The overexpression of the upstream regulator epidermal growth factor receptor, the loss of negative regulators such as proline-rich inositol polyphosphatase and phosphatase and tensin homolog (PTEN), in addition to mutations of the PI3K gene, may result in an upregulated PAM signaling pathway in HR- breast cancer [37,38,39]. The gene discussed is EGFR; the disease is breast cancer.