Normal breast tissue cells from breast cancer patients express epidermal growth factor receptor HER1-4 protein concentrations characteristic for cancer cells.

Abstract

Abstract Abstract #3052 Background: The epidermal growth factor receptor HER2 is expressed to higher than normal concentrations in 25%-30% of human breast cancers and in approximately 90% of these cases the overexpression is a result of gene amplification. The mechanism behind HER2 amplification is unknown but may be caused by continuous stimulation and activation of the HER1 system. Consequently we have mapped the concentrations of all four epidermal growth factor receptors HER1-4 in breast cancer tissue, in autologous non-cancer breast tissue and normal breast tissue from healthy women.
 Material and Methods: Tissue samples of malignant and adjacent normal breast tissue were collected from 118 consecutive women admitted for surgical treatment of breast cancer. In addition 26 samples of normal breast tissue from healthy women were collected. The tissue samples weighing between 10 and 40 mg were homogenized and the proteins were extracted. The total protein amount in the samples were measured and the protein concentrations of HER1-4 were determined quantitatively using ELISA expressed as pg/mg total protein.
 Results: HER1 demonstrated lower than normal concentrations both in autologous non-cancer tissue and cancer tissue. HER2 showed 4 times higher than normal concentrations in autologous reference tissue and 24 times higher in cancer tissue, while the corresponding figures for HER3 was factor 8 and 13 and for HER4 factor 10 and 8. These differences were significant at p<10-4. Further it was observed that correlations between the receptors were maintained from normal breast tissue to autologous reference breast tissue but were lost in cancer tissue. Adjusting the concentrations of receptors by differences in cell number content did not change differently in the cancer patients.
 Discussion: We propose these findings to indicate that breast cancer is a systemic disease where also non-cancer tissue cells in the cancer patients are continuously activated thus favouring the subsequent development of cancer. This may explain the observation that occurrence of new cancers are increased in patients previously treated for cancer. Measurement of decreased HER1 and increased HER2-4 in breast cells from healthy women may in the future be used as an indicator of increased risk for cancer development. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3052.