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HER2-positive metastatic breast cancer

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In metastatic breast cancer, or stage IV disease, the cancer cells have traveled from the breast and nearby lymph nodes and formed tumors in tissues or organs far away from the breast. Metastatic breast cancer can be:

  • Hormone receptor-positive
  • HER2-positive
  • Both hormone receptor-positive and HER2-positive
  • Triple-negative


Metastatic HER2-positive breast cancer can be treated with targeted therapy for HER2-positive breast cancer. You can find more information on how metastatic breast cancer is diagnosed on our pages about Metastatic breast cancer and Testing.

If you had early-stage HER2-positive breast cancer, the metastasis is likely to be HER2-positive as well. Your medical oncologist may recommend you have a biopsy of any abnormal finding from an imaging test. The biopsy helps to:

  • diagnose the cancer
  • confirm the cancer is metastatic
  • check the receptor status to make sure it did not change from your original diagnosis

Metastatic HER2-positive breast cancers are more likely than some other types of breast cancer to spread to the brain and spinal cord, which with the spinal fluid make up the central nervous system or CNS. Up to half of people diagnosed with HER2-positive metastatic breast cancer develop metastases to the central nervous system. There are local therapies available to treat these metastases.

Treatments for HER2-positive metastatic breast cancer

Treatment of HER2-positive breast cancer that has spread to organs other than the brain usually includes medicines that target the HER2 protein and block its actions. These HER2-targeted therapies are:

  • Trastuzumab (Herceptin). This medicine can attach to the HER2 proteins and block the signals that tell cells to multiply too quickly, causing cancer. It is often given with chemotherapy. Trastuzumab is available as a biosimilar as well.
  • Ado-trastuzumab emtansine (Kadcyla). This medicine is an antibody drug conjugate, a medicine that combines a targeted therapy with chemotherapy. Ado-trastuzumab emtansine sends the chemotherapy medicine straight to the cancer cells to prevent healthy cells from being affected.
  • Lapatinib (Tykerb). This medicine treats metastatic breast cancer when the standard trastuzumab has stopped working. Like trastuzumab, lapatinib blocks the action of the HER2 protein. But while trastuzumab works on the outside of the cell, lapatinib works on the inside. Lapatinib is given in combination with capecitabine (Xeloda) or, if the cancer is both HER2- and HR-positive, letrozole (Femara).
  • Margetuximab (Margenza). This medicine is given with chemotherapy to treat metastatic, HER2-positive breast cancer after treatment with at least two previous lines of targeted therapy.
  • Neratinib (Nerlynx). This medicine is approved for use with the chemotherapy pill capecitabine (Xeloda) if the cancer grew despite treatment with at least two previous lines of treatment with targeted therapies.
  • Pertuzumab (Perjeta). This medicine works by blocking signals that tell breast cancer cells to multiply.
  • Trastuzumab deruxtecan (Enhertu) is an antibody drug conjugate approved to treat people with metastatic, HER2-positive, hormone receptor-negative breast cancer that has grown after at least two past treatments.
  • Tucatinib (Tukysa). This medicine is given with trastuzumab (Herceptin) and the chemotherapy pill capecitabine (Xeloda) to treat cancers that have grown after previous HER2-targeted treatments.


If the cancer is also hormone receptor-positive, hormonal therapy may be used in combination with HER2-targeted therapies and chemotherapy.

You may also consider taking part in a clinical trial, a study that looks at how well new medical approaches work in people. Clinical trials offer access to new treatments that are not otherwise available and may prove to work better than standard treatments. Participating in a clinical trial also helps researchers develop better treatments for people diagnosed in the future.

Treatments for brain metastases

Most systemic, or whole-body, therapies have trouble reaching the brain. Medicines like trastuzumab and pertuzumab are monoclonal antibodies, molecules that have an even harder time than other treatments getting to the brain because of their large size.

Researchers are studying small molecules, called tyrosine kinaise inhibitors or TKIs, to see whether they can more easily cross the blood-brain barrier. Lapatinib, neratinib, and tucatinib are TKIs. Tucatinib was specifically studied in people with brain metastases, and clinical trials suggest it gets through the blood-brain barrier to allow tucatinib to treat metastases in the brain more effectively than other types of treatments.

Surgery, usually followed by radiation therapy, is used to treat HER2-positive breast cancer that has spread to the brain. Treatments help reduce symptoms and protect the function of your brain. Learn more on our Metastatic breast cancer to the brain page.

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Reviewed and updated: August 31, 2015

Reviewed by: Pallav K. Mehta, MD

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