ESR1 and neoplasm: The mechanisms of primary resistance mainly include: induction of apparent silence of ER by histone deacetylation modification, ER gene mutation (such as conversion of ERα351 site tyrosine to aspartic acid), promotion of tamoxifen (TAM) to act as an agonist and tumour growth, gene mutation of ER alpha (ESR) and p21‐activated kinase 1 (Pak1) and aromatase gene polymorphism.17