TUMOR RECURRENCE AND TAMOXIFEN RESISTANCE: IS THERE ANY HARM IN CONTINUING TO TAKE TAMOXIFEN EVEN IF MY DOCTOR RECOMMENDS STOPPING?
Perhaps one of the most alarming findings in the study of tamoxifen resistance is the evidence in humans and animals that after continued exposure to tamoxifen, tumors may actually become dependent on the drug for growth. The process is poorly understood and is being studied primarily in laboratory animals. Estrogen-receptor-positive tumors are grown in mice; when the animals are given tamoxifen, the tumors initially shrink. After about six months of continuous tamoxifen administration, however, the tumors begin to grow again. This time frame is approximately the same as is observed for the development of tamoxifen resistance in humans. Of further interest is the preliminary observation that if tamoxifen is given to mice for up to five years, then stopped, and estrogen is administered instead, the tamoxifen-resistant tumors disappear. It appears that the tumors not only avoid the inhibitory action of tamoxifen but somehow become dependent on it for continued growth.This evidence and other data on prolonged exposure of cells to tamoxifen suggest that breast cancer cells under conditions of long-term tamoxifen exposure can in fact learn to depend on the drug for growth and even be stimulated by it. Because these findings have been noted in laboratory studies on cultured cells and in animals, extrapolation to human patients is controversial. Nevertheless, several clinical studies have shown that in some women whose breast cancers began growing in the presence of tamoxifen, discontinuing the tamoxifen can itself produce a tumor stabilization or tumor regression.CAN TAMOXIFEN RESISTANCE BE PREVENTED?Although a number of advances have been made, little can yet be done to avoid tamoxifen resistance. On the assumption that tamoxifen resistance may be related to metabolism of the drug to estrogenic compounds, several laboratories are looking at experimental drugs that are similar to tamoxifen in chemical structure but cannot be metabolized into estrogenic metabolites. Some of these, as well as other new agents, are showing promise against tamoxifen-resistant tumors.*45\320\2*