ANTI-ESTROGEN CROSS RESISTANCE IN HUMAN BREAST CANCER

Abstract Introduction: Recently, the STAR study showed that raloxifene works at least as well as tamoxifen in preventing breast cancer. It is of interest to know whether raloxifene may be used in the treatment of breast cancer and whether it would be effective in those who have developed resistance to other anti-estrogens. Methods: Estrogen receptor positive (er+) and negative (er-) breast cancer cells were exposed to tamoxifen, raloxifene or faslodex for 48 hours and the efficacy and potency of these drugs determined. MCF-7 breast cancer sub-lines lines resistant to tamoxifen (TAMR), raloxifene (RALR) or faslodex (FASR) were developed and used to determine cross-resistance among anti-estrogens Results: The efficacy of tamoxifen, raloxifene, and faslodex in inhibiting the proliferation of MCF-7 estrogen receptor positive er+ breast cancer were equivalent though theirs potencies differed. However, anti-estrogens were unable to inhibit the growth of er-breast cancer cells. TAMR sub-lines were resistant to raloxifene and faslodex, while FASR sub-lines were resistant to tamoxifen and raloxifene. RALR sub-lines however, were sensitive to treatment with tamoxifen in vitro and in vivo. Conclusions: The anti-estrogens tamoxifen, raloxifene and faslodex are equally efficacious in inhibiting breast cancer growth in er+ tumors. RALR sub-lines are sensitive to tamoxifen treatment