessment from biopsy specimen including ER, PR, HER2 status, and Ki67 proliferation index 1, 2

Risk-Stratified Approach to Distant Metastasis Staging

The key to appropriate staging is risk stratification based on clinical and pathological features:

Low-Risk Patients (No Distant Staging Required)

• Stage I disease 1
• Stage II with ≤3 positive lymph nodes 1
• Asymptomatic patients without laboratory abnormalities 3

For these patients, routine chest CT, abdominal imaging, and bone scans provide no survival benefit and should be avoided 1.

High-Risk Patients (Full Distant Staging Indicated)

Distant metastasis staging is recommended for patients with:

• Large tumors (≥5 cm) 3, 1
• Clinically positive axillary nodes or ≥4 positive nodes 3, 1
• Stage III disease 1
• Clinical signs, symptoms, or laboratory abnormalities suggesting metastases 3, 1

For high-risk patients, the minimum staging workup includes:

• Chest CT 3, 1
• Abdominal imaging (CT, ultrasound, or MRI) 3, 1
• Bone scintigraphy 3, 1

Role of PET-CT in Staging

PET-CT should NOT be used for routine staging of early breast cancer due to high false-negative rates for small lesions (<1 cm) and poor sensitivity for axillary nodes 1.

PET-CT may be considered only in specific circumstances:

• When conventional imaging is inconclusive 3, 1
• Locally advanced or inflammatory breast cancer in patients being considered for neoadjuvant chemotherapy 1
• As an alternative to CT plus bone scan in metastatic disease staging 3

The evidence shows PET-CT has limited specificity compared to sentinel lymph node biopsy for locoregional staging 3.

Metastatic Disease Staging

For patients with confirmed or suspected metastatic breast cancer, a different approach applies:

• Biopsy of metastatic lesion to confirm diagnosis and reassess tumor biology (ER, PR, HER2) 3
• Minimum imaging includes CT chest and abdomen plus bone scintigraphy 3
• PET-CT may replace CT and bone scans in the metastatic setting 3
• Brain imaging for symptomatic patients or when CNS metastases would alter treatment choice 3

Additional Specialized Assessments

Cardiac Function

Cardiac ultrasound or MUGA scan is mandatory before starting anthracyclines and/or trastuzumab therapy 1.

Genetic Testing

BRCA1/BRCA2 testing should be offered to patients with:

• Strong family history of breast, ovarian, pancreatic, or high-grade prostate cancer 1
• Personal history of ovarian cancer, second breast cancer, or male breast cancer 1
• HER2-negative metastatic breast cancer (for treatment selection) 3

Biomarker Testing in Metastatic Disease

For patients with metastatic disease, additional biomarkers guide treatment:

• PIK3CA mutation status in ER-positive/HER2-negative disease 3
• PD-L1 status in triple-negative breast cancer 3
• Germline BRCA mutations in HER2-negative metastatic disease 3

Postoperative Pathological Assessment

The surgical specimen must be evaluated according to the pTNM system including:

• Number, location, and maximum diameter of tumors 3, 1
• Total number of removed and positive lymph nodes with extent of metastases (isolated tumor cells, micrometastases, or macrometastases) 3, 1
• Histological type and grade according to WHO classification 3, 2
• Confirmation of biomarker analysis (ER, PR, HER2, Ki67) 3, 1

Critical Pitfalls to Avoid

• Over-staging early disease: Intensive surveillance imaging in asymptomatic Stage I patients provides no survival benefit 1
• Routine use of PET-CT: This leads to high false-positive rates and unnecessary interventions in early-stage disease 1
• Incomplete biomarker testing: If ER/PR and HER2 are negative in biopsy, retest in surgical specimen to account for tumor heterogeneity 3
• Using different imaging modalities for monitoring: The baseline imaging modality should be consistently applied for disease monitoring to ensure comparability 3