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Increasingly, breast cancer is being recognized as a heterogeneous disease comprised of molecularly and phenotypically distinct intrinsic tumor subtypes with different clinical outcomes. This biological heterogeneity has significant implications, particularly as it relates to expression profiling of estrogen receptor (ER) status, as classifying breast cancers based on hormone receptor expression impacts not only prognosis but also treatment options and long-term outcomes. Epigenetics has emerged as a promising field for the assessment of hormone receptor status. Epigenetic aberrations have been shown to regulate ER and offer reversible targets for development of new therapies. This review covers ER-negative breast tumor epigenetic aberrations and summarizes the major epigenetic mechanisms governing ER expression and how it impacts treatment of ER-negative breast cancer.