Metastatic Breast Cancer

Treatment Strategies

The goal of treatment for metastatic breast cancer is to control the growth of disease for as long as possible and to improve the quality of life. Several treatment options are available, and the treatment for an individual woman depends on many factors, including:

• The site or sites of metastasis
• The hormone receptor and HER2 status of the cancer
• Your age, overall health, and menopausal status
• The time since your initial diagnosis and treatment (if the metastasis is recurrent cancer)

Types of Treatment

Even though metastatic cancer involves cancer in an organ other than the breast, the cancer cells are still breast cancer cells. Because of this, the same treatments used for earlier stage breast cancer are used for metastatic disease; these treatments include hormone therapy, chemotherapy, targeted therapy, surgery, and radiation therapy. However, these treatments are often used for different purposes or with different goals. For example, because chemotherapy is used to slow progression and prolong survival rather than to eradicate disease completely, the doses are usually lower than those used for earlier stage disease, when cure is possible.

Surgery or radiation therapy is typically not used as part of treatment for metastatic breast cancer. When they are used, it is usually to relieve symptoms or to prevent complications. (See Managing the Symptoms of Metastatic Breast Cancer).

Hormone Therapy

Hormone therapy, also known as endocrine therapy, is the recommended first choice for women who have metastatic breast cancer that tests positively for estrogen and/or progesterone receptors (ER-positive and/or PR-positive). Hormone therapy is also sometimes recommended if the hormone receptor status is not known. Hormone therapy is effective at slowing the growth of metastasis because it works directly at decreasing the amount of estrogen or progesterone in your body, the very substances that fuel the growth of breast cancer cells. Another advantage of hormone therapy is that it causes fewer side effects than chemotherapy.

Several types of drugs can be used for hormone therapy, and they differ with respect to how they work, who they can be used for, and what side effects they can cause. Your doctor will consider several factors when recommending the best type of hormone therapy for your particular case, most importantly, whether you are premenopausal or postmenopausal and whether you have received hormone therapy as previous treatment for earlier stage breast cancer (Table 1). An analysis of several studies showed that aromatase inhibitors offer a survival benefit compared with other hormone treatments for women with metastatic breast cancer.

Chemotherapy

Traditional chemotherapy, also referred to as systemic therapy, is another option to treat metastatic breast cancer, especially if the cancer is ER-negative or PR-negative or if the cancer progresses during hormone therapy. Several chemotherapy drugs are options for treating metastatic breast cancer (Table 2). Your doctor will discuss the advantages and disadvantages of these drugs so that you can decide together which treatment course is best for you.

Targeted Therapy

Targeted therapy is treatment directed at genes, proteins, or other substances that contribute in some way to the growth and development of cancer cells. Targeted therapy enables personalized treatment, or treatment tailored to the individual characteristics of the breast cancer cells in your body. Targeted therapy agents slow the progression of metastatic disease by blocking signals from various proteins that generate the growth of new cells. Blocking the signals inhibits new growth of cancer cells.

Three targeted therapy agents have been approved for use in the treatment of breast cancer (Table 3 on page 10), and others continue to be developed and evaluated in clinical trials. Two of the approved agents are known as anti-HER2 agents because they inhibit HER2; only tumors that are HER2-positive can respond to an anti-HER2 agent. The third targeted therapy agent inhibits vascular endothelial growth factor (VEGF), a protein that helps tumors form new blood vessels; without vessels to bring blood to the tumor, it cannot continue to grow. This type of drug is known as an antiangiogenesis agent.

Trastuzumab (Herceptin) was the first targeted therapy to be developed for any cancer and is perhaps the best known targeted therapy agent among all cancers. It is recommended—either as a single agent or in combination with a chemotherapy drug—as first-line treatment of metastatic breast cancer that is HER2-positive. The use of trastuzumab and chemotherapy has led to higher response rates and longer progression-free survival (length of time without progression of disease) than trastuzumab alone.

Another anti-HER2 agent is lapatinib (Tykerb). When used in combination with capecitabine, lapatinib has delayed the progression of breast cancer for nearly twice as long as did capecitabine alone in women with metastatic HER2-positive breast cancer.

In February 2010, the FDA approved the use of lapatinib with another drug, letrozole (Femara), an aromatase inhibitor. This combination is an option for women who have breast cancer cells that test positively for both hormone receptors and HER2. The FDA approval was based on a study in which the combination more than doubled the time before disease progressed compared with letrozole alone.

