Targeted therapy for breast cancer

Targeted therapy is usually used to treat breast cancer. It 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.

You may have targeted therapy to:

• stop breast cancer cells from growing and spreading
• lower the risk that the cancer will come back (recur)
• treat breast cancer that has spread (metastasized) to other parts of the body and that no longer responds to other breast cancer treatments

Your healthcare team will consider your personal needs to plan the drugs, doses and schedules of targeted therapy. You may also receive 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.

HER2 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 breast cancer cells overexpress HER2, it is called HER2-positive breast cancer.

The following targeted therapy drugs have been specially designed to attach to the extra HER2 proteins to stop the growth of HER2-positive breast cancer cells.

Trastuzumab is the most common targeted therapy drug used to treat HER2-positive breast cancer. It is given through a needle in a vein (intravenously).

Women with invasive or locally advanced breast cancer may be given trastuzumab in combination with chemotherapy drugs after surgery (called adjuvant therapy). Trastuzumab is usually given for up to a year after chemotherapy for breast cancer has finished.

Women with breast cancer that has spread to other parts of the body (called metastatic breast cancer) may be given trastuzumab by itself. It is continued until the breast cancer does not respond to the drug.

Pertuzumab may be used in combination with trastuzumab and chemotherapy to treat early HER2-positive breast cancer in people with lymph node positive or hormone receptor-negative disease. It is given through a needle in a vein (intravenously).

Pertuzumab may be used in combination with trastuzumab and docetaxel to treat metastatic HER2-positive breast cancer in people who have not had trastuzumab or chemotherapy to treat it.

Pertuzumab may be also be used in combination with trastuzumab and chemotherapy, before surgery, in people with HER2-positive breast cancer that is:

• locally advanced

• early stage

• inflammatory breast cancer

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

Phesgo may or may not be combined with chemotherapy to treat HER2-positive breast cancer:

• that has spread to the lymph nodes and other parts of the body (metastatic)

• that is hormone receptor negative or positive

• before surgery for locally advanced breast cancer

• after surgery for early stage breast cancer

• that is inflammatory breast cancer

Phesgo may be combined with the chemotherapy drug docetaxel to treat metastatic HER2-positive breast cancer that hasn't been treated with any HER2 targeted therapies or chemotherapy used for metastatic breast cancer.

Trastuzumab emtansine is a combination of trastuzumab and the chemotherapy drug emtansine (DM1). It may be used to treat HER2-positive metastatic breast cancer that has already been treated with one of the following:

• trastuzumab alone
• chemotherapy with paclitaxel (Taxol) or docetaxel
• trastuzumab with either paclitaxel or docetaxel

Trastuzumab emtansine may also be used to treat non-metastatic HER2-positive breast cancer if there is still evidence of cancer after treatment with chemotherapy and trastuzumab.

Trastuzumab deruxtecan (Enhertu) is a combination of trastuzumab and a chemotherapy drug called deruxtecan. It may be offered people who have unresectable or metastatic HER2–positive breast cancer who have already been treated with trastuzumab emtansine.

Tyrosine kinases are a type of enzyme (proteins that speed up certain chemical reactions in the body). They play an important role in cell development and division. Tyrosine kinase inhibitors block specific tyrosine kinases that tell cancer cells to grow. These drugs are also called signal-transduction inhibitors or small-molecule drugs.

Lapatinib and capecitabine (Xeloda) may be given to treat metastatic HER2-positive breast cancer when other types of chemotherapy or trastuzumab (Herceptin) no longer work.

Lapatinib and letrozole (Femara) may be given to post-menopausal women with HER2-positive and hormone receptor–positive metastatic breast cancer. Letrozole is a type of hormonal therapy. This combination is given when hormonal therapy stops working.

Palbociclib may be given with aromatase inhibitors to treat post-menopausal women with estrogen receptor–positive (ER+) and HER2-negative metastatic breast cancer. Palbociclib may not be covered by all provincial health plans.

Neratinib may be used to treat women with early-stage hormone receptor-positive and HER2-positive breast cancer after they have completed a year of trastuzumab (Herceptin) therapy.

It may also be used in combination with the chemotherapy drug capecitabine for the treatment of metastatic HER2-positive breast cancer, after 2 or more treatments for HER2-positive treatment have been used to treat metastatic disease.

Ribociclib succinate may be given with letrozole to treat post-menopausal women with hormone receptor–positive and HER2-negative advanced or metastatic breast cancer.

mTOR inhibitors block the mammalian target of rapamyin (mTOR). mTOR is a protein that regulates cell growth and reproduction. It is abnormal in some types of cancer, including breast cancer, which 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 for metastatic breast cancer. It is given with the hormonal therapy drug exemestane (Aromasin). This combination is used to treat post-menopausal women with hormone receptor–positive, HER2-negative metastatic breast cancer that no longer responds to hormonal therapy with letrozole or anastrozole (Arimidex).

Cyclin-dependent kinases (CDKs) are proteins that control the cell cycle. CDK inhibitors block these proteins to help slow or stop the growth of cancer cells.

Abemaciclib (Verzenio) is a CDK inhibitor used in women with hormone receptor–positive, HER2-negative advanced or metastatic breast cancer. It is taken as pill daily and may be given:

• with an aromatase inhibitor for post-menopausal women as hormonal-based therapy
• with fulvestrant (Faslodex) if the disease progresses after hormonal therapy
• alone if the disease progresses after hormonal therapy and at least 2 chemotherapy regime

Olaparib (Lynparza) can be used to treat people with metastatic, HER2-negative breast cancer who have a BRCA gene mutation and have already had chemotherapy. Olaparib is usually taken by mouth.

Talazoparib (Talzenna) can be used to treat people with locally advanced or metastatic, HER2-negative breast cancer who have a BRCA gene mutation and have already had chemotherapy. Talazoparib is taken by mouth once a day.

Side effects can happen with any type of treatment for breast cancer, but everyone’s experience is different. Some people have many side effects. Other people have few or none at all.

Targeted therapy attacks cancer cells but doesn’t usually damage healthy cells, so there are fewer and less severe side effects than with chemotherapy and radiation therapy. Chemotherapy and radiation therapy can damage healthy cells along with cancer cells.

If you develop side effects, they can happen any time during, immediately after or a few days or weeks after targeted therapy. Sometimes late side effects develop months or years after targeted therapy. Most side effects go away on their own or can be treated, but some side effects may last a long time or become permanent.

Side effects of targeted therapy will depend mainly on the type of drug or combination of drugs, the dose, how it’s given and your overall health. Some common side effects of targeted therapy for breast cancer are:

• fatigue
• headache
• sore mouth
• diarrhea
• nausea and vomiting
• increased risk for infection
• skin problems, including redness, itching and dryness
• loss of appetite
• constipation

Some people may have a reaction when the drugs are given, including:

• wheezing, difficulty breathing or coughing
• skin rash, flushing or itching
• anxiety
• chest pain or irregular heartbeat
• high or low blood pressure

Trastuzumab can cause heart damage, especially when it is given with doxorubicin (Adriamycin), which is a chemotherapy drug commonly used for breast cancer. Lapatinib can also cause heart damage. Heart function tests, such as a multigated acquisition (MUGA) scan or an echocardiogram, are done before the start of treatment and then regularly during treatment with trastuzumab.

Tell your healthcare team if you have these side effects or others you think might be from targeted therapy. The sooner you tell them of any problems, the sooner they can suggest ways to help you deal with them.

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

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