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Targeted Therapy

Targeted therapy uses drugs to target specific molecules on cancer cellsCell:
The basic structural and functional unit of all organisms.
that control various functions of the cancer cell, such as when to grow and divide. Targeting these molecules slows or stops the cancer from growing and spreading. The development of targeted therapies to treat breast cancer is a major area of breast cancer research.

HER-2 Therapy

Cells have many different proteins on their surface called receptorsReceptor:
Cells have many different proteins on their surface called receptors. Her-2 is one kind of receptor. In normal cells, HER-2 receptors are thought to be involved in cell growth and reproduction. In some breast cancers, there are too many HER-2 receptors and they speed up cancer cell growth.
. HER-2HER-2-neu:
Cells have many different proteins on their surface called receptors. HER-2 is a type of naturally occurring receptor. In normal cells, HER-2 receptors are thought to be involved in cell growth and reproduction. In some breast cancers, there are too many HER-2 receptors and they speed up cancer cell growth. HER-2 therapy is used to treat some breast cancers by targeting receptors that stimulate breast cancer growth.
(human epidermal growth factor receptor 2) is a type of naturally occurring receptor. In normal cells, HER-2 receptors are thought to be involved in cell growth and proliferation. In some breast cancers, there are too many HER-2 receptors and they speed up cancer cell growth.

HER-2 therapy is used to treat some breast cancers by targeting these HER-2 receptors that stimulate breast cancer growth.

Testing for HER-2

To find out their HER-2 receptor status, breast cancer cells are tested in a lab. This is done on breast tissue collected during a biopsyBiopsy:
A procedure in which tissue samples are removed from the body for examination under a microscope to determine if cancer or other abnormal cells are present.
.

In some people, testing shows that their breast cancer cells have the normal number of HER-2 receptors. These cancers are known as HER-2 negative. For patients with HER-2 negative breast cancer, there is no known benefit from taking HER-2 therapy.

In other people, testing shows that their breast cancer cells have more HER-2 receptors than is normal. These breast cancers are known as HER-2 positive. For patients with HER-2 positive breast cancer, HER-2 therapy is likely to help.

Approximately 20% of breast cancers are HER-2-positive. These cancers tend to grow and spread more aggressively, because the extra HER-2 receptors speed up cell growth.

Treatment

There are currently two HER-2 targeted treatments available for the treatment of breast cancer, trastuzumab (Herceptin) and lapatinib (Tykerb). These medications work in different ways.  Trastuzumab is an antibodyAntibody:
A protein that is part of the immune system. Antibodies bind to and neutralize substances that the body recognizes as foreign, such as bacteria and viruses.
which binds to and blocks HER-2 receptors of breast cancer cells. Trastuzumab is given as an intravenousIntravenous (I.V.):
A method of administering medication where the substance is given into a vein using a needle.
injection every 1-3 weeks. Lapatinib is a small molecule which interrupts the HER-2 pathways of the cell.  Lapatinib tablets are taken at home by mouth twice a day for several days in a row. It can be used together with another oral chemotherapyChemotherapy:
A treatment method that uses medication to destroy cancer cells.
drug called capecitabine (Xeloda) or a hormone therapyHormone therapy:
A treatment method for breast cancer that uses medication to block the production of the hormone estrogen, or the way that it works in the body.
called letrozole (Femara).

By interfering with the HER-2 pathway, these drugs disrupt the growth of HER-2 positive cancer cells, slowing the growth and spread of the cancer.

Trastuzumab (Herceptin) was first demonstrated to be very effective for the treatment of metastaticMetastatic (metastases):
The spread of cancer from its original (primary) location to another part of the body. A tumour that is formed by cancer cells that have spread to another part of the body is called a “metastatic tumour” or a “metastasis.”
breast cancer. Since then it has transformed the treatment of HER-2 positive, early stageStage:
A way of classifying breast cancer that describes how far a cancer has spread. It identifies whether breast cancer is at an early, locally advanced or metastatic stage. The stage of breast cancer can sometimes be represented as a number (e.g. between 0 and 4).
breast cancer. HER-2 therapy is often used after surgery, but can also be used before surgery to shrink large tumoursTumour:
An abnormal mass of tissue that occurs when cells divide more than they should or do not die when they should. Tumours may be benign (not cancer) or malignant (cancer). A tumour is also called a neoplasm.
.

