A landmark study on formalin-fixed paraffin-embedded (FFPE) tumor tissues from 46 patients with invasive BC revealed positive PAPP-A protein staining in 98% of the samples, with significantly higher detection in luminal B than luminal A. Interestingly, within the luminal B subtypes, no significant difference in PAPP-A expression could be observed between HER2- and HER2 + cases, between ER- and ER + cases, as well as between tumor grades. This evidence concerns the gene ESR1 and breast cancer.