hat is Biology Good For?
Treating Breast Cancer: Herceptin

(This assignment is optional. Read this essay and answer the questions at the bottom for 3 extra credit points. You may only turn in one per six weeks. The assignment is due one week before the end of the six weeks. It is not necessary to visit the links in the text unless you are interested in more information.)

On September 25, 1998 the U.S. Food and Drug Administration (FDA) approved Herceptin as a biologic approach for the treatment of metastatic breast cancer (cancer that has spread beyond the breast and lymph nodes under the arm). This approval was the result of over 15 years of scientific investigation and clinical testing that was done at Genentech, the UCLA Medical Center, and other labs around the world.

What is Herceptin?

Herceptin (generic name trastuzumab) is a monoclonal antibody that has been genetically engineered to bind to a specific protein called HER2 (or the HER2/neu protein), a protein receptor over-expressed on the surface of some breast cancer cells. Herceptin binds only to cells expressing the HER2 protein on the cell surface. Once bound to the cells, Herceptin slows the growth and spread of these tumors.

What is HER2?

HER2 (Human Epidermal growth factor Receptor 2) is a protein found on the surface of cells that plays a key role in regulating cell growth. When the HER2 gene is altered, extra HER2 proteins may be produced. This over-expression of HER2 causes increased cell growth and reproduction, often resulting in more aggressive tumor cells. Appromimately 25-30% of breast cancers over-express HER2 (produce excess amounts of HER2).

Does Herceptin work for all breast cancers?

No. Herceptin is very effective in the treatment of HER2-positive breast cancer, but HER2 protein over-expression affects only 25% to 30% of breast cancer patients. However, a tumor with HER2 over-expression is very aggressive in its ability to grow and metastisize, and as such, these tumors are often not responsive to standard breast cancer treatments like chemotherapy. Herceptin is used to control the spread of these particularly agressive HER2-overexpressing tumors that have not responded to traditional chemotherapy.

Pathologists test tumor tissue for HER2 over-expression at the time of breast biopsy or surgery, or on stored tumor tissue from previous biopsy. To test for HER2 over-expression, the tumor tissue is stained by a specific solution. Depending on the level of staining, the tumor tissue sample may be classified as HER2 positive. If the tumor cells should test positive for HER2 overexpression, Herceptin treatment is considered. Today, over 200,000 HER2 diagnostic tests are performed per year.

In clinical studies, Herceptin slowed the growth of tumors and in some cases, made tumors disappear altogether! On average, Herceptin by itself results in a 14% reduction of tumor size. Tumors disappeared completely in some patients (3%) who had disease limited to skin and lymph nodes! In combination with the chemotherapy drug Taxol, women who received Herceptin with chemotherapy had tumors were that reduced by 50% or more in size compared to chemotherapy alone. The one-year survival rate for women who received herceptin with chemotherapy was 79% compared to a survival rate of 68% for chemotherapy alone.

What are the risks of Herceptin?

Herceptin can cause weakening of the heart muscle, resulting in congestive heart failure. Heart damage is more common when Herceptin is used in combination with the chemotherapeutic drugs anthracycline and cyclophosphamide (AC). Therefore, Herceptin is not approved for use with AC regimens. Heart function should be checked before starting treatment, and monitored during treatment. If heart problems are detected, Herceptin therapy may be discontinued.

What are the side effects of Herceptin?

Typically, Herceptin is administered intravenously (through the vein) in an outpatient clinic setting. In combination with chemotherapy, Herceptin increases the frequency of the following chemotherapy-associated side effects:

Side effects of Herceptin are most common with the first dose. With subsequent doses, side effects are less likely. Side effects are treatable.

References for this Good For:
Genentech Inc., Herceptin backgrounder. The site is divided into separate sections for patients and health care professionals.Lots of breast cancer resources. Imaginis: Breast Cancer
A great book!!: Her-2: The Making of Herceptin, A Revolutionary Treatment for Breast Cancer. Written by Robert Bazell, the scientific correspondent for NBC News, and an excellent science writer for the layperson or scientist. "This book chronicles the dramatic discoveries, strong personalities, scientific investigation, money, politics, ego, corporate decisions, patient activism, and luck involved in getting Herceptin from the lab to the market." (Now out of print, but get out your library card and put a hold on it at the IMCPL if you are interested).

The text of this "What is Biology Good For" exercise is copyrighted under the name of Dr. Kathleen A. Marrs, 1999, 2000, 2001, 2003. There are no restrictions on its use by educators or by non-profit institutions as long as its content not modified, proper copyright acknowledgement is retained, and this statement is not removed.


Extra Credit Questions: Please answer the following questions on a piece of paper and turn it into me.

1. What is HER2 and how is it associated with breast cancer?
2. What are three
side effects associated with use of herceptin?
3. Why isn't Herceptin used to treat all breast cancers?