Brain Metastases

A potential complication of advanced-stage cancer, brain metastasis occurs when a tumor spreads from its site of origin to the brain, forming one or more secondary tumors (“mets”). Unlike primary brain tumors, which originate in the brain, metastatic brain tumors form when cancerous cells break away from a tumor in another part of the body, enter the bloodstream or lymphatic system and travel to the brain.

Studies suggest that metastatic brain tumors are much more common than primary brain tumors, affecting 10 to 30% of adults with cancer. Diagnoses are on the rise for several reasons, including enhanced awareness and screening tests. Additionally, new imaging technologies are allowing for earlier and more accurate brain tumor detection. Finally, advancements in systemic therapies and other cancer treatments are helping many cancer patients live longer, increasing the likelihood that cancer cells will spread from the primary tumor to the brain over time.

What causes brain metastasis?

The precise causes of brain metastasis are not fully understood. The mechanisms that allow cancer cells to invade the brain are complex, involving the ability of the cells to survive in circulation, breach the blood-brain barrier and adapt to the unique environment of the brain.

Certain types of cancer are more likely to metastasize to the brain than others. For example, lung cancer is the most common source of brain metastasis, followed by breast cancer and melanoma skin cancer, which has a particularly high tendency to spread to the brain. Secondary brain tumors are also often traced to kidney cancer and colon cancer.

Why does cancer sometimes spread to the brain?

Rapidly dividing cancer cells are often capable of separating themselves from a primary tumor. If tumor cells enter the bloodstream or lymphatic system, the body’s immune system will usually attempt to destroy them. However, if the number of circulating tumor cells is very high, the immune system may become overwhelmed or tolerant of them. Instead of being destroyed, the traveling cancer cells may exit the bloodstream or lymphatic system in another part of the body, and then invade a distant tissue or organ.

The growth rate of a metastatic tumor is unrelated to the growth rate of the primary tumor. For instance, because blood flows directly from the lungs to the brain, lung cancer can spread to the brain very quickly—sometimes so fast that a brain metastasis is detected before the primary lung cancer is diagnosed.

Primary cancers tend to spread to particular organs. Researchers believe these organ preferences may be caused by small attractant molecules (chemokines), which guide the tumor cells to the metastatic sites. Cancer cells may also adhere to certain organs due to the adherent molecules expressed by those organs.

What are the risk factors for brain metastasis?

Scientists have identified certain factors that may increase the risk of cancer spreading to the brain. These include:

• Type of primary cancer – Certain cancers are more prone to metastasizing to the brain, including lung cancer, breast cancer, melanoma, kidney cancer and colorectal cancer.
• Advanced cancer stage – The risk of brain metastasis is higher in patients with advanced or late-stage cancer, particularly when the tumor has already spread to another part of the body.
• Aggressive tumor characteristics – Some cancers grow and spread more rapidly than others. Tumors with a propensity for invasion and metastasis are more likely to reach the brain.
• Inadequate initial cancer control – If the primary cancer is not effectively treated or managed, there is a greater chance of malignant cells traveling to distant organs, including the brain.
• Genetic and molecular factors – Certain genetic mutations and molecular markers in cancer cells may make them more likely to metastasize to the brain. For example, HER2-positive breast cancer and EGFR-mutated lung cancer carry a high risk of brain metastasis.
• Weakened immune system – Individuals with a compromised immune system due to human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS), immunosuppressive medication or cancer treatment may be at heightened risk for brain metastasis because their body may be less able to prevent cancer cells from spreading.
• Young age at cancer diagnosis – While brain metastasis can occur at any age, younger patients with aggressive tumors may be at a higher risk due to the longer potential disease course.

Understanding these risk factors can help in monitoring high-risk patients and detecting metastatic brain cancer early, improving the likelihood of timely intervention and appropriate management of the condition.

What are the symptoms of brain metastasis?

The symptoms of brain metastasis can vary depending on the size, number and location of the mets. For example, a growing tumor can press on sensitive brain tissues and interfere with neurological functions. Warning signs of metastatic brain cancer may include:

• Headaches – Persistent or worsening headaches are a common symptom of brain metastasis. Usually, the headaches become more severe over time and do not respond to conventional pain relievers.
• Seizures – Some patients with brain metastasis experience seizures, which can range from mild twitching to full-body convulsions. Seizures may be the first noticeable sign of metastatic brain cancer, especially in a patient with no prior history of epilepsy.
• Cognitive changes – Memory loss, difficulty concentrating, mental confusion and impaired decision-making can occur if the tumor is located near the cognitive processing areas of the brain.
• Numbness and weakness – A tumor that affects the motor control areas of the brain can cause weakness, numbness or loss of coordination, often affecting one side of the body more than the other.
• Speech and vision problems – Depending on the location of the tumor, brain metastasis may cause difficulty speaking, difficulty understanding spoken language and/or visual disturbances, such as double vision or partial vision loss.
• Personality and behavioral changes – Some patients with brain metastasis experience mood swings, depression, anxiety or unusual personality changes due to the impact of the tumor on the emotional regulation centers of the brain.
• Nausea and vomiting – Tumor growth can increase pressure within the brain, potentially leading to nausea, vomiting and dizziness, particularly in the morning or when changing body positions.
• Loss of balance and muscle coordination – Brain metastasis can affect the cerebellum and other motor control centers of the brain, which may cause difficulty walking, frequent falls or loss of fine motor skills.

