NOTTINGHAM, UK--Some researchers have hypothesized that tamox-ifen resistance occurs because tumor cells lose estrogen receptors over time. But new data suggest that this is not the case.
To study changes in estrogen and progesterone(Drug information on progesterone) receptors during tamoxifen(Drug information on tamoxifen) (Nolvadex) therapy, researchers from City Hospital, Nottingham, and the Tenovus Institute, Cardiff, performed biopsies in patients receiving long-term tamoxifen who had accessible tumors. Biopsies were done before treatment began, 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 progression to 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 when patients become resistant," John Robertson, MD, said at the San Antonio Breast Cancer Symposium. "They're becoming resistant not because they are losing the ER mechanism but for some other reason, probably some growth factor-mediated event."
This may also explain the clinical situation of patients getting a response to second- or third-line hormonal therapy, he said. "Clearly, they still have the estrogen-receptor mechanism in place."