Over 40,000 American women will die of breast cancer in the next twelve months; one death approximately every 13 minutes. While the precise factors that affect a woman’s individual risk of developing breast remains largely unknown, exposure to natural (and both environmental and synthetic) ligands for the nuclear transcription factor ER are strongly implicated. However, the precise role of estrogenic exposures, and the relative importance of their timing in affecting the susceptibility of normal breast tissues to neoplastic transformation, is complex and incompletely understood.
Of the 192,370 cases of invasive breast cancer newly diagnosed in the next year, over 70% will express ER protein. Endocrine therapies that target ER function reduce breast cancer mortality in patients with ER+ disease, but advanced ER+ breast cancer remains an incurable disease. Reducing the impact of ER action on breast cancer risk requires a much greater understanding of the role of timing on estrogen exposure and the cellular systems that are perturbed in the normal breast. Similarly, preventing or reversing endocrine resistance in breast cancer, whether presenting do novo or arising following a response, also requires an understanding of how ER affects breast cancer cells and regulates cell fate, i.e., the decision to proliferate, differentiate, or die.
Integrating data from the cellular systems affected by ER in both the normal and neoplatic breast will be mutually informative and allow for a more rapid, complete, and robust modeling of ER action in the regulation of cell fate.