A Narrative Review on APOE in Breast Cancer: From Prognosis to Cognitive Decline

Context: Apolipoprotein E (APOE), encoded by three significant alleles (ε2, ε3, and ε4), is a multifunctional protein. Its well-established roles include lipid metabolism and neurological homeostasis. However, recent studies have expanded its relevance to cancer biology, particularly in breast cancer pathogenesis. Apolipoprotein E influences breast cancer development, tumor progression, and clinical outcomes, as well as cancer-related cognitive impairment (CRCI), especially after chemotherapy. The ε4 variant, in particular, has been implicated in tumor aggression and cognitive decline, underscoring its dual role in oncogenic and neurotoxic pathways. Evidence Acquisition: This narrative review synthesizes findings from recent studies investigating APOE’s role in breast cancer and CRCI. The focus is on the ε4 allele’s association with tumor aggression and cognitive dysfunction, drawing from molecular and clinical research to elucidate its underlying mechanisms. Results: The ε4 variant of APOE has been identified as a critical factor in both breast cancer progression and cognitive decline. It contributes to oncogenic pathways that drive tumor aggression and neurotoxic pathways linked to CRCI. These insights highlight the potential for precision medicine strategies that incorporate genetic profiling, such as APOE genotyping, into clinical guidelines. Such approaches could optimize treatment plans by mitigating cognitive side effects and improving the quality of life for survivors. Conclusions: Understanding the molecular mechanisms of APOE alleles, particularly ε4, is pivotal for developing targeted therapies in breast cancer. Precision medicine strategies that integrate genetic profiling hold promise for optimizing treatment outcomes and addressing neurological challenges in patients. By leveraging detailed insights into APOE’s complex roles, researchers can advance personalized therapies that improve both oncological and neurological outcomes. Consequently, breast cancer survivors may benefit from a better quality of life.