The exact reason why FASN facilitates resistance to endocrine therapy in HRG-overexpressing, ER+/HER2− luminal B-like breast cancer cells needs to be explored in depth; however, it is clear that FASN pro-survival signaling [27,28,31] is co-opted to support the cross-talk between HRG-driven HER2/HER3 pathway activation and ER signaling, thereby enabling estrogen-independence and resistance to SERMs/SERDs (Figure 5). The gene discussed is ESR1; the disease is breast carcinoma.