Breast Cancer and Metastasis to the Brain

What happens if your breast cancer spreads to your brain? Sometimes, brain metastases are found when breast cancer is first diagnosed, but the majority of the time, brain metastases occur as a distant recurrence of an early-stage breast cancer that was treated in the past. What symptoms may occur, and what treatment options are available if your breast cancer spreads to your brain?

Overall, brain metastases occur in 15% to 24% of women with metastatic breast cancer. As survival improves, however, this number is expected to increase.

Definition and Overview

The brain is one of the more common sites to which breast cancer spreads, along with the bones, lungs, and liver. When breast cancer spreads to the brain it is considered stage 4 or metastatic breast cancer. While there is no cure for brain metastases, the condition is treatable, and treatments may improve symptoms, help with quality of life, and sometimes extend survival.

When breast cancer spreads to the brain it is still breast cancer. If you were to take a sample of the mass or masses in the brain, they would contain cancerous breast cells, not brain cells. Brain metastases are not called "brain cancer" but rather "breast cancer metastatic to the brain" or "breast cancer with brain metastases." Hence, treatments are those which are used for advanced breast cancer, not those used for brain cancer.

In the past, brain metastases were never considered curable. The goal of treatment was "palliative," meaning to control symptoms but not attempt to cure the tumor. In recent years, the concept of "oligometastases" has been addressed. That is, when a person has only a single or a few metastases, and no significant metastases to other regions of the body, a curative approach to eliminate the metastases may be tried. In other words, while treatment often remains palliative, especially for those with several or widespread metastases, for some people, potentially curative therapy may be an option.

Symptoms

There are a number of different symptoms that may herald the presence of brain metastases. Sometimes there are no symptoms, and these metastases are only found when an imaging test, such as a brain MRI, is done. When symptoms are present they may include:

• Headaches: Headaches due to brain metastases can be similar to tension headaches or migraine headaches, but may be accompanied by other neurological symptoms as well (see below). In one study, headaches were present in 35% of people when brain metastases were discovered. Headaches related to brain metastases tend to be worse with lying down, worse in the morning or after a nap, and worse with coughing, sneezing, or bearing down for a bowel movement. That said, it can be difficult to distinguish between "normal" headaches and those due to metastases without imaging studies.
• Vomiting: Vomiting (with or without nausea) was the second most common symptom of brain metastases in one study. It may occur suddenly without any preceding nausea and is usually worst after lying down and in the morning. Vomiting due to brain metastases tends to become worse and more frequent over time.
• Weakness of one side of the body, numbness, or tingling in the extremities: Hemiparesis, weakness or paralysis of one side of the body, was the third most common neurological symptom of brain metastases in one study.
• Vision changes: Problems such as double vision, blurry vision, seeing flashes of light, or loss of vision may occur.
• Seizures: Seizures may be tonic-clonic (grand mal) in which the whole body shakes and a person loses consciousness; partial seizures, in which a limb, such as an arm, shakes; or other types of seizures, for example, those in which a person appears to stare off into space.
• Loss of balance: Loss of balance may first appear to be clumsiness, with running into counters or fender benders as symptoms.
• Psychological changes: Personality changes, behavior changes, mood changes, or impaired judgment may occur.

Risk Factors/Causes

Nobody is sure why some people develop brain metastases and others do not. We do know of some risk factors, however. Brain metastases are more likely in young women with breast cancer, and the incidence is exceptionally high in those diagnosed before the age of 35. Tumors that are more likely to spread to the brain include those with a higher tumor grade, those which are HER2 positive and estrogen receptor negative, and those which are triple negative.

Breast cancer is more likely to spread to the brain for those with larger breast tumors (greater than 2 cm in diameter), as well as for people who have positive lymph nodes at the time of their initial diagnosis. A shorter time between the original early-stage cancer and the recurrence is also linked with a greater risk of brain metastases.

Diagnosis

MRI is the most commonly used imaging technique to detect brain metastases; CT scans of the head may be used for those who are unable to have an MRI performed (for example, those with pacemakers), but CT scans are less effective in determining the presence of brain metastases. The diagnosis is usually made based on imaging findings and a history of breast cancer, but a biopsy may be needed. Since receptor status can change (whether a tumor is estrogen receptor, progesterone receptor, or HER2 positive) with metastases, a biopsy may be needed to choose the most appropriate treatment options.

The most common locations of brain metastases are the cerebellum (the part of the brain which controls balance) and the frontal lobes. At least half of people diagnosed with brain metastases from breast cancer will have multiple metastases present.

Treatment

Treatment options for brain metastases can be broken down into systemic treatments, those which treat cancer anywhere in the body, and local treatments, those which specifically address brain metastases. In addition to treatments used to address the cancer itself, steroids are often used to reduce brain swelling, and can sometimes significantly reduce side effects.

