Download The affects of HER2 Gene/Receptor Over

Introduction
• The effects of HER2 gene and receptor overexpression on breast cancer.
• Prognosis and treatment of HER2+ breast
cancer. (See figure 1)
•Figure 1.
•This graph depicts the comparative survival rates of HER2+ and HER2breast cancers, HER2+’s prognosis being lower. P<0.001 (Tovey, 2009)
Background of the HER2
Gene/Receptor
• The HER2 gene carries the biochemical
information necessary to produce the HER2
receptor. (Osin, 1999).
• This gene is located on chromosome 17, occurs
once on each side of the chromosome.
• Full name: Human epidermal growth protein
receptor tyrosine kinase 2 (Osin, 1999).
• This receptor is a cell surface bound protein that
uses the signal transduction pathway to promote
cellular growth (Carlson, 2006). (See Figure 2)
• There are about 20,000 HER2 receptors on a
normal healthy cell (Pritchard et al, 2006).
• Figure 2.
• This image shows the HER2 receptor’s function under
normal conditions.
• (“From HER2 to Herceptin: HER2 Structure and
Function”, 2001)
HER2 Gene Over-expression in Breast
Cancer
• During cancer cell transformation HER2 gene overexpression can occur (Osin, 1999)(Gancberg, 2002).
• We have found that there is often three to five copies
of the gene per chromosome 17.
• Multiples of chromosome 17 itself are often found
in cancer cell nuclei. The causes of which are not yet
discovered. (Carlson, 2006)(Osin, 1999).
• An amplification of the HER2 gene leads to an
amplification of the HER2 receptor. (See Figure 3).
Normal gene
amplification.
Gene Overexpression
Normal
Receptor
amplification
Receptor
Overexpression
•Figure 3.
•This figure shows gene amplification on the chromosome and
amplified HER2 receptors on the cancer cell.
•(“How Results are Interpreted”, 2010)
HER2 Receptor Over-expression in
Breast Cancer
• In HER2+ breast cancer there is an over-expression of
the HER2 receptor (Pritchard et al, 2006).
• There can be up to 2,000,000 (around 10 to 100 fold)
HER2 receptors per HER2+ cancer cell as opposed to
the normal 20,000 per healthy cell. This results in an
increased amount of division signals being sent to the
cancer cell (Slamon, 1987)(Campbell et al, 2008).
• HER2+ breast cancer multiplies much quicker, and is
known to metastasize to other parts of the body
(Gancberg, 2002).
• See figure 4
Normal Cell
Cancer Cell
Herceptin
Gene
Receptor
•Figure 4.
•Normal and cancer cell gene and receptor amplification.
•Herceptin binding to receptors as a competitive inhibitor.
•(“Herceptin Helps Even Patients with Unresponsive
Breast Cancer”, N.D.)
Mechanism: Treatment
• This rapid reproduction and growth rate makes
HER2+ much less susceptible to
chemotherapy. (Slamon, 1987).
• In the 1980’s a drug company called Herceptin
used trastuzumab to treat the HER2 issue
(Tovey, 2009).
• This drug flags the individual HER2 receptors
by binding as a competitive inhibitor to the
growth factor receptor. The flag is then easily
discovered by the anti-bodies of the patient’s
immune system (Pritchard et al, 2006).
• See figure 4
• This treatment was engineered for use with
chemotherapy (Tovey, 2009)(Gancberg, 2002).
Conclusion
• Awareness for HER2+ breast cancer is on the
rise.
• Treatments and new ways of diagnosing
HER2+ breast cancer are being made.
• Death rates are going down (Tovey, 2009).
References
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Campbell, N. A. & Reese (2008). Biology (8th ed.). Pearson.
Carlson, R. W., & Moench, S. J. (2006). HER2 testing in breast cancer:
NCCN task force
report and recommendations. Journal of the National Comprehensive Cancer Network,
4(3), 1-17.
From HER2 to Herceptin: HER2 structure and function. (2001). Retrieved November 7,
2010, from http://www.medscape.com/viewarticle/407813_2
Gancberg, D., & Di Leo, A. (2002). Comparison of HER-2 status between primary breast
cancer and corresponding distant metastatic sites. Oxford
Journals: Annals of Oncology,
13(7), 1036-1043.
Herceptin helps even patients with unresponsive breast cancer . (n.d.). Retrieved
November 6, 2010, from http://www.roche.com/pages/facets/9/ herc.htm
How results are interpreted. (2010). Retrieved November 6, 2010,
from http://www.herceptin.com/hcp/HER2-testing/interpreted-results.jsp
Osin, P. P., & Lakhani, S. R. (1999). The pathology of familial
breast cancer:
Immunohistochemistry and molecular analysis. Breast Cancer Research, 1(1), 36-40.
Pritchard K. I., Shephard, L. E., O'Malley, F. P., Andrulis, I. L., Tu, D., Bramwell, V. H., & Levine,
M. M. (2006) HER2 and responsiveness of breast cancer to adjuvant chemotherapy. The New
England Journal of Medicine. 2006;354:2103.
Slamon, D., Clark, G., & Wong, S. (1987). Human breast cancer: correlation of
relapse
and survival with amplification of the HER2/neu oncogene. Science, 235, 177-182.
Tovey, S. M., Brown, S., & Doughty, J. C. (2009). Poor survival
outcomes in HER2positive breast cancer patients with low-grade, node-negative tumours. British Journal of
Cancer, 100, 680-683. doi:10.1038