Mechanisms and Targeted Research Advances of the PI3K/AKT Pathway in Drug Resistance and Immune Microenvironment Regulation of HER2-Positive Breast Cancer

HER2-positive breast cancer accounts for 20–30% of all breast cancer cases, exhibiting high invasiveness and poor prognosis. Anti-HER2 targeted therapy remains the core clinical treatment strategy; however, 30–50% of patients develop primary or acquired resistance, presenting a significant therapeutic bottleneck.Abnormal activation of the PI3K/AKT pathway is a key mechanism mediating targeted resistance in this subtype of breast cancer, exhibiting close cross-regulatory interactions with the immunosuppressive state of the tumour immune microenvironment.This paper systematically reviews the regulatory mechanisms of the PI3K/AKT pathway in HER2-positive breast cancer targeted resistance, analyses its interaction patterns with the immune microenvironment, and summarises advances in combination therapy targeting this pathway. Findings indicate that the PI3K/AKT pathway synergistically mediates targeted resistance through regulating cell proliferation and immune molecule expression, leading to immune escape. - immune escape. Concurrently, combination regimens incorporating pathway inhibitors with anti-HER2 agents and immune checkpoint inhibitors demonstrate promising therapeutic potential. This study provides theoretical foundations for elucidating the nature of resistance in HER2-positive breast cancer and offers novel insights for developing personalised combination treatment strategies in clinical practice.