Although previous studies have shown that the addition of the RETi pralsetinib to CDK4/6i further suppressed the growth of breast cancer cells with active ESR1 fusions resistant to endocrine therapy compared to CDK4/6i alone (51), our study is the first, to our knowledge, to suggest an association between RET overexpression and resistance to combined CDK4/6i and endocrine therapy in ER+ breast cancer. This evidence concerns the gene ESR1 and breast carcinoma.