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
Researchers 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
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