Patient information: Treatment of metastatic breast cancer

INTRODUCTION

Metastatic breast cancer is usually not a curable condition. However, treatment can prolong life, delay the progression of the cancer, relieve cancer-related symptoms, and improve quality of life.

This article will discuss the treatment of metastatic breast cancer. More detailed information about metastatic breast cancer is available by subscription. (See "An overview of treatment for locally advanced, recurrent, and metastatic breast cancer".)

TREATMENT OPTIONS

There are three treatment options for women with metastatic breast cancer:

• Endocrine therapy — The presence of hormone receptors on a breast cancer indicates that the tumor may respond to treatments that interfere with the hormones (mainly estrogen) that fuel the growth of breast cancer cells.
• HER2 targeted therapy — Woomen whose breast cancers produce high levels of HER2 may benefit from treatments that target this protein. There are two drugs in this category, trastuzumab (Herceptin) and lapatinib (Tykerb). (See 'HER2-targeted treatment' below.)

• Chemotherapy — Chemotherapy is often recommended when a woman's breast cancer lacks both hormone receptors and HER2. (See 'Chemotherapy' below.)

ENDOCRINE THERAPY

Some breast cancers require female hormones to grow, while other breast cancers are able to grow without these hormone. Cancers that respond to hormones have hormone receptors; you may have estrogen receptors (ER), progesterone receptors (PR), or both.

If hormone receptors are present within a breast cancer (called hormone responsive), you are more likely to benefit from treatments that lower estrogen levels or block the actions of estrogen. These treatments are referred to as endocrine or hormone therapies.

The goal of endocrine therapy is to prevent breast cancer cells from being stimulated by estrogen. Endocrine therapy is often recommended as the first treatment for women with hormone receptor-positive metastatic breast cancer.

PREMENOPAUSAL ENDOCRINE THERAPY

In premenopausal women with metastatic breast cancer, endocrine therapy may include:

• Surgery to remove the ovaries (oophorectomy, (see 'Removal of the ovaries' below)
• A medication (tamoxifen or toremifene) to prevent the ovaries from using estrogen (see 'Tamoxifen' below)
• A medication (called gonadotropin releasing hormone antagonists) to prevent the ovaries from producing estrogen (see 'Gonadotropin releasing hormone agonists' below)

These treatments may be used alone or together. (See "Endocrine therapy of metastatic breast cancer".)

Tamoxifen — Tamoxifen is commonly used as a first-line endocrine therapy for premenopausal women with advanced breast cancer. Tamoxifen (Nolvadex®) prevents estrogen from stimulating growth of the breast cancer cells.

Tamoxifen is a pill that you take by mouth. Between 50 and 60 percent of women whose breast cancers are ER and/or PR-positive will respond to tamoxifen therapy.

Flare reaction — Up to 10 percent of women with metastatic breast cancer experience a "flare" of their breast cancer within two days to three weeks after starting tamoxifen. This may cause an increase in bone pain, a high blood calcium level, and in women who have tumors within the skin, an increase in the size and/or number of these skin nodules, or skin redness.

Tumor flares usually subside within four to six weeks. In the meantime, the symptoms can be treated with measures that reduce pain and lower blood levels of calcium. In severe cases, a woman may have to temporarily stop taking tamoxifen until the flare subsides. Many doctors consider a flare reaction to be a sign that endocrine therapy is working.

Resistance — Some ER/PR-positive breast cancers do not respond at all to tamoxifen. Other tumors respond to tamoxifen but later became resistant. Unfortunately, most if not all breast cancers eventually become resistant to tamoxifen.

Removal of the ovaries — Since the ovaries are not the main source of estrogen production in postmenopausal women, surgically removing the ovaries (called oophorectomy) may be recommended for premenopausal women.

About one-third of women with metastatic breast cancer will respond to oophorectomy. However, tamoxifen is as effective as oophorectomy and is usually recommended first (see 'Tamoxifen' above. If a breast cancer becomes resistant to tamoxifen, oophorectomy may then be considered, usually in conjunction with an aromatase inhibitor, since the woman would be postmenopausal.

Gonadotropin releasing hormone agonists — Gonadotropin releasing hormone (GnRH) agonists prevent the ovaries from functioning. All of the GnRH agonists (eg, goserelin (Zoladex®) and leuprolide (Lupron®)) must be injected to be effective. Some women experience a temporary flare of breast cancer symptoms when they first begin taking GnRH agonists.

GnRH agonists are as effective as oophorectomy for premenopausal women with ER or PR-positive metastatic breast cancer. However, women treated with a GnRH agonist are more likely to have hot flashes and a flare of breast cancer symptoms.

GnRH agonists may be combined with tamoxifen in premenopausal women. Combined therapy is sometimes favored over either approach alone because the cancer is more likely to respond, takes longer to progress, and length of survival may be better.

POSTMENOPAUSAL ENDOCRINE THERAPY

The ovaries of postmenopausal women no longer make estrogen, so removing the ovaries would not be helpful. Treatment of postmenopausal women with metastatic breast cancer usually includes either tamoxifen or an aromatase inhibitor. (See "Endocrine therapy of metastatic breast cancer".)

Tamoxifen — Tamoxifen is discussed above (see 'Tamoxifen' above.

Aromatase inhibitors — Aromatase inhibitors (AIs) are drugs that reduce estrogen levels in the body. Drugs in this class include anastrozole (Arimidex®), letrozole (Femara®) and exemestane (Aromasin®).

