This mechanism presumably accounts for the observation that in a large cohort of patients with primary breast cancer (N = 894), ERBB2 gene copy number (and resulting HER2 protein overexpression) was inversely correlated with ER and PR protein expression quantified by enzyme immunoassay or a radioligand-binding assay (by Scatchard analysis), thus validating seminal preclinical experimental predictions using a large number of actual human breast cancer clinical specimens8. This evidence concerns the gene ESR1 and breast carcinoma.