Genomic Subtyping Assays Identify High-Risk Early-Stage Breast Cancers

Emerging evidence points to intrinsic tumor biology as a key driver of these differences beyond social determinants and care patterns. A new multicenter genomic profiling analysis now identifies aggressive tumor subtypes that help explain survival differences and shows that outcomes are comparable when care is aligned to assay-defined risk.

Agendia’s MammaPrint and BluePrint assays were assessed in a study published in npj Breast Cancer that included 1,018 females with stages I–III hormone receptor positive, HER2-negative (HR+/HER2–) early-stage breast cancer. Participants were drawn from the FLEX study and the BEST registry. For a robust comparison, 509 White participants from FLEX were propensity score matched 1:1 with 509 Black participants from BEST by age or menopausal status at diagnosis.

MammaPrint is a 70‑gene expression test that stratifies risk of distant metastasis into UltraLow, Low, High 1, and High 2 categories. BluePrint is a molecular subtyping assay that classifies tumors by functional biology as Luminal-type, HER2-type, or Basal-type. MammaPrint is the only U.S. Food and Drug Administration (FDA)–cleared gene expression profiling test that assesses risk of distant metastasis in early-stage breast cancer.

Findings of the study showed that Black females were more than twice as likely as matched White females to have genomically High Risk 2 tumors (19.8% vs 8.4%; p<0.001) or BluePrint Basal-Type tumors (11.0% vs 4.8%; p<0.001). Recurrence at three years was driven by genomic subtype independent of race: compared with MammaPrint Low Risk, BluePrint Luminal A-Type, participants with MammaPrint High Risk, BluePrint Basal-Type tumors were over 10 times more likely to recur (hazard ratio 10.82; p=0.004), and those with MammaPrint High Risk, BluePrint Luminal B-Type tumors were over five times more likely to recur (hazard ratio 5.08; p=0.004). Among Black females in the BEST cohort, those with MammaPrint Low Risk tumors had a 10‑year recurrence‑free survival of 97.7%, the same as White females.

Despite the higher prevalence of aggressive subtypes, three‑year outcomes were similar between Black and White participants when therapy followed combined assay results. Genomic subtyping reclassified 55% of participants initially labeled low risk by immunohistochemistry (estrogen receptor positivity >10%) as Basal‑Type, emphasizing the limitations of standard clinical markers and the value of incorporating molecular subtyping into management.

“The over-representation of Basal-Type tumors among Black females with HR+/HER2– breast cancer underscores a critical need to move beyond standard clinical markers such as ER% staining for identifying higher-risk tumor types. BluePrint Basal-Type tumors demonstrate clinical behavior similar to triple-negative breast cancer and may warrant more aggressive treatment. Incorporating molecular subtyping enables more precise identification of high-risk participants and helps guide more tailored, personalized care.” said Sonya Reid, M.D., M.P.H., Associate Professor, Vanderbilt University Medical Center, and lead author of the study

“We’re proud to work alongside our collaborators at the Vanderbilt University Medical Center, which underscores our shared commitment to bringing precision medicine to all women,” said William Audeh, M.D., Chief Medical Officer of Agendia and co-author of the study. “The risk of recurrence of breast cancer in Black women has often been underestimated by traditional clinical features, driven largely by their underrepresentation in clinical trials. By providing a genomic assessment of tumor biology, we can ensure that women with breast cancer will receive individualized care that improves their long-term outcomes.”

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