In osteoblasts, BMP- 6 reporter activity increased with anti-oestrogen treatment, and decreased with oestradiol treatment, providing evidence that ER regulates BMP-6 differentially in breast and bone, and ERα-dependent pathways (such as BMPs) may influence skeletal secondary formation in breast cancer, which is consistent with the previous observation that patients with ER positive breast tumours are more likely to develop skeletal metastases (Ong et al. 2004). This evidence concerns the gene CLN5 and breast neoplasm.