Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease1. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10-8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.

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Contributor ABCTB Investigators , EMBRACE, GEMO Study Collaborators, HEBON, NBSC Collaborators
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Journal Nature Genetics
Milne, R.L, Kuchenbaecker, K.B, Michailidou, K, Beesley, J, Kar, S, Lindstrom, S, … Aalfs, C.M. (2017). Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. Nature Genetics, 49(12), 1767–1778. doi:10.1038/ng.3785