PURPOSE: This study, along with two others, was done to develop the 21-gene Recurrence Score assay (Oncotype DX) that was validated in a subsequent independent study and is used to aid decision making about chemotherapy in estrogen receptor (ER)-positive, node-negative breast cancer patients. EXPERIMENTAL DESIGN: Patients with >or=10 nodes diagnosed from 1979 to 1999 were identified. RNA was extracted from paraffin blocks, and expression of 203 candidate genes was quantified using reverse transcription-PCR (RT-PCR). RESULTS: Seventy-eight patients were studied. As of August 2002, 77% of patients had distant recurrence or breast cancer death. Univariate Cox analysis of clinical and immunohistochemistry variables indicated that HER2/immunohistochemistry, number of involved nodes, progesterone receptor (PR)/immunohistochemistry (% cells), and ER/immunohistochemistry (% cells) were significantly associated with distant recurrence-free survival (DRFS). Univariate Cox analysis identified 22 genes associated with DRFS. Higher expression correlated with shorter DRFS for the HER2 adaptor GRB7 and the macrophage marker CD68. Higher expression correlated with longer DRFS for tumor protein p53-binding protein 2 (TP53BP2) and the ER axis genes PR and Bcl2. Multivariate methods, including stepwise variable selection and bootstrap resampling of the Cox proportional hazards regression model, identified several genes, including TP53BP2 and Bcl2, as significant predictors of DRFS. CONCLUSION: Tumor gene expression profiles of archival tissues, some more than 20 years old, provide significant information about risk of distant recurrence even among patients with 10 or more nodes.
PURPOSE: This study, along with two others, was done to develop the 21-gene Recurrence Score assay (Oncotype DX) that was validated in a subsequent independent study and is used to aid decision making about chemotherapy in estrogen receptor (ER)-positive, node-negative breast cancerpatients. EXPERIMENTAL DESIGN:Patients with >or=10 nodes diagnosed from 1979 to 1999 were identified. RNA was extracted from paraffin blocks, and expression of 203 candidate genes was quantified using reverse transcription-PCR (RT-PCR). RESULTS: Seventy-eight patients were studied. As of August 2002, 77% of patients had distant recurrence or breast cancer death. Univariate Cox analysis of clinical and immunohistochemistry variables indicated that HER2/immunohistochemistry, number of involved nodes, progesterone receptor (PR)/immunohistochemistry (% cells), and ER/immunohistochemistry (% cells) were significantly associated with distant recurrence-free survival (DRFS). Univariate Cox analysis identified 22 genes associated with DRFS. Higher expression correlated with shorter DRFS for the HER2 adaptor GRB7 and the macrophage marker CD68. Higher expression correlated with longer DRFS for tumor protein p53-binding protein 2 (TP53BP2) and the ER axis genes PR and Bcl2. Multivariate methods, including stepwise variable selection and bootstrap resampling of the Cox proportional hazards regression model, identified several genes, including TP53BP2 and Bcl2, as significant predictors of DRFS. CONCLUSION: Tumor gene expression profiles of archival tissues, some more than 20 years old, provide significant information about risk of distant recurrence even among patients with 10 or more nodes.
Authors: Aman Russom; Palaniappan Sethu; Daniel Irimia; Michael N Mindrinos; Steve E Calvano; Iris Garcia; Celeste Finnerty; Cynthia Tannahill; Amer Abouhamze; Julie Wilhelmy; M Cecilia López; Henry V Baker; David N Herndon; Stephen F Lowry; Ronald V Maier; Ronald W Davis; Lyle L Moldawer; Ronald G Tompkins; Mehmet Toner Journal: Clin Chem Date: 2008-03-28 Impact factor: 8.327
Authors: Olivia Pagani; Shari Gelber; Edda Simoncini; Monica Castiglione-Gertsch; Karen N Price; Richard D Gelber; Stig B Holmberg; Diana Crivellari; John Collins; Jurij Lindtner; Beat Thürlimann; Martin F Fey; Elizabeth Murray; John F Forbes; Alan S Coates; Aron Goldhirsch Journal: Breast Cancer Res Treat Date: 2008-10-25 Impact factor: 4.872
Authors: Vered Stearns; Lisa K Jacobs; Maryjo Fackler; Theodore N Tsangaris; Michelle A Rudek; Michaela Higgins; Julie Lange; Zandra Cheng; Shannon A Slater; Stacie C Jeter; Penny Powers; Susanne Briest; Calvin Chao; Carl Yoshizawa; Elizabeth Sugar; Igor Espinoza-Delgado; Saraswati Sukumar; Edward Gabrielson; Nancy E Davidson Journal: Clin Cancer Res Date: 2013-05-29 Impact factor: 12.531