Targeted Drug Therapy for Breast Cancer

Targeted drug therapy uses medicines that are directed at (target) proteins on breast cancer cells that help them grow, spread, and live longer. Targeted drugs work to destroy cancer cells or slow down their growth. They have side effects different from chemotherapy and can be given in the vein (IV), as an injection under the skin, or as a pill.

Some targeted therapy drugs, for example, monoclonal antibodies, work in more than one way to control cancer cells and may also be considered immunotherapy because they boost the immune system.

Like chemotherapy, these drugs enter the bloodstream and reach almost all areas of the body, which makes them useful against cancers that have spread to distant parts of the body. Targeted drugs sometimes work even when chemo drugs do not. Some targeted drugs can help other types of treatment work better.

Several types of targeted therapy drugs can be used to treat breast cancer.

Targeted therapy for HER2-positive breast cancer

In about 15% to 20%  of breast cancers, the cancer cells make too much of a growth-promoting protein known as HER2 . These cancers, known as HER2-positive breast cancers, tend to grow and spread more aggressively than HER2-negative breast cancers. Different types of drugs have been developed that target the HER2 protein.

Monoclonal antibodies

Monoclonal antibodies are man-made versions of immune system proteins (antibodies) that are designed to attach to a specific target. In this case, they attach to the HER2 protein on cancer cells, which can help stop the cells from growing.

Trastuzumab (Herceptin and other brand names): Trastuzumab can be used to treat both early-stage and advanced breast cancer. This drug is often given with chemo, but it might also be used alone (especially if chemo alone has already been tried). When started before (neoadjuvant) or after (adjuvant) surgery to treat early breast cancer, this drug is usually given for 6 months to a year. For advanced breast cancer, treatment is often given for as long as the drug is helpful. This drug can be given into a vein (IV) or as an injection under the skin (subcutaneous).

Herceptin was the original brand name for trastuzumab, but several similar versions (called biosimilars) are now available as well, including Ogivri, Herzuma, Ontruzant, Trazimera, and Kanjinti.Trastuzumab and hyaluronidase injection (Herceptin Hylecta) is given as a subcutaneous (under the skin) shot over a few minutes.

Pertuzumab (Perjeta): This HER2 monoclonal antibody can be given with trastuzumab and chemo, either before or after surgery to treat early-stage breast cancer, or to treat advanced breast cancer. This drug is given into a vein (IV).

Trastuzumab, pertuzumab, and hyaluronidase injection (Phesgo): This is a combination of these drugs given as a subcutaneous (under the skin) shot over several minutes.

Margetuximab (Margenza): This HER2 monoclonal antibody can be used along with chemo to treat advanced breast cancer, typically after at least 2 other drugs that target HER2 have been tried. This drug is given into a vein (IV).

Antibody-drug conjugates

An antibody-drug conjugate (ADC) is a monoclonal antibody linked to a chemotherapy drug. In this case, the anti-HER2 antibody acts like a homing signal by attaching to the HER2 protein on cancer cells, bringing the chemo directly to them.

Ado-trastuzumab emtansine (Kadcyla): This antibody-drug conjugate connects the HER2 antibody to the chemo drug emtansine which is a drug similar to paclitaxel. It is used by itself to treat early-stage breast cancer after surgery (when chemo and trastuzumab were given before surgery, and there was cancer still present at the time of surgery), or to treat advanced breast cancer in women who have already been treated with trastuzumab and chemo. This drug is given in a vein (IV).

Fam-trastuzumab deruxtecan (Enhertu): This antibody-drug conjugate connects the HER2 antibody to a chemo drug deruxtecan which is a drug similar to irinotecan. It can be used by itself to treat breast cancer that can’t be removed with surgery or that has spread (metastasized) to another part of the body, typically after at least 1 other anti-HER2 targeted drug has been tried. This drug is given in a vein (IV).

Kinase inhibitors

HER2 is a type of protein known as a kinase. Kinases are proteins in cells that normally relay signals (such as telling the cell to grow). Drugs that block kinases are called kinase inhibitors.

Lapatinib (Tykerb): This drug is a pill taken daily. Lapatinib is used to treat advanced breast cancer. It is typically given along with trastuzumab and the chemo drug capecitabine.

