Prognostic Biomarkers

ER belongs to a superfamily of nuclear hormone receptors. It functions as a transcription factor when activated by its ligand estrogen and plays a key role in regulating growth, differentiation and tumorigenesis in breast. There are two known isoforms of estrogen receptor: ERα and ERβ. The current assays in clinical breast cancer measure only ERα. Nearly all the laboratories today measure ER by immunohistochemistry. For more information see ER by IHC.

PR belongs to a superfamily of nuclear hormone receptors. ER induces PR expression, and therefore PR status serves as an indicator of an intact ER pathway. There are two known isoforms of PR: PR-A and PR-B. The current assays in clinical breast cancer measure both isoforms. Nearly all the laboratories today measure PR by immunohistochemistry. For more information see PR by IHC.

Proliferation index is an important prognostic factor in breast cancer. The Ki-67 protein is expressed in all phases of the cell cycle except G0 and serves as a good marker for proliferation. Studies that have evaluated proliferation index by K-i67 IHC in breast cancer have shown a significant correlation between high proliferation rates and shorter disease free and overall survival(1-4). For more information see Ki-67 Proliferation Index.

The proto-oncogene HER-2/neu (c-erbB-2) resides on chromosome 17q and encodes a trans-membrane tyrosine kinase growth factor receptor. Amplification of the HER-2/neu gene, or overexpression of the HER-2/neu protein, is found in 20-30 percent of breast cancers. Amplified or overexpressed HER-2/neu is a weak unfavorable prognostic factor in untreated breast cancer patients. The predictive implications of HER-2 alterations are more complex and include resistance to hormonal therapy (1, 2), resistance to CMF chemotherapy (3, 4), responsiveness to doxorubicin (5-7), and responsiveness to Trastuzumab (Herceptin®) therapies (8, 9). The primary indication for assessing HER-2/neu today is to identify patients who might benefit from trastuzumab therapy.

The proto-oncogene HER-2/neu (c-erbB-2) resides on chromosome 17q and encodes a trans-membrane tyrosine kinase growth factor receptor. Amplification of the HER-2/neu gene, or overexpression of the HER-2/neu protein, is found in 20-30 percent of breast cancers. There is a greater than 90 percent correlation between gene amplification and protein overexpression. Some studies suggest that HER-2 gene amplification assessed by Fluorescent In Situ Hybridization (FISH) may improve the predictive ability of this marker for Trastuzumab (Herceptin®) therapies (1, 2), especially in the 10-20 percent of cases with equivocal (i.e. 2+) results for protein expression by IHC . The primary indication for assessing HER-2 by FISH today is in cases with equivocal IHC results (3, 4).