♦ Signaling pathways: Resistance to endocrine therapy for breast cancers can be brought on by cell surface receptors like epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER-2), and insulin-like growth factor 1 receptor (IGF-1R), and their downstream signaling pathways like PI3K/AKT/mTOR, RAS/MAPK/ERK, and upstream signaling pathways (49). The gene discussed is ERBB2; the disease is breast cancer.