Neratinib (Nerlynx): This kinase inhibitor is a pill taken daily. Neratinib is used to treat early-stage breast cancer after a woman has been treated with trastuzumab for one year, and it is usually given for one year. It can also be given along with the chemo drug capecitabine to treat people with metastatic disease, typically after at least 2 other anti-HER2 targeted drugs have been tried. 

Tucatinib (Tukysa): This kinase inhibitor is taken as a pill, typically twice a day. Tucatinib is used to treat advanced breast cancer, after at least one other anti-HER2 targeted drug has been tried. It is usually given along with trastuzumab and the chemo drug capecitabine.

Side effects of HER2 targeted drug therapy

The side effects of HER2 targeted drugs are often mild, but some can be serious. Discuss what you can expect with your doctor. If you are pregnant, you should not take these drugs. They can harm and even cause death to the fetus. If you could become pregnant, talk to your doctor about using effective birth control while taking these drugs.

Monoclonal antibodies and antibody-drug conjugates can sometimes cause heart damage during or after treatment. This can lead to congestive heart failure. For most (but not all) women, this effect lasts a short time and gets better when the drug is stopped. The risk of heart problems is higher when these drugs are given with certain chemo drugs that also can cause heart damage, such as doxorubicin (Adriamycin) and epirubicin (Ellence). Other factors that can increase your risk of heart problems are being older than 50, being overweight or obese, having heart problems, and taking medicines for high blood pressure.

Because these drugs can cause heart damage, doctors often check your heart function (with an echocardiogram or a MUGA scan) before treatment, and regularly while you are taking the drug. Let your doctor know if you develop symptoms such as shortness of breath, a fast heartbeat, leg swelling, and severe fatigue.

Lapatinib, neratinib, tucatinib, and the combination of pertuzumab with trastuzumab can cause severe diarrhea, so it’s very important to let your health care team know about any changes in bowel habits as soon as they happen.

Lapatinib and tucatinib can also cause hand-foot syndrome, in which the hands and feet become sore and red, and may blister and peel.

Lapatinib, neratinib, and tucatinib can cause liver problems. Your doctor will do blood tests to check your liver function during treatment. Let your health care team know right away if you have possible signs or symptoms of liver problems, such as itchy skin, yellowing of the skin or the white parts of your eyes, dark urine, or pain in the right upper belly area.

Fam-trastuzumab deruxtecan (Enhertu) can cause serious lung disease in some women. In some cases this might even be life threatening. It’s very important to let your doctor or nurse know right away if you’re having symptoms such as coughing, wheezing, trouble breathing, or fever.  

Targeted therapy for hormone receptor-positive breast cancer

About 3 of 4 breast cancers are hormone (estrogen or progesterone) receptor-positive. For women with these cancers, treatment with hormone therapy is often helpful. Certain targeted therapy drugs can make hormone therapy even more effective, although these targeted drugs might also add to the side effects.

CDK4/6 inhibitors

Palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio) are drugs that block proteins in the cell called cyclin-dependent kinases (CDKs), particularly CDK4 and CDK6. Blocking these proteins in hormone receptor-positive breast cancer cells helps stop the cells from dividing. This can slow cancer growth.

These drugs are approved for women with advanced hormone receptor-positive, HER2-negative breast cancer and are taken as pills, typically once or twice a day.

There are different ways to use these drugs.

  • Any of the three drugs can be given along with an aromatase inhibitor (AI) or fulvestrant to women who have gone through menopause.
  • Any of these three drugs can also be given with fulvestrant or an aromatase inhibitor to women who are still having regular periods (premenopausal) or are almost in menopause (perimenopausal). These women, however, must also be on medicines, such as luteinizing hormone-releasing hormone (LHRH) analogs, that stop the ovaries from making estrogen or have their ovaries removed with surgery.
  • Abemaciclib can also be used by itself in women who have previously been treated with hormone therapy and chemotherapy.

For women with early-stage breast cancer that is hormone receptor-positive, HER2-negative, and has spread to the lymph nodes, and has a high chance of coming back, abemaciclib can be given after surgery along with tamoxifen or an AI. It is typically given for 2 years as a pill twice a day.

