A long-standing question in cancer biology is why women who have their first child early in life have a lower lifetime risk of developing breast cancer. To investigate the basis for this phenomenon, Blakely et al. used microarray expression profiling to identify persistent pregnancy-induced changes in mammary gene expression that are tightly associated with protection against tumorigenesis in four different rat models.Expression profiling of parous and nulliparous mammary tissue yielded a common 70-gene signature that implicates alterations in TGF- signaling, extracellular matrix(ECM) proteins, amphiregulin expression, and the growth hormone-Igf1 axis in the pregnancy-induced reduction in breast cancer risk (right panel). The down-regulation of ECM protein expression by pregnancy is illustrated by Mason.s Trichrome-stained nulliparous (top left) and parous (bottom left) mammary glands. The conservation of this gene expression signature suggests that persistent alterations in these pathways may contribute to pregnancy-induced protection against breast cancer. For details,see the article by Blakely et al. on page 6421 of this issue.