These symptoms can appear suddenly or develop gradually depending on the growth rate of the tumor and the affected areas of the brain. Any new or unexplained neurological symptoms should be promptly discussed with a physician to help ensure early detection and appropriate treatment of brain metastasis.

How is brain metastasis diagnosed?

Brain metastasis is usually diagnosed through a combination of clinical evaluation, medical history review and advanced imaging tests. The diagnostic process may include:

• Neurological examination – The physician will evaluate the patient’s reflexes, coordination, balance, vision and cognitive function to check for neurological impairments that may indicate brain metastasis.
• Magnetic resonance imaging (MRI) – Contrast-enhanced MRI scans can provide detailed visuals of the brain structures, helping the physician identify the size, number and location of metastatic brain tumors.
• Computed tomography (CT) – CT scans may be used if an urgent evaluation is needed or MRI is not available. This imaging modality can also be useful for detecting brain swelling or bleeding caused by a metastatic tumor.
• Positron emission tomography (PET) – By highlighting areas of the body with high metabolic activity, such as tumor sites, a PET scan can help the physician determine whether cancer has spread beyond the brain. This imaging test may be combined with CT scans to help the physician assess the extent of metastasis throughout the body.
• Biopsy – If imaging tests are inconclusive, a biopsy may be performed to confirm the presence of metastatic brain cancer. This procedure involves removing a small sample of brain tissue or tumor cells for microscopic analysis by a pathologist. While a biopsy is a highly accurate diagnostic test, it may not be needed if there is a known history of cancer elsewhere in the body.
• Lumbar puncture (spinal tap) – In rare cases, a lumbar puncture may be used to allow the physician to examine a sample of cerebrospinal fluid for cancerous cells, especially if symptoms suggest metastasis to the protective membranes surrounding the brain and spinal cord (meninges).

After a diagnosis of brain metastasis is confirmed, additional tests may be performed to help the physician pinpoint the origin of the primary cancer if it has not already been identified.

How is brain metastasis treated?

Brain metastasis treatment can vary based on several factors, including the number, size and location of the mets, the characteristics of the primary tumor and the overall health of the patient. Options may include:

Radiation therapy for brain metastasis

A cornerstone treatment for brain metastasis, radiation therapy can be delivered in two main ways:

• Whole-brain radiation therapy (WBRT) – Often used to address multiple mets, WBRT targets the entire brain to treat both visible and microscopic tumors.
• Stereotactic radiosurgery (SRS) – A highly precise form of radiation therapy, SRS may be used to treat a limited number of brain tumors while minimizing exposure to the surrounding healthy tissues.

Surgery for brain metastasis

Surgery may be an option for a patient with a single brain tumor or a limited number of mets that can be safely accessed and removed. The procedure may be followed by radiation therapy to target any remaining microscopic cancer cells.

Systemic therapies for brain metastasis

Certain cancers that metastasize to the brain may respond well to systemic treatments, including:

• Targeted therapy – Specialized drugs can target specific genetic mutations or proteins in cancer cells, such as HER2-targeted therapies for breast cancer metastases.
• Immunotherapy – Checkpoint inhibitors and other immune-based treatments can be effective for certain cancers, such as lung cancer and melanoma, that have spread to the brain.
• Chemotherapy – Although traditional chemo has limited effectiveness in treating brain metastases due to the blood-brain barrier, some drugs can penetrate this selective filtering mechanism and may be used in specific cases.

Supportive care for brain metastasis

In addition to therapeutic options, many patients with secondary brain tumors benefit from supportive care. For example, corticosteroids can help reduce brain swelling and alleviate the associated symptoms, such as headaches and neurological complications. Anti-seizure medications may also be prescribed for a patient experiencing seizures due to brain metastasis.

Brain metastasis treatment is tailored to each patient’s specific condition and goals, often involving a combination of therapies for heightened effectiveness. Advances in treatment, including precision medicine and emerging therapies, continue to improve outcomes and quality of life for patients with secondary brain tumors.

Brain Metastases FAQs

The following pages answer frequently asked questions about cancers that spread to the brain:

• Debunking the myths about brain metastasis
• Diet and lifestyle tips for patients with brain metastases
• Questions to ask your medical team about brain metastases
• How brain metastases can affect your daily life and how to adapt

Benefit from world-class care at Moffitt Cancer Center

At Moffitt, the scientists and clinicians in our comprehensive Neuro-Oncology Program are continually investigating new and better ways to treat brain metastasis through clinical trials, and we are making great strides. Our research breakthroughs have received national acclaim, including a Comprehensive Cancer Center designation by the National Cancer Institute.

If you would like to learn more about brain metastasis, you can request an appointment with a specialist in Moffitt’s Neuro-Oncology Program by calling 1-888-663-3488 or submitting a new patient registration form online. We do not require referrals.