The Who, What, Where, When and Sometimes, Why.

Treatments for Metastatic Breast Cancer

Important information about coronavirus (COVID-19).

What is metastatic breast cancer?

Metastatic breast cancer (also called stage IV or advanced breast cancer) is not a specific type of breast cancer. It’s the most advanced stage of breast cancer.

Metastatic breast cancer is breast cancer that has spread beyond the breast and nearby lymph nodes to other parts of the body (most often the bones, lungs, liver or brain).

Although metastatic breast cancer has spread to another part of the body, it’s still breast cancer and treated as breast cancer.

For example, breast cancer that has spread to the bones is still breast cancer (not bone cancer). It may also be called metastatic breast cancer in the bones or bone metastases. It’s not the same as cancer that starts in the bone. Breast cancer cells have invaded the bones. So, it’s treated with breast cancer drugs rather than treatments for cancer that began in the bones.

When can metastatic breast cancer occur?

Some people have metastatic breast cancer when they are first diagnosed with breast cancer (about 6 percent of diagnoses in U.S. women and 9 percent of diagnoses in U.S. men) [3]. This is called de novo metastatic breast cancer.

Most often, metastatic breast cancer arises years after a person has completed treatment for early or locally advanced breast cancer. This is sometimes called a distant recurrence.

A diagnosis of metastatic breast cancer is not your fault. You did nothing to cause the cancer to spread.

Most metastatic breast cancers are breast cancer cells that remained in the body after treatment for early breast cancer. The breast cancer cells were always there, but were dormant (inactive) and could not be detected. For some unknown reason, the cancer cells began to grow again. This process is not well-understood.

The risk of metastatic breast cancer

If you’ve been diagnosed with metastatic breast cancer, you’re not alone. It’s estimated there will be more than 168,000 women living with metastatic breast cancer in the U.S. in 2020 [1]. Men can also get metastatic breast cancer.

The risk of metastasis after breast cancer treatment varies from person to person. It depends on:

  • The biology of the tumor (characteristics of the cancer cells)
  • The stage at the time of the original diagnosis
  • The treatments for the original cancer (trying to prevent breast cancer recurrence)

Treatment

As hard as it is to hear, metastatic breast cancer cannot be cured today. Unlike breast cancer that remains in the breast or nearby lymph nodes, you can’t get rid of all the cancer that has spread to other parts of the body.

However, metastatic breast cancer can be treated. Treatment focuses on extending life and improving quality of life.

Your treatment plan is guided by many factors, including:

  • The biology of the tumor (characteristics of the cancer cells)
  • Where the cancer has spread
  • Your symptoms
  • Past breast cancer treatments

It’s always OK to get a second opinion at any time during your treatment.

Learn more about factors that affect treatment options.

Learn about emerging areas in treatment.

Personal genetic testing for inherited gene mutations

The National Comprehensive Cancer Network recommends everyone diagnosed with metastatic breast cancer get genetic testing for BRCA1 and BRCA2 gene mutations [4]. If you have a mutation in one of these genes, a PARP inhibitor may be included in your treatment plan.

Learn more about BRCA1/2 gene mutations.

Learn more about genetic testing.

The biology of the tumor

Many tests will be done on a sample of the metastatic tumor (from a biopsy of the metastases). The main tests are:

Which tumors are tested?What does the tumor test determine?How do the test results guide treatment?
All tumorsHormone receptor status (estrogen and progesterone receptor status)If the cancer is hormone receptor-positive, the first treatment is usually hormone therapy, often with a CDK4/6 inhibitor.
All tumorsHER2 statusIf the cancer is HER2-positive, HER2-targeted therapies, such as trastuzumab (Herceptin), are included in the treatment plan.
Tumors that are both hormone receptor-positive and HER2-negativeWhether the tumor has a PIK3CA gene mutationIf the tumor has a PIK3CA gene mutation, the cancer may be treated with the PI3 kinase inhibitor alpelisib and the hormone therapy fulvestrant.
Triple negative breast cancers (tumors that are both hormone receptor-negative and HER2-negative)PD-L1 statusIf the cancer is PD-L1-positive, the first treatment may be the immunotherapy drug atezolizumab (Tecentriq) in combination with chemotherapy.
Adapted from NCCN, 2020 [4]

Quality of life

Talking about quality of life issues with your health care providers and your family can help you decide what treatments are best for you.

Joining a support group may also help you think through these issues.

Learn about managing side effects and supportive care.

Learn about pain management.

