Breast Cancer - Metastatic: Types of Treatment

Aprobado por la Junta Editorial de Cancer.Net, 11/2021

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, also known as therapies, 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 discuss with your doctor whether clinical trials are an option. A clinical trial is a research study that tests a new approach to treatment. Doctors learn through clinical trials whether a 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 for all stages of cancer. Your doctor can help you consider all your treatment options. Learn more about clinical trials in the About Clinical Trials and Latest Research sections of this guide.

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.

How metastatic breast cancer is treated

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. Breast cancer multidisciplinary care teams typically include medical oncologists, surgical oncologists, radiation oncologists, radiologists, and pathologists. In addition, cancer care teams include a variety of other health care professionals, such as physician assistants, nurse practitioners, oncology nurses, genetic counselors, social workers, pharmacists, counselors, dietitians, financial advisors, and other supportive care members. 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. The treatment plan can be updated over time as your treatments change.

The main goals of metastatic breast cancer treatment are to make sure 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 breast 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 the type of breast cancer, 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 over time, you may need to change treatments fairly often.

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. These types of talks are called “shared decision-making.” Shared decision-making is when you and your doctors work together to choose treatments that fit the goals of your care. Shared decision-making is particularly important for metastatic breast cancer because there are different treatment options. Learn more about making treatment decisions.

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.

Therapies using medication

The treatment plan may include medications to destroy cancer cells. Medication may be given through the bloodstream to reach cancer cells throughout the body. When a drug is given this way, it is called systemic therapy.

This treatment is generally prescribed by a medical oncologist, a doctor who specializes in treating cancer with medication.

Medications are often given through an intravenous (IV) tube placed into a vein using a needle or as a pill or capsule that is swallowed (orally). If you are given oral medications, be sure to ask your health care team about how to safely store and handle them.

The types of medications used for metastatic breast cancer include:

  • Hormonal therapy

  • Chemotherapy

  • Targeted therapy

  • Immunotherapy

Each of these types of therapies are discussed below in more detail. A person may receive 1 type of medication at a time or a combination of medications given at the same time. The first set of drugs used for metastatic disease is called first-line treatment. If the cancer worsens, another combination of drugs 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. It is also important to let your doctor know if you are taking any other prescription or over-the-counter medications or supplements. Herbs, supplements, and other drugs can interact with cancer medications, causing unwanted side effects or reduced effectiveness. 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 estrogen receptors (ER) or progesterone receptors (PR).

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

In general, hormonal therapy is recommended for all patients with hormone receptor-positive breast cancer. The available treatment options are based on several factors:

  • Whether you are still menstruating or have gone through menopause

  • The type of treatment you have already received or are currently receiving

  • How long it had been before the cancer recurred

  • How widespread the cancer is and whether you have symptoms that need to be managed

  • Your gender

Options for hormonal therapy include:

  • Tamoxifen (available as a generic drug). 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. Very rare risks include a cancer of the lining of the uterus, cataracts, and blood clots. This treatment is an option for anyone and does not depend on menopausal status.

  • Aromatase inhibitors (AIs; available as generic drugs). AIs decrease the amount of estrogen made by tissues other than the ovaries by blocking the aromatase enzyme. This enzyme changes hormones called androgens into estrogen when the ovaries have stopped making estrogen after menopause, and AIs block this change. 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, patients who experience too many side effects while taking 1 AI may have fewer side effects with another AI for unclear reasons. Both premenopausal women and men can take AIs as long as they are given in combination with an injectable medication. People who have not gone through menopause should not take AIs without the injectable medication to block ovarian function, as they do not block the effects of estrogen made by the ovaries. Often, doctors will monitor blood estrogen levels in people whose periods have recently stopped, or in those whose periods have stopped because of chemotherapy, to be sure that the ovaries are no longer making estrogen. The ovaries typically stop producing estrogen around age 50 to 55.

  • 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, an AI, or fulvestrant (see below). Drugs called gonadotropin or luteinizing releasing hormone (GnRH or LHRH) analogs can stop the ovaries from making estrogen, causing temporary menopause. Some examples of these medicines include goserelin (Zoladex) or leuprolide (Eligard, Lupron), both of which are usually taken monthly. Surgery to remove both ovaries also permanently stops estrogen production.

