The specificity of this association (comparing ER + /PR− with ER + /PR + cancers, Phet = 0.001) and our replication of Ruth and colleagues report of a signal at the CYP3A locus in their analysis of circulating progesterone levels10 raise the possibility that premenopausal progesterone levels might influence risk of ER + /PR + breast cancers. Here, CYP3A4 is linked to breast carcinoma.