Local Cells Affect Tamoxifen Sensitivity
Breast cancer cells that express estrogen receptor (ER) can be treated with tamoxifen only as long as they remain sensitive to the drug. Resistance to tamoxifen is a common problem in breast cancer treatment, but researchers are identifying the factors that influence sensitivity versus resistance.
When tamoxifen-sensitive, premalignant breast cancer cells were cultured with fibroblasts derived from ER-negative tumors, breast cancer cells became less sensitive to tamoxifen. Further, these cells were also less sensitive to inhibitors of cell growth. Conversely, tamoxifen resistance could not be restored in tamoxifen-resistant, malignant breast cancer cells by incubating with fibroblasts from ER-positive tumors.
These data demonstrate that fibroblasts influence the sensitivity of breast cancer cells to tamoxifen. Fibroblasts represent major components of the extracellular environment and perform important roles in maintaining that environment and influencing cell growth. Future research is directed at identifying the growth factors and other proteins released from fibroblasts involved in modulating these effects on breast cancer cells.
Shekhar MPV, Santner S, Carolin KA, Tait L. Direct involvement of breast tumor fibroblasts in the modulation of tamoxifen sensitivity. Am J Pathol 2007 170:1546