    Ovarian suppression is commonly used as a part of treatment for hormone receptor-positive metastatic breast cancer in people who have not been through menopause. This is because completely blocking estrogen may be helpful against the cancer.

  • Fulvestrant (Faslodex). Fulvestrant is a selective estrogen receptor downregulator (SERD) that blocks the ability of estrogen to attach to estrogen 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 the first 3 doses and then continued monthly. Fulvestrant is only for people who have been through menopause or who are also receiving a shot to stop their ovarian function. It can also be used to treat men. A combination of anastrozole or letrozole and fulvestrant is an option for patients who have not previously had hormonal therapy.

  • Other hormonal therapies. Other hormonal therapies occasionally used to treat metastatic breast cancer include megestrol acetate (Megace) and high-dose estradiol.

If the first hormonal therapy, given either by itself or combined with a targeted therapy (see below), no longer works or is not tolerated, switching to another type of hormonal therapy may be an option unless the cancer has worsened quickly and is affecting how well the body’s organs are working. The new hormonal therapy can also be combined with some types of targeted therapy. If treatment with hormonal therapy with or without targeted therapy no longer works, the American Society of Clinical Oncology (ASCO) recommends chemotherapy regimens using 1 drug for people with metastatic hormone-receptor positive breast cancer. Chemotherapy combined with hormonal therapy is not recommended.

For men with metastatic hormone receptor-positive, HER2-negative breast cancer, ASCO recommends hormonal therapy with tamoxifen. Other options include an AI combined with a medication to lower androgen production, such as goserelin or leuprolide, or fulvestrant. If metastatic hormone receptor-positive, HER2-negative breast cancer recurs or progresses during hormonal therapy, different hormonal therapy should be offered when possible. Learn more about types of treatment for breast cancer in men in a different guide on this website. This information is based on ASCO's recommendations for the management of male breast cancer. Please note that this link takes you to a separate ASCO website.

Learn more about the basics of hormone therapy.

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Chemotherapy

Chemotherapy is the use of drugs to destroy cancer cells, usually by keeping the cancer cells from growing, dividing, and making more cells.

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, 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 person with metastatic breast cancer usually receives a regimen that includes only a single type of chemotherapy at a time, rather than a combination. ASCO recommends that people with metastatic triple-negative breast cancer that does not express PD-L1 and people with metastatic hormone receptor-positive, HER2-negative breast cancer who are no longer benefiting from hormonal therapy be offered chemotherapy regimens that use only 1 drug. However, some people with these types of cancer may be offered a combination chemotherapy regimen depending on their symptoms and prognosis.

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. People with inherited BRCA mutations who have metastatic breast cancer should be offered platinum chemotherapy, if possible.

Drugs that may be used for metastatic breast cancer include:

  • Capecitabine (Xeloda, available as a generic drug)

  • Carboplatin (Paraplatin, available as a generic drug)

  • Cisplatin (Platinol, available as a generic drug)

  • Cyclophosphamide (Cytoxan, available as a generic drug)

  • Docetaxel (Taxotere)

  • Doxorubicin (Adriamycin, available as a generic drug)

  • Pegylated liposomal doxorubicin (Doxil)

  • Epirubicin (Ellence, available as a generic drug)

  • Eribulin (Halaven)

  • Fluorouracil (5-FU, Adrucil, available as a generic drug)

  • Gemcitabine (Gemzar, available as a generic drug)

  • Ixabepilone (Ixempra)

  • Methotrexate (available as a general drug)

  • Nab-paclitaxel (Abraxane)

  • Paclitaxel (Taxol, available as a generic drug)

  • Vinorelbine (Navelbine, available as a generic drug)

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, mouth sores, hair loss, rash, loss of appetite, numbness and tingling from nerve damage, and diarrhea. These side effects can often be very successfully prevented or managed during treatment with supportive medications, and most 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.

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Targeted therapy (updated 06/2022)

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. This type of treatment blocks the growth and spread of cancer cells and limits 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, trastuzumab deruxtecan, ado-trastuzumab emtansine, sacituzumab govitecan-hziy, and pembrolizumab.

  • 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 metastatic breast cancer include lapatinib, neratinib, tucatinib, palbociclib, ribociclib, abemaciclib, olaparib, talazoparib, alpelisib, and everolimus (see below).

