Title: Characterization of MammaPrint UltraLow Risk tumors in more than 1400 patients from the real-world evidence FLEX study

Publication: SABCS 2023, PO1-02-11


Cathy Graham, Kent Hoskins, V.K. Gadi, Suzanne Hoekstra, Gordan Srkalovic, Douglas K. Marks, Beth Sieling, Christine Carruth, Patricia Dauer, William Audeh, Joyce O’Shaughnessy, and FLEX Investigators Group


MammaPrint is a gene expression signature used to determine the risk of distant recurrence for patients with early-stage breast cancer. Previous studies from MINDACT, FOCUS, IKA, and STO-3 trials have demonstrated that postmenopausal node-negative patients with MammaPrint UltraLow Risk tumors are considered indolent and patients have excellent long-term survival outcomes up to 20 years with little to no endocrine treatment. These studies suggest that patients with UltraLow Risk tumors are ideal candidates for treatment optimization which has resulted in the inclusion of the UltraLow Risk result in the NCCN guidelines. Here, we characterized patients with UltraLow Risk tumors from the real-world evidence FLEX study.


FLEX (NCT03053193) is a prospective, observational registry study with 99 sites open in the United States, Canada, Greece, and Israel. Patients enrolled in FLEX have early-stage breast cancer and receive MammaPrint testing as standard of care (with or without BluePrint molecular subtyping), and consent to full transcriptome analysis and clinical data collection. MammaPrint is a gene expression signature of 70 genes that classifies tumors as having a Low Risk or High Risk of distant recurrence. Within Low Risk tumors, a subcategory of UltraLow Risk (MammaPrint Index > 0.355) has been defined in previous studies. Clinical data for this analysis was locked February 2023. Clinical risk was defined as low risk or high risk based on Adjuvant Online criteria.


Among the 12,328 patients enrolled in FLEX, 1465 (11.9%) have UltraLow Risk tumors. All tumors with available BluePrint molecular subtyping were classified as Luminal-Type. Of the patients with detailed clinical data, the majority had clinically low risk tumors (78.8%; Table 1). Notably, 34.6% of patients with UltraLow Risk tumors had Ki67 tumor staining of greater than 10%, 16.7% were pre- or peri-menopausal, 43.6% had grade 2-3 tumors, and 20.1% had tumors > 2 cm (Table 1). Among patients with treatment information, 6.5% received a combination of chemotherapy with or without endocrine and HER2-targeted therapy, 82.4% received endocrine therapy, 4.8% received other treatment (endocrine with targeted therapy (CDK4/6), radiation alone, novel treatment regimen, or supporting agents), and 6.3% did not receive treatment (Table 1).


Previous trials have demonstrated the utility of MammaPrint UltraLow Risk in patients with clinically low risk features. In this large real-world evidence study of patients with early-stage breast cancer, UltraLow Risk tumors can be identified across all clinical categories. Overall, we report a substantial number of premenopausal patients with UltraLow Risk tumors, and these young women would be good candidates for treatment optimization. Future studies will assess long-term outcomes in this cohort further stratified by treatment.