Breast Cancer - Metastatic: Types of Treatment

Approved by the Cancer.Net Editorial Board, 05/2018

ON THIS PAGE: You will learn about the different types of treatments doctors use for people with metastatic breast cancer. Use the menu to see other pages.

This section explains the types of treatments that are the standard of care for metastatic breast cancer. “Standard of care” means the best treatments known. When making treatment plan decisions, you are encouraged to consider clinical trials as an option. A clinical trial is a research study that tests a new approach to treatment. Doctors want to learn whether the new treatment is safe, effective, and possibly better than the standard treatment. Clinical trials can test a new drug and how often it should be given, a new combination of standard treatments, or new doses of standard drugs or other treatments. Clinical trials are an option to consider for treatment and care for all stages of cancer. Your doctor can help you consider all your treatment options. To learn more about clinical trials, see the About Clinical Trials and Latest Research sections.

Researchers are also using other methods to better understand metastatic breast cancer and identify new treatment approaches. For example, the Metastatic Breast Cancer Project allows people with metastatic breast cancer to enroll themselves. Please note that this link takes you to another, independent website.

If you are diagnosed with metastatic breast cancer, it is a good idea to talk with doctors who have experience in treating it. Doctors can have different opinions about the best standard treatment plan. Learn more about getting a second opinion before starting treatment, so you are comfortable with your chosen treatment plan.

Treatment overview

In cancer care, different types of doctors often work together to create a patient’s overall treatment plan that combines different types of treatments. This is called a multidisciplinary team. Cancer care teams include a variety of other health care professionals, such as physician assistants, oncology nurses, social workers, pharmacists, counselors, dietitians, and others. Ask the doctor in charge of your treatment which health care professionals will be part of your treatment team and what they do. This can change over time as your health care needs change.

A treatment plan is a summary of your cancer and the planned cancer treatment. It is meant to give basic information about your medical history to any doctors who will care for you during your lifetime. Before treatment begins, ask your doctor for a copy of your treatment plan. You can also provide your doctor a copy of the ASCO Treatment Plan form to fill out.

The main goals of metastatic breast cancer treatment are to ensure that you have the:

  • Longest survival possible with the disease

  • Fewest possible side effects from the cancer and its treatment

  • Best and longest quality of life possible

There is no cure for metastatic cancer, but a good quality of life is possible for months or even years.

Treatment options for metastatic breast cancer vary based on:

  • Where in the body the cancer has spread

  • The presence and level of hormone receptors and/or HER2 in the tumor

  • Gene mutations in the tumor

  • Specific symptoms

  • Previous cancer treatments

  • Your overall health

How well treatment works depends on many factors as well, including how widespread the cancer is and what treatments have already been used. Because it is not unusual for metastatic breast cancer to stop responding to drugs, you may need to change treatments fairly often.

After testing is done, you and your doctor will talk about your treatment options. Your treatment plan may include certain treatments described below, but they may be used in a different combination or at a different pace. Your care plan also includes treatment for symptoms and side effects, an important part of cancer care.

Take time to learn about all of your treatment options and be sure to ask questions about things that are unclear. Talk with your doctor about the goals of each treatment and what you can expect while receiving the treatment. Learn more about making treatment decisions.

Therapies using medication

Systemic therapy is the use of medication to destroy cancer cells. This type of medication is given through the bloodstream to reach cancer cells throughout the body. Systemic therapies are generally prescribed by a medical oncologist, a doctor who specializes in treating cancer with medication.

Common ways to give systemic therapies include an intravenous (IV) tube placed into a vein using a needle or in a pill or capsule that is swallowed (orally).

The types of systemic therapies used for metastatic breast cancer include:

  • Hormonal therapy

  • Chemotherapy

  • Targeted therapy

Each of these types of therapies are discussed below in more detail. A person may receive only 1 type of systemic therapy at a time or a combination of systemic therapies given at the same time. The first set of drugs used for metastatic disease is called first-line treatment. If the cancer worsens or comes back, another regimen may be used, called second-line treatment. These therapies can also be given as part of a treatment plan that includes surgery and/or radiation therapy.

The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications prescribed for you, their purpose, and their potential side effects or interactions with other medications. Learn more about your prescriptions by using searchable drug databases.

Hormonal therapy

Hormonal therapy, also called endocrine therapy, is an effective treatment for many tumors that test positive for either ER or PR.

