Breast cancer (BC) is the most frequent malignant neoplasm in women, with metastases being the cause of 98% of deaths. Hormone-dependent BC represents approximately 80% of diagnosed cases and most frequently occurs in postmenopausal women, who often present elevated levels of gonadotropins. Currently, molecules directed against the gonadotropin-releasing hormone receptor (GnRHR) have been designed, such as the agonist leuprorelin (LEU) and the antagonist degarelix (DEGA) for the treatment of certain hormone-dependent tumors. These therapies aim to disrupt the hormonal environment that supports tumor growth. By reducing the levels of gonadotropins, these treatments can slow down or even halt the progression of hormone-sensitive BC. Tumor progression depends on the ability to invade and metastasize to distant sites, cell migration being essential in this process. Key proteins in these processes include the proto-oncogene tyrosine-protein kinase Src and focal adhesion kinase (FAK), which play critical roles in signaling and modulating metastatic pathways. In this work, we combined GnRH analogs with Src and FAK inhibitors to counteract tumor progression. By in silico analysis, we analyzed by miniarrays the effect of LH (5 and 50 mUl/ml) on genes involved in tumor development and progression. To compare the action of GnRHR agonist and antagonist, we explored the molecular interactions between GnRHR and LEU or DEGA. Through orthotopic tumor growth assay, we determined that DEGA decreases tumor growth while LEU has the opposite effect. PP2 and FAKi were found to reduce tumor volume and interestingly, combining DEGA plus PP2 or FAKi enhanced the inhibitory effect, increasing mice survival. Our findings reveal how gonadotropins regulate genes involved in tumorigenic processes. Despite the complexity of the LH signaling in BC, the approach based on GnRH antagonists administered in combination with PP2 or FAKi may be an effective strategy for treating BC patients.