Distinct @entity876 gene signatures are needed to predict prognosis and response to chemotherapy in ER-positive and ER-negative XXXX .

@entity172 @entity0 @entity440 @entity5 @entity876 @entity3
PURPOSE: @entity172 receptor-positive (ER+) and -negative (ER) @entity0 are molecularly distinct diseases. We hypothesized that @entity876 mutations may lead to different transcriptional changes and carry different prognostic value in these two different types of @entity5 . EXPERIMENTAL DESIGN: We developed a 39-gene @entity876 signature derived from 213 ER+ and a separate 30-gene signature from 38 @entity5 with known mutation status and tested their prognostic and chemotherapy response predictive values in ER+ and @entity5 , respectively. RESULTS: External validation to predict @entity876 status (n = 103) showed sensitivity and specificity of 89% and 54% for the 39-gene signature, and 82% and 61% for the 30-gene signature. The 39-gene signature was predictive of worse distant @entity3 free survival in ER+ @entity5 in two separate prognostic data sets (n = 255, HR: 2.3, P = 0.005 and n = 198, HR: 2.17, P = 0.09). It also predicted for poor prognosis even with adjuvant @entity440 therapy (n = 277, HR = 2.43, P < 0.0001) but it was not prognostic in @entity5 . It was also associated with higher chemotherapy sensitivity in ER+ but not in @entity5 . The prognostic and predictive values remained significant in multivariate analysis. The 30-gene, ER-, @entity876 signature showed no prognostic or predictive values in ER+ @entity5 but it was associated with better prognosis in @entity5 . It also had no chemotherapy response predictive value in ER- or ER+ @entity5 . CONCLUSIONS: @entity876 dysfunction is prognostically most relevant in ER+ @entity5 and supports the hypothesis that different predictive or prognostic markers will be needed for different molecular subsets of @entity0 .
