A 2016 pilot study found that the combination of ipilimumab, an immune modulator, with cryoablation in women with invasive breast cancer of any HER2+ and hormone receptor status led to peripheral elevations in Th1-type cytokines, activated and proliferating CD4+ and CD8+ T cells, and post-treatment proliferative T-effector cells relative to T-regulatory cells within the tumor. This evidence concerns the gene NR4A1 and neoplasm.