A better definition of the molecular factors that define the endocrine response in ER+ breast cancer patients and HER2-targering therapy in HER2-positive breast cancer patients will be essential for the development of an improved treatment and for the selection of patients who may be less responsive to these treatments and more prone to the development of chemoresistance and could be shifted to alternative treatments aiming to prevent the generation of drug resistance. This evidence concerns the gene ESR1 and breast cancer.