Breast Cancer – Stage IV

Overview

Cancer of the breast is the most frequently diagnosed cancer in U.S. women. Fewer than 1% of breast cancer cases occur in men. Because this summary is focused only on female breast cancer, men searching for information about male breast cancer may want to begin by visiting the National Cancer Institute’s overview of male breast cancer.

If you have been diagnosed with stage IV (also called metastatic) breast cancer, you probably have many questions and concerns about treatment. This treatment summary, which is based on the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™), will help you understand the best available treatments for stage IV breast cancer.  Talk to your doctor about these options so that together you can decide on a treatment plan that is right for you.

Background

Invasive breast cancer is cancer that has spread beyond the breast tissue where your cancer started and into surrounding healthy breast tissue. Metastatic breast cancer is cancer that has spread to other parts of your body, such as bones, liver, lung, or brain.

Even if breast cancer has spread to other parts of your body, it can be treated, and you may live a high-quality life for many years after diagnosis, with proper management. 

Rapid advances in the treatment of breast cancer have occurred in recent years. Doctors have an increasingly clearer understanding of the underlying disease processes, and this helps them identify which women are likely to respond best to specific treatments. 

Diagnosis

Metastatic (also called distant) breast cancer is most commonly diagnosed when breast cancer has recurred. This means it has returned in the months or years after the initial treatment of a localized breast cancer. However, there are some women who are initially diagnosed with metastatic breast cancer.

A few of the symptoms/signs of recurrent or metastatic breast cancer may are:

However, the symptoms are associated with the specific area to which the cancer has spread; for example, bone pain is typically associated with the spread of cancer cells to the bones. 

Diagnosis includes determining the stage of the disease; learning about specific characteristics of the cancer, such as whether it does or does not need certain hormones to grow; and discovering where in the body the cancer cells have spread. 

Stage

Staging describes the extent or severity of the cancer.  Breast cancer stages range from stage I through stage IV, with a higher stage indicating a more extensive or widespread cancer. 

When breast cancer is diagnosed as stage IV, it means that the cancer has spread (metastasized) to other organs within the body, such as lung, bone, or liver; it does not depend on the size of the tumor in the breast or whether cancer is found in the lymph nodes.

For a more detailed discussion of staging, see the Cancer Staging Guide.

Treatment

Treatment for women with stage IV breast cancer is highly individualized; no single treatment plan is right for every woman. Factors to consider when you and your health care team decide on treatment include:

Different treatment options may be appropriate at different times. To make the best decisions for you, talk to your doctor about the benefits, risks, and possible side effects of the treatment options discussed below.

Although metastatic breast cancer is rarely curable, many effective treatments can slow the disease and provide you with the longest, best quality of life possible. Your doctor will carefully balance the probable effectiveness of treatment with the likely side effects.

When you discuss your treatment options with your doctor, you should make sure that your doctor knows what is most important to you. Some women want to have the most aggressive treatment possible regardless of side effects, whereas others want to ensure that they have the best possible quality of life while they are being treated, and may therefore choose treatments that are less-aggressive but provide comfort and relief from symptoms. 

Your treatment will include one or more of the following: surgery, radiation therapy, or systemic therapy, which is treatment in the form of drugs that is administered or absorbed into your bloodstream and travels through your body. This type of treatment affects both normal and abnormal cells and is designed to impede the abnormal cells’ ability to grow, divide, reproduce, and repair themselves.

The primary factors that will determine which specific treatment is right for you are: 

Estrogen and progesterone are hormones in the body.  They can stimulate the growth of breast cancer cells that have estrogen and/or progesterone receptors. Breast cancer cells with too many HER2 protein receptors are more aggressive and grow faster. When you test positive for estrogen receptors, progesterone receptors, or HER2 status, your cancer may have a better chance of responding well to certain systemic therapies.

The three types of systemic therapy are:

Your doctor should provide you with a written care plan explaining

You will be asked to sign an informed consent form indicating that you have been told about your treatment and what to expect. It is very important that you ask your doctor or nurse any questions that you have.  Cancer and its treatment are complicated, and most patients have questions.

Hormone therapy

If you have breast cancer that has tested positive for the estrogen receptor and/or the progesterone receptor tumor markers, you may be a candidate for hormone therapy. Hormone therapies are usually taken as pills, and their side effects are usually relatively mild.

Tamoxifen is one drug used for hormone therapy; it binds to hormone receptors and blocks the hormonal stimulation of tumor growth. 

Another type of hormone therapy uses drugs called aromatase inhibitors (such as anastrozole, letrozole, or exemestane), which stop estrogen from being produced in postmenopausal women. Aromatase inhibitors are appropriate only for postmenopausal women, because premenopausal women produce much higher amounts of estrogen that cannot be significantly reduced with these drugs.

