Breast Cancer is on a steep rise in India and is fast catching up in terms of incidence with that of US. Latest statistics have predicted the incidence of Breast cancer as to be present in 1 out of every 22 women in India. The incidence of Breast cancer in US is around 1 out of 8 women. In the year 2008, 1, 15,000 new cases of Breast Cancer were diagnosed in India, a number which is fast catching up with that of the United States.
Another cancer, which ranks as the second leading cause of mortality in the world is Gastric Cancer. HER2 overexpression has been found in most gastric cancers including metastatic as well as cancers of the gastro-espophageal junction.
AdvertisementResearchers have found that about 20-30% or even higher numbers of Breast Cancers exhibit an 'overexpression' of HER2 (human epidermal growth factor receptor 2). An overexpression of HER2 refers to the fact that this oncogene (cancer causing gene) is permanently in a switched-on or active mode at the site of cancer. HER2 is found in low levels in the normal epithelial cells. This overexpression of HER2 in the breast cancer as well as gastric cancer increases the multiplication of cells thus increasing the tumor aggressiveness and risk of recurrence.
About 25% of women with early breast cancer have been diagnosed with HER2 overexpression. Overexpression of HER2 makes the cancers faster growing and more resistant to chemotherapy.
Early of detection of HER2 in these cancers thus becomes an important part of their treatment and prevention of further growth.
How to control and treat HER2 overexpression?
Trastuzumab (Herceptin) is an antibody which inhibits the growth of HER2 protein by inducing cellular toxicity through the antibody-dependent cellular toxicity mechanism. Researches have demonstrated a diminished mortality rate with the use of Trastuzumab in combination with chemotherapy in both gastric and breast cancer cases. Trastuzumab has also demonstrated a better response rate as well as duration of treatment response in the gastric and breast cancer cases.
Trastuzumab treatment is administered to the patients after a thorough evaluation of the clinical history of the case. The Hercep test is an aid in helping selection and decision of trastuzumab treatment amongst cases of breast cancer as well as gastric cancers. These include the Adenocarcinoma of the stomach including the gastro-espophageal junction.
According to Martinez et al, results from 5 studies have demonstrated that the inclusion of trastuzumab produces a 50% improvement in disease-free survival and 33% improvement in overall survival, regardless of the chemotherapy regimen or sequence of trastuzumab delivery. Based on these results, trastuzumab has been approved by FDA for the treatment of HER2 positive cancer.
How is HER2 overexpression detected?
The Hercep Test is an immunocytochemical assay used to determine the overexpression of HER2 protein in breast cancer and gastric cancer cell lines. The test checks of over-expression of HER2 protein in the tissue samples which are routinely collected by the physician for histological evaluation as well on the formalin fixed paraffin embedded cancer tissues.
A positive or negative outcome of the Hercep test helps in the clinical decision for the use of Trastuzumab therapy.
Other recent tests that have come up for detecting HER2 overexpression include reverse-transcriptase polymerase chain reaction and chromogenic in situ hybridization (CISH). These tests have not been validated yet.
In order to ensure accuracy of the HER testing, guidelines have been developed by the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP). According to these recommendations, the breast cancer tissues should undergo a validated immunohistochemistry (IHC) such as Hercep test to determine HER2 overexpression based on cell membrane staining pattern.
The samples with an equivocal IHC should undergo another test called FISH (Fluorescent in situ hybridization). According to Martinez et al, as much as 15% results of IHC may be ambiguous, but FISH outcomes are seen to be uncertain in less than 3 % of invasive breast cancer cases which were thought to be HER2 positive. FISH, however, is a more expensive test than Hercep.
How accurate is Hercep Test?
The efficacy of Hercep test has been evaluated based on two studies. The first study compared Hercep test outcomes of the tissue samples with those tested using CTA (clinical trial assay- no longer available) and Hercep test results matched with those of CTA in around 79% of the cases.
The other study compared Hercep test with five different assays including FISH, Northern blot, Southern blot, Western blot and immunocytochemistry. The results of Hercep test were in agreement with these assays in 85% of the cases. None of specimens that were considered negative by these five assays was tested positive with the Hercep test.
The Hercep test appears to be a safe, reliable and economic method for the detection and initial assessment of HER2 overexpression in breast and gastric cancers based on ASCO and CAP recommendations. The test is also proven to correlate well with other testing assays. Hercep test has so far been approved for breast and gastric cancers only.
HercepTest for the Detection of HER2 Protein Overexpression in Breast and Gastric Cancers; Laura Martinez et al; US Pharmacist.com.
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