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. A rare but possible life-threatening side effect is inflammation of the lungs, also called interstitial lung disease or pneumonitis.

mTOR inhibitor

Everolimus (Afinitor) blocks mTOR, a protein in cells that normally helps them grow and divide. Everolimus may also stop tumors from developing new blood vessels, which can help limit their growth. In treating breast cancer It seems to help hormone therapy drugs work better. Everolimus is a pill that is taken once a day.

This drug is used for women who have gone through menopause and have advanced hormone receptor-positive, HER2-negative breast cancer. It is used with the aromatase inhibitor exemestane (Aromasin) for women whose cancers have grown while being treated with either letrozole or anastrozole (or if the cancer started growing shortly after treatment with these drugs was stopped). It might also be used with fulvestrant, a hormone therapy drug. 

Common side effects of everolimus include mouth sores, rash, diarrhea, nausea, feeling weak or tired, low blood counts, shortness of breath, and cough. Everolimus can also increase blood lipids (cholesterol and triglycerides) and blood sugars, so your doctor will check your blood work regularly while you are taking this drug. It can also increase your risk of serious infections, so your doctor will watch you closely for infection.

PI3K inhibitor

Alpelisib (Piqray) blocks a form of the PI3K protein in cancer cells, which can help them stop growing. This drug is a pill taken once a day.

It can be used along with fulvestrant to treat postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer with a PIK3CA gene mutation that has grown during or after treatment with an aromatase inhibitor. About 30% to 40% of breast cancers have a mutated PIK3CA gene. Your doctor will test your blood or tumor for this mutation before starting treatment with this drug.

Side effects can include a rash, high blood sugar levels, signs of kidney, liver, or pancreatic problems, diarrhea, rash, low blood counts, nausea and vomiting, fatigue, decreased appetite, mouth sores, weight loss, low calcium levels, blood clotting problems, and hair loss. Very severe skin reactions, such as rashes with peeling and blistering, are possible and should be reported to a doctor. Patients with a history of severe skin reactions should tell their doctor before taking alpelisib. Your cancer care team might recommend that you take anti-histamine medicine to help prevent the rash and to also check your blood sugar levels regularly.

Targeted therapy for women with BRCA gene mutations

Olaparib (Lynparza) and talazoparib (Talzenna) are drugs known as PARP inhibitors. 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. These drugs are pills and are taken once or twice a day. They can be used in different ways to treat breast cancer.

  • Olaparib can be given to women with a BRCA mutation with early-stage HER2-negative breast cancer after surgery who have been treated with chemotherapy (before or after surgery) and are at high risk of the cancer recurring. It is typically given for one year. When given in this way, it can help some women live longer.

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

Only a small portion of women with breast cancer are born with a mutated BRCA gene, which is in all the cells of the body. This is different from the gene change happening after you are born which is found only in the cancer cells. If you are not known to have a BRCA mutation, your doctor will test your blood to be sure you have one before starting treatment with these drugs.

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

Targeted therapy for triple-negative breast cancer

In triple-negative breast cancer (TNBC), the cancer cells don’t have estrogen or progesterone receptors and they make very little or none of the HER2 protein.

Antibody-drug conjugate

An antibody-drug conjugate (ADC) is a monoclonal antibody joined to a chemotherapy drug.

Sacituzumab govitecan (Trodelvy): In the case of this ADC, the monoclonal antibody part attaches to the Trop-2 protein on breast cancer cells and brings a chemo drug, similar to irinotecan, directly to them. (Some breast cancer cells have too much Trop-2, which helps them grow and spread quickly.)

This antibody-drug conjugate can be used by itself to treat advanced TNBC, after at least 2 other chemo regimens have been tried. This drug is given in a vein (IV) weekly for 2 weeks, followed by one week off, then restarted.

Some common side effects of this drug include nausea, vomiting, diarrhea, constipation, feeling tired, rash, loss of appetite, hair loss, low red blood cell counts, and belly pain. Very low white blood cell counts and severe diarrhea can also happen, as can reactions when the drug is infused. Medications to lower the chances of an allergic reaction are normally given before treatment with this drug.

More information about targeted therapy

To learn more about how targeted drugs are used to treat cancer, see Targeted Cancer Therapy.

To learn about some of the side effects listed here and how to manage them, see Managing Cancer-related Side Effects.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Almuwaqqat Z, Meisel JL, Barac A, Parashar S. Breast Cancer and Heart Failure. Heart Fail Clin. 2019 Jan;15(1):65-75.

