By Diagnostics World Staff
April 10, 2026 | New research released in pre-print from npj Breast Cancer digs deeper into the racial disparities of breast cancer and how the MammaPrint and BluePrint genomic tests from Agendia handle the differences.
Researchers from Vanderbilt University and Agendia used RNA -based expression analyses through the MammaPrint risk of recurrence signature and BluePrint molecular subtyping signature to examine whether tumor genomic differences contribute to racial survival disparities among women with hormone-receptor positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer. (Pre-print version DOI: 10.1038/s41523-026-00932-1)
In the United States, Black women have a 5% lower incidence of breast cancer compared to White women yet have 40% higher mortality rates. In fact, “The largest proportion of the Black -White breast cancer survival disparity is due to lower survival among Black women with HR+HER2- breast cancer, with more pronounced differences in those under 50 years of age,” the authors write. While social determinants of health and patterns of care contribute to this survival gap, it persists even after controlling for socioeconomic factors and despite similar treatment regimens, suggesting that intrinsic tumor biology plays a significant role in these disparities.
The researchers conducted an observational study of 1,018 females with stages I to III HR+HER2- breast cancer enrolled in the FLEX (Full-genome Data Linked with Clinical Data to Evaluate New Gene Expression Profiles) Study and BEST (Black Women with Breast Cancer: Etiology, Survival and Treatment Outcomes) registry, one of the largest cohorts of Black participants with HR+HER2- early-stage breast cancer for whom gene expression and survival data are available. To ensure a robust comparison, 509 White participants from FLEX were propensity score matched 1:1 with 509 Black participants based on age or menopausal status at diagnosis.
The findings shed light on why the racial disparity exists between outcomes for Black and White women.
MammaPrint classifies tumors as high-risk or low-risk of recurrence. BluePrint uses molecular subtyping to classify tumors as Luminal A-type, Luminal B-type, or Basal-type. The study found that Basal-type tumors were twice as prevalent among Black vs White participants (11.0% vs 4.8%). Independent of race, participants with Basal-type tumors had lower 3-year recurrence-free survival compared to Luminal B-type and Luminal A-type. Multivariate analysis revealed that participants with high-risk, Luminal B- and Basal-type tumors had significantly worse 3-year outcomes compared to those with low-risk Luminal A-type, after controlling for race and potential confounders, the authors write.
“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,” said Dr. Sonya Reid, M.D., M.P.H., Associate Professor at Vanderbilt University Medical Center and lead author of the study in a statement. “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.”
Previous analyses of ER+ tumors revealed a significantly higher occurrence of the ERΔ7 dominant-negative splice variant in Basal-type compared to Luminal-type tumors, a variant that is associated with ER dysfunction and endocrine therapy resistance. The authors theorize that Black females may have a greater frequency of tumors harboring the ERΔ7 splice variant relative to White females, though this hypothesis needs further investigation.
The findings also clarified some of the differences in recurrence rates. Participants with high-risk Basal-type tumors were over 10 times more likely to recur and participants with high-risk, Luminal B-type tumors were over 5 times more likely to recur. Among Black females in the BEST cohort, those with MammaPrint low-risk tumors experienced excellent 10-year outcomes, with a 97.7% recurrence-free survival rate, the same outcome as White females.
“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,” said William Audeh, M.D., Chief Medical Officer of Agendia and co-author of the study in a statement.