Project description:PURPOSE: To develop a predictive test for response and survival following neoadjuvant taxane-anthracycline chemotherapy for HER2-negative invasive breast cancer. METHODS: We developed a microarray-based gene expression test from pre-treatment tumor biopsies (310 patients) to predict favorable outcome based on estrogen receptor (ER) status,pathologic response to chemotherapy, 3-year disease outcomes, and sensitivity to endocrine therapy. Tumors were classified as treatment-sensitive if predicted to have pathologic response (and not resistance) to chemotherapy, or sensitive to endocrine therapy. We tested predictive accuracy, with 95% confidence interval (CI), for pathologic response (PPV, positive predictive value), distant relapse-free survival (DRFS), and absolute risk reduction at median follow-up in 198 other patients. Independence from clinical-pathologic factors was assessed in a multivariate Cox regression analysis based on the likelihood ratio test. Other evaluable, published response predictors (genomic grade index (GGI), intrinsic subtype (PAM50), pCR predictor (DLDA30)) were compared. Neoadjuvant validation cohort of 198 HER2-negative breast cancer cases treated with taxane-anthracycline chemotherapy pre-operatively and endocrine therapy if ER-positive. Response was assessed at the end of neoadjuvant treatment and distant-relapse-free survival was followed for at least 3 years post-surgery.
Project description:PURPOSE: To develop a predictive test for response and survival following neoadjuvant taxane-anthracycline chemotherapy for HER2-negative invasive breast cancer. METHODS: We developed a microarray-based gene expression test from pre-treatment tumor biopsies (310 patients) to predict favorable outcome based on estrogen receptor (ER) status,pathologic response to chemotherapy, 3-year disease outcomes, and sensitivity to endocrine therapy. Tumors were classified as treatment-sensitive if predicted to have pathologic response (and not resistance) to chemotherapy, or sensitive to endocrine therapy. We tested predictive accuracy, with 95% confidence interval (CI), for pathologic response (PPV, positive predictive value), distant relapse-free survival (DRFS), and absolute risk reduction at median follow-up in 198 other patients. Independence from clinical-pathologic factors was assessed in a multivariate Cox regression analysis based on the likelihood ratio test. Other evaluable, published response predictors (genomic grade index (GGI), intrinsic subtype (PAM50), pCR predictor (DLDA30)) were compared. Neoadjuvant study of 310 HER2-negative breast cancer cases treated with taxane-anthracycline chemotherapy pre-operatively and endocrine therapy if ER-positive. Response was assessed at the end of neoadjuvant treatment and distant-relapse-free survival was followed for at least 3 years post-surgery.
Project description:PURPOSE: To develop a predictive test for response and survival following neoadjuvant taxane-anthracycline chemotherapy for HER2-negative invasive breast cancer. METHODS: We developed a microarray-based gene expression test from pre-treatment tumor biopsies (310 patients) to predict favorable outcome based on estrogen receptor (ER) status,pathologic response to chemotherapy, 3-year disease outcomes, and sensitivity to endocrine therapy. Tumors were classified as treatment-sensitive if predicted to have pathologic response (and not resistance) to chemotherapy, or sensitive to endocrine therapy. We tested predictive accuracy, with 95% confidence interval (CI), for pathologic response (PPV, positive predictive value), distant relapse-free survival (DRFS), and absolute risk reduction at median follow-up in 198 other patients. Independence from clinical-pathologic factors was assessed in a multivariate Cox regression analysis based on the likelihood ratio test. Other evaluable, published response predictors (genomic grade index (GGI), intrinsic subtype (PAM50), pCR predictor (DLDA30)) were compared.
Project description:PURPOSE: To develop a predictive test for response and survival following neoadjuvant taxane-anthracycline chemotherapy for HER2-negative invasive breast cancer. METHODS: We developed a microarray-based gene expression test from pre-treatment tumor biopsies (310 patients) to predict favorable outcome based on estrogen receptor (ER) status,pathologic response to chemotherapy, 3-year disease outcomes, and sensitivity to endocrine therapy. Tumors were classified as treatment-sensitive if predicted to have pathologic response (and not resistance) to chemotherapy, or sensitive to endocrine therapy. We tested predictive accuracy, with 95% confidence interval (CI), for pathologic response (PPV, positive predictive value), distant relapse-free survival (DRFS), and absolute risk reduction at median follow-up in 198 other patients. Independence from clinical-pathologic factors was assessed in a multivariate Cox regression analysis based on the likelihood ratio test. Other evaluable, published response predictors (genomic grade index (GGI), intrinsic subtype (PAM50), pCR predictor (DLDA30)) were compared.
Project description:We performed RNA-seq on pre-treatment endoscopic biopsies from 114 patients, including 97 patients treated with NAT that qualified for outcome analyses We then performed gene expression profiling analysis using data obtained from RNA-seq
Project description:Interventions: Gold Standard:Pathologic diagnosis;Index test:diagnostic model of intestinal microbiome progressive markers 
Primary outcome(s): Sensitivity;The area under the ROC curve
Study Design: Factorial