Treatment guidelines

Although the exact treatment for metastatic breast cancer varies from person to person, guidelines help ensure high-quality care. These guidelines are based on the latest research and agreement among experts.

The National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) are respected organizations that regularly review and update their guidelines.

In addition, the National Cancer Institute (NCI) has treatment overviews.

Talk with your health care providers about which treatment guidelines they use.

Prognosis

Modern treatments continue to improve survival for people with metastatic breast cancer. However, survival varies greatly from person to person.

About one-third of women diagnosed with metastatic breast cancer in the U.S. live at least 5 years after diagnosis [1]. Some women may live 10 or more years beyond diagnosis [2].

Your oncologist can give you some information about your prognosis, but they don’t know exactly how long you will live.

Monitoring metastatic breast cancer

Tumors can respond to many different drug therapies for metastatic breast cancer. This means the drugs can shrink the tumors.

However, over time, tumors can become resistant (stop responding) to drugs used to treat metastatic breast cancer.

Monitoring

If you have metastatic breast cancer, you’ll be monitored every few months to see if the cancer is responding to treatment. This is called “restaging.” Tests may include a physical exam, blood tests and/or imaging tests (such as an X-ray, CT scan, PET scan or bone scan).

Drug resistance

Some metastatic breast cancer cells need specific proteins or cell pathways to grow. Drugs that target the proteins or pathways can slow or stop the growth of these cancer cells for a period of time.

You can think of the proteins as traffic signs and the pathways as roads. Breast cancer cells must pass through the signs to continue along the road.

If the cancer cell hits a roadblock (such as a drug that targets the protein), it can’t continue down that pathway.

At some point however, the cancer cell finds a detour around the roadblock and uses another pathway to continue to grow.

Scan anxiety (scanxiety)

It’s normal to feel anxious before these tests (some call this scan anxiety or scanxiety). If it helps, talk to a friend or family member, or bring them with you to the appointment. You can also talk with your health care provider about ways to cope with this stress.

Learn more about coping with stress, such as mindfulness meditation.

Susan G. Komen®’s Breast Care Helpline:
1-877 GO KOMEN (1-877-465-6636)
  

Calls to our Breast Care Helpline are answered by a trained and caring staff member Monday through Friday from 9:00 a.m. to 10:00 p.m. ET. Our helpline provides free, professional support services to anyone with questions or concerns about breast cancer, including people diagnosed with breast cancer and their families.

You can also email the helpline at helpline@komen.org.

Changing drug therapies

Because metastatic breast cancers often develop resistance to drugs, it’s common to change therapies multiple times.

You usually start a drug therapy and then see whether:

  • It controls the growth of the cancer
  • The side effects can be managed

If the treatment is working at the time of restaging (and the side effects aren’t too bad), the treatment is typically continued.

If the treatment is no longer working or if you’re having a lot of side effects, your oncologist may switch you to a different drug. Your oncologist may also change the dose or schedule of the treatment to reduce the side effects.

Blood tests for tumor markers

In some cases, blood tests for tumor markers may be used to help monitor metastatic breast cancer.

For example, you may have blood tests every few months for cancer antigen 15-3 (CA15-3) or cancer antigen 27.29 (CA27.29) [4]. These tests are similar. Health care providers usually check one, but not both of these blood tests.

Whether the tumor marker test score rises or falls over time may give some information on tumor response to a drug or tumor spread.

Tumor marker tests are not helpful in every case. Some people with rising tumor marker levels don’t have tumor growth and some people with tumor growth have normal or unchanged tumor marker levels.

Health care providers don’t make treatment decisions based on serum tumor marker testing alone. They may combine findings from a tumor marker test with information on symptoms and findings from imaging tests (such as bone scans). This combined information can help your providers understand if your treatment is working well for your cancer.

Talk with your provider about whether tumor marker testing is right for you.

Hormone therapy

Hormone therapy is usually the first treatment for hormone receptor-positive metastatic breast cancers. Hormone therapy is also called endocrine therapy.

Hormone therapy drugs work by preventing the cancer cells from getting the estrogen they need to grow.

For women, the choice of hormone therapy depends on menopausal status and any past hormone treatment for early breast cancer [4].

Some hormone therapy drugs (like tamoxifen and aromatase inhibitors) are pills. Others (like goserelin or fulvestrant) are given by injection (a shot).

Find a list of hormone therapy drugs used to treat metastatic breast cancer and whether they are pills or given by injection.