An important factor to consider when selecting an appropriate hormone therapy is whether you have been treated with hormone therapy for breast cancer within the past 12 months. If this is the case, your doctor may suggest starting a different type of hormone therapy. 

If you have not yet gone through menopause and have received hormone therapy within the past 12 months, the NCCN Guidelines ^TM  for Breast Cancer recommend combining hormone therapy with either surgery or certain medications called LH-RH antagonists to stop estrogen production by the ovaries.  If it has been more than 12 months, your doctor may recommend either the same hormone therapy you had before or a different one. 

In some cases, your doctor might recommend that you try hormone therapy even when estrogen or progesterone tumor markers are not present, especially if you have certain types of metastatic breast cancer (for example, breast cancer that has spread only to the bones). This is because hormone therapy usually has fewer side effects than other systemic treatments and it may be effective in treating your cancer.

In other cases, even if you do have estrogen and/or progesterone receptors, your doctor may recommend that you begin treatment along with chemotherapy, especially if your cancer has spread to vital organs, like your lungs or liver. 

Women often take several types of hormone therapy drugs, switching to a different one if the cancer gets worse or they experience problems related to side effects of the therapy. If you are starting a second type of hormone therapy but have not yet gone through menopause and have not had treatment to stop estrogen production by the ovaries, NCCN Guidelines for Breast Cancer recommend that you first undergo treatment to stop the ovaries from producing estrogen. This treatment may be in the form of drugs that stop estrogen production or surgical removal of the ovaries.

Side effects associated with hormone therapies are usually mild. For tamoxifen, these may include hot flashes and a slightly increased risk for blood clots and cancer of the uterus. For aromatase inhibitors, side effects may include decreased bone mass (thinning of the bones) and joint pain.  If you experience troublesome side effects with one of these drugs, talk with your doctor; you may be able to change to another drug that provides similar benefits but has more tolerable side effects.  Strategies for early detection of these side effects include having bone health monitored through periodic measurements of bone mineral density and alerting your doctor about any abnormal uterine bleeding and symptoms/signs of a blood clot, such as swelling and pain in a leg or arm, so that it can be investigated promptly.

Hormone therapies are usually taken as pills and are often given for at least 5 years. It is important that you do not stop hormone therapy without informing your doctor, because these drugs are more effective when taken for long periods of time.

Chemotherapy

Chemotherapy drugs are given to destroy cancer cells. When high levels of estrogen and/or progesterone receptors are present, chemotherapy is not usually given as the first treatment for stage IV breast cancer unless the cancer has spread to your vital organs and is causing significant illness. Chemotherapy is recommended as initial therapy for most women with tumors that do not have estrogen and/or progesterone receptors.

The NCCN Guidelines for Breast Cancer provide a list of chemotherapy drugs that are preferred either as single agents or in combination with other chemotherapy drugs. Little evidence shows that any one of the preferred drugs and combinations listed in the guidelines consistently works better than another, so other considerations often determine the choice of treatment. 

Some of the considerations that determine the choice of treatment include:

The NCCN Guidelines for Breast Cancer also list other drugs and combinations that have shown activity against breast cancer.

Often, as with hormone therapy, one chemotherapy drug is given at a time, and you are switched to a different one only if your cancer gets worse or you experience problems related to the side effects of a certain drug.

The advantages of using a single drug are that it may limit side effects, makes scheduling treatment easier, and does not pose any clear disadvantage in length of survival.

The disadvantage of this approach, however, is that you may experience a shorter time before your cancer gets worse and you need to switch to a different drug. 

Sometimes, and especially if you have serious symptoms from your cancer, a large amount of disease, a particularly aggressive type of breast cancer, or a very short time during which you were free of disease, your doctor may recommend combination chemotherapy, which is treatment with more than one chemotherapy drug on a specified schedule. Many women’s cancer responds favorably to this approach; it may also extend the time before you need a change in therapy. However, combination chemotherapy often produces more side effects and has not conclusively been shown to extend the length of life.

Most chemotherapy drugs are given intravenously (injected into a vein), although some are taken by mouth. See Guide to Chemotherapy.

Some chemotherapy regimens can produce uncomfortable side effects, such as hair loss, intestinal disturbances (including nausea and vomiting or diarrhea), and a decreased production of certain types of blood cells, which can lead to other conditions, including anemia or bleeding problems. Talk to your doctor or oncology nurse about how to manage these effects.

The most common side effect of chemotherapy is an abnormal reduction in the number of infection-fighting white blood cells (called neutropenia). Therefore, infection is a common side effect of chemotherapy. If you develop a fever of 101°F or more, contact your doctor or nurse, because this may indicate that you have an infection that your body cannot fight off on its own.

