Treatment for metastatic breast cancer varies from person to person. The first treatment may be hormone therapy (tamoxifen or an aromatase inhibitor), chemotherapy and/or trastuzumab (Herceptin). The exact treatment depends on characteristics of the breast cancer, including where it has spread. Tumors often develop resistance to drug therapies used to treat metastatic cancer. Therefore, it is common to change the type of therapy being used fairly often. To learn more about factors that affect treatment options, see the Diagnosis section.
Hormone Therapies
Hormone therapies are a first line of treatment for metastatic cancers that are hormone receptor-positive. These cancers need estrogen to grow. Some hormone therapies, like tamoxifen, bind with the cancer's hormone receptors so that they cannot bind with estrogen. Other hormone therapies, such as aromatase inhibitors, decrease the production of estrogen in the body, limiting the amount of estrogen available to the cancer cells. Although there are many hormone therapies, they all slow the cancer's growth by depriving it of the hormones it needs.
For a woman, choices about hormone therapies are often made based on menopausal status and prior hormone therapy she may have had for early breast cancer [37,79].
For premenopausal women, hormone therapy often begins with ovarian suppression. This may involve surgery to remove the ovaries (oophorectomy) or, more often, drugs to stop the ovaries from producing hormones. Tamoxifen is also used to treat metastatic cancer in premenopausal women, although it may not be an option for women whose cancer progressed during prior tamoxifen treatment. Sometimes, both oophorectomy and drug therapy are used together. Some studies suggest this may improve survival over either ovarian suppression treatment alone [81].
Postmenopausal women still make a small amount of estrogen from fat tissue and the adrenal glands, but not in the ovaries. Hormone therapy in postmenopausal women can be tamoxifen or an aromatase inhibitor, which stops estrogen production. Ovarian suppression is not helpful in postmenopausal women because the ovaries have already stopped producing large amounts of estrogen.
With hormone therapies, if the first drug stops working and the cancer begins to grow again, a second drug can be used. If the second drug stops working, another can then be tried. At some point—even though it may be years down the line—hormone therapy almost always stops being effective. At this point, chemotherapy may be recommended.
Learn more about hormone therapies.
Chemotherapy
Chemotherapy is an important tool in the treatment of metastatic breast cancer. It is used to treat cancers that no longer respond to hormone therapy and is also a first treatment for people with hormone receptor-negative tumors or who have life-threatening metastases. One benefit of chemotherapy compared to hormone therapy is response time. Chemotherapy shrinks tumors sooner than hormone therapy.
As with hormone therapies, if the first chemotherapy drug stops working and the cancer begins to grow again, a second or third drug can be used. With each new drug, though, the chance that the cancer will shrink drops by about half [81]. And, if the cancer does shrink, it often does so for a shorter period of time with each new drug. It is not uncommon for people to have multiple chemotherapy regimens (often five or more) over the course of treatment for advanced breast cancer.
Learn more about chemotherapy.
Targeted therapy: Anti-HER2/neu drugs
Trastuzumab (Herceptin)
About 20 percent of breast cancers have high numbers of a protein called HER2/neu on the surface of their cancer cells (called HER2/neu positive) [56]. Trastuzumab (Herceptin) is a specially made antibody that targets the HER2/neu protein. When attached to the HER2/neu protein, trastuzumab slows or stops the growth of the cancer cells.
Because trastuzumab only works on HER2/neu positive breast cancers, you are only eligible for the drug if your tumor is HER2/neu positive. The HER2/neu status of a tumor is determined by testing the tissue that is removed during biopsy. For more on this, see the Diagnosis section.
Clinical trials in women with metastatic breast cancer have shown that trastuzumab can shrink tumors and slow the growth of cancer, whether it is combined with chemotherapy or used alone [82-89]. And, trastuzumab causes fewer side effects than chemotherapy. It does not cause hair loss, nausea and vomiting, and has no effect on bone marrow.
In rare cases, deaths due to heart or lung problems have been linked to the use of trastuzumab [84,85]. Although the chance of such an event is small, you discuss this with your health care provider before starting treatment. Your heart will be checked before and during treatment with trastuzumab to help ensure there are no problems.
In some cases, HER2/neu tumors may metastasize to the brain. Because trastuzumab is not able to cross the blood-brain barrier, it is not used to treat brain metastases.
Lapatinib (Tykerb) and Other Tyrosine-Kinase Inhibitors
Tyrosine-kinase inhibitors, such as lapatinib (Tykerb), are a class of drugs that target enzymes important for cell functions. Whereas antibody therapies, such as trastuzumab (Herceptin), target a single protein, tyrosine-kinase inhibitors block a tyrosine-kinase enzyme. This enzyme can target many points along the cancer growth pathway. These drugs are a new wave of targeted therapies for HER2-positive tumors. A randomized controlled trial comparing lapatinib plus capecitabine (Xeloda) to capecitabine alone among women with HER2-positive locally advanced or metastatic breast cancer found that lapatinib plus capecitabine increased the time before cancer spread [90]. Lapatinib is FDA-approved for the treatment of advanced HER2-positive breast cancer in women who have already received chemotherapy and trastuzumab. Lapatinib is taken in pill form.
Bevacizumab (Avastin) and Other Anti-Angiogenesis Drugs
Anti-angiogenesis drugs, such as bevacizumab (Avastin), block the growth of new blood vessels that feed tumors. Without a blood supply, the cancer cannot grow. Bevacizumab in combination with paxlitaxel is FDA-approved for the treatment of metastatic breast cancer. Bevacizumab improves progression-free survival, but not overall survival in women with advanced breast cancer [91]. Side effects of bevacizumab include headache, fatigue, nausea and problems with wound healing. About 15 percent of women starting bevacizumab will develop high blood pressure [91]. And, in rare cases, it has been linked with perforation (holes) in the wall of the stomach or intestines (mainly among people treated for colon cancer and ovarian cancer) and bleeding in the lungs and brain [92].
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For more information on treatment for metastatic breast cancer, visit the American Society for Clinical Oncology’s website for people living with cancer (www.cancer.net).
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Updated 10/19/09
