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 receptors during 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
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."