Concomitant presence of any rare homozygote from each of the two disease-associating blocks is associated with decreased breast cancer survival, through disenabling breast cancer cell proliferation and DNA repair signaling pathways as represented by INPP4B and RAD50. Our study provides genetic evidence on the prognostic synergies between INPP4B and RAD50 on breast cancer outcome and deepens our understandings toward cancer progression that ultimately facilitates cancer precision medicine. Here, INPP4B is linked to cancer.