Negative 18 F-FES PET/CT Despite Estrogen Receptor Positivity by Immunohistochemistry

Immunohistochemistry (IHC) is routinely used to determine the estrogen receptor (ER) expression status of breast cancer. 18 F-fluoro-estradiol ( 18 F-FES) PET/CT is indicated for select breast cancer patients with ER+ breast cancer, and patients with tracer-avid disease typically enjoy favorable responses to endocrine therapy (ET). We present 2 patients with metastatic breast cancer that were ER+ on IHC but lacked tracer avidity on 18 F-FES PET/CT. We hypothesize that despite ER detection on IHC, these receptors were nonfunctional, lacking the ability to bind estrogen. Since functional ER is a prerequisite for response to ET, these patients are not likely to respond to ET.