Linkage between EGFR family receptors and nuclear factor kappaB (NF-κB) signaling in breast cancer

In the United States there are 225,000 new cases of invasive breast cancer annually, and at least 50,000 women are diagnosed with ductal carcinoma in situ (DCIS). Breast cancer is a collection of disorders of mammary epithelial cells with distinct pathological characteristics and diverse clinical manifestations. Breast cancers are divided broadly into four classes by the level of the biomarkers HER2 (erbB2/neu) and the estrogen receptor (ER). Histologic grade is also an important modifier of breast cancer taxonomy and behavior. Broadly speaking, breast cancer can be divided into those that are HER2-positive, containing cancers that are both ER-positive and negative, cancers that are ER-positive and divided into high-grade and low-grade tumors, and the remaining but important class of cancers that are both ER-negative and HER2-negative. These last cancers are called basal-like and were first recognized as a distinct group by gene expression arrays. Nuclear factor kappaB (NF-kappa B) is family of multifunctional transcription factors that when activated generate pleotrophic changes in target cells. Elevated levels of active NF-kappa B are detected in many human diseases including breast cancers. High-level active NF-kappa B is detected in specific subclasses of breast cancers briefly described above, predominantly in ER-negative and epidermal growth factor family receptor (EGFR) overexpressing breast cancers (predominantly HER2 amplified cancers). This article is focused on the role of NF-kappa B activation initiated by the EGFR family receptors in subclasses of breast cancer. The combined influence of EGFR family receptors and NF-kappa B signaling on the transformation of ER-negative human mammary epithelial cell is illustrated.