Our interpretation of these data is that some ER+ tumors rely more heavily on GFR/PI3K signaling than on estrogen for growth, and that by blocking PI3K, these tumors would be forced to resort to the alternative estrogen-signaling pathway for continued growth; by blocking both PI3K and estrogen pathways together, therefore, the tumor may be left with even fewer options. Here, RAPGEF5 is linked to neoplasm.