Beyond imaging receptor-binding function, the use of serial PET imaging in a hormone-challenge paradigm, as we have done with FDG-PET to assess changes in tumor metabolism and FFNP-PET to assess changes in PgR gene expression, goes beyond hormone binding function; it rapidly evaluates the functional status of ER regulation of cellular activities in cancer that are associated with response to endocrine therapy. This evidence concerns the gene ESR1 and cancer.