  • Tumor-agnostic treatments. A tumor-agnostic treatment is a drug treatment that is used to treat any kind of cancer, regardless of where in the body it started or the type of tissue from which it developed. This type of treatment can be used when the tumor has a very specific molecular alteration that is targeted by the drug. The drugs larotrectinib (Vitrakvi) and entrectinib (Rozlytrek) are examples of tumor-agnostic targeted therapies. They are approved for any cancer with an NTRK fusion (see Diagnosis), including breast cancer that is metastatic or cannot be removed with surgery and has worsened with other treatments. Another tumor-agnostic treatment for breast cancer is a type of immunotherapy called pembrolizumab (Keytruda; see "Immunotherapy," below).

ASCO recommendations support using the same targeted therapies to treat metastatic breast cancer in both men and women. Talk with your doctor about possible side effects of specific targeted therapies and how they can be managed.

Targeted therapy for metastatic hormone receptor-positive, HER2-negative breast cancer (updated 06/2022)

  • Palbociclib (Ibrance). This oral drug targets a protein in breast cancer cells called CDK4/6, which may stimulate cancer cell growth. It is called a CDK4/6 inhibitor. Used along with the AI medication letrozole or anastrozole, this drug is an option for first-line treatment for women who have been through menopause and have ER-positive, HER2-negative metastatic breast cancer. Palbociclib can also be used with fulvestrant for any patient whose cancer has worsened or recurred after receiving an AI medication by itself. 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 also targets CDK4/6. Used with an AI, it is an option for women who have been through menopause and have ER-positive, HER2-negative metastatic breast cancer. Ribociclib can also be used with fulvestrant for any patient whose cancer has worsened or recurred after receiving an AI medication by itself. 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 U.S. Food and Drug Administration (FDA) as a first-line treatment along with the AI medication letrozole or anastrozole for women who have been through menopause and have ER-positive, HER2-negative metastatic breast cancer. It may also be used along with fulvestrant for any patient whose cancer has worsened or recurred after receiving an AI medication by itself. It may also be used alone, without a hormone 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.

In people with male breast cancer or in women who have not gone through menopause, an AI and CDK4/6 inhibitor should be combined with a gonadotropin-releasing hormone analog or ovarian suppression.

  • 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.

  • Alpelisib (Piqray). Alpelisib is an option along with the hormonal therapy fulvestrant for some people with hormone receptor-positive, HER2-negative metastatic breast cancer that has a PIK3CA gene mutation (as diagnosed through biomarker testing on a blood or tumor tissue sample; see Diagnosis) and has worsened during or after hormonal therapy. This includes patients who have gone through menopause and those with male breast cancer. Side effects include diarrhea, rash, fatigue, changes in numbers of blood cells, nausea and vomiting, mouth sores, and changes in certain substances found in the blood, including high sugar levels and enzymes linked with liver damage.

Targeted therapy for people with metastatic HER2-negative breast cancer (updated 06/2022)

PARP inhibitors are a type of treatment that destroy cancer cells by preventing them from fixing damage. Two PARP inhibitor medications, olaparib and talazoparib, are described below. ASCO recommends that people with metastatic hormone receptor-positive, HER2-negative breast cancer who have a BRCA1 or BRCA2 gene mutation be offered an oral PARP inhibitor as an alternative to chemotherapy if they are no longer benefiting from hormonal therapy. In addition, ASCO recommends that people with metastatic triple-negative breast cancer who have a BRCA1 or BRCA2 gene mutation and who have previously received treatment with chemotherapy be offered an oral PARP inhibitor as an alternative to starting treatment with a new type of chemotherapy. Therefore, ASCO recommends that people who are candidates for treatment with a PARP inhibitor should undergo testing to see if they have an inherited 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 as an alternative to chemotherapy. Common side effects include fatigue, nausea and vomiting, headaches, diarrhea, decreased appetite, and lower levels of certain blood cells.

  • Talazoparib (Talzenna). This drug is another option for patients with metastatic HER2-negative breast cancer and a BRCA1 or BRCA2 gene mutation as an alternative to chemotherapy. The most common side effects include fatigue, nausea and vomiting, headache, diarrhea, decreased appetite, hair loss, and lower levels of certain blood cells.

This information is based on several ASCO guidelines for the treatment of breast cancer. Read more about these recommendations on the ASCO website.

