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HER2 Receptors & Cancer Cells

Receptors allow certain types of proteins and hormones to attach to a cell, influencing the cells development. With some cancers, there can be an abundance of receptors which increase cell growth rate and the chance that cancer will spread.

For example, high levels of HER2 (a protein receptor) and ER (a hormone receptor) can be found in the cells of some breast cancer patients and influence the outcome of this disease.

Diagnosis Based On Levels Of HER2 & ER Receptors

In patients with breast cancer, a tissue sample from a biopsy is usually taken to determine if cancer cells have raised levels of certain receptors or genes which influence cell development. Where a patient has a high level of a particular receptor their type of cancer is denoted by a positive symbol; where low levels are shown a negative symbol is given (-).

For example, tumors from breast cancer patients with high levels of receptors for the protein, HER2, are usually diagnosed as being HER2+. Tumors from breast cancer patients with high levels of oestrogen receptors are usually diagnosed as being ER+ (oestrogen receptor positive). Patients with tumors which do not have high levels of oestrogen receptors are ER- (oestrogen receptor negative).

Breast cancer patients can be ER+ and HER2+, ER- and HER2-, ER- and HER+ (and vice versa) and treatments are adjusted accordingly. For example, HER2+ patients may respond to the medication trastuzumab (Herceptin) and ER+ patients to hormonal treatments which are more likely to be effective on ER+ tumors. Chemotherapy, another type of cancer treatment, may be given alongside these treatments.

In this article we will focus on HER2+ Breast Cancer which accounts for around 20% of all breast cancer cases.

What Is A HER2 Receptor?

HER2 is an acronym for 'Human Epidermal Growth Factor Receptor 2' and is a protein encoded by the ERBB2 gene.

Genes form part of our DNA. DNA is often referred to as the building blocks of life and can be seen as a type of biological code which determines how the body operates. Cells contain genes which provide instructions on how the cell functions through the creation and action of certain types of proteins.

For example, the ERBB2 gene gives instructions for creating the HER2 protein which controls how fast a cell grows.

HER2 protein receptors are found on the outer surface of a cell. High numbers of the HER2 receptor have been linked to breast cancer and HER2 can act as a biomarker for this disease. High levels of the HER2 protein mark or indicate breast cancer; in such cases patients are diagnosed as having HER2+ (or HER2 positive) breast cancer.

In the cancer cells of patients with HER2 positive breast cancer there is an amplification of the ERBB2 gene. A normal cell will have 2 copies of the ERBB2 gene. In HER2+ patients their cancer cells have multiple copies of this gene and a subsequent over production of the HER2 protein.

HER2+ Breast Cancer Cells have multiple ERBB2 Genes And HER2 Receptors.

Normal human cells have around 20,000 HER2 receptors. However, in HER2+ breast cancer, cancer cells can have up to 2 million HER2 receptors on a given cell. This increased, dense concentration of HER2 receptors can promote uncontrolled cell growth, over active cell signalling and malignant (cancerous) tumor formation [6,7].

Characteristics Of HER2+ Breast Cancer

  • Increased Risk Of Metastasis (the disease spreading to other areas of the body)
  • Resistance To Chemotherapy
  • Low levels of oestrogen and progesterone receptors
  • Reduced life expectancy
  • Reduced chance of surviving disease free

HER2 Testing

There are two different types of tests which can be used to determine if a patient has HER2+ breast cancer. These tests involve a tissue sample being taken (biopsy) which is then analyzed. One test, Immunohistochemistry (IHC), is used to determine the level of HER2 receptors in a cell. Another test, Fluorescence in-situ hybridization (FISH), determines the number of ERBB2 genes in a cell. The number of receptors or genes required to qualify a person as having HER2+ breast cancer can vary between testers. It's important an accurate diagnosis is made so appropriate treatment can be given.

Treatment For HER2 Positive Breast Cancer

Patients who have HER2+ breast cancer can be given treatments which target the HER2 protein and slow down or even stop the growth rate of cancer cells. HER2 positive patients may be given the medication trastuzumab (brand name: Herceptin); often in conjunction with chemotherapy. This drug treatment may be given during early or advanced stages of this disease.

Herceptin has side effects which can include flu like symptoms, diarrhoea, headaches, allergic reactions and heart problems. Therefore, it is important that only HER2+ breast cancer patients are given this treatment; an accurate diagnosis is required.

HER2 Breast Cancer Statistics, Prognosis & Survival Rate

The incidence of HER2 positive breast cancer is significant; studies have shown that around twenty percent of breast cancer cases, 1 in 5, have high levels of the HER2 receptor [3].

HER2+ breast cancer is an aggressive form of breast cancer and the outlook or prognosis for patients who are HER2+ is not so good. This is a disease with a poor prognosis.

Due to its aggressive nature, HER2+ breast cancer carries an increased chance of the disease spreading to other areas of the body away from the breast (metastasizing) and also reoccurring. Compared to HER2 negative breast cancer, HER2+ breast cancer has a reduced life expectancy [1,2].

For example, studies suggest that a woman diagnosed with early stage HER2 positive breast cancer (in which cancer has not spread to other areas of the body) has a 68% chance of surviving more than 5 years [4]. This is lower than the overall survival rates for early stage breast cancer which range from around 74% to 88% depending on their actual sub stage. [5]

Compared to HER2 negative patients, HER2 positive breast cancer patients have a higher risk of breast cancer reoccurring after diagnosis.[8]

References

  1. Menard S, Tagliabue E, Campiglio M, Pupa SM. Role of HER2 gene overexpression in breast carcinoma. J Cell Physiol.2000;182:150-162.PMID:10623878
  2. Jones KL, Buzdar AU. Evolving novel anti-HER2 strategies. Lancet Oncol.2009;10:1179-1187.PMID: 19959074
  3. The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine.Ross JS,Slodkowska EA,Symmans WF,Pusztai L,Ravdin PM,Hortobagyi GN.Oncologist.2009 Apr;14(4):320-68.Epub 2009 Apr 3.
  4. Curigliano G, Viale G, Bagnardi V, et al. Clinical relevance of HER2 overexpression/amplification in patients with small tumor size and node-negative breast cancer.J Clin Oncol.2009;27:5693-5699.PMID: 19884553
  5. http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-survival-by-stage
  6. Hicks DG , Kulkarni S. HER2+ breast cancer: review of biologic relevance and optimal use of diagnostic tools.Am J Clin Pathol.2008;129:264-273
  7. Rosen LS, Ashurst HL, Chap L. Targeting signal transduction pathways in metastatic breast cancer: a comprehensive review.Oncologist. 2010; 15:216-235
  8. Urigliano G, Viale G, Bagnardi V, et al. Clinical relevance of HER2 overexpression/amplification in patients with small tumor size and node-negative breast cancer.J Clin Oncol.2009;5693-5699.