Treatment of Stage IV (Metastatic) Breast Cancer

People with hormone receptor-positive breast cancer (estrogen and/or progesterone) are usually treated first with hormone therapy. This is commonly combined with a targeted drug. Your options will depend on specific gene changes in your cancer.

• This hormone therapy is usually tamoxifen or an aromatase inhibitor.
• The targeted drug is usually a CDK4/6 inhibitor or a PI3K alpha inhibitor (Inavolisib).

Some people may be treated with a different type of hormone therapy, including:

• Elacestrant (Orserdu)
• Imlunestrant (Inluriyo)
• Vepdegestrant (Veppanu)

Targeted drugs that may be used include:

• Everolimus (Afinitor)
• Alpelisib (Piqray)
• Inavolisib (Itovebi)
• Capivasertib (Truqap)

Women who have not yet gone through menopause are often treated with tamoxifen or with medicines that keep the ovaries from making hormones, along with other drugs.

If your cancer is both hormone receptor-positive and HER2-positive, palbociclib (Ibrance) may be added to trastuzumab (Herceptin), with or without pertuzumab (Perjeta), and hormone therapy (fulvestrant or an aromatase inhibitor). This option is for people whose cancer has not progressed after initial treatment with a taxane chemotherapy and anti-HER2 therapy.

If your stage IV breast cancer is HER2-positive, your options for initial treatment could include:

• Chemotherapy plus trastuzumab (Herceptin, other names) and pertuzumab (Perjeta), both HER2-targeted drugs
• Fam-trastuzumab deruxtecan (T-DXd) plus pertuzumab

If the cancer grows, other options might include:

• An antibody-drug conjugate
• A kinase inhibitor with an anti-HER2 drug, a chemo drug, or both
• Other HER2-targeted drugs with chemo

If your cancer is also hormone receptor-positive, hormone therapy might be added to these drug combinations.

Hormone receptor-negative cancers

Chemo is the main treatment for people with hormone receptor-negative cancers because hormone therapy is not helpful for these cancers.

HER2-low cancers

For breast cancers that are considered HER2-low and have spread to distant parts of the body, the antibody-drug conjugate fam-trastuzumab deruxtecan (T-DXd) might be an option.

HER2-negative cancers in people with a BRCA gene mutation

Treatment is usually a targeted drug called a PARP inhibitor, such as olaparib or talazoparib. Chemotherapy drugs and hormone drugs are also very helpful in treating these cancers.

If you have advanced triple-negative breast cancer and your tumor makes the PD-L1 protein, you might be treated with immunotherapy along with chemotherapy or an antibody-drug conjugate (ADC). The PD-L1 protein is found in about 1 in 5 women with triple-negative breast cancer.

If your TNBC has certain gene or protein changes (mutations)

For people with TNBC and a BRCA mutation, medicines called PARP inhibitors may be considered. Examples include olaparib and talazoparib.

The immunotherapy drug pembrolizumab might be used if the cancer cells show high levels of gene changes called microsatellite instability (MSI), high tumor mutation burden, or changes in any of the mismatch repair (MMR) genes MLH1, MSH2, MSH6, or PMS2.

Pembrolizumab might also be an option for TNBC that has other gene or protein changes.

If your TNBC does not have these gene or protein changes

For TNBC that does not have any specific gene or protein changes, chemo alone or an antibody-drug conjugate such as sacituzumab govitecan (Trodelvy) or datopotamab (Dato-DXd, Datroway) may be an option.

You can find more treatment details in Treatment for Triple-negative Breast Cancer.

If a hormone receptor-positive breast cancer progresses while it’s being treated with hormone therapy, switching to a different type of hormone therapy and/or adding a targeted therapy sometimes helps.

Medicines that block or break down the estrogen receptor may be used, sometimes along with a CDK4/6 inhibitor. Some of these medicines are approved only for cancers with a specific gene change called an ESR1 mutation:

• Fulvestrant (Faslodex)
• Elacestrant (Orserdu)
• Imlunestrant (Inluriyo)
• Vepdegestrant (Veppanu)

ESR1 mutations are common in cancers that have been treated with hormone therapy before. Testing for this mutation can be done with a blood or tumor test.

If the cancer has a PIK3CA gene mutation and has grown during treatment with an aromatase inhibitor, options may include:

• Fulvestrant (Faslodex) combined with alpelisib (Piqray)
• Inavolisib (Itovebi), palbociclib (Ibrance), and fulvestrant taken together

If the cancer has a PIK3CA, AKT1, or PTEN gene mutation, fulvestrant combined with capivasertib (Truqap) may be an option.

Chemotherapy, immunotherapy, antibody-drug conjugates, or PARP inhibitors might be options if the cancer is no longer responding to any hormone medicines. This will depend on specific features of the cancer.

If the cancer is no longer responding to one chemo regimen, trying another may be helpful.

Many different medicines and combinations can be used to treat breast cancer. However, each time a cancer progresses during treatment, it becomes less likely that further treatment will have an effect.

Other options might include:

• Using a PARP inhibitor alone
• Using an antibody-drug conjugate, for hormone receptor-positive cancers

These options will depend on the features of the cancer and specific gene changes in the cancer cells.

HER2-positive cancers that no longer respond to trastuzumab (Herceptin) might respond to other medicines that target the HER2 protein.

Options may include:

• Pertuzumab (Perjeta) with chemo and trastuzumab
• Ado-trastuzumab emtansine (Kadcyla)
• Fam-trastuzumab deruxtecan (T-DXd, Enhertu)
• Margetuximab (Margenza) with chemo
• Lapatinib (Tykerb) and the oral chemo medicine capecitabine
• Lapatinib and an aromatase inhibitor, for hormone receptor-positive cancers

For cancers that have spread to the brain, the main tools are radiation therapy and sometimes surgery. Medicine options may include:

• Neratinib (Nerlynx) and the chemo medicine capecitabine
• Tucatinib (Tukysa), trastuzumab, and the chemo medicine capecitabine