Patey Prize 07

Abstract

Expression of estrogen receptor (ER) is used to indicate response to endocrine therapy. However, assays, e.g. immunohistochemistry (IHC), that meausre ER and ER regulated progesterone receptor (PR), predict response in only 40–60% of cases. We have developed a functional assay (FERA) based on interaction of ER with estrogen response elements (EREs). The assay uses adenovirus containing 2 EREs linked to a lac-Z reporter (ERE-lacZ). Breast cancer cells were purified from 29 surgical specimens obtained from 24 patients. The cells were infected with ERE-lacZ and cultured in medium containing 10 nm estrogen (E2), 100 nm tamoxifen (OHT), or 100 nm ICI 182 780 (ICI, a complete ER antagonist). A colorimetric assay was used to assess reporter activity. The results of FERA were compared with IHC. Eleven patients were ER+/PR+, five were ER+/PR– and eight were ER–/PR– by IHC. Three ER+/PR+ and one ER–/PR– were recurrent cancers and all except one patient (ER+/PR+) had received OHT previously. Using FERA, in 12/16 ER+ and 1/8 ER– cancers, E2 induced a 2–10-fold increase in reporter activity. OHT and ICI were inhibitory in primary cancers. Three patients with ER+ cancer showed no ER activity. Of the recurrences, 2 ER+ cancer showed agonistic activity with OHT and in one this was greater than with E2. ICI remained inhibitory. ER activity can be reliably assessed using FERA. Three ER+ patients who may not benefit from OHT and one ER– patient who may benefit were identified. In addition, resistance to OHT was demonstrated. FERA indicates that ICI (as Faslodex) may be beneficial in these cases.