Hormone therapy for premenopausal women

For premenopausal women with metastatic breast cancer, hormone therapy almost always begins with ovarian suppression.

Ovarian suppression lowers hormone levels in the body so the tumor can’t get the estrogen it needs to grow. This may involve surgery to remove the ovaries (oophorectomy) or, more often, drugs (such as goserelin or leuprolide) to stop the ovaries from producing hormones.

Tamoxifen is also used to treat metastatic breast cancer in premenopausal women. However, it may not be an option for women whose cancer progressed during past tamoxifen treatment.

Combining ovarian suppression and tamoxifen improves survival over either treatment alone [5].

Hormone therapy for postmenopausal women

After menopause, hormone therapy for women with metastatic breast cancer can be an aromatase inhibitor, tamoxifen, fulvestrant or another hormone therapy drug.

If the first hormone therapy stops working and the cancer starts to grow again, a second hormone therapy can be used. If the second drug stops working, another can be tried.

Ovarian suppression isn’t helpful for postmenopausal women because their ovaries have already stopped producing large amounts of estrogen. (Postmenopausal women still make a small amount of estrogen in fat tissue and the adrenal glands.)

When hormone therapy stops working

At some point, even though it may be years away, hormone therapy almost always stops working. At this point, chemotherapy may be recommended.

Drugs used in combination with hormone therapy

CDK4/6 inhibitors, mTOR inhibitors and PI3 kinase inhibitors are types of drugs used in combination with hormone therapy to treat some metastatic breast cancers.    

Abemaciclib (Verzenio), palbociclib (Ibrance) and ribociclib (Kisqali) and hormone therapy

The CDK4/6 inhibitors FDA-approved for metastatic breast cancer treatment are:

  • Abemaciclib (Verzenio)
  • Palbociclib (Ibrance)
  • Ribociclib (Kisqali)

CDK4 and CDK6 are enzymes important in cell division. CDK4/6 inhibitors are a class of drugs designed to interrupt the growth of cancer cells.

Although the CDK4/6 inhibitors abemaciclib, palbociclib and ribociclib have not been compared directly to one another, studies show similar results with each drug [6-14].

A CDK4/6 inhibitor in combination with hormone therapy can be used to treat hormone receptor-positive, HER2-negative metastatic breast cancers. Compared to treatment with hormone therapy alone, this combination can give people more time before the cancer spreads and increase overall survival [6-14].

The CDK4/6 inhibitor abemaciclib may also be used alone to treat hormone receptor-positive, HER2-negative cancers that have progressed during past hormone therapy and chemotherapy.

Abemaciclib, palbociclib and ribociclib are pills.

The table below lists some possible side effects for CDK4/6 inhibitors.

CDK4/6 InhibitorSide Effects
AbemaciclibSome possible side effects include diarrhea, low white blood cell counts, low red blood cell counts (anemia), blood clots, nausea, abdominal pain, fatigue and vomiting.

In some cases, it can cause liver problems. Your liver function will be checked before treatment begins and throughout your treatment.

In rare cases, it can cause lung inflammation, which can cause death. Tell your provider right away if you have shortness of breath or other breathing problems while taking this drug.

PalbociclibSome possible side effects include low white blood cell counts, low red blood cell counts (anemia), fatigue, nausea, mouth sores, hair thinning, diarrhea and in rare cases, blood clots.

In rare cases, it can cause lung inflammation, which can cause death. Tell your provider right away if you have shortness of breath or other breathing problems while taking this drug.

RibociclibSome possible side effects include low white blood cell counts, nausea, fatigue, diarrhea, hair loss, vomiting, constipation, headache and back pain.

In some cases, it can cause liver problems. Your liver function will be checked before treatment begins and throughout your treatment.

In rare cases, it can cause changes on an EKG (electrocardiogram). An EKG gives information on the electrical activity of the heart. You will get an EKG before treatment begins and throughout your treatment to check for any changes.

In rare cases, it can cause lung inflammation, which can cause death. Tell your provider right away if you have shortness of breath or other breathing problems while taking this drug.

Adapted from select sources [6-18].

 

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For a summary of research studies on the use of CDK4/6 inhibitors in treating metastatic breast cancer, visit the Breast Cancer Research Studies section.

Everolimus (Afinitor) and hormone therapy

Everolimus (Afinitor) is an mTOR (mammalian target of rapamycin) inhibitor. mTOR inhibitors are a class of drugs that may increase the benefit of hormone therapy.

