In the first stage, we identified three lipid metabolites—myristoleate (14:1n5), tricosanoyl sphingomyelin (d18:1/23:0), and 5α-androstan-3β,17β-diol monosulfate (2)—that exhibited significant causal associations with ER+ breast cancer after false discovery rate (FDR) correction. This evidence concerns the gene ESR1 and breast cancer.