Background: Simvastatin which is a lipophilic statin shows some antitumor activity, and when used in combination with Letrozole as a example of drug repurposing in adjuvant postmenopausal females with early HR positive breast cancer showed a significant reduction in breast cancer recurrence. Objective: We evaluated the role of simvastatin in combination with letrozole in denovo postmenopausal metastatic Her2neu negative Luminal Breast cancer as regard overall response rate (ORR), progression free survival (PFS) as a primary objectives, and overall survival (OS), and safety as a secondary objectives. especially in communities where novel drugs as CDK inhibitors are not always within reach. Patients and Methods: This study is designed as a prospective phase II randomized controlled trial that carried out on denovo metastatic Her2neu negative luminal breast cancer patients attending medical oncology unit at Oncology Center Mansoura University (OCMU) and followed up for 2 years. Group1(investigational group):40 patients received letrozole and simvastatin at 20mg daily dose. Group 2(control group):40 patients received letrozole. Results: There is no statistically significant difference in 2 year PFS in (p 0.709), and in OS (p 0.713), there was significant PR at investigational arm at 4th month (p 0.023), which lost with follow up along the study. Conclusion: Although our results not achieved the original study landscape as regard PFS, but there was a marginal significance in response rate, together with the good safety and tolerability it encourages further study with a higher dosage.