One significant problem in treating brain metastases is that many drugs are unable to penetrate the blood-brain barrier. The blood-brain barrier is a tight network of capillaries that is designed to keep toxins out of the brain. Unfortunately, it is also very effective at keeping chemotherapy drugs, and some other medications out of the brain. Studies are currently looking at methods to increase the permeability of the blood-brain barrier.

In addition to steroids and systemic or local treatments for brain metastases, it's important to address the other symptoms related to metastatic cancer, such fatigue, loss of appetite, depression, and more. Your oncologist may recommend a palliative care consult, and this can be frightening if you are not familiar with the field. Palliative care is not the same as hospice, but is a treatment approach used to treat the physical, emotional, and spiritual symptoms that go along with a diagnosis of cancer. Palliative care may be helpful even with highly curable tumors.

Systemic Options

Systemic treatment options are those used to address your breast cancer no matter where it is located in your body. Whether or not you have local treatments for your brain metastases, the mainstay of treatment is usually these therapies. Systemic treatments for metastatic breast cancer may include:

Chemotherapy

Chemotherapy is often used for metastatic breast cancer, usually using different drugs than you had if you had chemotherapy previously. There are many different options or "lines" of therapy which can be used. As noted, many chemotherapy agents do not penetrate the blood-brain barrier, but frequently metastases to other regions are present along with brain metastases. It may also help reduce the risk of further metastases to the brain.

Hormonal therapy

Hormonal therapies for metastatic breast cancer may be recommended if your tumor is estrogen receptor positive. The use of these drugs depends on whether you were on hormonal therapy previously, and if so, which medication you were taking. When breast cancer metastasizes it's not uncommon for the receptor status to change, for example, a previously estrogen receptor positive tumor may be estrogen receptor negative and vice versa. It's usually assumed that if you were on a particular hormonal therapy when your cancer metastasized, that the tumor is resistant to that drug. Unlike many treatment options, tamoxifen and aromatase inhibitors do appear to cross the blood-brain barrier

Targeted therapies

Treatment options for metastatic HER2 positive breast cancer depend on what, if any, medication you were on when your tumor metastasized. Like estrogen receptor status, HER2 status can change, so that tumor which was HER2 positive before may be HER2 negative when it spreads to the brain and vice versa.

Two of the newer drugs, which have been found to be very effective are:

• Tukysa (tucatinib): HER2 is a type of protein called a kinase. Tukysa is a kinase-inhbitor, hence it blocks these proteins. It is taken in pill form, usually twice a day, and is typically given along with trastuzumab and the chemotherapy drug capecitabine after at least one other anti-HER2 targeted drug has been tried.
• Enhertu (fam-trastuzumab deruxtecan): This antibody-drug conjugate can be used to treat HER2-positive and HER2-low breast cancers that cannot be surgically removed or that have metastasized. It is administered by IV, typically after at least one other anti-HER2 targeted drug or chemotherapy has been tried.

For those who have not previously received HER2 targeted therapy, treatment with either Herceptin (trastuzumab) or Perjecta (pertuzumab) can improve survival. If brain metastases develop while someone is taking Herceptin (or within 12 months of stopping the drug), the drug T-DM1 (trastuzumab emtansine) was found to significantly improve survival. Unfortunately, HER2 targeted therapies do not usually cross the blood-brain barrier.

The combination of Tykerb (lapatinib) and Xeloda (capecitabine) may also be used, but seems to lead to only modest improvement with considerable toxicity (even though these drugs do appear to cross the blood-brain barrier). It appears that Tykerb might work better when combined with Xeloda than when used alone.

Clinical trials

Combinations of the above treatments, as well as newer categories of drugs such as immunotherapy drugs and PARP inhibitors, are being studied in clinical trials for stage 4 breast cancer

Local Options

Local treatments are those designed to treat the brain metastases specifically and are most often recommended if brain metastases are causing significant symptoms, or if only a few metastases are present with the goal to eradicate the metastases. When many metastases are present, the goal is to reduce symptoms (palliative). With only a few metastases, eradication of the metastases may be attempted with a goal of improving survival (with a curative intent). In general, it's felt that more intensive local treatments (such as SBRT and metastasectomy) should be considered primarily for those people who are expected to survive more than 6 to 12 months.

Whole Brain Radiotherapy (WBRT)

Whole brain radiotherapy has fallen out of favor in recent years because of the side effects. It is most often recommended now for people who have widespread brain metastases which are causing significant symptoms. Cognitive changes, such as problems with memory, immediate recall, and verbal fluency are very common, and frustrating for those who have to cope with these symptoms. Since a good quality of life is often the most important goal in treating metastatic breast cancer, the use of WBRT needs to be carefully weighed with regard to benefits and risks. Recently, the use of Namenda (memantine) along with WBRT has been found to reduce the cognitive decline often seen.

