HER-2/NEU TESTING AND HERCEPTIN

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by Dr. Joginder Singh, M.D.

About 200,000 women are diagnosed with breast cancer each year in the United States and 40,000 women die each year due to this disease. There are different factors which determine the chances for recurrence after primary surgery (of mastectomy or lumpectomy and radiation therapy) and different factors which determine survival of patients who have metastatic breast cancer.

It’s known that tumor characteristics such as estrogen and progesterone receptors, as well as grading of the tumor, determine the prognosis in women with breast cancer. However, clinicians have been surprised many times that some women with large tumors and many positive lymph nodes have no recurrence while other women with only small tumors have recurrences. Similarly, in patients with metastatic breast cancer (breast cancer spread to other organs) it is known that women with disease only in the bones live longer than women who have disease in the lungs, liver and brain. However, there are exceptions to the rule.

The clinicians and scientists have been studying women with small tumors who had recurrences and a subset of metastatic breast cancer patients who have a rapid progression of disease to determine why some patients have aggressive cancers and others do not. One of the genes that was found to be of prognostic value, and later found to be useful for treatment, is HER2/NEU.

HER-2/NEU is a gene that helps control how the cells grow, divide and repair themselves. About 30% of breast cancers have too many copies of the HER-2/NEU gene. The HER-2/NEU gene directs the production of special proteins, called HER-2 receptors, on the cells.

​Cancer with too many copies of HER-2 or too many HER-2 receptors tends to grow fast and are associated with an increased risk of spread. They do respond very well to the treatment that works against HER-2/NEU. This targeted therapy is called Herceptin. It works specifically by binding to HER2/NEU positive cancer cells and killing them.

There are two tests for HER2/NEU:
IHC Test (ImmunoHistoChemistry)
The IHC test shows if there are too many HER-2 receptor proteins in the cancer cells. The results of the IHC test can be zero (negative), 1+ ​(negative), 2+ (borderline) or 3+ (positive).

FISH Test (Fluorescent In Situ Hybridization)
The FISH test shows if there are too many copies of HER-2/NEU gene in the cancer cells. The results of the FISH test can be positive (extra copies) or negative (normal number of copies) Finding out which HER-2/NEU test was done is important. Only cancers that have 3+ or FISH positive will respond well to therapy that works against HER2/NEU. If you have 2+ test results on immunohistochemistry, the test result is borderline. Some patients respond to Herceptin and others do not. If the results by immunohistochemistry are 2+ you should ask to have the tissue tested by FISH test. The results by FISH test are more accurate and determine whether the tumor will respond to Herceptin or not. The FISH test is the preferred method for testing at this time.

HERCEPTIN IN METASTATIC BREAST CANCER
Herceptin alone
The studies of patients with HER2/NEU positive breast cancers given Herceptin as a single agent showed 14% of the women’s tumors were resistant to chemotherapy. This was a significant result, especially since metastatic breast cancer, which is HER-2/NEU positive, tends to be aggressive.

Herceptin with chemotherapy
In other studies, women with breast cancer got even better results when they took Herceptin together with chemotherapy drugs. Herceptin has been studied with many drugs including Taxol, Adriamycin (doxorubicin) and Navelbine. The combination of Herceptin and chemotherapy also improved survival in women with metastatic breast cancer. A small number of women who took Adriamycin and Herceptin had significant heart problems, including congestive heart failure. This is a condition in which the heart is unable to pump effectively. At this time, Herceptin along with Adriamycin should be avoided.

Herceptin in adjuvant treatment of breast cancer
Adjuvant treatment is a treatment given to women whose cancers have been removed by surgery. The purpose of adjuvant treatment is to prevent recurrences of the breast cancer in other organs of the body. In recent trials, 3,300 women with early stage breast cancer, whose tumors were removed by surgery, were given adjuvant treatment with a combination of Herceptin and chemotherapy or chemotherapy alone. Patients showed a 52% decrease in disease recurrence when Herceptin was given with chemotherapy compared with chemotherapy alone.

​This is a major advance for thousands of women with breast cancer. These results are examples that we are at a major turning point in the use of targeted therapies to eliminate suffering and death from cancer. Herceptin, however, is not for everybody. Patients with breast cancer, which do not have HER2/NEU expression, do not respond or benefit from Herceptin.

Heart failure
One of the most fearful side effects of Herceptin is heart failure and this poses a dilemma for patients who have a small chance for recurrence. In these patients, the benefit from adding Herceptin to chemotherapy or Herceptin therapy alone, is small. Patients on Herceptin therapy should be monitored regularly even though the chance of heart failure is low (up to 4.1%). Anytime there is evidence that Herceptin is causing a decrease in the pumping force of the heart (ejection fraction), Herceptin should be stopped. 

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