Hormone receptor-positive tumors may use hormones to fuel their growth. The goal of this type of therapy is to lower the levels of estrogen and progesterone in the body or to block these hormones from getting to cancer cells. If the hormones cannot get to the cancer cells, the cancer cannot use them to grow.

The choices of hormonal therapy for women vary depending on whether a woman is still menstruating or has gone through menopause. Hormonal therapy options also depend on what treatments a person has already received. Options for hormonal therapy include:

  • Tamoxifen (Nolvadex). Tamoxifen is a drug that blocks estrogen from binding to breast cancer cells. It is a pill taken daily by mouth. Common side effects of tamoxifen include hot flashes as well as vaginal discharge or bleeding. Very rare risks include a cancer of the lining of the uterus, cataracts, and blood clots. However, tamoxifen may improve bone health and cholesterol levels. The treatment is an option for both premenopausal and postmenopausal women.

  • Aromatase inhibitors (AIs). AIs decrease the amount of estrogen made by tissues other than the ovaries in women who have gone through menopause by blocking the aromatase enzyme. This enzyme changes hormones called androgens into estrogen when the ovaries have stopped making estrogen after menopause. These drugs include anastrozole (Arimidex), exemestane (Aromasin), and letrozole (Femara). All of the AIs are pills taken daily by mouth.

    Side effects of AIs may include joint stiffness, sometimes with joint aches. AIs may also cause hot flashes, vaginal dryness, an increased risk of osteoporosis and broken bones, and increased cholesterol levels. Research shows that all 3 AIs work equally well and have similar side effects. However, women who experience too many side effects while taking 1 AI may have fewer side effects with another AI for unclear reasons. Women who have not gone through menopause should not take AIs, as they do not block the effects of estrogen made by the ovaries. Often, doctors will monitor blood estrogen levels in women whose periods have recently stopped, or those whose periods stop with chemotherapy, to be sure that the ovaries are no longer making estrogen.

  • Ovarian suppression. This is the use of drugs or surgery to stop the ovaries from producing estrogen. It may be used in combination with tamoxifen or an AI. Drugs called gonadotropin or luteinizing releasing hormone (GnRH or LHRH) analogs can stop the ovaries from making estrogen, causing temporary menopause. Surgery permanently stops estrogen production. Ovarian suppression is commonly used to treat hormone receptor-positive metastatic breast cancer in premenopausal women, as complete estrogen suppression may be helpful against the cancer.

  • Fulvestrant (Faslodex). Fulvestrant is a selective estrogen receptor downregulator (SERD). That means it binds to the estrogen receptors, blocking the ability of estrogen to attach to these receptors. Unlike other oral hormonal therapies, fulvestrant is given monthly by an injection into a muscle. Most commonly, 2 injections are given every 2 weeks for 3 doses and continued monthly. Fulvestrant is a medication for postmenopausal women only.

  • Other hormonal therapies. Other hormonal therapies occasionally used to treat metastatic breast cancer after AIs, fulvestrant, tamoxifen, and targeted therapy (see below) include megestrol acetate (Megace) and high-dose estradiol, which is an estrogen replacement.

Learn about ASCO’s recommendations for hormonal therapy for metastatic breast cancer.

Chemotherapy

Chemotherapy is the use of drugs to destroy cancer cells, usually by ending the cancer cells’ ability to grow and divide.

Chemotherapy for metastatic breast cancer can be given on many different schedules depending on what worked best in clinical trials for that specific type of regimen, or schedule. It may be given once a week, once every 2 weeks (also called dose-dense), once every 3 weeks, or even once every 4 weeks. Weekly schedules often include weeks off as a break. In general, chemotherapy is often given continuously as long as it is working against the cancer and the patient isn’t experiencing too many side effects.

A patient with metastatic breast cancer usually receives 1 drug at a time, which means 1 after another, rather than as a combination, although occasionally a combination regimen is recommended. The best chemotherapy option for each patient depends on several factors, including the previous treatment received, potential side effects, the patient’s overall health, and the patient’s preferences.

