Targeted therapy for breast cancer

Targeted therapy uses drugs to target specific molecules (such as proteins) on cancer cells or inside them. These molecules help send signals that tell cells to grow or divide. By targeting these molecules, the drugs stop the growth and spread of cancer cells and limit harm to normal cells. Targeted therapy may also be called molecular targeted therapy.

Many people with breast cancer have targeted therapy. If you have targeted therapy, your healthcare team will use what they know about the cancer and about your health to plan the drugs, doses and schedules.

You may have targeted therapy to treat:

• locally advanced breast cancer that has spread to lymph nodes before breast-conserving surgery (called neoadjuvant targeted therapy) or after surgery (called adjuvant targeted therapy)
• breast cancer that has spread to other parts of the body (metastatic)
• breast cancer that has stopped responding to treatment or has come back (recurred) after other treatments

ERBB2 is a gene that has changed (mutated) so that it helps a tumour grow (called an oncogene). It is more commonly known as HER2 (or HER2/neu). HER2 stands for human epidermal growth factor receptor 2.

The HER2 gene controls a protein on the surface of breast cells that helps them grow. Each healthy cell contains 2 copies of the HER2 gene. Sometimes too many copies of the HER2 gene are present in a cell and the body makes too much HER2 protein. This is called overexpression of HER2.

HER2 status testing is done on all breast cancer tumours at the time of diagnosis.

• If the cancer cells overexpress HER2, it is called HER2-positive (HER2+) breast cancer.

• If the cancer cells do not overexpress HER2, it is called HER2-negative (HER2-) breast cancer.

• If the cancer cells overexpress lower numbers of HER2, it is called HER2-low breast cancer.

The following targeted therapy drugs are used to treat HER2-positive breast cancer.

Trastuzumab (Herceptin and biosimilars) is the most common targeted therapy drug used to treat HER2-positive breast cancer. It is given through a needle in a vein (by intravenous, or IV).

Locally advanced breast cancer is treated with trastuzumab in combination with chemotherapy drugs before or after surgery. When targeted therapy is given in combination with chemotherapy, trastuzumab is given with taxane chemotherapy drugs. There is a risk of heart problems if targeted therapy is given with anthracycline chemotherapy drugs.

Trastuzumab is usually given by itself for a year after adjuvant chemotherapy for breast cancer has finished.

Because trastuzumab can cause heart problems, heart function tests such as a multigated acquisition (MUGA) scan or an echocardiogram are done before treatment starts to make sure you don't have any heart problems. These tests are done regularly during treatment with trastuzumab. Heart problems caused by trastuzumab are usually temporary.

Pertuzumab (Perjeta) may be used in combination with trastuzumab and chemotherapy before or after surgery for HER2-positive breast cancer that has spread to the lymph nodes. It is also used to treat inflammatory breast cancer. It is given by IV.

Phesgo is pertuzumab and trastuzumab combined into a single dose. It is given by a needle just under the skin (subcutaneously) instead of by IV. This means that treatment can be given more quickly and easily than it can be by giving the 2 drugs separately.

Pertuzumab and trastuzumab may be offered as:

• neoadjuvant therapy of HER2-positive, locally advanced, inflammatory or early-stage (stage 1 or 2) breast cancer

• adjuvant therapy of early-stage HER2-positive breast cancer that has spread to the lymph nodes or is hormone-receptor negative
• treatment in combination with the chemotherapy drug docetaxel for people who have metastatic HER2-positive breast cancer that has not yet been treated with targeted therapy or has recurred since chemotherapy was finished

When a targeted therapy drug is combined with a chemotherapy drug, it is called an antibody-drug conjugate. Trastuzumab emtansine (Kadcyla or T-DM1) is a combination of trastuzumab and the chemotherapy drug emtansine (DM1). It is given by IV.

Trastuzumab emtansine is used to treat HER2-positive breast cancer if there is still evidence of cancer in the breast or lymph nodes after treatment with chemotherapy and trastuzumab (with or without pertuzumab). The drug is given to complete a year of anti-HER2 therapy.

Trastuzumab emtansine may be given to treat metastatic breast cancer that no longer responds to the combination of trastuzumab and pertuzumab.

Trastuzumab deruxtecan (Enhertu) is another antibody-drug conjugate. It is a combination of trastuzumab and the chemotherapy drug deruxtecan. It is given by IV.

It may be used for unresectable or metastatic HER2-positive breast cancer that has already been treated with trastuzumab and pertuzumab.

Trastuzumab deruxtecan is also used to treat HER2-low breast cancer.

Neratinib (Nerlynx) may be used to treat early-stage HER2-positive breast cancer after a year of treatment with trastuzumab. It may be started within one year of finishing trastuzumab.

Neratinib may also be used in combination with capecitabine for the treatment of metastatic HER2-positive breast cancer after 2 or more treatments have been used.

Lapatinib (Tykerb) may be combined with capecitabine to treat metastatic HER2-positive breast cancer when other types of chemotherapy or trastuzumab no longer work.

Lapatinib may be combined with letrozole to treat metastatic breast cancer that is hormone-receptor positive and HER2 positive.

Tucatinib (Tukysa) may be offered to treat locally advanced or metastatic breast cancer that is HER2 positive and has been treated with at least 3 other targeted therapy drugs. Tucatinib is combined with trastuzumab and capecitabine.

This combination may also be used to treat brain metastases from HER2-positive breast cancer.

