ESR1 and breast cancer: Furthermore, multivariate analysis revealed that the mutations remained as a significantly unfavorable factor for RFS (adjusted HR 6.52; 95% CI: 2.32–18.31; P < 0.001) and DRFS (adjusted HR 8.09; 95% CI: 2.83–23.18; P < 0.001) (Table 5) after adjustment for age, tumor grade, tumor size, lymph node metastasis, ER, PR, and adjuvant therapy in those breast cancer patients without HER2 expression.