Everolimus is FDA-approved for the treatment of hormone receptor-positive, HER2-negative metastatic breast cancers in postmenopausal women. The combination of everolimus and the aromatase inhibitor exemestane can slow the growth of such cancers better than exemestane alone [19].

Everolimus is a pill.

 Side Effects
EverolimusSome possible side effects include mouth ulcers, infections, rash, fatigue, diarrhea and decreased appetite.

In rare cases, it can cause lung inflammation, which can cause death. Tell your provider right away if you have shortness of breath or other breathing problems while taking this drug.

Adapted from select sources [19-20]. 

 

Alpelisib (Piqray) and hormone therapy

Alpelisib (Piqray) is a PI3 kinase inhibitor.

PI3 kinase is an enzyme important in cell growth. The PIK3CA gene helps control PI3 kinase enzyme activity. Some breast cancers have a PIK3CA gene mutation. This gene mutation is in the genes of breast cancer, not the person.

PI3 kinase inhibitors are a class of drugs designed to interrupt PI3 kinase signals and stop the growth of breast cancer cells with PIK3CA gene mutations.

Alpelisib in combination with the hormone therapy fulvestrant is FDA-approved to treat hormone receptor-positive, HER2-negative metastatic breast cancers with a PIK3CA gene mutation that have been treated with hormone therapy in the past.

The combination of alpelisib and fulvestrant can give more time before the cancer spreads compared to fulvestrant alone [21].

If alpelisib is being considered for your treatment plan, your tumor will be checked to see if it has a PIK3CA gene mutation. This can be done by testing tumor tissue or testing for tumor DNA in your blood [4].

Alpelisib is a pill.

 Side Effects
AlpelisibSome possible side effects include high blood sugar, diarrhea, nausea, decreased appetite, rash, vomiting, fatigue and hair loss.

Blood sugar levels are monitored while taking alpelisib because nearly everyone who takes it develops high blood sugar.

It’s recommended you take an antihistamine (such as cetirizine (Zyrtec)) to lower the risk of rash.

Adapted from select sources [21-22].

Chemotherapy

Chemotherapy is the preferred treatment for metastatic breast cancers that are:

One benefit of chemotherapy is response time. Chemotherapy may shrink tumors faster than hormone therapy.

As with hormone therapies, if the first chemotherapy drug (or combination of drugs) stops working and the cancer begins to grow again, a second or third drug can be used.

The use of each type of chemotherapy drug (or combination of drugs) for metastatic breast cancer is called a “line” of treatment. For example, the first chemotherapy used is called the “first-line” treatment and the second is called the “second-line” treatment.

With each line of treatment, it becomes less likely the cancer will shrink. And, if the cancer does shrink, it’s often for a shorter period of time with each new drug.

It’s common to get multiple lines of chemotherapy regimens (often 4 or more) over the course of treatment for metastatic breast cancer.

Learn more about chemotherapy.

This table lists the most common chemotherapy drugs (used alone or in combination) to treat metastatic breast cancer. This list is not exhaustive and does not include drugs rarely used or no longer in use.

Chemotherapy drugs for metastatic breast cancer

Drug (abbreviation)

Brand name

Pill or IV drug (given by vein through an IV)

Capecitabine

Xeloda

Pill

Carboplatin

Paraplatin

IV drug

Cisplatin

Platinol

IV drug

Cyclophosphamide (C)

Cytoxan

Pill or IV drug

Docetaxel (T)

Taxotere

IV drug

Doxorubicin (A)

Adriamycin

IV drug

Epirubicin (E)

Ellence

IV drug

Eribulin

Halaven

IV drug

5-Fluorouracil (5FU or F)

Adrucil

IV drug

Gemcitabine

Gemzar

IV drug

Ixabepilone

Ixempra

IV drug

Liposomal doxorubicin

Doxil

IV drug

Methotrexate (M)

Maxtrex

Pill or IV drug

Paclitaxel (T)

Taxol

IV drug

Paclitaxel, albumin bound (nab-paclitaxel)

Abraxane

IV drug

Vinorelbine

Navelbine

IV drug

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

To learn more about a specific chemotherapy drug, visit the National Institutes of Health’s Medline Plus website.

 

HER2-targeted therapy

HER2-positive breast cancer

About 10-20 percent of breast cancers have high amounts of a protein called HER2 on the surface of the cancer cells (called HER2-positive breast cancer) [23-24]. The HER2 protein is important for cancer cell growth.

