OT2-03-02: Prospective Neo-Adjuvant Registry Trial Linking MammaPrint, Subtyping and Treatment Response: Neoadjuvant Breast Registry – Symphony Trial (NBRST).

Abstract

Abstract Background MammaPrint is performed on a diagnostic multi-gene array featuring >4,500 genes. This platform enables additional gene expression profiles to be analyzed simultaneously on one tumor specimen. BluePrint, an eighty gene Molecular Subtyping Profile, discriminates between three distinctive subtypes; Basal-type, Luminal-type, and ERBB2 (HER2)-type. Studies have shown marked differences in response to neo-adjuvant treatment in groups stratified by MammaPrint and BluePrint. Trial design A prospective observational, case-only study linking MammaPrint, BluePrint, TargetPrint, TheraPrint (together referred to as the Symphony suite) and possible additional profiles of interest to neoadjuvant treatment response and Distant Metastases Free Survival (DMFS) and Relapse Free Survival (RFS). 20-30 institutions in the US will be invited to contribute clinical patient data from enrolled patients after a MammaPrint, TargetPrint, BluePrint and TheraPrint (Symphony suite) has been successfully performed and the patient has started neo-adjuvant therapy. Treatment is at the discretion of the physician, adhering to NCCN approved regimens or a recognized alternative. Eligibility criteria Women with histologically proven breast cancer, who have started or are scheduled to start neo-adjuvant chemotherapy therapy or neo-adjuvant hormone therapy, after successful Symphony suite assessment Age 18–90 Written informed consent No excisional biopsy or axillary dissection No confirmed distant metastatic disease No prior therapy for the treatment of breast cancer Scope The scope of this registry study is to measure chemosensitivity as defined by pCR (primary endpoint), or endocrine sensitivity as defined by partial response, (a primary endpoint for neo-adjuvant endocrine therapy and a secondary endpoint for neoadjuvant chemotherapy), metastasis-free survival and relapse-free survival (secondary endpoints) in molecular subgroups, determined by the MammaPrint and BluePrint; as well as correlation to Targetprint and Theraprint read outs in addition to investigating novel response profiles. Statistical methods The response rate and corresponding confidence intervals will be presented as a proportion of all patients enrolled. The confidence intervals will be calculated using the normal approximation to the binomial distribution. Comparison of response rates between different molecular subgroups will be conducted using Pearson Chi-square test. Correlation of chemosensitivity and endocrine sensitivity (as defined by pCR) to TheraPrint will be determined using Pearson correlation and linear fit models. Kaplan-Meier curves for RFS and DMFS will be calculated for different molecular subgroups. Present accrual and target accrual The target accrual is to enroll approximately 500 patients in 4 years. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-03-02.