Although most side effects are not serious, some chemotherapy drugs, such as doxorubicin, can affect the heart, and you may need to have periodic testing to monitor your heart function when taking these drugs. Make sure you discuss this possibility with your health care professionals and understand fully what you can expect.

If you are premenopausal and have not received treatment to stop estrogen production from the ovaries, your menstrual periods may still stop, either temporarily or permanently, after you undergo chemotherapy.

Talk to your doctor about what to expect from each treatment and what can be done to help you cope with these side effects.

Targeted Therapy

Some treatments are specifically directed toward certain markers on tumor cells or certain processes that occur in tumor cells. For example, drugs like trastuzumab (Herceptin) and lapatinib (Tykerb) target cancer cells with high quantities of the HER2 receptor, because breast cancer cells with many HER2 receptors are more aggressive and grow faster.

It is very important that testing for HER2 be accurate, because these targeted therapies have not been shown to be effective in women who do not have high quantities of HER2 on their tumor cells, and can have substantial side effects.

Ask your doctor whether the laboratory that will be used is accredited by either the College of American Pathologists or The Joint Commission. If your doctor doesn’t know, you can call the head of the laboratory (often a pathologist) and ask about accreditation. If the laboratory is not accredited to perform HER2 testing, ask your doctor to send your tumor sample to a laboratory that is accredited by one of these organizations. Laboratories that are connected with large cancer centers and perform a high volume of HER2 tests are more likely to meet the standards for accreditation. More information is provided in HER2 Testing: Summary for Breast Cancer Patients.

Targeted therapies may be given as a single agent or in combination with specific chemotherapy drugs (listed in the NCCN Guidelines for Breast Cancer). In some cases, trastuzumab and lapatinib may be given together without any other chemotherapy. The NCCN Guidelines for Breast Cancer recommend that women who have metastatic breast cancer with high levels of the HER2 tumor marker first receive trastuzumab-containing therapy, with lapatinib-containing therapy given only after the cancer gets worse on trastuzumab-containing therapy.

Trastuzumab (Herceptin) can affect the heart. You may need to have periodic testing to monitor your heart function if you are taking trastuzumab (Herceptin).

Another targeted therapy used to treat some patients with metastatic breast cancer is bevacizumab (Avastin). This drug is believed to help decrease the production of new blood vessels that supply nutrients to the tumor or tumors, thereby helping to “starve” the tumor. Bevacizumab is usually used with paclitaxel (Taxol).

Surgery and Radiation Therapy

For women who are found to have stage IV breast cancer at the time that breast cancer is first diagnosed, the NCCN Guidelines for Breast Cancer recommend that systemic therapy (therapy that treats the entire body, such as hormone therapy or chemotherapy) be given first, and that breast surgery and radiation therapy (the use of high-energy beams to kill cancer cells) be reserved for women who experience uncomfortable symptoms in the area of the breast. If your initial diagnosis is stage IV metastatic breast cancer, surgery will only be undertaken under certain circumstances, with radiation considered as another option. You should discuss whether you meet the criteria for these treatment possibilities with your doctor.

If you have recurrent stage IV breast cancer and have already undergone breast surgery and radiation for a previous diagnosis of stage I, II, or III breast cancer, radiation is an option only to provide relief of specific symptoms, such as pain from bone metastases.

Supportive Care

Treatments are also available for any symptoms you develop as a result of your cancer or its treatment.  This approach to cancer treatment is called supportive, or palliative, care. If you experience pain, nausea or vomiting, fatigue, or other troublesome symptoms, let your doctor know.  There is no reason to suffer when there are treatments that can help you feel better.

Your doctor may also recommend treatment to prevent other problems. For example, if cancer has spread to the bones, a woman should receive a drug called a bisphosphonate, which has been shown to strengthen bone to help prevent bone fractures and relieve bone pain.

If your doctor recommends a bisphosphonate drug, you should first see a dentist for a complete dental evaluation, as well as to receive any needed dental treatment, because bisphosphonates can increase the risk for certain complications after dental treatment.  Your doctor may also recommend certain drugs to control nausea related to chemotherapy or pain. For more information on palliative care, see Palliative Care Gets New Life.

Prognosis

In determining a prognosis—the likely course or outcome of a disease and its treatment—a doctor may look at breast cancer survival statistics taken from studies of large groups of patients. However, these statistics:

Your individual prognosis will be affected by many factors, including

Ask your doctor which treatment(s), in his or her judgment, will give you the best life expectancy and quality of life. You may want see whether you are eligible to participate in a clinical trial in which new and experimental therapies are tested against standard treatments in women with stage IV breast cancer.