ER Loss Not Seen in Tamoxifen-Resistant Tumors

NOTTINGHAM, UK--Some researchers have hypothesized that tamox-ifen resistanceoccurs because tumor cells lose estrogen receptors over time. But new datasuggest that this is not the case.

To study changes in estrogen and progesterone receptors during tamoxifen(Nolvadex) therapy, researchers from City Hospital, Nottingham, and theTenovus Institute, Cardiff, performed biopsies in patients receiving long-termtamoxifen who had accessible tumors. Biopsies were done before treatmentbegan, at six weeks, six months, and at the time of progression on tamoxifen.

ER expression decreased at six weeks and six months, but rose at progressionto levels that were not significantly different from pretreatment levels,and ER expression was never lost.

"So the phenotype that started ER positive is maintained even whenpatients become resistant," John Robertson, MD, said at the San AntonioBreast Cancer Symposium. "They're becoming resistant not because theyare losing the ER mechanism but for some other reason, probably some growthfactor-mediated event."

This may also explain the clinical situation of patients getting a responseto second- or third-line hormonal therapy, he said. "Clearly, theystill have the estrogen-receptor mechanism in place."