In conclusion, this MR study identified three circulating lipid metabolites—myristoleate (14:1n5), tricosanoyl sphingomyelin (d18:1/23:0), and 5α-androstan-3β,17β-diol monosulfate (2)—as putative causal factors for ER+ breast cancer, with results validated in an independent GWAS dataset. Here, ESR1 is linked to breast cancer.