Targeted Therapies for Breast Cancer

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 that 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 the treatment of estrogen receptor-positive breast cancers, HER2-positive breast cancers, and 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 treating metastatic breast cancer.

For HER2-Positive Cancer

In around 25% of breast cancers, a gene known as human epidermal growth receptor 2 (or HER2/neu) results in the overexpression of the HER2 protein (receptors) on the surface of breast cancer cells.

The presence of HER2 receptors may result in the growth and proliferation of HER2-positive cancers. Thus, medications that interfere with these receptors interfere with the signal to these cancer cells, limiting their growth.

Medications that target HER2 include:

  • Herceptin (trastuzumab): Herceptin, a monoclonal antibody, 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 to 5% 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.
how herceptin works
 Verywell / Gary Ferster
  • Kadcyla (ado-trastuzumab): Kadcyla is a medication that includes both Herceptin and a very potent chemotherapy drug called emtansine. The Herceptin portion of the drug binds to HER2 positive cancer cells, but instead of simply blocking the receptor to prevent growth hormones from attaching, it 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. Kadycla may be effective even when Herceptin has been ineffective.
  • Perjeta (pertuzumab): Perjeta, a monoclonal antibody, is FDA-approved for the treatment of metastatic breast cancer, and can increase the survival rate for people who have metastatic, HER2-positive breast cancer. It may be used alone or in combination with Herceptin or chemotherapy.
  • Tykerb (lapatinib): Tykerb—which is 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.
  • Enhertu (trastuzumab deruxtecan): This drug binds to the HER2 receptor on the cancer cells to initiate a reaction in the cell that causes cell death. Enhertu is the first FDA-approved treatment for unresectable or metastatic HER2-low breast cancer.
  • Tukysa (tucatinib): This drug is a combination of Herceptin and Xeloda (capecitabine). It inhibits the growth of HER2-expressing tumor proteins.
  • Margenza (margetuximab): This monoclonal antibody targets the HER2 protein.
  • Nerlynx (neratinine): This drug inhibits the HER2 receptor.

Your healthcare provider may check your heart function before treatment, and again while you are taking the drug. Let your healthcare provider know if you develop symptoms such as shortness of breath, leg swelling, and severe fatigue.

For Estrogen Receptor-Positive Cancer

These drugs are used for the treatment of breast cancer for females who are postmenopausal (or who are premenopausal and have received ovarian suppression therapy) to make hormonal therapies more effective.

  • Ibrance (palbociclib): This drug inhibits enzymes called cyclin-dependent kinases (CDK4 and CDK6) and is used as initial therapy in combination with hormonal therapy or 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 HER2-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 healthcare provider will check your blood work periodically while you are taking this drug. It can also increase your risk of serious infections, so your healthcare provider will watch you closely for infection as well.
  • Piqray (alpelisib): This drug is used with fulvestrant for the treatment of advanced or metastatic breast cancer that's hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-), PIK3CA-mutated in postmenopausal women, and men.
  • Kisqali (ribociclib): This kinase inhibitor is used with an aromatase inhibitor for the treatment of pre/perimenopausal or postmenopausal women with HR-positive, HER2 negative advanced or metastatic breast cancer as initial endocrine-based therapy. It is used with fulvestrant for the treatment of postmenopausal women with HR-positive, HER2 negative advanced or metastatic breast cancer as initial endocrine-based therapy or following disease progression on endocrine therapy.
  • Verzenio (abemaciclib): This drug is indicated for the treatment of HR-positive, HER2 negative advanced or metastatic breast cancer in combination with an aromatase inhibitor for postmenopausal women as initial endocrine-based therapy or in combination with fulvestrant for women with disease progression following endocrine therapy or as a single agent following endocrine therapy and prior chemotherapy in the metastatic setting.

For Women With BRCA Gene Mutations

Drugs known as PARP inhibitors are used for women with BRCA1 and BRCA2 gene mutations. They come in pill form and include Lynparza (olaparib) and Talzenna (talazoparib).

Poly ADP ribose polymerase (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 cancer cells.

Olaparib and talazoparib can be used to treat metastatic, HER2-negative breast cancer in people with a BRCA mutation who have already gotten chemotherapy. Olaparib can also be used to treat high-risk early-stage breast cancer in people who have been treated with chemotherapy. Olaparib can 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 (MDS) or acute myeloid leukemia (AML).

For Triple-Negative Breast Cancer

Tumors that are estrogen receptor negative, progesterone receptor negative, and HER2 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 HER2 therapies are usually ineffective.

Trodelvy (sacituzumab) is used to treat metastatic or inoperable triple-negative breast cancer for people who have received two or more prior treatments, including at least one treatment for metastatic disease. It binds to the antigen Trop-2 and inhibits DNA replication and stimulates cell death.

In some cases, the targeted therapy Avastin (bevacizumab) may be considered. It is classified as an angiogenesis inhibitor. Angiogenesis inhibitors work by preventing cancers from growing new blood vessels, essentially “starving” cancer.

A Word From Verywell

In addition to targeted therapy, immunotherapy for breast cancer is also an option that works a little differently—immunotherapy involves a procedure that stimulates your body's immune system to fight cancer. 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.

Breast Cancer Discussion Guide

Get our printable guide for your next healthcare provider's appointment to help you ask the right questions.

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4 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Liedtke C, Kolberg HC. Systemic Therapy of Advanced/Metastatic Breast Cancer - Current Evidence and Future Concepts. Breast Care (Basel). 2016;11(4):275-281. doi:10.1159/000447549

  2. Women Treated With Herceptin Need Heart Monitoring No Matter Their Age.

  3. Food and Drug Administration. Fda approves first targeted therapy for her2-low breast cancer.

  4. Yi M, Dong B, Qin S, Chu Q, Wu K, Luo S. Advances and perspectives of PARP inhibitorsExp Hematol Oncol. 2019;8:29. doi:10.1186/s40164-019-0154-9

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

By Lynne Eldridge, MD
 Lynne Eldrige, MD, is a lung cancer physician, patient advocate, and award-winning author of "Avoiding Cancer One Day at a Time."