Currently, a number of groups are investigating inhibition of progesterone and/or RANK/RANKL signalling as an alternative chemopreventive strategy in BRCA1 carriers, which may present a more tolerable approach.24 However, a recent study using a well-characterised mouse model of BRCA1-associated breast cancer suggests that oestrogen is the predominant driver of tumourigenesis rather than progesterone.25 Given that RANK/RANKL signalling is progesterone-dependent, the efficacy of these progesterone and RANK/RANKL-targeted chemopreventive approaches remains unproven. This evidence concerns the gene TNFSF11 and breast cancer.