Using in vitro, genetic, and epidemiologic analyses, we have identified ribosomal RNA processing 1 homolog B (Rrp1b) as a factor that physically interacts with the metastasis modifier gene, Sipa1, modulates elements of metastasis predictive gene expression signatures, suppresses tumor progression in animal models, and is associated with progression and survival in pilot human breast cancer epidemiology cohorts. The gene discussed is SIPA1; the disease is breast cancer.