Common Sites of Metastatic Breast Cancer

Understanding stage 4 breast cancer

If you’ve been diagnosed with metastatic breast cancer, or if you had early-stage breast cancer in the past and are having new symptoms, it's natural to have questions. Some of the things you may be wondering about include:

  • Where does breast cancer spread?
  • What are the most common sites of breast cancer metastases?
  • How often does breast cancer travel to these regions of the body? 
  • What are the symptoms to be aware of?
  • How is breast cancer treated when it spreads?

The spread of breast cancer is important as it is responsible for most deaths from the disease.

The word “metastatic” is used in different ways with breast cancer, so it's important to understand some terms you may come across.

Defining "Metastatic"

Metastatic breast cancer is the same thing as stage 4 breast cancer and is considered the most advanced stage. It refers to breast cancers that have spread beyond the breast and nearby lymph nodes to other regions of the body, which are called distant metastases.

Doctors aren't certain why cancer recurs and spreads, nor how it can appear to lie dormant for years and even decades and then recur. Since distant metastases are the cause of death for most cancers, much research is being conducted looking at why metastases occur, as well as methods that might inhibit the spread of cancers.

The areas of the body to which breast cancer spreads can vary. The most common sites include:

A 2013 study looked at the most common first site of metastases in women with early-stage breast cancer. The frequencies were:

  • Bones - 41 percent
  • Lungs - 22 percent
  • Liver - 7.3 percent
  • Brain - 7.3 percent
  • All less common sites - 22.4 percent

Invasive lobular carcinoma tends to have a significantly different pattern of metastases than ductal breast cancer. In one 2017 study, almost 70 percent of people with metastases from lobular carcinoma had peritoneal metastases.

For roughly a third of women (and men, as men get breast cancer too), cancer spreads to multiple organs at the same time.

Breast cancer can spread through the lymphatic system, the bloodstream, or by local invasion—for instance, when cancer cells actually invade nearby tissues, such as the chest wall or ribs. When breast cancers spread and enter the lymphatic system they usually arrive first at nearby lymph nodes and may still be an early stage breast cancer.

Note that when breast cancer spreads it is still breast cancer. If you were to take a sample of the cancerous tumor in these locations and look at it under the microscope, the appearance would be of cancerous breast cells, not bone, liver, or lung cells. Thus, for example, breast cancer that has spread to the bones is not called bone cancer, but rather “breast cancer metastatic to the bones.”

While treatment options for metastatic breast cancer are similar no matter where cancer has spread, some treatments are used for specific sites of metastasis as well.

The spread of breast cancer to lymph nodes does not mean that it's metastatic, even though a pathology report may state "breast cancer metastatic to lymph nodes." When cancer recurs in a lymph node near the breast, it is considered a regional recurrence and not a distant recurrence. Lymph-node positive breast cancer can be stage II, III, or IV.


Invasive vs. Non-Invasive

The term invasive breast cancer is frightening, but like metastases to lymph nodes, it doesn't mean that the cancer is metastatic. The term invasive breast cancer refers to any cancer that has spread beyond an area called the “basement membrane,” meaning they haven't moved beyond the breast ducts. In fact, the only stage of breast cancer that's not considered invasive is ductal carcinoma in situ (DCIS) or stage 0 breast cancer. Stage 1 to stage 4 breast cancers are all considered invasive breast cancer.

Bone Metastases from Breast Cancer

The most common site of distant breast cancer metastases, occurring in around 70 percent of people with metastatic breast cancer, is to bones. The most common bones include:

  • Spine
  • Ribs
  • Pelvis
  • The long bones of the arms and legs

Bone metastases tend to have a fairly good prognosis relative to metastases to some other regions of the body.

Bone metastases may be found on a scan done to look for metastases (when no symptoms are present) or found on scans that are done to evaluate symptoms, such as pain.

Some people are unaware that they have bone metastasis until they suffer a fracture from what should've been a minor trauma. Fractures through a portion of a bone weakened by cancer metastases are called pathologic fractures.

Several types of treatment are available for bone metastases from breast cancer, and some of these can control the disease for quite some time.