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Immunotherapy (updated 06/2022)

Immunotherapy, also called biologic therapy, is designed to boost the body's natural defenses to fight the cancer. It uses materials made either by the body or in a laboratory to improve, target, or restore immune system function. The following drugs, which are a type of immunotherapy called immune checkpoint inhibitors, are used for recurrent and advanced or metastatic breast cancer. Pembrolizumab is also used for high-risk, early-stage disease. ASCO recommends that people with metastatic cancer who are candidates for receiving one of the following drugs have their tumors tested for molecular alterations called microsatellite instability-high (MSI-H), DNA mismatch repair deficiency (dMMR), and/or tumor mutational burden (see Diagnosis).

  • Pembrolizumab (Keytruda). This is a type of immunotherapy that is approved by the FDA to treat metastatic cancer or cancer that cannot be treated with surgery. For people with metastatic cancer, ASCO recommends biomarker testing for tumor mutational burden, which is the number of mutations in a cancer cell, as well as MSI-H and dMMR, to determine if they can receive pembrolizumab alone. Pembrolizumab is also approved in combination with a few different chemotherapy drugs to treat metastatic or locally recurrent triple-negative breast cancer that cannot be treated with surgery and that tests positive for PD-L1 (see Diagnosis).
  • Dostarlimab (Jemperli). This type of immunotherapy is approved by the FDA to treat recurrent or metastatic breast cancers that have dMMR and have progressed during or after previous treatment.

Different types of immunotherapy can cause different side effects. Common side effects include skin reactions, flu-like symptoms, diarrhea, and weight changes. Talk with your doctor about possible side effects for the immunotherapy recommended for you. Learn more about the basics of immunotherapy and immunotherapy and breast cancer.

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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. This is radiation therapy that is directed at the entire brain.

  • Stereotactic radiosurgery. This 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. This 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 that depend on the type of radiation therapy given and where on the body it is directed.

Learn more about the basics of radiation therapy.

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Surgery

Surgery is the removal of the 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 an option 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.

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Summary of treatment options for metastatic breast cancer

Hormone receptor-positive, HER2-negative breast cancer

Hormonal therapy is considered the standard initial treatment for HER2-negative metastatic breast cancer that is also hormone receptor-positive. It is often given in combination with targeted therapy. However, chemotherapy may also be given. A clinical trial may also be an option for treatment at any stage.

  • Hormone therapy and targeted therapy. As described above, hormone therapy with or without targeted therapy is generally given as front-line treatment for metastatic breast cancer. If the first hormonal therapy given no longer works or is not tolerated, switching to another type of hormonal therapy may be an option unless the cancer has worsened quickly and is affecting how well the body’s organs are working.

  • Chemotherapy. Chemotherapy is typically given after hormone therapies are no longer effective. There is no specific type of chemotherapy recommended for this type of breast cancer. Many drugs are available, including those discussed under "Chemotherapy," above. The best chemotherapy option for each patient depends on several factors, including the previous treatments received, potential side effects, overall health, and the patient’s preference. Generally, chemotherapy should continue until the disease worsens if a patient is not experiencing unmanageable side effects. At some point, chemotherapy may no longer be able to control the cancer’s growth. When this happens, patients may choose to stop chemotherapy while continuing to receive palliative care.

  • Immunotherapy. As described above, immunotherapy can be used to treat this type of breast cancer if it has dMMR or a high tumor mutation burden. Immunotherapy is not usually used in combination with chemotherapy to treat hormone receptor-positive breast cancer.

  • Targeted therapy. Some targeted therapies, such as PARP inhibitors, can be used to treat specific subsets of hormone receptor-positive, HER2-negative breast cancer that occurs in patients with mutations in BRCA genes.

Hormone receptor-negative, HER2-negative breast cancer

In general, chemotherapy or targeted therapy is given for treatment of triple-negative breast cancer. A clinical trial may also be an option for treatment at any stage.

  • Chemotherapy. There is no specific type of chemotherapy recommended for this type of breast cancer. Many drugs are available, including those discussed under "Chemotherapy," above. The best chemotherapy option for each patient depends on several factors, including the previous treatments received, potential side effects, overall health, and the patient’s preference.

    Generally, chemotherapy should continue until the disease worsens if a patient is not experiencing unmanageable side effects. At some point, chemotherapy may no longer be able to control the cancer’s growth. When this happens, patients may choose to stop chemotherapy while continuing to receive palliative care.

