ESR1 and neoplasm: It has long been recognized that human and canine mammary neoplasms lose estrogen receptor (ER) expression along with increasing tumor grade [44,45], and a high target score for ESR1 mRNA for both miR-18a and miR-18b, together with their overexpression in malignant cases, indicate that specific miRNAs such as miR-18a and miR-18b may contribute to this loss of hormone receptor activity, providing a potential molecular mechanism for the loss of ER with increased grade of malignancy.