Bardia A, Mayer IA, Diamond JR, et al. Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer. J Clin Oncol. 2017;35(19):2141‐2148. doi:10.1200/JCO.2016.70.8297.

Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012;366:520−529.

Chan A, Delaloge S, Holmes FA, Moy B, Iwata H, Harvey VJ et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016 Mar;17(3):367-77.

Henry NL, Shah PD, Haider I, Freer PE, Jagsi R, Sabel MS. Chapter 88: Cancer of the Breast. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, Pa: Elsevier; 2020.

Jagsi R, King TA, Lehman C, Morrow M, Harris JR, Burstein HJ. Chapter 79: Malignant Tumors of the Breast. In: DeVita VT, Lawrence TS, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 11th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2019.

Ma CX and Sparano JA. Treatment approach to metastatic hormone receptor-positive, HER2-negative breast cancer: Endocrine therapy and targeted therapy. In Vora SR, ed. UpToDate. Waltham, Mass.: UpToDate, 2021. https://www.uptodate.com. Last updated August 10, 2021. Accessed August 13, 2021.

Morgan JP. Cardiotoxicity of trastuzumab and other HER2-targeted agents. In Vora SR, ed. UpToDate. Waltham, Mass.: UpToDate, 2021. https://www.uptodate.com. Accessed August 12, 2021.

Mukohara T. PI3K mutations in breast cancer: prognostic and therapeutic implications. Breast Cancer (Dove Med Press). 2015;7: 111–123.

National Cancer Institute. Physician Data Query (PDQ). Breast Cancer Treatment – Health Professional Version. 2021. Accessed at https://www.cancer.gov/types/breast/hp/breast-treatment-pdq on August 12, 2021.

National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: Breast Cancer. Version 6.2021. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf on August 13, 2021.

Schott AF. Systemic treatment for HER2-positive metastatic breast cancer. In Vora SR, ed. UpToDate. Waltham, Mass.: UpToDate, 2021. https://www.uptodate.com. Accessed August 12, 2021.

References

Almuwaqqat Z, Meisel JL, Barac A, Parashar S. Breast Cancer and Heart Failure. Heart Fail Clin. 2019 Jan;15(1):65-75.

Bardia A, Mayer IA, Diamond JR, et al. Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer. J Clin Oncol. 2017;35(19):2141‐2148. doi:10.1200/JCO.2016.70.8297.

Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012;366:520−529.

Chan A, Delaloge S, Holmes FA, Moy B, Iwata H, Harvey VJ et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016 Mar;17(3):367-77.

Henry NL, Shah PD, Haider I, Freer PE, Jagsi R, Sabel MS. Chapter 88: Cancer of the Breast. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, Pa: Elsevier; 2020.

Jagsi R, King TA, Lehman C, Morrow M, Harris JR, Burstein HJ. Chapter 79: Malignant Tumors of the Breast. In: DeVita VT, Lawrence TS, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 11th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2019.

Ma CX and Sparano JA. Treatment approach to metastatic hormone receptor-positive, HER2-negative breast cancer: Endocrine therapy and targeted therapy. In Vora SR, ed. UpToDate. Waltham, Mass.: UpToDate, 2021. https://www.uptodate.com. Last updated August 10, 2021. Accessed August 13, 2021.

Morgan JP. Cardiotoxicity of trastuzumab and other HER2-targeted agents. In Vora SR, ed. UpToDate. Waltham, Mass.: UpToDate, 2021. https://www.uptodate.com. Accessed August 12, 2021.

Mukohara T. PI3K mutations in breast cancer: prognostic and therapeutic implications. Breast Cancer (Dove Med Press). 2015;7: 111–123.

National Cancer Institute. Physician Data Query (PDQ). Breast Cancer Treatment – Health Professional Version. 2021. Accessed at https://www.cancer.gov/types/breast/hp/breast-treatment-pdq on August 12, 2021.

National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: Breast Cancer. Version 6.2021. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf on August 13, 2021.

Schott AF. Systemic treatment for HER2-positive metastatic breast cancer. In Vora SR, ed. UpToDate. Waltham, Mass.: UpToDate, 2021. https://www.uptodate.com. Accessed August 12, 2021.

Last Revised: May 25, 2022

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