Metastatic breast cancer is a type of cancer that has metastasized, or spread, beyond the breast and lymph nodes to other parts of the body. The most common locations for distant metastatic breast cancer are the bones, lungs, liver and brain.
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When cancer starts in an organ and spreads to a different site, it is called metastatic. Cancers move from the original site using lymph channels or the bloodstream. Cancer spreads to the nearby region when tumor cells are identified in the lymph-node-draining areas of the breast. This regional breast cancer spread represents stage II or stage III breast cancer.
However, once the cancer cells travel beyond the regional lymph nodes, metastatic disease can be seen anywhere in the body. The most common locations for distant metastatic breast cancer are the bones, lungs, liver and brain. Spread to a distant body part is considered metastatic, or stage IV breast cancer.
Sometimes cancers will have already spread to other parts of the body at the time of original diagnosis. However, this is rare, as approximately only 5% of patients will be considered metastatic or stage IV when they are first diagnosed. Usually, distant metastasis of the breast occurs after a woman has been diagnosed with an earlier staged cancer.
Metastatic breast cancer can occur in only one body part (for example, only the bone) but usually occurs in multiple organs (such as the lung, bone and liver). Most patients will have symptoms that mean breast cancer has spread to another body part, and these symptoms will depend on the organ(s) involved. For example, patients with breast cancer that has spread to the lung may note cough and shortness of breath; whereas, patients whose cancer has spread to the bone will more likely have bone pain. Sometimes patients will have no symptoms, but the doctor will suspect distant cancer based on a physical finding such as a swollen lymph node or nodule on the skin. It is also possible that blood tests may detect an abnormal finding for which your doctor may recommend additional testing.
When advanced or metastatic cancer is suspected, your physician team will perform a generalized medical history about breast cancer and other cancers that run in the family as well as other information regarding your previous and current health, prior breast biopsies and radiation exposure. A physical examination will enable your team to decide if there are abnormalities on the exam suspicious for organs that could be involved with breast cancer. Blood testing is often performed to look for signs of this disease. This will include a CBC (complete blood count), which looks at the number of white blood cells (infection fighters), red cells (oxygen-carrying cells) and platelets (blood clotting cells).
Other tests will include assessment of liver function, bone function and kidney function. Sometimes a tumor blood test will also be evaluated. Imaging tests may also be recommended as these scans will provide a picture of the inside of your body. The majority of these imaging tests will be performed within the Department of Radiology and Nuclear Medicine and can include CT scans of the chest, abdomen and pelvis, a bone scan, brain MRI and sometimes a PET scan or a PET/CT test. Your healthcare team will determine the types of imaging tests needed.
Because there are many different types of metastatic breast cancer, it is very important for your breast cancer team to obtain information about the distant metastasis. Understanding the biology or the behavior of the cancer will enable your breast cancer team to personalize treatment for your specific advanced cancer.
Frequently, a biopsy of the suspected abnormal organ will be recommended. Obtaining this information will enable your team to be certain that the abnormality is metastatic breast cancer. In addition, this tumor can be analyzed for estrogen and progesterone receptors, HER-2/neu activity and potentially other genes which may guide your doctors on appropriate treatment. Performing a biopsy involves removing a sample of the tissue or fluid from the body. Many times this can be done in the radiology suite or perhaps by a surgeon or other healthcare provider. Tissue obtained from the distant organ will be tested and compared to any other tissues previously biopsied. If you have previously been diagnosed with breast cancer, the biology of the original breast cancer will be compared to the biology of the new metastasized cancer identified in the distant organ. Most of the time, the biology including the hormone receptor activity and HER-2/neu analysis will be similar to the original cancer; however, 30% of the time the hormone receptor activity may change as cancer spreads to other organs, and less than 20% of the time the HER-2/neu status will change from the original breast cancer compared to the distant metastasis. Changes can provide information about how fast the cancer is growing as well as types of treatment more likely to successfully treat your cancer.
Metastatic breast cancer can be a very overwhelming diagnosis; however, newer treatments for stage IV breast cancer have markedly improved survival. Unfortunately, once breast cancer is considered metastatic, it is unlikely to be cured. Long-term cancer control and symptom improvement are possible with treatments.