  • Radiation therapy is often done when rapid relief is needed, and it can be very effective for the local treatment of bone metastases.
  • Drugs such as Strontium 89 include a particle of radiation attached to another chemical which is injected into the bloodstream. These treatments, in contrast to radiation therapy, are often effective when a person has multiple or widespread bone metastases.
  • Sometimes surgery is needed to stabilize a bone which has fractured or is at risk of fracturing due to metastases. When bone metastases occur in the spine, they can sometimes lead to spinal cord compression, a condition that requires immediate attention to prevent paralysis and more.
  • Bone-modifying medications are a newer treatment for bone metastases and can be very effective.
  • Bisphosphonates such as Zometa (zoledronic acid) are not only effective in reducing pain from metastases but appear to have anticancer effects as well. These medications may also reduce the chance of further bone metastases and improve survival. The medication Xgeva (denosumab) may also be effective in treating bone metastases while improving survival. Bisphosphonates are now often used for women with early stage breast cancer to decrease the risk of bone metastases. It's thought that these drugs alter the "microenvironment" in bone so that cancer cells are less likely to "stick."

    Liver Metastases from Breast Cancer

    Breast cancer metastases to the liver are also very common. They may be present without any symptoms and are often detected on tests such as a PET scan.

    Sometimes these metastases are suspected based on abnormal liver function tests. Symptoms of liver metastases may include abdominal pain, nausea, itching (which can be severe), and jaundice (a yellowish discoloration of the skin and the whites of the eyes.)

    General treatments for metastatic cancer (such as chemotherapy, hormonal therapies, and targeted therapies) may decrease these metastases, but since the liver acts as the "detoxification" center of the body, treatments must be delicately balanced. Sometimes, liver metastases reduce the ability to tolerate chemotherapy.

    Radiation therapy to the liver can decrease pain and may improve survival.

    At times, other local treatments may be used to treat liver metastases such as surgery, radioembolization, chemoembolization, radiofrequency ablation, or stereotactic body radiotherapy.

    Lung Metastases from Breast Cancer

    Just as the blood is filtered by the liver, blood passes through the lungs, making this a common site of metastasis.

    Lung metastates may be suspected based on a scan, which often shows multiple small areas of metastases (in contrast to lung cancer, for example, which is more likely to appear as a single large mass). The most common symptom is shortness of breath, which may be mild and only occur with exercise at first. Other symptoms can include a persistent cough or pain with breathing.

    In addition to spreading to the lungs, metastatic breast cancer often causes pleural effusions—a build-up of fluid in the space between the membranes (the pleura) which line the lungs. Pleural effusions occur not only when breast cancer spreads to the lungs, but with spread to the lymph nodes in the area between the lungs (the mediastinum). The fluid may be benign (without cancer cells) and related to inflammatory changes, or instead, contain cancer cells (a malignant pleural effusion).

    Lung metastases are often treated by the general treatments for metastatic breast cancer, but radiation therapy may be helpful, especially if the metastases cause an obstruction in the airways (bronchi). If only a few metastases are present, treatment to eradicate these may be considered (see oligometastases below under brain metastases). Before treatment, however, it's important to make sure that a nodule in the lung is due to breast cancer. A recent study found that nodules in the lung thought to be metastases from breast cancer were almost as likely to be a primary lung cancer (lung cancer can and does occur in people who've never smoked).

    Pleural effusions can be quite large and cause significant shortness of breath. Fluid is often removed by placing a needle through the chest wall and into the pleural cavity to drain the fluid. Unfortunately, pleural effusions often recur. When this happens, a shunt may be placed, or a pleurodesis recommended (a procedure in which the layers of the pleura are scarred together so fluid cannot reaccumulate).

    Brain Metastases From Breast Cancer

    Breast cancer spreads to the brain in about 10 to 15 percent of people with metastatic breast cancer overall. Brain metastases are more common in women with HER2 positive tumors and triple negative breast cancer, with brain metastases occurring in roughly a third of people with HER2 positive breast cancers that metastasize.

    Symptoms of brain metastases often include headaches, visual changes, dizziness or seizures (sometimes a seizure is the first symptom). Other symptoms may include weakness on one side of the body, problems with coordination, or personality changes.

    Unlike metastases to some other regions, treatments such as chemotherapy and targeted therapies are often ineffective against brain metastases due to the blood-brain barrier, which is a tight network of capillaries designed to protect the brain from toxins (such as chemotherapy).

