Treatment of Stage IV (Metastatic) Breast Cancer

Stage IV cancers have spread (metastasized) beyond the breast and nearby lymph nodes to other parts of the body. When breast cancer spreads, it most commonly goes to the bones, liver, and lungs. It may also spread to the brain or other organs.

For women with stage IV breast cancer, systemic drug therapies are the main treatments. These may include:

• Hormone therapy
• Chemotherapy (chemo)
• Targeted drugs
• Immunotherapy
• Some combination of these

Surgery and/or radiation therapy may be useful in certain situations (see below).

Treatment can often shrink tumors (or slow their growth), improve symptoms, and help some women live longer. These cancers are considered incurable.

Systemic (drug) treatments for stage IV breast cancer

Treatment often continues until the cancer starts growing again or until side effects become unacceptable. If this happens, other drugs might be tried. The types of drugs used for stage IV breast cancer depend on the hormone receptor status, the HER2 status of the cancer, and sometimes gene mutations that might be found.

Hormone receptor-positive cancers

Women with hormone (estrogen or progesterone) receptor-positive cancers are sometimes treated first with hormone therapy (tamoxifen or an aromatase inhibitor). This may be combined with a targeted drug such as a CDK4/6 inhibitor, everolimus, or a PI3K inhibitor.

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

Hormone receptor-negative cancers

Chemo is the main treatment for women with hormone (estrogen and progesterone) receptor-negative cancers, because hormone therapy isn’t helpful for these cancers.

HER2-positive cancers

The first therapy given is usually chemotherapy in combination with trastuzumab (Herceptin, other names) and pertuzumab (Perjeta), both HER2 targeted drugs. If the cancer grows, other options might include:

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

Hormone therapy might be added to these drug combinations if the cancer is also hormone-receptor positive.

HER2-low cancers

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

HER2-negative cancers in women with a BRCA gene mutation

These women are typically treated with 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. 

HER2-negative cancers in women with a PIK3CA gene mutation

 About 30% to 40% of metastatic ER-positive breast cancers have a PIK3CA gene mutation. Alpelisib is a targeted drug known as a PIK3 inhibitor that can be used along with the hormone drug fulvestrant to treat postmenopausal women with advanced hormone receptor-positive breast cancer. For this drug to work, there must be a PIK3CA mutation found on a biopsy done on the tumor tissue or of the cancer cells in the blood (liquid biopsy). 

Triple-negative breast cancer (TNBC)

An immunotherapy drug along with chemotherapy might be used in people with advanced triple-negative breast cancer whose tumor makes the PD-L1 protein. The PD-L1 protein is found is about 1 in 5 women with triple-negative breast cancer. For women with TNBC and a BRCA mutation, drugs called PARP inhibitors (like olaparib or talazoparib) may be considered.

For breast cancers in which the cancer cells show high levels of gene changes called microsatellite instability (MSI) or changes in any of the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, or PMS2), immunotherapy with the drug pembrolizumab might be used. Pembrolizumab might also be an option for TNBC that has other gene or protein changes.

For TNBC that does not have any specific gene or protein changes, chemo alone or the antibody-drug conjugate sacituzumab govitecan (Trodelvy) might be an option.

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

Local or regional treatments for stage IV breast cancer

Although systemic drugs are the main treatment for stage IV breast cancer, local and regional treatments such as surgery, radiation therapy, or regional chemotherapy are sometimes used as well. These can help treat breast cancer in a specific part of the body, but they are very unlikely to get rid of all of the cancer. These treatments are more likely to be used to help prevent or treat symptoms or complications from the cancer.

Radiation therapy and/or surgery may also be used in certain situations, such as:

• When the breast tumor is causing an open or painful wound in the breast (or chest)
• To treat a small number of metastases in a certain area, such as the brain
• To help prevent or treat bone fractures
• When a cancer is pressing on the spinal cord
• To treat a blood vessel blockage in the liver
• To provide relief of pain or other symptoms anywhere in the body

In some cases, regional chemo (where drugs are delivered directly into a certain area, such as into the fluid around the brain and spinal cord, called intrathecal chemo) may be useful as well.

If your doctor recommends such local or regional treatments, it is important that you understand the goal—whether it is to try to cure the cancer or to prevent or treat symptoms.

Relieving symptoms of advanced breast cancer

Treatment to relieve symptoms depends on where the cancer has spread. For example, pain from bone metastases may be treated with radiation therapy, drugs called bisphosphonates such as pamidronate (Aredia) or zoledronic acid (Zometa), or the drug denosumab (Xgeva). For more, see treatment of bone metastases.

Advanced cancer that progresses during treatment

Treatment for advanced breast cancer can often shrink the cancer or slow its growth (sometimes for many years), but after a time, it tends to stop working. Further treatment options at this point depend on several factors, including previous treatments, where the cancer is located, a woman's menopause status, general health, desire to continue getting treatment, and whether the hormone receptor status and HER2 status have changed on the cancer cells.

Progression during hormone therapy

For hormone (estrogen or progesterone) receptor-positive cancers that were being treated with hormone therapy, switching to another type of hormone therapy sometimes helps. For example, if either letrozole (Femara) or anastrozole (Arimidex) were given, using exemestane, possibly with everolimus (Afinitor), may be an option. Another option might be using elacestrant (Orserdu), fulvestrant (Faslodex), or a different aromatase inhibitor, sometimes along with a CDK inhibitor. If the cancer has a PIK3CA mutation and has grown while being treated with an aromatase inhibitor, fulvestrant with alpelisib might be considered. If the cancer is no longer responding to any hormone drugs, chemotherapy immunotherapy, or PARP inhibitors might be options depending on specific features of the cancer or any gene changes that might be present.

Progression during chemotherapy

If the cancer is no longer responding to one chemo regimen, trying another may be helpful. Many different drugs 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. Sometimes, other options include adding an immunotherapy drug to the chemo or using a PARP inhibitor alone depending on specific features of the cancer or any gene changes that might be present.

Progression while being treated with HER2 drugs

HER2-positive cancers that no longer respond to trastuzumab (Herceptin) might respond to other drugs that target the HER2 protein. Options for women with HER2-positive cancers might include:

• Pertuzumab (Perjeta) with chemo and trastuzumab
• Ado-trastuzumab emtansine (Kadcyla)
• Fam-trastuzumab deruxtecan (Enhertu)
• Margetuximab (Margenza) with chemo
• Lapatinib (Tykerb) and the oral chemo drug capecitabine
• Lapatinib and an aromatase inhibitor (for hormone receptor-positive cancers)
• Neratinib (Nerlynx) and the chemo drug capecitabine (this combination can be helpful for cancers that have spread to the brain)
• Tucatinib (Tukysa), trastuzumab, and the chemo drug capecitabine (this combination can be helpful for cancers that have spread to the brain)

Because current treatments are very unlikely to cure metastatic breast cancer, if you are in otherwise good health, you may want to think about taking part in a clinical trial testing a newer treatment.