A pathologist determines HER2 status by testing tumor tissue removed during a biopsy.

HER2-targeted therapies are used to treat HER2-positive breast cancers.

 HER2-targeted therapies for HER2-positive metastatic breast cancers

Drug name

Brand name(s)

Pill, injection under the skin, or IV drug (given by vein through an IV)?

Trastuzumab

Herceptin (IV drug), Herceptin Hylecta (injection)

IV drug or injection

Pertuzumab

Perjeta

IV drug

Pertuzumab, trastuzumab and hyaluronidase–zzxf

Phesgo

Injection

Ado-trastuzumab emtansine (T-DM1)

Kadcyla

IV drug

Fam-trastuzumab deruxtecan (trastuzumab deruxtecan)

Enhertu

IV drug

Tucatinib

Tukysa

Pill

Neratinib

Nerlynx

Pill

Lapatinib

Tykerb

Pill

 

Trastuzumab (Herceptin)

Trastuzumab (Herceptin) is a specially made antibody that targets HER2-positive cancer cells. When attached to the HER2 protein, trastuzumab can slow or stop the growth of these cells.

Trastuzumab is only used to treat HER2-positive breast cancers.

It can shrink tumors and slow the growth of HER2-positive metastatic breast cancers when used alone or combined with chemotherapy [25-27].

Trastuzumab is given by vein (through an IV) or by injection.

 Side Effects
TrastuzumabSome possible side effects include headache, fever and chills.

It does not cause hair loss, nausea or vomiting, and has no effect on bone marrow.

Serious heart problems have been linked to the use of trastuzumab. Your heart will be checked before and during treatment to help ensure there are no problems.

Adapted from select sources [4,25].

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For a summary of research studies on trastuzumab and treatment of metastatic breast cancer, visit the Breast Cancer Research Studies section.

Biosimilar trastuzumab

A biosimilar drug is a “generic-like” version of a drug that contains biological products (biologics) such as antibodies or proteins. Trastuzumab is a biologic drug.

There are some FDA-approved biosimilar forms of trastuzumab. These biosimilars are safe and effective treatments for early and metastatic HER2-positive breast cancers.

Learn more about biosimilars.

Pertuzumab (Perjeta)

Pertuzumab (Perjeta) is a specially made antibody that targets HER2-positive cancer cells, but in a different way than trastuzumab.

Pertuzumab is FDA-approved as a first treatment of HER2-positive metastatic breast cancers.

Study findings have shown pertuzumab in combination with trastuzumab and chemotherapy can slow the growth of HER2-positive metastatic breast cancer and increase survival better than trastuzumab and chemotherapy alone [28-29].

Pertuzumab is given by vein (through an IV) or, when combined with trastuzumab, it may be given by injection under the skin.

 Side Effects
PertuzumabSome possible side effects include diarrhea, rash, vomiting, headache and dry skin.

Adapted from select sources [28-29].

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For a summary of research studies on pertuzumab and treatment of metastatic breast cancer, visit the Breast Cancer Research Studies section.

Ado-trastuzumab emtansine (Kadcyla, T-DM1, trastuzumab emtansine)

Ado-trastuzumab emtansine (Kadcyla, T-DM1, trastuzumab emtansine) is a type of HER2 antibody-drug conjugate. It consists of trastuzumab and a chemotherapy called DM1 (so it’s sometimes called T-DM1).

Combining trastuzumab and DM1 allows the targeted delivery of the chemotherapy to HER2-positive cancer cells.

Ado-trastuzumab emtansine is FDA-approved for the treatment of HER2-positive metastatic breast cancers that have progressed on trastuzumab and a taxane-based chemotherapy.

Study findings have shown ado-trastuzumab emtansine can increase overall survival better than lapatinib plus the chemotherapy drug capecitabine for women with metastatic HER2-positive breast cancers [30].

Ado-trastuzumab emtansine is given by vein (through an IV).

 Side Effects
Ado-trastuzumab emtansineSome possible side effects include nausea, fatigue, muscle and joint pain, low platelet counts, headache and constipation.

It can also cause liver problems.

It does not usually cause hair loss.

Because ado-trastuzumab emtansine contains trastuzumab, it can also cause serious heart problems. Discuss this risk with your health care provider before starting treatment.

Your heart will be checked before and during treatment to help ensure there are no problems.

Adapted from select sources [31]. 

