Overall, we demonstrate in ERα-positive MCF-7 cells, a model of Luminal A subtype of breast cancer that the Lep-EVs were able to convey protein machinery required for mitochondrial metabolism with important impact on the metabolic behavior of recipient tumor and immune cells that can be located in situ or far from the site of release (e.g., the premetastatic niche). This evidence concerns the gene ESR1 and breast cancer.