Drugs that may be used for metastatic breast cancer include:

  • Capecitabine (Xeloda)

  • Carboplatin (available as a generic)

  • Cisplatin (available as a generic)

  • Cyclophosphamide (Cytoxan)

  • Docetaxel (Taxotere)

  • Doxorubicin (available as a generic)

  • Pegylated liposomal doxorubicin (Doxil)

  • Epirubicin (Ellence)

  • Eribulin (Halaven)

  • Fluorouracil (5-FU, Efudex)

  • Gemcitabine (Gemzar)

  • Irinotecan (Camptosar)

  • Ixabepilone (Ixempra)

  • Methotrexate (Rheumatrex, Trexall)

  • Paclitaxel (Taxol)

  • Protein-bound paclitaxel (Abraxane)

  • Vinorelbine (Navelbine)

Chemotherapy may be combined with other types of treatments. For example, therapies that target the HER2 receptor, such as the antibody trastuzumab, may be given with chemotherapy for HER2-positive breast cancer (see Targeted therapy, below).

The side effects of chemotherapy depend on the individual, the drug(s) used, and the schedule and dose used. These side effects can include fatigue, risk of infection, nausea and vomiting, hair loss, loss of appetite, numbness from nerve damage, and diarrhea. These side effects can often be very successfully prevented or managed during treatment with supportive medications, and they usually go away after treatment is finished.

Many patients feel reasonably well during chemotherapy treatment and are active taking care of their families, traveling, and exercising during treatment, although each person’s experience can be different. Talk with your health care team about the possible side effects of your specific chemotherapy plan.

Learn more about the basics of chemotherapy.

Targeted therapy

Targeted therapy is a treatment that targets the cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. These treatments are very focused and work differently than chemotherapy or hormonal therapy. This type of treatment blocks the growth and spread of cancer cells while limiting damage to healthy cells.

Not all tumors have the same targets. To find the most effective treatment, your doctor may run tests to identify the genes, proteins, and other factors in your tumor. This helps doctors better match each patient with the most effective treatment whenever possible. In addition, research studies continue to find out more about specific molecular targets and new treatments directed at them. Learn more about the basics of targeted treatments.

There are different types of targeted therapies that vary in how they target the cancer cells:

  • Monoclonal antibodies. A monoclonal antibody recognizes and attaches to a specific protein in the cancer cells, and it does not affect cells that do not have that protein. Examples of monoclonal antibodies used for breast cancer include trastuzumab, pertuzumab, and TDM-1 (see below).

  • Small molecule inhibitors. Small molecule inhibitors are drugs designed to specifically target parts of a cancer cell that contribute to its growth and survival. The parts of a cancer cell that these drugs target may be receptors on the outside of the cell, enzymes on the inside of a cell, or a protein important for cell growth. Some of these types of drugs may target different parts of a cell. These are called “multi-targeted.” Small molecule inhibitors are often pills. Examples used for breast cancer include lapatinib, palbociclib, ribociclib, and everolimus (see below).

Talk with your doctor about possible side effects of specific targeted therapies and how they can be managed.

Targeted therapy for metastatic HER2-positive breast cancer

HER2-targeted therapies can be used to treat HER2-positive metastatic breast cancer. Some of these drugs may be used together with chemotherapy. In general, for a person with HER2-positive metastatic breast cancer, there is almost always a HER2-targeted therapy being used along with another systemic therapy.

Some of the HER2-taregted therapies may not penetrate into the brain as easily as the rest of the body. So, HER2-positive metastatic breast cancer that has spread to the brain is often treated with surgery and/or radiation therapy (see below).

  • Trastuzumab (Herceptin, Ogivri). For metastatic breast cancer, trastuzumab can be given in combination with different types of chemotherapy or with hormonal therapy. Trastuzumab can be given as a weekly infusion, or once every 3 weeks. Patients receiving trastuzumab have a small (2% to 5%) risk of heart problems and should have monitoring with an echocardiogram every few months.

  • Pertuzumab (Perjeta). Research shows that adding pertuzumab to trastuzumab and chemotherapy as part of first-line therapy for HER2-positive metastatic breast cancer lengthens lives with few additional side effects. Based on this data, the combination of trastuzumab, pertuzumab, and chemotherapy has become a standard of care for the first-line treatment of untreated metastatic HER2-positive breast cancer. Pertuzumab is an intravenous medication and generally causes few side effects, although it can occasionally cause diarrhea.

  • Ado-trastuzumab emtansine or T-DM1 (Kadcyla). This is approved for the treatment of metastatic breast cancer for patients who have previously received trastuzumab and chemotherapy with either paclitaxel or docetaxel. T-DM1 is a combination of trastuzumab linked to very small amount of a strong chemotherapy. This allows the drug to deliver chemotherapy into the cancer cell while lessening the chemotherapy received by healthy cells. T-DM1 is given by vein every 3 weeks.