There are many different ways to treat metastatic breast cancer. Keep in mind that our major goals of treatment are to improve your quality of life and to hopefully extend it. Choosing the appropriate pathway involves a detailed discussion with you and your support team (family, friends, clergy, etc.) along with your healthcare team. Clinical trials are often suggested as they may provide access to new treatments. Treatment options will be based on your personal characteristics, previous health issues, as well as the personal gene findings (biomarkers) on your cancer. The approach often taken is to utilize one treatment regimen until it stops working and then to switch to another treatment. This strategy has proven to provide long-term cancer control for many women. If the cancer does not respond to multiple regimens, stopping cancer treatment and receiving supportive care may be the best option. Supportive care will help relieve symptoms from the cancer or treatments but it does not treat the cancer itself. This decision is best made in close discussion with you, your personal support system and your breast cancer team.
One possible treatment for metastatic breast cancer can be hormone therapy. Approximately 80% of metastatic breast cancers will be hormone receptor-positive. Cancers that are estrogen (ER)- or progesterone receptor (PR)-positive are more likely to respond to hormone treatment. Estrogen and progesterone are usually made by the ovaries in premenopausal women. In postmenopausal women the ovaries no longer function. However, in postmenopausal women estrogen and progesterone precursors are released by the adrenal glands (small glands on top of the kidneys) and body fat. These precursors can be converted into usable estrogen. Understanding these pathways of hormone production enables your breast cancer team to develop a strategy THAT can treat your cancer.
Anti-estrogen or selective estrogen receptor modulators (SERMs) are drugs that block the effect of estrogen on cancer cells. Tamoxifen and toremifene block estrogen from attaching to the estrogen receptor. These medicines can be prescribed for both premenopausal and postmenopausal women. Fulvestrant (Faslodex), another anti-estrogen, not only blocks but also reduces the number of estrogen receptors. This drug is called a selective estrogen receptor degrader (SERD) and is currently prescribed for postmenopausal women only.
Aromatase inhibitors are effective drugs for postmenopausal women who have advanced hormone-dependent breast cancer. Currently, there are three drugs that can be prescribed: anastrozole (Arimidex), letrozole (Femara) and exemestane (Aromasin). Sometimes, other medicines (such as everolimus [Afinitor] and palbociclib [Ibrance]) that block genes important in hormone-dependent breast cancer will be prescribed with hormone therapy. Your physician team may recommend that you receive one or sometimes two of these medications to better control the advanced breast cancer. Clinical trials are currently underway to better assess how to prescribe hormone therapy in metastatic breast cancer.
Healthy ovaries are the main source of estrogen and progesterone in premenopausal women. Surgically removing them with bilateral oophorectomies can decrease the amount of estrogen and progesterone in a woman’s body. Occasionally radiating the ovaries may be recommended. Although radiation is recommended less frequently today, both of these treatments can successfully decrease ovarian production of hormones.
Ovarian suppression involves administering drugs that make the ovaries less effective in producing hormones. These drugs are called luteinizing hormone releasing hormone agonists (LHRH). The brain regulates the ovaries’ production of estrogen and progesterone by releasing LHRH. Agonists against LHRH stop this production, which in turn, stops the ovaries from producing estrogen. Goserelin (Zoladex) and leuprolide (Lupron), which are administered as monthly injections under the skin, are the most commonly used LHRH agonists.
Chemotherapy drugs kill cancer cells by damaging DNA or disrupting the making of DNA. Many chemotherapy drugs only work when cells are actively dividing or growing. There are four classes of chemotherapy drugs commonly used in the treatment of metastatic breast cancer:
Alkylating agents such cyclophosphamide (Cytoxan), carboplatin or cisplatin, which damage DNA by adding a chemical to them.
Anthracyclines such as doxorubicin (Adriamycin) or epirubicin which disrupt the making of DNA.
Antimetabolites such as capecitabine (Xeloda), gemcitabine (Gemzar), fluorouracil (5-FU) and methotrexate, which prevent the building blocks of DNA from being used.
Microtubule inhibitors, which prevent cells from dividing into two cells. Drugs in this class include docetaxel (Taxotere), emtansine, eribulin (Halaven), ixabepilone (Ixempra), paclitaxel (Taxol) and vinorelbine (Navelbine).
