ERBB2 is the name of the gene for human epidermal growth factor receptor 2 (HER2). This receptor is a cell surface protein which belongs to the family of epidermal growth factor receptors. ERBB2 activation stimulates cell proliferation and inhibits programmed cell death. ERBB2 has an important role in breast cancer. About 20 % of all breast cancers show an overexpression of this receptor, which is associated with poor prognosis and clinical outcome.
Patients with an ERBB2 overexpression can benefit from an anti-HER2 therapy, where antibodies target the receptor and inhibit its function.
The Estrogen receptor 1 gene (ESR1) belongs to the family of steroid receptors. The protein is expressed intracellularly. It is a transcription factor regulating the expression of genes and is activated by estrogen. Estrogen receptors are overexpressed in about 70 % of all breast cancer cases. There are hypotheses, that overexpression causes tumorigenesis.
ESR1 overexpressing tumors can be treated with endocrine therapies such as tamoxifen (ESR anatagonist) or anastrozol (aromatase inhibitor).
The progesterone receptor (PGR) also belongs to the gene family of steroid receptors. Upon binding of progesterone, the receptor is activated and modifies expression of several downstream genes. Estrogen and progesterone receptors are found in breast cancer cells that depend on estrogen and related hormones (such as progesterone) to grow. All patients with invasive breast cancer or a breast cancer recurrence should have their tumors tested for estrogen and progesterone receptors. In case of cancers that are ESR1 and/or PGR positive, endocrine therapy blocks the tumor from using estrogen and/or progesterone, thus slowing or stopping tumor growth.
The marker of proliferation MKI67 is a nuclear protein associated with cell proliferation. MKI67 protein is present during all active phases of the cell cycle (G1, S, G2, and mitosis), but is absent from resting cells (G0). In breast cancer MKI67 expression is a prognostic marker for survival and tumor recurrence.