Abstract OT1-13-01: MammaPrint, BluePrint, and full-genome data linked with clinical data to evaluate new gene expression profiles (FLEX)
Authors: Brufsky AM , Crozier JA , Grady I , Lomis T , Whitworth P , Rehmus E , Srkalovic G , Lee L , Blumencranz P , Baron P , Mavromatis B , Untch S , Blumencranz L , Yoder EB , Audeh W ,   FLEX Investigators Group
Published: May 2019

Abstract
BACKGROUND: Genomic signatures are revolutionizing the definition, identification, and treatment of breast cancer subtypes. The ability of genomic signatures to enable fine grained stratification of breast cancers to the granular disease level is still generally untested because of the difficulties in aggregating large clinical data sets. In order to stratify breast cancers into actionable subtypes both the full genome data and clinical data must be collected for patients at scale.
DESIGN & METHODS: FLEX is designed as a novel, large-scale, population based, prospective registry. All patients with stage I-III breast cancer who receive MammaPrint (MP) or BluePrint (BP) testing on a primary breast tumor are eligible. FLEX utilizes an adaptive design which enables additional study arms at low incremental effort and cost by allowing targeted substudies to be added. Patients who are enrolled in the initial study will also be eligible for inclusion in any additional study arm where they meet all criteria. Additional study arms and substudies may be investigator-initiated.
SPECIFIC AIMS:
Primary: Create a big-data registry of full genome expression data and clinical data to investigate new gene associations with prognostic and/or predictive value.
Secondary: Generate hypotheses for targeted subset analyses and trials based on full genome data. To date the following substudies have been proposed:
DR. JENNIFER A. CROZIER, BAPTIST MD ANDERSON CANCER CENTER
(1) MP and BP in male breast cancer TYPE: SUBSTUDY; NO ADDITIONAL CONSENT (ICF) REQUIRED. ARMS: ALL (2) MP BP evaluation in breast cancer patients ≥70. TYPE: SUBSTUDY; NO ADDITIONAL ICF REQUIRED. ARMS: ALL (3) FG evaluation in ILC. TYPE: SUBSTUDY; NO ADDITIONAL ICF REQUIRED. ARMS: ALL (4,5) MP BP relation to PR positivity, Ki67. TYPE: SUBSTUDY; NO ADDITIONAL ICF REQUIRED. ARMS: ALL (6) MP BP in metaplastic breast cancer. TYPE: SUBSTUDY; NO ADDITIONAL ICF REQUIRED. ARMS: ALL
DR. ADAM M. BRUFSKY, UNIVERSITY OF PITTSBURGH MEDICAL CENTER MAGEE WOMENS HOSPITAL
(1) Response to standard chemotherapy regimens in clinically ER+/PR+/HER2+ (triple positive) patients according to BP molecular subtypes. (2) Expression signatures by response to bisphosphonates in ER+ patients receiving adjuvant therapy, or for osteoporosis after primary treatment. (3) Gene expression in breast cancer patients with obesity. TYPE: SUBSTUDY; DUAL ICF UTILIZED. ARMS: NEOADJUVANT AND ADJUVANT
DR. IAN GRADY, NORTH VALLEY BREAST CLINIC
Impact of genomic risk classification on travel time to receive breast cancer care. TYPE: SUBSTUDY; NO ADDITIONAL ICF REQUIRED. ARMS: ALL
DR. THOMAS LOMIS, VALLEY BREAST CARE
Complementary data collection for patients participating in the ODM-201 trial. FLEX provides gene expression for exploratory and signature discovery. TYPE: COMPLEMENTARY; DUAL ICF UTILIZED. ARM: NEOADJUVANT
DR. PAT WHITWORTH, NASHVILLE BREAST CENTER
Genomic reclassification of large tumors eligible to receive NCT therapy. TYPE: SUBSTUDY; NO ADDITIONAL ICF REQUIRED. ARM: NEOADJUVANT
ELIGIBILITY, ACCRUAL
FLEX will enroll a minimum of 10000 patients aged ≥18 with stage I-III breast cancer who sign ICF. Enrollment began April 2017 and 623 patients have been enrolled as of June 2018.
Citation Format: Brufsky AM, Crozier JA, Grady I, Lomis T, Whitworth P, Rehmus E, Srkalovic G, Lee L, Blumencranz P, Baron P, Mavromatis B, Untch S, Blumencranz L, Yoder EB, Audeh W, FLEX Investigators Group. MammaPrint, BluePrint, and full-genome data linked with clinical data to evaluate new gene expression profiles (FLEX) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-13-01.