  • Lapatinib (Tykerb). Women with HER2-positive metastatic breast cancer may benefit from lapatinib when other medications are no longer effective at controlling the cancer’s growth. The combination of lapatinib and the chemotherapy capecitabine is approved to treat metastatic HER2-positive breast cancer when a patient has already received chemotherapy and trastuzumab. The combination of lapatinib and letrozole is also approved for metastatic HER2-positive and ER-positive cancer. Lapatinib is also used in combination with trastuzumab for patients whose cancer is growing while receiving trastuzumab. Lapatinib may be able to enter into the brain, and could be an option for HER2-positive breast cancer that has spread to the brain.

Targeted therapy for metastatic hormone receptor-positive, HER2-negative breast cancer
  • Palbociclib (Ibrance). This oral drug targets a protein in breast cancer cells called CDK4/6, which may stimulate cancer cell growth. Used along with the AI letrozole, the drug is an option for women who have been through menopause and have ER-positive, HER2-negative metastatic breast cancer. Palbociclib can also be used with fulvestrant if the cancer has worsened after receiving other hormonal therapy. Palbociclib generally has few side effects. It can lower the number of white blood cells. But it does not appear to increase the risk of serious infections that are linked to low numbers of white blood cells.

  • Ribociclib (Kisqali). This oral drug targets a protein in breast cancer cells called CDK4/6, which may stimulate cancer cell growth. Used with an AI, this drug is an option for women who have been through menopause and have ER-positive, HER2-negative metastatic breast cancer. Side effects of ribociclib can include low numbers of white blood cells, increases in enzymes linked with liver damage, and changes in heart rhythms.

  • Abemaciclib (Verzenio) This is another oral drug that targets CDK4/6. It is approved by the FDA as a first-line treatment along with an AI for women who have been through menopause and have ER-positive, HER2-negative metastatic breast cancer. It may also be used along with fulvestrant if the cancer has worsened with other hormonal therapies. Abemaciclib may also be used as alone as a treatment. It does not lower blood counts as much as the other CDK4/6 drugs, but it is more likely to cause diarrhea, which can be severe at times.

  • Everolimus (Afinitor, Zortress). Everolimus is used with the AI exemestane for ER-positive, HER2-negative metastatic breast cancer that has grown despite treatment with another AI. Side effects of everolimus can include mouth sores, rash, diarrhea, and, rarely, an inflammation of the lungs called interstitial pneumonitis.

Learn about ASCO’s recommendations for treating HER2-negative breast cancer.

Targeted therapy for people who have a BRCA1 or BRCA2 gene mutation
  • Olaparib (Lynparza). This oral drug may be used for patients with metastatic HER2-negative breast cancer and a BRCA1 or BRCA2 gene mutation who have previously received chemotherapy. It is a type of drug called a PARP inhibitor, which destroys cancer cells by preventing them from fixing damage. Common side effects include fatigue, anemia, and occasionally nausea, vomiting, and diarrhea.

Radiation therapy

Radiation therapy is the use of high-energy x-rays or other particles to kill cancer cells. A doctor who specializes in giving radiation therapy to treat cancer is called a radiation oncologist. The most common type of radiation treatment is called external-beam radiation therapy, which is radiation given from a machine outside the body. When radiation is given by placing radioactive sources into the tumor, it is called brachytherapy.

Radiation therapy may be used to shrink or slow tumor growth. It can also treat symptoms from the cancer, such as pain. Used by itself, or in combination with surgery, radiation therapy can also treat breast cancer that has spread to the brain. Several different types of radiation therapy are used to treat brain metastases, including whole brain radiation, stereotactic radiosurgery, and fractionated stereotactic radiotherapy.

  • Whole brain radiation therapy is directed at the entire brain.
  • Stereotactic radiosurgery is the use of a single, high dose of radiation given directly to the tumor to avoid harming the surrounding healthy tissues.
  • Fractionated stereotactic radiation therapy is similar to stereotactic radiosurgery but divided into small daily doses called fractions that are given over multiple days or weeks, in contrast to the 1-day radiosurgery.

A radiation therapy regimen, or schedule, usually consists of a specific number of treatments given over a set period of time. Doctors will set the schedule and radiation dose for breast cancer metastases based on a patient’s individual medical needs and prior use of radiation therapy.

Radiation therapy can cause general side effects, such as fatigue and skin problems. In addition to general side effects, other side effects may occur and depend on the type of radiation therapy given and where on the body it is directed.

Learn more about the basics of radiation therapy.