Many times, chemotherapy drugs will be used for first line treatment, particularly if the metastatic breast cancer’s biology suggests that the cancer is not fed by hormones or is particularly aggressive. Your physician team may also recommend chemotherapy if a hormone therapy has been tried with no success in treating your cancer. These chemotherapy drugs may be used as a single agent or in combination. The side effects of chemotherapy will be extensively discussed with you by your breast cancer team.
Targeted therapy stops the action of molecules that cause cancer cells to grow. This form of treatment is less likely to harm normal cells than traditional cytotoxic chemotherapy. There are several targeted treatments that can be used for metastatic breast cancer:
Trastuzumab (Herceptin) and pertuzumab (Perjeta). These drugs treat cancers that are HER-2/neu positive. They work by attaching to the HER-2 receptor outside the cell; however, each drug attaches to a different part of the HER-2/neu molecule. Ado-trastuzumab (emtansine, Kadcyla) is a specific combination of trastuzumab and a cancer chemotherapy drug. Once the drug attaches to the HER-2 positive cancer cell, the link breaks apart, releasing the chemotherapy within the cancer cell.
Lapatinib (Tykerb) is an oral HER-2/neu blocker. It works by attaching to the end of the HER-2/neu molecule inside the cancer cell.
Everolimus (Afinitor) is an oral agent that blocks a protein kinase, MTOR. Protein kinases are molecules that move chemicals from one molecule to another. Everolimus stops MTOR from transferring a phosphate, which stops the cell from receiving signals to grow. This oral pill is sometimes given with exemestane, a hormone pill.
Palbociclib (Ibrance) is an oral pill that blocks a different enzyme, a cyclin-dependent kinase. This drug was recently approved for some postmenopausal women with metastatic hormone receptor-positive breast cancer. Currently, it is prescribed with a hormone agent.
The use of these targeted treatments depends on the presence of particular genes on cancer cells. If your cancer is HER-2/neu positive, your physician will discuss with you the appropriate HER-2/neu driven treatment strategy for your cancer. In certain cases, your physician may recommend other targeted treatments.
Radiation is another effective way to control cancer. However, in advanced breast cancer it is used to control symptoms such as pain or the development of cancer in the brain. The most common type of radiation used is called external beam radiation therapy in which a machine outside of the body delivers the radiation. Radiation beams are aimed at the cancer based upon ink spots placed on the skin. Before beginning radiation therapy, you will meet with a radiation oncologist, who will discuss with you the potential advantages and disadvantages to this particular treatment.
For women with metastatic breast cancer in the bone or at very high risk for the development of bone metastasis, intravenous bisphosphonate therapy zoledronic acid (Zometa) or denosumab (Xgeva) may be recommended. The regular administration of these medicines can reduce the rate of bone fractures, bone pain and compression of the bones around the spinal cord. These medicines can also be helpful in treating high-levels of blood calcium (hypercalcemia). Like all treatments, these drugs may have side effects including osteonecrosis of the jaw, pain or fever. It is important to be certain that your dentist is aware that you are receiving these bone strengthening agents as special precautions may need to occur during certain dental procedures.
The Breast and Ovarian Cancer High Risk Program exists to promote awareness about breast and ovarian cancer risk to patients, families and healthcare providers. The program provides an expert evaluation for patients who are identified as high risk for either breast or ovarian cancer.
After a patient is evaluated, he or she is offered appropriate counseling, testing and primary prevention measures to reduce the likelihood of cancer development. This multidisciplinary approach to women’s cancer risk assessment and management (RAMP) will utilize the services of breast imaging and genetics along with surgical oncology, medical oncology and gynecologic oncology.
Who would be considered at high risk?
A person who has one or more first-generation relatives with breast or ovarian cancer before the age of 50.
An individual who has one first-generation relative with bilateral breast cancer.
Individuals with a known personal or family genetic abnormality in a breast cancer-causing gene, such BRCA or CHEK-2.
A person with prior breast biopsy showing atypical ductal hyperplasia or lobular neoplasia.
Individuals with a Gail Model breast cancer risk of greater than or equal to 1.67% over the next five years or greater than 20% lifetime risk.
An individual with a history of chemoradiotherapy to treat Hodgkin’s disease.
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