What are the most common primary solid tumors that metastasize to the brain in adult patients?

Common Primary Cancers That Metastasize to the Brain

Lung cancer is the single most common source of brain metastases, accounting for approximately half of all cases, followed by breast cancer, melanoma, and renal cell carcinoma. 1, 2

Primary Tumor Types by Frequency

Lung Cancer (Most Common)

• Lung cancer represents roughly 43-50% of all brain metastases, making it the dominant primary source 1, 2, 3
• Small cell lung cancer (SCLC) has the highest propensity for brain spread, with approximately 80% of SCLC patients developing brain metastases by time of death 2
• Non-small cell lung cancer (NSCLC) also frequently metastasizes to the brain, particularly adenocarcinoma subtypes 1
• The incidence proportion of patients with metastatic lung adenocarcinoma who have brain metastases on initial diagnosis exceeds 25% 1

Breast Cancer (Second Most Common)

• Breast cancer accounts for approximately 20% of all brain metastases 3
• Within 1 year of initial cancer diagnosis, 5-7% of breast cancer patients develop brain metastases 1
• At initial diagnosis of metastatic disease, approximately 7% of breast cancer patients have brain involvement 1
• HER2-positive breast cancer carries particularly high risk, with approximately 50% of patients who die from HER2-positive disease developing intracranial metastases 2
• Infiltrating lobular subtype has higher rates of leptomeningeal spread 1

Melanoma (Third Most Common)

• Melanoma comprises approximately 8% of brain metastases but has the highest predilection for brain metastasis relative to its overall incidence 2, 3
• The incidence proportion of patients with metastatic melanoma who have brain metastases on initial diagnosis exceeds 25% 1
• BRAF-mutant melanoma has been incorporated into prognostic scoring systems due to its clinical significance 1

Renal Cell Carcinoma (Fourth Most Common)

• Renal cell carcinoma accounts for approximately 5% of brain metastases 3
• Within 1 year of initial cancer diagnosis, 5-7% of renal cell cancer patients develop brain metastases 1
• At initial diagnosis of metastatic disease, approximately 10% have brain involvement 1

Other Primary Sources

• Colorectal cancer accounts for approximately 4% of brain metastases 3
• Gastrointestinal cancers (non-esophageal) have approximately 2% incidence of brain metastases at initial metastatic diagnosis 1
• Head and neck cancers have approximately 5% incidence of brain metastases at initial metastatic diagnosis 1
• Esophageal cancer has approximately 5% incidence of brain metastases at initial metastatic diagnosis 1

Critical Clinical Context

Underestimation of True Incidence

• The reported incidence for many cancers is significantly underestimated because routine brain screening is not performed for most cancer types, and brain metastases are often discovered only when symptomatic 2
• Autopsy series reveal that asymptomatic leptomeningeal involvement averages 20% across all cancers, far higher than clinical detection rates of 4-7% 1

Unknown Primary

• In up to 15% of patients presenting with brain metastases, no primary tumor can be identified despite thorough evaluation 2
• These patients may benefit from surgical resection to establish diagnosis 1

Temporal Trends

• Recent data from 2008-2018 shows a decreasing proportion of brain metastases from breast cancer (23.8% decrease) and melanoma (46.7% decrease), likely reflecting improved systemic therapies 3
• Brain metastases from rare primary sites increased by 34.4% over the same period 3
• The overall incidence of brain metastases has increased over time due to expanding MRI availability and improved systemic control of extracranial disease 1

Important Pitfalls to Avoid

• Do not assume absence of brain metastases based on initial negative imaging alone—a substantial proportion of patients without brain metastases at initial cancer diagnosis will develop intracranial disease during their clinical course 2
• Do not overlook the need for surveillance imaging in high-risk populations, particularly patients with SCLC, HER2-positive breast cancer, BRAF-mutant melanoma, and EGFR-mutant or ALK-rearranged NSCLC 4
• Do not confuse relative frequency with absolute risk—while melanoma has the highest propensity for brain metastasis relative to its incidence, lung cancer causes far more total cases due to its higher overall prevalence 2, 3