An Overview of Targeted Therapies for Breast Cancer

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Targeted therapies are a newer treatment for breast cancer which may be used alone or in combination with other treatments. Unlike traditional chemotherapy which attacks any rapidly growing cells, targeted therapies directly target cancer cells or signaling pathways which contribute to the growth of cancer cells. For this reason, many of the drugs may have fewer side effects than chemotherapy.

Targeted therapies are available for those with estrogen receptor-positive breast cancersHER 2 positive breast cancers, and even triple negative breast cancer.

These drugs can work very well at times, but like the other medications used to treat metastatic breast cancer, resistance usually develops over time. Some of these drugs are used for both early stage and metastatic breast cancer, whereas others are used primarily for people with metastatic breast cancer.

For HER2 Positive Cancer

As noted earlier, in around 25 percent of breast cancers, a gene known as human epidermal growth receptor 2 (or HER 2/neu) results in the overexpression of the HER 2 protein (receptors) on the surface of breast cancer cells.

Similar, in a way, to the mechanism by which estrogen receptors are responsible for signaling a cancer cell to grow and proliferate, HER 2 receptors may result in the growth and proliferation of HER 2 positive cancers. Medications which interfere with these receptors thus interfere with the signal to these cancer cells, limiting their growth.

Medications which target HER 2 include:

  • Herceptin (trastuzumab) – Herceptin is given IV usually once a week or once every three weeks. Side effects include fever and chills early on. Heart failure may develop in three to five percent of people treated with the drug, but unlike the heart failure related to chemotherapy drugs such as Adriamycin (doxorubicin), this heart failure may be reversible when the treatment is stopped. Side effects from Herceptin usually improve over time.
  • Kadcyla (ado-trastuzumab) – Kaydcyla is a medication which includes both Herceptin and a very potent chemotherapy drug called emtansine. The Herceptin portion of the drug binds to HER 2 positive cancer cells, but instead of simply blocking the receptor to prevent growth hormones from attaching, it delivers its “payload”—the chemotherapy drug—right to the cancer cells.

    Herceptin allows the chemotherapy to enter the cancer cells, where the emtansine is released. While this chemotherapy agent is mostly delivered right to cancer cells, there is also some general absorption of the drug into the systemic circulation.

    For this reason, the drug may have side effects common to chemotherapy drugs include bone marrow suppression and peripheral neuropathy. Kaydycla may be effective even in people for whom Herceptin has been ineffective.
  • Perjeta (pertuzumab) – Perjeta was FDA approved for metastatic breast cancer in 2013 and studies have subsequently found an increase in the survival rate for women with metastatic breast cancer (HER 2 positive) who are treated with the drug. It may be used alone or in combination with Herceptin or chemotherapy.
  • Tykerb (lapatinib) – Tykerb also attacks HER 2 positive breast cancer cells, but by a different mechanism than Herceptin. Tykerb, which unlike Herceptin is not an antibody, may be used alone, or in combination with Herceptin or chemotherapy. The most common side effects are a rash which appears similar to acne (but is not treated like acne) and diarrhea.

    Side Effects of These Medications

    Herceptin, Kaydcyla, and Perjeta have similar mechanisms of action and hence, similar side effects. One of the more concerning side effects of these drugs is heart damage. Your oncologist may recommend screening tests for your heart before you begin these medications and will advise you of symptoms that indicate you should call.

    For Estrogen Receptor Positive Cancer

    For women with hormone receptor-positive breast cancer, targeted therapies are available as well. These drugs are used for women who are postmenopausal (or who are premenopausal and have received ovarian suppression therapy) to make hormonal therapies more effective.

    Drugs include:

    • Ibrance (palbociclib) – This drug inhibits enzymes called cyclin-dependent kinases (CDK4 and CDK6) and is used after an estrogen receptor-positive breast cancer in a postmenopausal woman becomes resistant to hormonal therapy. It may be used along with an aromatase inhibitor such as Femara (letrozole) or with the anti-estrogen drug Faslodex (fulvestrant.)
    • Afinitor (everolimus) – This drug blocks a protein in the body known as mTOR. Affinitor is usually used for an estrogen receptor positive and HER 2 negative tumor after it becomes resistant to an aromatase inhibitor such as Aromatase (exemastine).

    For Triple Negative Breast Cancer

    Tumors which are estrogen receptor negative, progesterone receptor negative, and HER 2 negative (triple negative breast cancer) can be more of a challenge to treat, as hormonal therapies and HER 2 therapies are usually ineffective. While used infrequently at this time, the targeted therapy Avastin may be considered for some people.

    • Avastin (bevacizumab) – This is not commonly used anymore to treat breast cancer due to sometimes serious bleeding side effects. It is classified as an angiogenesis inhibitor. The term angiogenesis means “new blood” and refers to the new blood vessels which need to form to allow cancers to grow.

      Angiogenesis inhibitors work by preventing cancers from growing new blood vessels, and essentially “starve” the cancer.

    Sources:

    DeVita, Vincent., et al. Cancer: Principles & Practice of Oncology. Cancer of the Breast. Wolters Kluwer, 2016.

    Liedtke, C., and H. Kolberg. Systemic Therapy of Advanced/Metastatic Breast Cancer—Current Evidence and Future ConceptsBreast Care. 2016. 11(4):275-281.

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