PersonalizedMedicineandImaging.PDF

Published OnlineFirst May 16, 2016; DOI: 10.1158/1078-0432.CCR-16-0148 Personalized Medicine and Imaging Clinical Cancer Research TransCONFIRM: Identi?cation of a Genetic Signature of Response to Fulvestrant in Advanced Hormone Receptor–Positive Breast Cancer Rinath Jeselsohn1,2, William T. Barry1,3, Ilenia Migliaccio4, Chiara Biagioni4,5, Jin Zhao2, Jonas De Tribolet-Hardy2, Cristina Guarducci4, Martina Bonechi4, Naomi Laing6, Eric P. Winer1, Myles Brown1,2, Angelo Di Leo4,5, and Luca Malorni4,5 Abstract Purpose: Fulvestrant is an estrogen receptor (ER) antago- Results: Pathway analysis demonstrated that increased EGF nist and an approved treatment for metastatic estrogen pathway and FOXA1 transcriptional signaling is associated with t receptor–positive (ER ) breast cancer. With the exception of decreased response to fulvestrant. Using a multivariate Cox mod- ER levels, there are no established predictive biomarkers of el, we identi?ed a novel set of 37 genes with an expression that is response to single-agent fulvestrant. We attempted to identify independently associated with progression-free survival (PFS). a gene signature of response to fulvestrant in advanced breast TFAP2C, a known regulator of ER activity, was ranked second in cancer. this gene set, and high expression was associated with a decreased Experimental Design: Primary tumor samples from 134 response to fulvestrant. The negative predictive value of TFAP2C patients enrolled in the phase III CONFIRM study of patients expression at the protein level was con?rmed by IHC. t with metastatic ER breast cancer comparin