Importantly, this finding in in situ breast cancer confirms the association of the HER-2 receptor with COX-2 overexpression reported in breast cancer cell line studies (Vadlamudi et al, 1999; Subbaramaiah et al, 2002a) (and by immunohistochemistry; Ristimaki et al, 2002), which suggest that signalling through HER-2/Ras/Map kinase pathway may play a role in upregulating COX-2 in neoplasia and this may occur at the preinvasive stage of breast cancer carcinogenesis. This evidence concerns the gene ERBB2 and breast cancer.