Introduction

• The effects of HER2 gene and receptor over-expression 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 HER2- breast 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 over-expression 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).

•Figure 3.•This figure shows gene amplification on the chromosome and amplified HER2 receptors on the cancer cell. •(“How Results are Interpreted”, 2010)

Normal gene amplification.

Gene Over-expression

Normal Receptor amplification

Receptor Over-expression

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

Gene

Receptor

Cancer Cell Herceptin

•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• 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 HER2-positive breast cancer patients with low-grade, node-negative tumours. British Journal of Cancer, 100, 680-683. doi:10.1038