Estrogen Receptor pathway activity score to predict clinical response or resistance to neo-adjuvant endocrine therapy in primary breast cancer

Endocrine therapy is important for management of patients with estrogen receptor (ER) positive breast cancer, however positive ER staining does not reliably predict therapy response. We assessed the potential to improve prediction of response to endocrine treatment of a novel test that quantifies functional ER pathway activity from mRNA levels of ER pathway-specific target genes. ER pathway activity was assessed on datasets from three neoadjuvant treated ER-positive breast cancer patient cohorts. Edinburgh: 3 months letrozole, 55 pre-/two-week/post-treatment matched samples; TEAM IIa: 3-6 months exemestane, 49 pre-/28 post-treatment paired samples; NEWEST: 16 weeks fulvestrant, 39 pre-treatment samples. ER target gene mRNA levels were measured in Fresh Frozen tissue (Edinburgh, NEWEST) with Affymetrix microarrays, and in Formalin Fixed Paraffin Embedded samples (TEAM IIa) with RT-qPCR. Approximately one third of ER-positive patients had a functionally inactive ER pathway activity score (ERPAS), which was associated with a non-responding status. Quantitative ERPAS decreased significantly upon therapy (p