Trastuzumab (Herceptin) is given by vein (intravenously or I.V.) once a week or once every 3 weeks. In this procedure, a thin needle is inserted into your hand or arm and connected to a tube through which the medication flows, and this can take some time. An oncology nurseOncology nurse:
A nurse who specializes in the care of cancer patients.
will be with you while you are receiving your treatment. When the treatment session is complete, the needle will be removed. If you are having your treatments as an outpatient, you will be allowed to go home then. When treatment includes chemotherapy, it is usually given for up to 1 year when chemotherapy is complete. In the treatment of metastatic breast cancer, it can be given indefinitely to try to keep the cancer cells under control for as long as possible.

Resistance to HER-2 Therapy

It is possible for cancer cells to withstand the effects of (become resistant to) HER-2 therapy. Resistance to HER-2 therapy can be present from the beginning, or can develop during the course of the treatment.

Breast cancers that develop resistance can make it more difficult to plan treatment because the options may become more limited. Research is currently looking into ways to overcome resistance to drugs used in HER-2 therapy.

Side Effects

Possible side effects of trastuzumab (Herceptin) therapy include flu-like symptoms such as fever, chills and headache. The side effects are usually mild in comparison to the side effects of chemotherapy and decrease in severity after the first treatment.

A less common but serious side effect of trastuzumab therapy affects the heart, weakening the muscle and causing shortness of breath, leg swelling and extreme fatigue. If you are on trastuzumab and experience these side effects, contact your health care provider or oncologistOncologist:
A doctor or surgeon who specializes in treating cancer. A medical oncologist specializes in drug therapy (chemotherapy) for cancer. A radiation oncologist specializes in treating cancer with radiation.
immediately—or go directly to your local emergency department.

Lapatinib (Tykerb) is generally well tolerated but can commonly cause diarrhea, fatigue and skin changes. Rare but serious side effects of lapatinib include heart rhythm disturbances, weakening of the heart muscle, and toxicity to the liver and lungs. Lapatinib is prone to interactions with many other drugs and things we eat. Your oncologist and oncology pharmacistOncology pharmacist:
A pharmacist who has special training in how to design, give, monitor, and change chemotherapy for cancer patients.
will counsel you about this before prescribing lapatinib.

Ask your health care team about the benefits, limitations and possible side effects of HER-2 therapy to help you make an informed decision about your treatment.

Other targeted therapies

Other therapies targeting the HER2 pathway are currently being studied (pertuzumab, T-DM1, everolismus) and show promising activity in advanced breast cancer. Your oncologist might discuss and encourage you to participate in clinical trials with new agents.

 

Sources:

Banarjee, S. & Smith, I. E (2010). Management of small HER2-positive breast cancers. Lancet Oncology 2010: 11: 1193-99.

Breastcancer.org. Targeted therapies. Accessed January 12, 2014.

Canadian Cancer Society. Biological therapy for breast cancer. Accessed January 12, 2014

Canadian Cancer Society. Targeted Therapy. Accessed January 12, 2014.

Kelly, C. M., Pritchard, K. I, Trudeau, M., Andreopoulou, E., Hess, E. & Pusztai, L. (2011). Coping with uncertainty: T1a,bN0M0 HER2-positive breast cancer, do we have a treatment threshold? Annals of Oncology, 22 (11), 2387-2393.

Mackay et al (2008). Cardiac Management during adjuvant trastuzumab therapy: Recommendations of the Canadian Trastuzumab Working Group. Current Oncology, 15 (1), 24-35.

National Comprehensive Cancer Network. (2014).  Practice Guidelines in Oncology – Breast Cancer. V1.2014. Accessed June 3, 2014.