Initial Site of Distant Metastasis in Breast Cancer
The most common initial site of distant metastasis in breast cancer is the bones (c). According to the American College of Radiology guidelines, bone is historically the most likely site of breast cancer metastases, accounting for 51% of cases, followed by liver/soft tissue (19%), pleura (16%), lung (14%), and brain (4%) 1.
Evidence Supporting Bone as the Primary Metastatic Site
The predominance of bone metastases in breast cancer is well-established in the medical literature:
The 2024 ACR Appropriateness Criteria explicitly states that "bone is the most common site for breast cancer metastasis; up to 70% of women with stage IV disease have bone metastasis" 1.
Population-based studies show that bone metastases account for 62.5% of patients with initial metastatic breast cancer 2.
Historical data consistently demonstrates that bone is the most frequent first site of distant spread (51%), followed by lung (17%), brain (16%), and liver (6%) 3.
Factors Influencing Metastatic Patterns
The pattern of metastasis varies by breast cancer subtype:
Hormone receptor status: Bone metastases are more common in hormone receptor-positive (HR+) breast cancers. Up to 82% of patients who develop bone metastases have either ER and PR or ER positivity in the primary tumor 1.
Molecular subtypes:
- Luminal cancers (HR+/HER2-) have a propensity to metastasize first to bone
- HER2-enriched cancers tend to spread to liver and lung
- Triple-negative/basal-type cancers more commonly metastasize to liver and brain 1
Tumor grade: Well-differentiated (grade 1) tumors are more likely to relapse in bone than in visceral sites 4.
Clinical Implications
Understanding that bone is the most common site of initial metastasis has important clinical implications:
Survival impact: Patients with bone-only metastases have a better prognosis compared to those with visceral metastases. Median survival is approximately 24 months for disease confined to the skeleton versus 3 months for liver metastases 4.
Screening approach: Bone scintigraphy (bone scan) is recommended as the initial imaging modality for evaluating suspected bone metastasis, with high sensitivity (96%) 5.
Complications: Bone metastases can lead to significant morbidity through skeletal-related events including pain, pathologic fractures, spinal cord compression, and hypercalcemia 6, 7.
Pitfalls and Caveats
The predilection for bone metastases does not apply to all breast cancer subtypes, particularly basal-like/triple-negative tumors, which more commonly spread to visceral sites 1.
Bone metastases may be missed on standard CT imaging without bone windows or dedicated bone scans.
While bone is the most common site of initial metastasis, many patients will eventually develop metastases at multiple sites as the disease progresses.
Approximately 10% of patients with breast cancer will develop hypercalcemia, with 85% of these cases associated with widespread skeletal involvement 4.
In conclusion, bone represents the most common initial site of distant metastasis in breast cancer, particularly in hormone receptor-positive disease, which comprises the majority of breast cancer cases.