Genome-wide analysis of the three-way interplay among gene expression, estrogen receptor expression and chemotherapeutic sensitivity in breast cancer

The expression of estrogen receptor α (ER) in breast cancers may be indicative of a favorable prognosis and most of these cancers respond to anti-estrogens or aromatase inhibitors. However, ER-positive (ER(+)) breast cancers receiving anti-hormone and/or chemotherapy sometimes lose their ER expression, which leads to the evolution of the disease to higher aggressiveness and drug resistance. In the present study, an ER-modified signature (EMS) was developed from the expression profile of a chemoresistant MCF-7 breast cancer cell line that lost ER expression during long-term treatment with a chemotherapeutic agent. The EMS could discriminate the ER-negative (ER(−)) breast cancer cells from the ER(+) ones, which included seven pathways essential for the ER(−) cell development. Furthermore, the EMS indicated a more malignant subgroup of the ER(−) cells by discriminating the chemoresistant ER(−) cells from the chemosensitive ones. In addition, the classified chemoresistant ER(−) patients demonstrated worse prognosis. In conclusion, we developed a new method to discriminate subgroups of ER(−) breast cancer cells.