In accordance with these data, while primary ER+/HER2− breast cancer is normally highly PR+ with decreasing levels in metastatic disease, mutations in ATR and TP53 associate with 1.7-fold higher likelihood of PR negativity even in primary disease relative to wild-type tumors (P = 2.7 × 10−10) (fig. This evidence concerns the gene ATR and metastatic neoplasm.