What is the HER2 Gene?

The HER2 gene codes for a receptor on the surface of some cancer cells, human epidermal growth factor receptor 2. These cancer cells may contain more than the usual two copies of the HER2 gene which can lead to overproduction of the receptors that are displayed on the cell's surface. Excess presence of these receptors leads to a more aggressive form of breast cancer that grows more quickly than other forms of cancer. Cancers with an excess presence of these receptors are termed HER2 positive.

Epidemiology and impact of HER2 gene

There are around 180,000 breast cancers diagnosed in the United States annually and of these around 25% are HER2 positive. These cancers grow more quickly, spread more rapidly and easily and are less responsive to hormonal therapy and chemotherapy compared with HER2 negative cancers.

HER2 targeted therapy

Overactivity of the HER2 gene was identified as a pharmaceutical target for cancer drug development in the 1980s.

The first such development was the drug Herceptin or trastuzumab, manufactured by Genentech. In 1998, the drug was approved for the treatment of HER2- positive breast cancer that was advanced and had metastasized to other organs.

Herceptin paved the way for the development of more agents that can target this gene specifically, such as Tykerb (lapatinib) which is used in combination with the oral chemotherapy drug capecitabine.

HER2 status and testing

As herceptin is useful only in patients with HER2 positive breast cancer, the HER2 status of cancers needs to be determined. Biopsies are taken and assessed in all cases of newly diagnosed invasive breast cancers as well as in cases of cancer recurring after remission.

The United States Food and Drug Administration has approved two testing methods for HER2 status. These include:

  • Immunohistochemistry (IHC) which uses special antibodies that can bind to the HER2 protein and then be detected when stained or illuminated under a microscope. HER2 positivity is indicated if an IHC score of "3 plus" is obtained, which indicates a greater intensity and uniformity of staining in more than 30 percent of the tumour cells. Scores of 0 or 1+ indicate HER2 negative status while a score of 2+ is a borderline result that requires further testing.
  • Fluorescent in situ hybridization (FISH) uses a special microscope to check for copies of the HER2 gene within the tumor cells. The HER2 genes are tagged with fluorescent bits of genetic material that attach to any area of the chromosome that contains the HER2 gene. HER2 positivity is indicated if there are more than six copies of the HER2 gene per cell or if more than 2.2 HER2 genes are found for each copy of chromosome 17. The latter is termed the HER2 chromosome enumeration probe 17 or the CEP17 ratio.

Sources

  1. http://media.curetoday.com/downloads/documents/HER2_pocketguide.pdf
  2. http://www.ncbi.nlm.nih.gov/pubmed/10623878
  3. http://www.diagnosticpathology.org/content/pdf/1746-1596-7-60.pdf
  4. http://cancerdiscovery.aacrjournals.org/content/3/2/224.abstract
  5. www.christie.nhs.uk/…/her2.aspx

Further Reading

  • All Breast Cancer Content
  • What is Breast Cancer?
  • Breast Cancer Classification
  • Breast Cancer Symptoms
  • Breast Cancer Causes
More…

Last Updated: Feb 26, 2019

Written by

Dr. Ananya Mandal

Dr. Ananya Mandal is a doctor by profession, lecturer by vocation and a medical writer by passion. She specialized in Clinical Pharmacology after her bachelor's (MBBS). For her, health communication is not just writing complicated reviews for professionals but making medical knowledge understandable and available to the general public as well.

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