  • Immunotherapy and targeted therapy. As described above, a number of immunotherapies and targeted therapies can be used to treat triple-negative breast cancer. Some can be used to treat specific subsets of triple-negative breast cancer, such as those that are PD-L1 positive or occur in patients with mutations in BRCA genes. Others can be used to treat any patients with triple-negative breast cancer.

HER2-positive breast cancer that has spread to parts of the body other than the brain (updated 05/2022)

In general, HER2-targeted therapy is regularly 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 described 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, unless the patient is unable to take taxanes. 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. After chemotherapy ends, HER2-targeted therapy is generally continued until the disease worsens. For people with hormone receptor-positive cancer, hormonal therapy is usually added after chemotherapy ends.

  • 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.

Second-line treatment

  • For people with advanced breast cancer that has grown during or after first-line treatment with a HER2-targeted therapy, ASCO recommends trastuzumab deruxtecan as a second-line treatment.

Third-line or higher treatment

  • Trastuzumab emtansine 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. It is usually given in combination with trastuzumab.

  • For patients who have already received trastuzumab emtansine and pertuzumab, there are multiple other options available for treatment in the third line and beyond. They include tucatinib with capecitabine and trastuzumab, trastuzumab deruxtecan (if not previously received), neratinib with capecitabine, lapatinib with capecitabine or trastuzumab, other combinations of chemotherapy with trastuzumab, or hormonal therapy when appropriate. There is not yet enough information on which of these third-line treatments is best.

This information is based on ASCO’s recommendations on Systemic Therapy for Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer. Please note that this link takes you to a separate ASCO website.

HER2-positive breast cancer that has spread to the brain (updated 05/2022)

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 number, size, and location of the tumor(s) in the brain and whether they are causing symptoms, as well as the patient’s general health and the risk of removing the tumors with surgery.

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

  • People with 1 brain metastasis have several treatment options. One option is surgery followed by radiation therapy. Another option is stereotactic radiosurgery, possibly followed by whole brain radiotherapy. A third option is hypofractionated stereotactic radiation therapy, which is when a person receives a higher dose of radiation therapy each day given over a fewer number of days, as opposed to lower doses given over a longer period of time. Finally, systemic therapy may also be an option for certain patients if the brain metastasis is not causing any symptoms. After treatment, imaging tests every 2 to 4 months may be recommended.

  • People with 2 to 4 brain metastases may undergo surgery followed by radiation therapy, stereotactic radiosurgery alone, or a combination of stereotactic radiosurgery with whole brain radiation therapy. Hypofractionated stereotactic radiation therapy may also be an option, particularly for metastases that are larger than 3 to 4 cm and that cannot be removed with surgery.

  • People with brain metastases smaller than 3 to 4 cm may undergo surgery followed by radiation therapy, particularly if the metastases are causing symptoms. Other options include stereotactic radiosurgery alone or with whole brain radiation therapy, or hypofractionated stereotactic radiation therapy. Systemic therapy may also be an option if the brain tumors are not causing symptoms.

  • For people with widespread or extensive metastases, treatment options include stereotactic radiosurgery alone or with whole brain radiotherapy. For those whose cancer has spread to the surface of the brain and are experiencing symptoms, treatment may include 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, a clinical trial, palliative care, and/or a systemic drug that can affect the whole body, such as chemotherapy or HER2-targeted therapy. In particular, the combination of tucatinib, capecitabine, and trastuzumab has been approved for treatment of some patients with HER2-positive breast cancer that has spread to the brain. It may be offered to people who have been treated with 1 or more HER2-targeted treatment and whose brain metastases have worsened, as well as to people whose brain metastases have stabilized. In addition, for people whose brain metastases have stabilized, another treatment option is trastuzumab deruxtecan.

  • 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, HER2-targeted therapy may be added or changed based on the recommendations for HER2-positive cancer that has spread to parts of the body other than the brain (see above).

The information in this section is based on the ASCO guideline, “Management of Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases,” and a joint guideline from ASCO, the Society for Neuro-Oncology (SNO), and the American Society for Radiation Oncology (ASTRO), “Treatment for Brain Metastases.” Please note that these links take you to a different ASCO website.

Learn about caring for someone with cancer that has spread to the brain.

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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.