Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5="" x="" 10-="" 8)="" in="" stage="" 1="" and="" 2="" combined.="" results="" also="" suggested="" a="" substantial="" enrichment="" of="" significantly="" associated="" variants="" among="" the="" single="" nucleotide="" polymorphisms="" (snps)="" analyzed="" in="" stage="" 2.="" variants="" from="" 25="" of="" 74="" known="" breast="" cancer="" susceptibility="" loci="" were="" also="" associated="" with="" risk="" of="" tn="" breast="" cancer="" (p="">< 0.05).="" associations="" with="" tn="" breast="" cancer="" were="" confirmed="" for="" 10="" loci="" (lgr6,="" mdm4,="" casp8,="" 2q35,="" 2p24.1,="" tert-rs10069690,="" esr1,="" tox3,="" 19p13.1,="" raly),="" and="" we="" identified="" associations="" with="" tn="" breast="" cancer="" for="" 15="" additional="" breast="" cancer="" loci="" (p="">< 0.05:="" pex14,="" 2q24.1,="" 2q31.1,="" adam29,="" ebf1,="" tcf7l2,="" 11q13.1,="" 11q24.3,="" 12p13.1,="" pthlh,="" ntn4,="" 12q24,="" brca2,="" rad51l1-rs2588809,="" mkl1).="" further,="" two="" snps="" independent="" of="" previously="" reported="" signals="" in="" esr1="" [rs12525163="" odds="" ratio="" (or)="1.15," p="4.9" x="" 10-="" 4]="" and="" 19p13.1="" (rs1864112="" or="0.84," p="1.8" x="" 10-="" 9)="" were="" associated="" with="" tn="" breast="" cancer.="" a="" polygenic="" risk="" score="" (prs)="" for="" tn="" breast="" cancer="" based="" on="" known="" breast="" cancer="" risk="" variants="" showed="" a="" 4-fold="" difference="" in="" risk="" between="" the="" highest="" and="" lowest="" prs="" quintiles="" (or="4.03," 95%="" confidence="" interval="" 3.46-4.70,="" p="4.8" x="" 10-="" 69).="" this="" translates="" to="" an="" absolute="" risk="" for="" tn="" breast="" cancer="" ranging="" from="" 0.8%="" to="" 3.4%,="" suggesting="" that="" genetic="" variation="" may="" be="" used="" for="" tn="" breast="" cancer="" risk="" prediction.="">