Tamoxifen Resistance in Breast Cancer May Be Linked to Estrogen Exposure in Mother’s Womb

Tamoxifen Resistance in Breast Cancer May Be Linked to Estrogen Exposure in Mother’s Womb
Exposure to high levels of estrogen in the mother's womb may be linked to resistance to tamoxifen therapy in estrogen receptor (ER)-positive breast cancers, according to the results of a recent animal study. The study, "Effects of In Utero Exposure to Ethinyl Estradiol on Tamoxifen Resistance and Breast Cancer Recurrence in a Preclinical Model," published in the Journal of the National Cancer Institute, showed that in utero estrogen exposure causes epigenetic changes in four genes linked to tamoxifen resistance. But the researchers think this effect can be reversed with epigenetic modifying drugs, such as Depakene (valproic acid) or Apresoline (hydralazine). "Higher estrogen levels in utero have been known to increase risk of estrogen positive breast cancer in laboratory animals — and humans — but it wasn't known until this study that these elevated levels may also be responsible for tamoxifen resistance," Leena Hilakivi-Clarke, PhD, a professor of oncology at Georgetown University's Lombardi Comprehensive Cancer Center, and the study's co-lead author, said in a press release. Elevated estrogen during pregnancy is known to increase breast cancer risk in several subsequent generations. Because previous studies have shown that this occurs through epigenetic changes (modifications in the DNA that change the expression rates of specific genes) in the
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