Targeted Therapies for Breast Cancer

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Targeted therapies are a relatively new form of treatment for breast cancer and 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 cancers, HER 2 positive breast cancers, and even triple negative breast cancer.

These drugs can work very well, 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.

Therapies for HER2 Positive Cancer

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 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 that interfere with these receptors thus interfere with the signal to these cancer cells, limiting their growth.

Medications that target HER 2 include:

  • Herceptin (trastuzumab): Herceptin, one in a class of drugs called monoclonal antibodies, is given intravenously (IV), usually once a week or once every three weeks. Side effects include fever and chills early on. Heart failure may develop in 3 percent to 5 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, 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 system. For this reason, the drug may have side effects common to chemotherapy drugs, including bone marrow suppression and peripheral neuropathy. Kaydycla may be effective even in people for whom Herceptin has been ineffective.
  • Perjeta (pertuzumab): Perjeta, a monoclonal antibody, 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, but a kinase inhibitor, may be used alone or in combination with Herceptin or chemotherapy. The most common side effects are an acne-like rash and diarrhea.

Herceptin, Kaydcyla, and Perjeta have similar mechanisms of action and hence, similar side effects, including heart damage. Because these drugs can cause heart damage, doctors often check your heart function before treatment, and again while you are taking the drug. Let your doctor know if you develop symptoms such as shortness of breath, leg swelling, and severe fatigue.

Therapies for Estrogen Receptor Positive Cancer

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), Aromasin (exemestane), or Arimidex (aromasin), or with the anti-estrogen drug Faslodex (fulvestrant.) The most common side effects are low blood cell counts and fatigue. Nausea and vomiting, mouth sores, hair loss, diarrhea, and headache are less common side effects. Very low white blood cell counts can increase the risk of serious infection.
  • 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. Common side effects of everolimus include mouth sores, diarrhea, nausea, feeling weak or tired, low blood counts, shortness of breath, and cough. Everolimus can also increase cholesterol, triglycerides, and blood sugars, so your doctor will check your blood work periodically while you are taking this drug. It can also increase your risk of serious infections, so your doctor will watch you closely for infection.

    Targeted therapy for women with BRCA gene mutations

    Drugs known as PARP inhbitors are used for women with BRCA1 and BRCA2 gene mutations. They come in pill form and include Lynparza (olaparib) and Talzenna (talazoparib). PARP proteins normally help repair damaged DNA inside cells. The BRCA genes (BRCA1 and BRCA2) also help repair DNA (in a slightly different way), but mutations in one of those genes can stop this from happening. PARP inhibitors work by blocking the PARP proteins. Because tumor cells with a mutated BRCA gene already have trouble repairing damaged DNA, blocking the PARP proteins often leads to the death of these cells.

    Olaparib and talazoparib can be used to treat metastatic, HER2-negative breast cancer in women with a BRCA mutation who have already gotten chemotherapy. Olaparib can also be used in women who have already received hormone therapy if the cancer is hormone receptor-positive.

    Side effects can include nausea, vomiting, diarrhea, fatigue, loss of appetite, taste changes, low red blood cell counts (anemia), low platelet counts, low white blood cell counts, belly pain, and muscle and joint pain. Rarely, some people treated with a PARP inhibitor have developed a blood cancer, such as myelodysplastic syndrome or acute myeloid leukemia (AML).

    Targeted Therapies for Triple Negative Breast Cancer

    Tumors that are estrogen receptor negative, progesterone receptor negative, and HER 2 negative result in what's known as triple negative breast cancer. This form can be more of a challenge to treat, as hormonal therapies and HER 2 therapies are usually ineffective.

    In some cases, the targeted therapy Avastin (bevacizumab) may be considered. 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.

    One 2018 study found that Avastin, when used in conjunction with chemotherapy, may provide a significant improvement in women with triple negative breast cancer that has spread to the chest wall.

    Avastatin, in addition to the side effects common to some of these drugs—such as nausea, diarrhea, low blood counts—can also cause hemorrhaging and gastrointestinal perforation in rare cases, making its use controversial.

    A Word From Verywell

    If you've been diagnosed with breast cancer, take time to do some research on targeted therapies. With medicine changing so rapidly, it's important to keep up with the latest treatments and understand options for your particular type of cancer. Armed with that information, you'll be able to have a more productive conversation with your oncologist about the therapies that will be most effective for you.

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