 

Fam-trastuzumab deruxtecan-nxki (Enhertu, trastuzumab deruxtecan)

Fam-trastuzumab deruxtecan-nxki (Enhertu, trastuzumab deruxtecan) is a HER2 antibody-drug conjugate. It consists of trastuzumab and the chemotherapy drug deruxtecan. Combining these drugs allows the targeted delivery of the chemotherapy to HER2-positive cancer cells.

Fam-trastuzumab deruxtecan-nxki is FDA-approved for the treatment of HER2-positive metastatic breast cancers that have progressed on 2 or more HER2-targeted therapies.

Study findings have shown fam-trastuzumab deruxtecan-nxki helps shrink tumors in some women with metastatic HER2-positive breast cancers [32].

Fam-trastuzumab deruxtecan-nxki is given by vein (through an IV).

 Side Effects
Fam-trastuzumab deruxtecan-nxkiSome possible side effects include low white blood cell counts, low red blood cell counts (anemia), nausea, vomiting, fatigue, hair loss, constipation and diarrhea.

It can cause lung problems that can lead to breathing difficulty and death. You will be checked throughout your treatment for signs and symptoms of new or worsening breathing problems.

Tell your health care provider right away if you have shortness of breath, cough or other breathing problems while taking this drug.

Because fam-trastuzumab deruxtecan-nxki contains trastuzumab, it can also cause serious heart problems. Discuss this risk with your health care provider before starting treatment.

Your heart will be checked before and during treatment to help ensure there are no problems.

Adapted from select sources [32].   

 

Tucatinib (Tukysa), neratinib (Nerlynx) and lapatinib (Tykerb)

The tyrosine-kinase inhibitors FDA-approved for metastatic breast cancer treatment are:

  • Tucatinib (Tukysa)
  • Neratinib (Nerlynx)
  • Lapatinib (Tykerb)

Tyrosine-kinase inhibitors are a class of drugs that target enzymes important for cell functions (called tyrosine-kinase enzymes). These drugs can block tyrosine-kinase enzymes at many points along the cancer growth pathway.

A tyrosine-kinase inhibitor in combination with trastuzumab (Herceptin) and chemotherapy can be used to treat of HER2-positive metastatic breast cancer. This combination may give women with HER2-positive metastatic breast cancer more time before the cancer spreads compared to treatment with trastuzumab and chemotherapy alone [33-39].

Adding tucatinib to treatment with trastuzumab and chemotherapy may also increase overall survival in women with HER2-positive metastatic breast cancer [33].

Neratinib is also used to treat HER2-positive early breast cancer.

Tucatinib, neratinib and lapatinib are pills.

Learn about neratinib and treatment of early breast cancer.

Tucatinib, neratinib and lapatinib and brain metastases

Many drug therapies cannot pass through the blood to the brain (called the blood-brain barrier). So, they can’t treat breast cancer that has spread to the brain.

Tucatinib, neratinib and lapatinib can pass through the blood-brain barrier and may be used to treat some metastatic breast cancers that have spread to the brain.

Tucatinib, neratinib or lapatinib in combination with trastuzumab and capecitabine may give women who have HER2-positive metastatic cancer with brain metastases more time before the cancer spreads compared to treatment with trastuzumab and capecitabine alone [33,40-43,102].

Lapatinib combined with hormone therapy

Compared to use of the aromatase inhibitor letrozole alone, letrozole combined with lapatinib may give women with HER2-positive metastatic breast cancer more time before the cancer spreads [37-38].

Tyrosine-Kinase InhibitorsSide Effects
Tucatinib, neratinib or lapatinibThe most common side effect is diarrhea. Your health care provider will recommend medications to help control the diarrhea.

Other possible side effects include nausea, vomiting and fatigue.

In rare cases, each of these drugs has been linked to liver problems. Your liver function will be checked throughout your treatment.

Adapted from select sources [33-37,41,44].

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For a summary of research studies on the use of lapatinib in treating metastatic breast cancer, visit the Breast Cancer Research Studies section.

PARP inhibitors

Olaparib (Lynparza) and talazoparib (Talzenna) are poly(ADP-ribose) polymerase (PARP) inhibitors.

PARP is an enzyme involved in DNA repair. Some chemotherapy drugs damage tumor DNA. PARP inhibitors work to stop PARP from repairing tumor DNA to help the chemotherapy kill the cancer cells.

PARP inhibitors are only used in breast cancer treatment for people who have a BRCA1 or BRCA2 gene mutation. BRCA1/2-related breast cancers seem to be sensitive to DNA damage involving the PARP enzyme.

