The dynamics of estrogen receptor status in breast cancer: re-shaping the paradigm.

In this issue of Clinical Cancer Research , Bayliss et al. (1) report that inhibiting inherent p42/44 mitogen-activated protein kinase (MAPK) activity in estrogen receptor (ER) a–negative breast cancer established cell lines, and in ex vivo tissue and primary cultures of human ER-negative breast tumors, frequently results in re-expression of ER as well as in recovery of tumor cell responsiveness to antiestrogen treatment. The authors have previously shown that in the ER-positive MCF7 cell line, inducing hyperactive MAPK by genetically engineered up-regulation of growth factor signaling leads to a reversible loss of ER expression (2). These intriguing findings highlight the dynamic and heterogeneous nature of ER status in breast cancer and broaden the therapeutic horizon for patients with ER-negative tumors by suggesting that a subset of this group may benefit from a treatment strategy combining signal transduction inhibitors with endocrine therapy.