Background: Clinical trials have been an invaluable tool in providing improvements in the discovery, treatment, and quality of life for various diseases and disorders including breast cancer, which impacts millions of people each year. Historically, patient trial populations have not been racially diverse due to several factors such as bias, healthcare distrust, access, and eligibility criteria. However, current efforts are focused on improving diversity and inclusion to promote efficacy and health equity across all races/ethnicities. The ongoing, multi-center FLEX trial (NCT03053193), which pairs clinical data and full transcriptome expression data, seeks to enroll 30,000 patients to accelerate real world research. Due to the size of the database, it is also expected to capture patients typically underrepresented in clinical trials. Methods: FLEX is the first of its kind, prospective, observational trial that enrolls patients who are ≥ 18 years old with histologically proven stage I-III breast cancer with up to 3 positive lymph nodes. Patient eligibility for study enrollment include standard of care MammaPrint testing with or without BluePrint and consent to clinically annotated full transcriptome data collection. The study infrastructure facilitates the generation of hypotheses for targeted sub-studies. The FLEX network fosters collaboration with 114 sites, including one site in Greece and Israel, encouraging participating investigators to initiate sub-studies that can address research questions that are important for breast cancer management. All proposed sub-studies are vetted and approved by Research and Scientific Review Committees. Since launching in April 2017, 12,569 patients have been enrolled including those who have been historically underrepresented in trials (African American n= 1025; Latin n= 341; Asian n=156). Forty-two investigator initiated sub-studies have been approved and are in progress, with 40 abstracts accepted in national and international congresses. Five ongoing sub-studies within FLEX address differences in underlying biology and treatment response/management among African American, Latina, and Asian American patients with early-stage breast cancer. These studies provide a broader understanding of how differential gene expression patterns unique to racial/ethnic groups can impact treatment outcomes. With the large FLEX database, enrollment and sub-studies are extended to other racial/ethnic groups that are underrepresented in clinical trials, but not limited to specific groups. Overall, the FLEX study strives to use full transcriptome data to improve precision medicine in early-stage breast cancer. Clinical trial information: NCT03053193.