Selective reduction of estrogen receptor (ER) positive breast cancer occurrence by estrogen receptor modulators supports etiological distinction between ER positive and ER negative breast cancers

Unified Concept I and II. To overcome limitations of described concept a unified concept is presented. Cancers from ER positive ductal cells start as pure ER positive tumors and those from ER negative ductal cells as pure ER negative tumors. During the preclinical phase, in some ER positive tumors, clonal selection introduces ER negative clones. These tumors become mosaic in the cellular ER expression, some of them predominantly ER positive other ER negative. Estrogen deprivation, or SERMs can help mostly to patients with pure ER positive, or mosaic ER positive tumors. Since the dominant metastatic clone can have different ER status from the primary breast tumor, both surprising successes and failures of endocrine therapy can be expected in tumors with mosaic ER expression.