HER2-negative breast cancer does not overexpress the HER2 protein. The following targeted therapy drugs treat hormone receptor–positive and HER2-negative breast cancer by stopping proteins different form HERS on the cancer cells.

Mammalian target of rapamycin (mTOR) is a protein that controls cell growth and reproduction. In some types of cancer, including breast cancer, mTOR causes cancer cells to keep growing and dividing. mTOR inhibitors block the action of mTOR, which can stop the growth of cancer.

Everolimus (Afinitor) is the mTOR inhibitor used to treat locally advanced or metastatic hormone receptor–positive, HER2-negative breast cancer that has come back or has continued to progress during treatment with letrozole or anastrozole (Arimidex). It is combined with the hormone therapy drug exemestane (Aromasin).

CDK4/6 inhibitors are drugs that slow or stop breast cancer cells from dividing and multiplying. They target specific proteins called cyclin-dependent kinases 4 and 6 (CDK4/6). These proteins are found in higher numbers in breast cancer that is both hormone-receptor positive and HER2 negative.

CDK4/6 inhibitors are combined with hormone therapy to make treatment more effective. They are given as pills.

The following CDK4/6 inhibitors may be used to treat advanced or metastatic hormone receptor–positive, HER2-negative breast cancer.

Palbociclib (Ibrance) may be used in combination with:

• an aromatase inhibitor as the first treatment

• fulvestrant if breast cancer has kept growing (progressed) while on hormone therapy

Treatment continues as long as the cancer does not grow and no new metastatic tumours are found.

Ribociclib (Kisqali) may be used in combination with:

• an aromatase inhibitor as the first treatment given

• fulvestrant as the first treatment given, or if the cancer has progressed during treatment with other hormone therapy drugs

Ribociclib is combined with a GnRH agonist if you are premenopausal or perimenopausal.

Abemaciclib (Verzenio) may be used in combination with:

• an aromatase inhibitor as the first hormone therapy treatment
• fulvestrant if the cancer has progressed during treatment with hormone therapy
• a GnRH agonist and fulvestrant if you are premenopausal or perimenopausal

Abemaciclib may be used by itself for metastatic breast cancer that has progressed after hormone therapy, and has been treated with chemotherapy using at least one taxane drug.

Abemaciclib may be used to treat early-stage breast cancer that is hormone-receptor positive and HER2 negative, has spread to some lymph nodes and has a high risk of recurrence.

Sacituzumab govitecan (Trodelvy) is an antibody drug conjugate, which is a targeted therapy drug combined with a chemotherapy drug.

It is used to treat unresectable locally advanced or metastatic breast cancer that is hormone-receptor positive and HER2 negative and has been treated with hormone therapy and at least 2 other chemotherapy drugs used for metastatic breast cancer.

Sacituzumab govitecan is also used to treat unresectable triple-negative breast cancer (TNBC) that is locally advanced or metastatic and has been treated with 2 or more chemotherapy regimens (at least one of them for metastatic disease).

PIK3CA is a gene that makes a protein that helps with a cell's growth, movement, division and survival.

PIK3CA inhibitors stop the PIK3CA gene from making this protein so that cancer cells can no longer grow or divide.

Alpelisib (Piqray) is a PIK3CA inhibitor. It is used to treat locally advanced or metastatic breast cancer that is hormone-receptor positive and HER2 negative and has mutations in the PIK3CA gene. It is used for post-menopausal people.

Alpelisib may be offered in combination with fulvestrant if the cancer has stopped responding to hormone therapy.

Poly (ADP-ribose) polymerase (PARP) is another type of enzyme that is used by cells to repair themselves. PARP inhibitors stop PARP from repairing cancer cells, so they die.

PARP inhibitors may be used to treat breast cancer with BRCA gene mutations. Tests are done to confirm that the cancer has BRCA gene mutations before these drugs are used.

The following PARP inhibitors are used to treat BRCA gene-mutated breast cancer. All of these drugs are given as pills.

Olaparib (Lynparza) can be used to treat people with metastatic HER2-negative breast cancer who have already had chemotherapy. If the cancer is also hormone-receptor positive, olaparib can be used if the cancer stopped responding to hormone therapy or wasn't able to be treated with hormone therapy.

Olaparib may also be given as an adjuvant therapy to people with an BRCA gene mutation who are at high risk of recurrence of breast cancer.

Talazoparib (Talzenna) can be used to treat people with locally advanced or metastatic HER2-negative breast cancer who have already had chemotherapy.

Side effects of targeted therapy drugs used for breast cancer will depend mainly on the type of drug or combination of drugs, the dose, how it's given and your overall health. Tell your healthcare team if you have side effects that you think are from targeted therapy. The sooner you tell them of any problems, the sooner they can suggest ways to help you deal with them.

• flu-like symptoms (fever, chills, headache)

• nausea and vomiting

• diarrhea, which can be severe
• fatigue
• low blood cell counts
• skin problems, especially hand-foot syndrome with lapatinib
• heart problems
• lung problems
• liver problems
• bladder problems
• kidney problems
• tingling in the hands and feet (called peripheral neuropathy)
• confusion
• loss of appetite
• constipation
• changes to taste
• hair loss
• sleep problems
• pain in the muscles, joints and bones

Find out more about targeted therapy. To make the decisions that are right for you, ask your healthcare team questions about targeted therapy.

Details on specific drugs change regularly. Find out more about sources of drug information and where to get details on specific drugs.