Side effects of aromatase inhibitors include bone loss and bone fractures, pain in the muscles and joints, blood clots in the legs, and cardiovascular events (stroke, heart attack).

Pure antiestrogens — Pure antiestrogens such as fulvestrant (Faslodex®) block the influence of estrogen on breast cancer cells. Fulvestrant is given as a monthly intramuscular (IM) injection, and it is effective in women whose cancers have progressed on tamoxifen.

Estrogen deprivation — In postmenopausal women, estrogen deprivation therapies are usually recommended when or if the cancer becomes resistant to an aromatase inhibitor or tamoxifen, rather than as initial treatment. The most commonly used options for postmenopausal women include hormones such as progestins and estrogen.

Progestins — The most commonly used drug in this class is oral megestrol acetate (Megace®). Medroxyprogesterone acetate (Depo-Provera®) is an injectable form of treatment that is given every 12 weeks.

Progestins like megestrol can be associated with significant side effects, including weight gain, fluid retention, and vaginal bleeding. Progestins also increase the risk of blood clots and are not recommended for women who have previously had blood clots or women who have risk factors for blood clots (eg, smokers).

Estrogen — Women who have previously taken endocrine therapy (tamoxifen, an aromatase inhibitor, megestrol acetate) may respond to high dose estrogen. Side effects of estrogen including breast tenderness, vaginal discharge, nausea/vomiting, and more seriously, heart failure and blood clots. As with progestins, estrogens are not recommended for women with a blood clotting disorder or women who have risk factors for blood clots (eg, smokers).

HER2-TARGETED TREATMENT

Trastuzumab — Trastuzumab (Herceptin®) is drug that targets a protein called HER2, which is found in high levels in some breast cancers. It may be given alone or in combination with chemotherapy. (See "Systemic therapy for HER2-positive metastatic breast cancer".)

Trastuzumab is generally given IV once per week or once every three weeks. The most common side effect of trastuzumab is fever and/or chills. Heart failure develops in about 3 to 5 percent of women treated with trastuzumab. Trastuzumab-related heart damage may not be permanent, and improvements have been seen once trastuzumab is discontinued.

Lapatinib — Lapatinib (Tykerb®) is an oral medication that targets HER2 in a different way than trastuzumab. Lapatinib may be used alone, in combination with chemotherapy, or even in combination with trastuzumab.

The most common side effects of lapatinib alone are diarrhea, a skin rash that resembles acne, and nausea.

CHEMOTHERAPY

Chemotherapy is a treatment given to slow or stop the growth of cancer cells. Chemotherapy is not given every day but instead is given in cycles. A cycle of chemotherapy (which is typically 21 or 28 days) refers to the time it takes to give the treatment and then allow the body to recover from the side effects of the medicines. Chemotherapy drugs may be given alone, one after another, or in combination. (See "Systemic chemotherapy for HER2-negative metastatic breast cancer".)

Who needs chemotherapy? — Chemotherapy may be recommended:

• For women with hormone receptor-positive (ER or PR-positive) metastatic breast cancer, when endocrine therapy is no longer effective.
• For women with hormone receptor-negative (ER or PR-negative) metastatic breast cancer, as an initial treatment.
• For women with metastatic breast cancer of any type that is growing quickly, affecting other organs, or causing symptoms.

How long is chemotherapy given? — It is not clear how many doses of chemotherapy are best for women with metastatic breast cancer. Several studies have compared the benefit of continuous chemotherapy (giving chemotherapy until it becomes ineffective) versus intermittent chemotherapy (giving approximately six cycles of chemotherapy followed by no chemotherapy until the cancer progresses). In general, overall survival is the same in women treated with continuous or intermittent chemotherapy, although tumor growth may be slowed somewhat in women treated with continuous therapy.

Intermittent chemotherapy may allow for a better quality of life; this is a reasonable option if your cancer-related symptoms stay under control during treatment.

Bevacizumab (Avastin®) — Bevacizumab (Avastin®) is an antibody (a type of protein) that targets a different protein called vascular endothelial growth factor (VEGF). VEGF helps a growing cancer develops its own blood supply, which is essential for the tumor to grow and spread. Bevacizumab disrupts the process of new blood vessel formation, thereby depriving the tumor of its supply of nutrients.

Bevacizumab may be used in combination with chemotherapy to treat HER2-negative metastatic breast cancer. However, bevacizumab can cause some serious side effects, including high blood pressure, bleeding, strokes, and infection.

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:

Professional Level Information:
An overview of treatment for locally advanced, recurrent, and metastatic breast cancer
Bisphosphonates in breast, prostate, and other solid tumors
Endocrine therapy of metastatic breast cancer
General principles of management of metastatic breast cancer
Metastatic breast cancer: Surgical resection
Systemic chemotherapy for HER2-negative metastatic breast cancer
Systemic therapy for HER2-positive metastatic breast cancer
Treatment of metastatic breast cancer in older women

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• American Society of Clinical Oncology

      (www.cancer.net/portal/site/patient)

• National Comprehensive Cancer Network

      (www.nccn.com)

• National Cancer Institute

       1-800-4-CANCER (226237)
       (www.nci.nih.gov)

• American Cancer Society

       1-800-ACS-2345
      (www.cancer.org)

• National Library of Medicine

      (www.nlm.nih.gov/medlineplus/healthtopics.html)

• Susan G. Komen Breast Cancer Foundation

       (www.komen.org)

Patient support — There are a number of online forums where patients can find information and support from other people with similar conditions.

• About.com Breast Cancer Forum

      (http://breastcancer.about.com/forum)

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