A common phenotypic consequence of the genetic changes that occur in breast cancer is a loss of steroid hormone growth sensitivity, a feature manifested clinically by primary or acquired resistance to antihormones. Although it appears that the absence of steroid receptor machinery determines the failure of oestrogen receptor (ER) negative tumours to respond to endocrine therapies, the erbB signalling pathway seems far from redundant in these tumours and in vivo evidence suggests that elevated epidermal growth factor receptor (EGFR) and c-erbB-2 proteins are fundamental elements in ER negative disease growth control. In contrast, neither diminished ER nor elevated EGFR expression appears to be essential in determining any primary endocrine insensitivity demonstrated by ER positive tumours, although elevated expression of additional erbB pathway components (e.g. transforming growth factor-α, Fos, Myc and c-erbB-2 protein) may be important. However, none of these factors appears to direct endocrine unresponsive, ER positive cell proliferation. Furthermore, it is unlikely that selective outgrowth of endocrine unresponsive, EGFR membrane positive/ER negative cells constitutes a major event in ER positive tumours during their progression towards endocrine resistance.