Surgery

Surgery is the removal of a tumor and some surrounding healthy tissue during an operation. Surgery is not often used to treat metastatic breast cancer. However, doctors may recommend surgery to remove a tumor that is causing discomfort. Research continues on whether people who are first diagnosed with metastatic breast cancer live longer if the primary breast tumor is removed.

Surgery, used by itself or with radiation therapy, can be options to treat breast cancer that has spread to the brain. The goal is to shrink or temporarily get rid of the cancer in the brain. Usually, surgery of this type is done by a neurosurgeon, a specialist who operates on the head, brain, and central nervous system.

Before surgery, talk with your health care team about the possible side effects from the specific surgery you will have. Learn more about the basics of cancer surgery.

Summary of treatment options for metastatic breast cancer

The following summary is based on ASCO recommendations for the treatment of HER2-positive breast cancer that has spread beyond the breast. Read a summary of recommendations for metastatic HER2-negative breast cancer on a separate page.

HER2-positive breast cancer that has spread to parts of the body other than the brain

In general, HER2-targeted therapy should be added to treatment for HER2-positive breast cancer that has spread. The drugs used depend on the treatments already given and whether the cancer is hormone receptor-positive. The treatment recommendations for first-line, second-line, and third-line or higher treatment are listed below. A clinical trial may also be an option for treatment at any stage.

First-line treatment
  • Treatment is usually a combination of pertuzumab, trastuzumab, and a type of chemotherapy called a taxane.

  • If the cancer is hormone receptor-positive, treatment may be a combination of hormonal therapy plus HER2-targeted therapy with either trastuzumab or lapatinib. Hormonal therapy may also be given alone if the cancer has not spread widely, a patient has other health conditions that could be worsened with HER2-targeted therapies, or the cancer has recurred after a long time.

  • Chemotherapy is generally given for at least 4 to 6 months or until the patient experiences too many severe side effects, or the disease worsens. For patients with hormone receptor-positive cancer, HER2-targeted therapy and hormonal therapy usually continue after chemotherapy ends.

Second-line treatment
  • For patients with early-stage breast cancer who had the cancer spread during initial treatment with trastuzumab or return within 12 months after stopping treatment with trastuzumab, second-line treatment is used.

  • The preferred second-line treatment is the drug T-DM1.

Third-line or higher treatment
  • T-DM1 is a treatment option for patients who have not already received it.

  • Pertuzumab is also an option for patients who have not already received it, and it is usually given in combination with trastuzumab.

  • For patients who have already received T-DM1 and pertuzumab, other options include lapatinib with capecitabine, other combinations of chemotherapy with HER2-targeted therapy, or hormonal therapy when appropriate.

Learn more about the recommendations for treating metastatic HER2-positive breast cancer on a separate ASCO website.

HER2-positive breast cancer that has spread to the brain

The treatment of HER2-positive breast cancer that has spread to the brain often involves different types of radiation therapy. Sometimes, surgery and/or chemotherapy or targeted therapy may be used. Treatment in a clinical trial may also be an option.

In general, the treatment options available depend on the size and location of the tumor(s) in the brain, and the symptoms they are causing, as well as the patient’s general health.

Below is a general summary of when and how the above treatment options are used to treat brain metastases:

  • People with a single brain metastasis and good overall health generally receive surgery, followed by some type of radiation therapy. If the metastasis in the brain cannot be removed by surgery and the person is not having symptoms, stereotactic radiosurgery may be used.

  • People with 2 to 4 brain metastases generally receive stereotactic radiosurgery.

  • Treatment for people with cancer that has spread widely throughout the brain usually includes whole brain radiation therapy.

  • For people whose cancer in the brain is worsening even after receiving radiation therapy, additional treatment options depend on the initial treatment and include surgery, the types of radiation therapy discussed above, and/or a drug that can affect the whole body, such as chemotherapy or HER2-targeted therapy.

  • People who also have metastatic HER2-positive breast cancer in parts of the body other than the brain usually continue their treatment regimen if the disease outside the brain is not worsening. If the disease is worsening, a HER2-targeted therapy may be added/changed based on the recommendations for HER2-positive cancer that has spread to parts of the body other than the brain (see above).

Learn more about the recommendations for treating HER2-positive breast cancer that has spread to the brain on a separate ASCO website.

The next section in this guide is About Clinical Trials. It offers more information about research studies that are focused on finding better ways to care for people with cancer. You may use the menu to choose a different section to read in this guide.