    The treatment of metastases usually includes steroids to decrease swelling in the brain. Whole brain radiation may be used to address the metastases, along with medication to reduce the risk of cognitive problems afterward.

    Oligometastases

    If only a single or a few "spots" of metastasis are present, they're referred to as oligometastases. In this case, stereotactic body radiotherapy (SBRT) may be used in an attempt to destroy the metastasis completely. SBRT, also known as Cyberknife or gamma knife is a procedure in which high doses of radiation are delivered to a small and very precise area of tissue.

    The treatment of oligometastases or only one or a few spots of spread is a relatively new approach in oncology, and few studies had been done to evaluate the potential survival benefit. A 2019 study, however, looked at survival in people with a few different types of cancer who had local treatment for up to five metastases (in the same region or different regions). They found that treating these oligometastases significantly improved overall survival.

    Leptomeningeal Metastases

    Leptomeningeal metastases, also called carcinomatous meningitis differs from brain metastases in that the cancer cells spread to the cerebrospinal fluid that bathes the brain and spinal cord. Since cancer cells float freely in the space between the leptomeninges (the subarachnoid space) they have constant access to nutrition and don't usually form a discreet mass. Leptomeningeal metastases often occur late in the disease, but are becoming more common as people live longer with metastatic cancer. Treatment often involves injecting chemotherapy directly into this space (intrathecal chemotherapy).

    Less Common Sites of Distant Metastases

    Breast cancer can spread to nearly any region of the body. Some of the less common sites (with the exception of lobular carcinoma) of metastasis include:

    • Bone marrow
    • Peritoneal metastases (accounting for two-thirds of people with metastatic lobular carcinoma)
    • The opposite breast
    • An ovary
    • Adrenal glands
    • Pancreas
    • Skin and soft tissue

    Recurring Cancer

    Most of the time (90 percent to 95 percent of the time) metastatic breast cancer represents a recurrence of previous breast cancer.

    A recurrence following primary breast cancer may occur months, years, or even decades after the original tumor. The timing of the recurrence may give your oncologist some important information about your cancer. For example, tumors that recur within three years tend to be more aggressive than those that recur later, although this is not always the case.

    It isn't clear how cancer cells can “hide” or why they appear again. One theory is that there is a hierarchy among cancer cells, with cancer stem cells being more resistant to the treatments we use for early-stage breast cancer. For some reason, these cancer cells survive the treatments and lie dormant, waiting to begin growing at some later point in time.

    Breast cancers that are estrogen receptor positive (ER+), which means they're "fueled" by hormones, are less likely to recur early on, than those which are estrogen receptor negative (ER-), but are more likely to recur many years or even decades later (late recurrence).

    Sometimes it can be difficult to know whether a recurrence is a true recurrence. It’s thought that cancers which recur in the first three months after treatment are not a true recurrence but rather a progression of original cancer.

    Coping With Metastatic Breast Cancer

    If you have been diagnosed with metastatic breast cancer, you are probably feeling frightened and perhaps overwhelmed by all of the information you've been given. Metastatic breast cancer is different than early stage breast cancer in many ways.

    Talk to your friends and family. Many people find it helpful to become involved in a support group or support community designed specifically for those with metastatic cancer. Learn all you can about your disease. Treatment, even those for metastatic breast cancer, is improving, and survival is lengthening.

    One of the most important steps you can take is to be your own advocate in your cancer care. You have a lot of decisions to make about treatment options, and only you can say which choices are best for you.

    For Friends and Family

    If your loved one has been diagnosed with distant metastases, they're probably a little overwhelmed. Breast cancer is different the second time around, and your loved one will need your support to face this yet again.

    Treatments options for metastatic breast cancer are different, and the philosophy about treatment for metastatic breast cancer differs significantly from that for early-stage breast cancer. With early-stage breast cancer, the goal is usually to be as aggressive as possible to reduce the chance that it will come back.

    With metastatic breast cancer, however, the philosophy is usually to use the minimum amount of treatment needed in order to control the disease. Treating the disease aggressively does not improve survival, but it does increase side effects and lessen the quality of life.

    The lack of widespread understanding of these differences has led to many emotionally painful moments for those coping with metastatic breast cancer. Take a moment to learn about what not to say to someone with metastatic breast cancer.

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