The National Comprehensive Cancer Network recommends everyone with metastatic breast cancer get BRCA1/2 genetic testing to see if a PARP inhibitor may be used for treatment [4].

Although PARP inhibitors have side effects, they are often easier to tolerate than chemotherapy drugs.

Olaparib (Lynparza) and talazoparib (Talzenna)

The PARP inhibitors olaparib and talazoparib are FDA-approved for metastatic breast cancer treatment.

Olaparib and talazoparib are used to treat HER2-negative metastatic breast cancer in people who have a BRCA1/2 gene mutation and have been treated with chemotherapy in the past (including chemotherapy for early breast cancer).

If the metastatic breast cancer is hormone receptor-positive, people should have also been treated with hormone therapy in the metastatic setting.

Compared to chemotherapy alone, adding olaparib or talazoparib may give women with a BRCA1/2 gene mutation who have HER2-negative metastatic breast cancer more time before the cancer spreads [45-46].

Both olaparib and talazoparib are pills.

PARP InhibitorSide Effects
OlaparibSome possible side effects include low red blood cell counts (anemia), nausea, vomiting, fatigue and low white blood cell counts.

In rare cases, it can cause acute myeloid leukemia.

TalazoparibSome possible side effects include fatigue, low red blood cell counts (anemia), nausea, vomiting, headache and diarrhea.

In rare cases, it can cause acute myeloid leukemia.

Adapted from select sources [45-48].

Immunotherapy

Atezolizumab (Tecentriq) and pembrolizumab (Keytruda) are immunotherapy drugs.

Immunotherapy drugs help the body’s immune system attack cancer cells. They are used to treat many cancers (including melanoma, lung cancer, bladder cancer, kidney cancer and other cancers).

Immunotherapy drugs (including vaccines) for breast cancer haven’t shown results as strong as have been seen for other cancers. However, some breast cancers may benefit from them.

Researchers are studying how to identify the cancers that will respond best to immunotherapy.

“Checkpoint inhibitors” are the most widely used type of immunotherapy drugs. These drugs “take the brakes off” the natural factors that limit how the immune system can control tumor cells.

Other immunotherapy drugs are under study for breast cancer.

Atezolizumab (Tecentriq)

Atezolizumab is a checkpoint inhibitor immunotherapy drug used to treat some PD-L1-positive breast cancers.

PD-L1-positive breast cancers express (have a lot of) programmed cell death protein 1 (PD-L1). Metastatic triple negative breast cancers should be tested for PD-L1 status to find out whether atezolizumab would be helpful.

Atezolizumab in combination with the chemotherapy drug nab-paclitaxel is FDA-approved as a first treatment for PD-L1-positive metastatic triple negative breast cancer.

Compared to chemotherapy alone, atezolizumab in combination with nab-paclitaxel may give people with PD-L1-positive metastatic triple negative breast cancer more time before the cancer spreads [49].

Atezolizumab is less effective for the treatment of metastatic triple negative breast cancers that do not express (have little or no) PD-L1 is under study [49].

Pembrolizumab (Keytruda)

Pembrolizumab is a checkpoint inhibitor immunotherapy drug used to treat metastatic breast cancers that have a high tumor mutational burden [101]. This means there’s a high number of gene mutations in the cancer cells.

It’s not common for metastatic breast cancers to have a high tumor mutational burden. However, high tumor burden is more common in triple negative metastatic breast cancers than in ER-positive or HER2-positive metastatic breast cancers.

 Side Effects
Atezolizumab
(plus nab-paclitaxel)
Some possible side effects of atezolizumab plus paclitaxel include hair loss, pain or numbness in the hands or feet, fatigue, nausea, diarrhea, anemia, constipation, cough, headache and vomiting.

Atezolizumab increases the risk of diabetes, thyroid problems, liver problems and colitis (inflammation of the intestines).

In rare cases, it can cause lung inflammation, which can cause death. Tell your provider right away if you have shortness of breath or other breathing problems while taking this drug.

PembrolizumabSome possible side effects include fatigue, muscle pain, decreased appetite, itchiness, diarrhea, nausea, rash and constipation.

Pembrolizumab can cause colitis (inflammation of the intestines), liver problems and hormone gland problems.

In rare cases, it can cause lung inflammation, which can cause death. Tell your provider right away if you have shortness of breath or other breathing problems while taking this drug.

Adapted from select sources [49-50,101]. 