Surgery (Metastasectomy)

Surgery to remove a single or only a few metastases (called a metastasectomy) has been used in recent years and may improve survival when used for people who are good candidates for the procedure (have only a few metastases and are in otherwise good health). Surgery may be a better option (than SBRT below) for large metastases (greater than 3 cm in diameter). Unlike SBRT, surgery has immediate results which can reduce brain swelling. There is, however, a greater risk of neurological damage, as well as the risk of "tumor spill" (spreading the cancer cells through the brain) with surgery.

Stereotactic Body Radiotherapy (SBRT)

Also referred to as "Cyberknife" or "gamma knife," stereotactic body radiotherapy or SBRT uses a high dose of radiation to a small area of tissue to attempt to eradicate metastases. It is usually used when only a few metastases are present, but some centers have treated people with up to 10 metastases at a time. The procedure can also be repeated to treat additional metastases which are present or which occur over time. SBRT can be a better option than surgery for metastases which are deep in the brain, or in sensitive regions where surgery would cause too much damage to healthy brain tissue. It is most effective with small metastases, and surgery may be a better option for metastases greater than 3 cm in diameter. There is less cognitive decline seen with SBRT than with whole brain radiotherapy, although some side effects, such as radiation necrosis, may occur.

Other Possible Options

Other potential treatments for brain metastases that have not been well established include radiofrequency ablation (RFA) and hyperthermia.

Metastases in More Than One Region

While in the past, local treatment of brain metastases was most often considered if there were not other sites of metastasis, some believe that treatment of oligometastases in more than one site may also result in improved survival. Such treatments, referred to as "radical radiation" therapy for oligometastatic breast cancer, are now being evaluated in clinical trials. Thus far, it's thought that, for appropriately selected people, long-term progression-free survival with minimal toxicity may be possible for some people with only a few metastases to different sites including the brain, lungs, bones, and liver.

Prognosis

Brain metastases tend to be fast-growing. A 2020 study found that it takes 86 days for brain metastases from breast cancer to double in size.

The prognosis for stage 4 breast cancer which has spread to the brain is not what we would wish for, especially if extensive metastases are present. That said, brain metastases due to breast cancer have a better prognosis than brain metastases due to several other solid cancers.

Historically, survival with brain metastases was only around 6 months but this is changing. A 2016 study found that overall survival for breast cancer with brain metastases (all types combined) was a little over 2 years, with a life expectancy of 3 years for those with HER2 positive tumors. It's too soon to know how this will change with treatments such as SBRT and metastasectomy, but early studies are promising. It's also important to note that there are long-term survivors, and roughly 15% of people with metastatic breast cancer live at least 10 years.

Coping

Coping with brain metastases can be challenging both from the standpoint of having metastatic breast cancer, and the symptoms they may cause. Oncology is changing rapidly, and it's helpful to learn all you can about your disease so that you can play an active role in your care. Ask a lot of questions. Take a moment to learn how to research your cancer. Ask about any clinical trials which may be available. There are also clinical trial matching services available in which nurse navigators can help you determine (free) if there are any clinical trials anywhere in the world that might be applicable to your particular cancer. As noted above, some studies are finding that long-term survival may be possible even with metastases, but many of the new approaches are still considered experimental. It's important to be your own advocate in your cancer care.

It's important to take care of yourself emotionally as well. Ask for help, and allow people to help you. Nobody can face metastatic cancer alone. Consider taking part in a support group or join one of the online metastatic breast cancer survivor communities. Many people with metastatic breast cancer find it helpful to locate groups focused specifically on metastatic cancer, rather than those which include people with all stages of breast cancer. For those who are facing metastatic breast cancer with young children, keep in mind that there are support groups (and camps and retreats) for children who have a parent who is living with cancer.

Sometimes brain metastases are extensive or accompanied by extensive metastases in other locations. Even if treating your breast cancer no longer makes sense, palliative care to control your symptoms and give you the best quality of life with the time you have left is still critically important. We've learned that conversations to address end of life concerns with metastatic breast cancer happen far too infrequently. Unfortunately, people with advanced cancer and their family caregivers often have to initiate these discussions.

Choosing to stop treatment does not mean you are giving up. Instead, it means you are choosing to have the best quality of life at the end of your journey. If it's your loved one who has breast cancer, taking a moment to read up on caring for a loved one with metastatic breast cancer might make the days ahead just a bit easier to navigate.

A Word From Verywell

If you've been diagnosed with brain metastases, you're probably feeling frightened and confused. Brain metastases often occur as a distant recurrence following an earlier early-stage breast cancer. Hearing that your cancer came back and is no longer curable is heartbreaking.

Both systemic and local therapies are available to treat brain metastases. When only a few metastases are present and if your general health is good, treating the metastases with procedures such as SBRT or surgery may improve survival. If your metastases are extensive, there are still many things that can be done to improve your quality of life with whatever time you have left.

Every person's journey is different, and what is right for you may not be the choice another would make. Welcome the input from others, but remember that this is your journey. Make sure to honor your own wishes in the decisions you make.