Bevacizumab (Avastin) has been effective for other types of cancer and is now approved for use as first-line treatment of HER2-negative metastatic breast cancer when given in conjunction with paclitaxel (Taxol). In one study, the combination enabled women to live nearly twice as long without progression of the cancer compared with paclitaxel alone. Bevacizumab plus a chemotherapy agent may be used for breast cancers that are triple negative, that is, cancer that has tested negatively for ER, PR, and HER2.

Choosing Treatment

Choosing a treatment can be challenging because of the number of options, but the advantage is that if the first treatment doesn’t work—which is often the case—other treatments can be tried. Your doctor will talk to you about the various options for your particular type of breast cancer, and you should learn as much as you can about each option.

In deciding on a treatment, it is important to think about your personal priorities. Some women want the most aggressive treatment available, whereas other women wish to focus on supportive care, or treatment that is focused on enhancing the quality of life. You should communicate your priorities to your doctor; while he or she will make recommendations, the final decision is yours. Note, too, that your priorities may change over time as you continue through treatment, and you should talk to your doctor about these changes.

Some women prefer to take a break from treatment if disease has stabilized and their quality of life is good. If you think you may wish to do this, talk to your doctor about the benefits and risks. If you do take a break, you can always resume treatment when you feel ready or if disease starts to progress.

The choice to stop treatment permanently is not an easy one, but at some point, it may seem like the right decision for you. If you decide to stop treatment directed at the metastatic disease, it is important to receive palliative care, or treatment that is designed to help you live more comfortably. You should consider receiving palliative care as part of hospice care. Most people misunderstand hospice care and do not appreciate its value. Hospice is not about dying, it is about living with a higher quality of life. Hospice care can be delivered in your own home and provides pain relief and other supportive care; psychologic, spiritual, and logistical support for you and your family; and help with daily living tasks. Most people have reported that once they started hospice care, they regretted not choosing it sooner.

Clinical Trials

New treatments and combinations of treatment for metastatic breast cancer are being evaluated in hundreds of clinical trials, and many treatments have shown promise in early studies. For example, two classes of drugs—PARP inhibitors and EGFR inhibitors—are being evaluated in clinical trials as treatments for triple-negative metastatic breast cancer.

Clinical trials provide the highest quality of care and monitoring and offer access to the very latest treatments that are not otherwise available. All women with metastatic breast cancer should talk to their doctor about the possibility of participating in a clinical trial. Participating in a clinical trial is a personal decision, and you should carefully weigh all the options before making this decision.

You can search for clinical trials on stage IV breast cancer on a number of Web sites, such as the following:

• American Cancer Society Clinical Trials Matching Service (http://clinicaltrials.cancer.org)
• Center Watch (www.centerwatch.com)
• National Cancer Institute (www.cancer.gov/clinicaltrials)
• US National Institutes of Health (www.clinicaltrials.gov)

Table 1. Hormone Therapy Options for Metastatic Breast Cancer

Table 2. Chemotherapy Options for Metastatic Breast Cancer

Table 3. Targeted Therapy Options for Metastatic Breast Cancer

Additional Sources of Information

• American Cancer Society: www.cancer.org
    Breast Cancer: Treatment Options
    Guide to Cancer Drugs
    Targeted Therapy
• Breast Cancer.org: www.breastcancer.org
    Treatments for Metastatic Disease
    Taking Breaks from Treatment
    When Do You Stop Treatment?
• Hospice Foundation of America: www.hospicefoundation.org
• Living Beyond Breast Cancer: www.lbbc.org
    Understanding Treatment Options for Advanced Breast Cancer
    Guide to Understanding Triple-Negative Breast Cancer
• National Cancer Institute: www.cancer.gov
    Breast Cancer Treatment (PDQ)
    Tamoxifen: Questions and Answers
• Natonal Comprehensive Cancer Network: www.nccn.org
    Breast Cancer - Stage IV
    Living with Cancer: Palliative Care Gets New Live
    Living with Cancer: Palliative Chemotherapy is Personal Decision
• National Hospice and Palliative Care Organization: www.nhpco.org
• Susan G. Komen for the Cure: ww5.komen.org
    Treatment: Metastatic Breast Cancer End-of-Life Care
• Triple Negative Breast Cancer Foundation: www.tnbcfoundation.org