Trop-2 antibody-drug conjugates

Special antibody drugs are designed to target certain cancer cells. Antibody-drug conjugates are a combination of an antibody therapy and a chemotherapy drug. Combining these into one drug allows the targeted delivery of the chemotherapy to specific cancer cells.

Some breast cancers have cells with higher levels of the protein Trop-2 than other breast cancers (they express Trop-2). Triple negative breast cancers tend to express Trop-2.

Sacituzumab govitecan-hziy (Trodelvy)

Sacituzumab govitecan-hziy (Trodelvy) is a Trop-2 antibody-drug conjugate. It combines a Trop-2 antibody and the chemotherapy drug irinotecan. This combination allows the targeted delivery of iriotecan to cancer cells that express Trop-2.

Sacituzumab govitecan-hziy is FDA-approved for the treatment of metastatic triple negative breast cancers that have already been treated with at least 2 drug therapies in the metastatic setting.

Study findings have shown sacituzumab govitecan-hziy helps shrink tumors in women with metastatic triple negative breast cancers [51].

Sacituzumab govitecan-hziy is given by vein (through an IV).

 Side Effects
Sacituzumab govitecan-hziySacituzumab govitecan-hziy increases the risk of having a low white blood cell count. Your blood cell counts will be monitored while taking sacituzumab govitecan-hziy.

Some possible side effects include diarrhea, nausea, vomiting, fatigue, low red blood cell counts (anemia), hair loss, constipation and rash.

Adapted from select sources [51-52].

Clinical trials

Clinical trials offer the chance to try new treatments and possibly benefit from them.

Susan G. Komen® Breast Cancer Clinical Trial Information Helpline

If you or a loved one needs information or resources about clinical trials, call our Clinical Trial Information Helpline at 1-877 GO KOMEN (1-877- 465- 6636) or email clinicaltrialinfo@komen.org.

Learn about clinical trials for people with metastatic breast cancer and access Metastatic Trial Search, a web-based personalized clinical trial matching tool.

 

About my cancer

  • Where in my body has the breast cancer spread?
  • What is my prognosis with treatment? What is my prognosis without treatment?
  • Will you do a biopsy to learn more about the tumor in the new location(s)?
  • What are the hormone receptor status and HER2 status of my cancer? How do these affect my treatment options?
  • Should my tumor be tested for a PIK3CA gene mutation?
  • Should my tumor be tested for PD-L1 status?
  • Should I get BRCA1/2 genetic testing to see if a PARP inhibitor may be used in my treatment plan?

Treatment

  • What are my treatment options? What are the pros and cons of each option? Which do you recommend for me and why?
  • Are there clinical trials I can join? If so, how do I learn more?
  • How long do I have to make treatment decisions?
  • Should I get a second opinion? How do I do that?
  • How will I know if treatment is working? What tests will I need and how often will I need them?
  • How will treatment affect my quality of life?

Side effects and supportive care

  • What side effects should I expect? How long will they last? Which should I report to you right away?
  • Will I have any pain? If so, how can I manage it? Will you refer me to a palliative care specialist or pain specialist?
  • If you have bone metastases: Should I be concerned about my bones? How can I protect them from fractures (breaks) or other problems? Will I get bone-strengthening medications?
  • Are there any restrictions on my activity?
  • Where can I find a support group or a counselor for one-on-one support? What support is available for my family?

Stopping treatment for the cancer

  • How will I know it’s time to stop treatment for the cancer?
  • Who will be in charge of my medical care after treatment for the cancer ends?
  • When will hospice care be considered?

Learn more about talking with your health care provider.

It may be helpful to download and print Susan G. Komen®‘s Questions to Ask Your Doctor About Metastatic Breast Cancer resource and take it with you to your next doctor appointment. There’s plenty of space to write down the answers to these questions, which you can refer to later.

There are other Questions to Ask Your Doctor resources on many different breast cancer topics you may wish to download. They are a nice tool for people recently diagnosed with metastatic breast cancer, who may be too overwhelmed to know where to begin to gather information.

 

If you have metastatic breast cancer, talk with your health care provider before getting a seasonal flu shot to make sure it’s safe for you.

If you are a caregiver, the Centers for Disease Control and Prevention (CDC) recommends you get the seasonal flu shot.

Find more information from the CDC about the seasonal flu.

 

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Komen Perspectives

Read our perspective on living with metastatic breast cancer.*

  

*Please note, the information provided within Komen Perspectives articles is only current as of the date of posting. Therefore, some information may be out of date.