The MammaPrint 70-gene assay has demonstrated significant predictive utility for identifying chemotherapy benefit in patients with hormone receptor-positive, HER2-negative early-stage breast cancer, according to findings from the ongoing FLEX study published in JNCI Cancer Spectrum. The real-world evidence strengthens the case for genomic testing to guide personalized treatment decisions across diverse patient populations.
Strong Predictive Performance Across Risk Categories
The study revealed that the MammaPrint Index was significantly predictive of 5-year distant recurrence-free interval for both endocrine therapy alone (R² = .99; P < .001) and combination chemotherapy with endocrine therapy (R² = .90; P < .001). The analysis of 1,002 propensity-score matched patients showed clear stratification of chemotherapy benefit based on genomic risk classification.
Patients with MammaPrint High Risk 2 breast cancer experienced the greatest absolute reduction benefit from chemotherapy, with a maximum of 14.2% and an average of 10.9%. High Risk 1 patients showed moderate benefit with an average of 5.6%, while Low and Ultralow risk categories demonstrated minimal benefit at 1.7% and less than 1.0%, respectively.
"This propensity-score matched population offers statistically robust evidence supporting the benefit of chemotherapy for patients with MammaPrint High Risk cancers," stated Adam Brufsky, MD, PhD, professor of medicine at University of Pittsburgh Medical Center and first author of the study. "At the same time, it supports foundational results from the phase 3 MINDACT trial that showed no significant benefit of chemotherapy for patients with MammaPrint Low Risk breast cancer."
Multivariate Analysis Confirms Independent Predictive Value
A multivariate Cox analysis demonstrated a significant interaction between the MammaPrint Index and chemotherapy benefit (HR, 0.15; 95% CI, 0.02-0.97; P = .047), independent of traditional clinical factors including age, tumor stage, nodal status, or grade. Notably, pre- or peri-menopausal status was significantly associated with chemotherapy benefit (HR = 0.08; 95% CI, 0.01-0.74; P = .025).
The FLEX study enrolled 1,407 patients aged 18 years and older with stage I to III invasive breast cancer who underwent standard-of-care MammaPrint genomic testing. Within the study population, 859 received endocrine therapy alone, and 548 received combination therapy with chemotherapy.
Clinical Utility in Older Patient Populations
Additional real-world evidence from the FLEX registry demonstrated the assay's utility in guiding treatment decisions for patients aged 70 and older. Analysis of over 4,000 patients showed that older patients with MammaPrint high-risk tumors were less likely to receive chemotherapy compared to younger patients, even when genomic risk was elevated.
Specifically, patients 70 years and older were less likely to receive chemotherapy versus patients younger than 70 if they had MammaPrint High 1 tumors (55.8% vs 73%; P <.001) or High 2 tumors (72.6% vs 82.2%; P = .07). However, among older patients with high-risk tumors, chemotherapy conferred improved 3-year recurrence-free interval outcomes versus endocrine therapy alone for those with High 1 (97% vs 94%; P = .137) and High 2 tumors (90% vs 79%; P = .078).
"The MammaPrint assay can help guide chemotherapy decisions in older women, potentially sparing low-risk patients from unnecessary treatment while identifying those who may benefit from chemotherapy despite their age," explained Reshma L. Mahtani, DO, chief of breast medical oncology at Miami Cancer Institute of Baptist Health South Florida.
Study Population and Methodology
The propensity-score matched cohort included 501 patients who received endocrine therapy alone and 501 who received combination therapy. The mean age was 59 years, with the majority being post-menopausal (70.1%) and White (79.2%). Most patients presented with T1 (37.9%) or T2 (43.7%) tumors, had node-negative disease (70.0%), and grade 2 disease (51.2%).
The study used nearest neighbor propensity-score matching to balance menopausal status, tumor stage, and lymph node status between treatment groups. Kaplan Meier analysis calculated empirical 5-year distant recurrence-free interval, while quadratic polynomial regression modeled the relationship between MammaPrint Index and clinical outcomes.
"This study marks a milestone in the large body of data supporting the predictive value of MammaPrint in breast cancer, and underscores Agendia's commitment to providing robust, clinically actionable genomic insights that personalize care and improve outcomes for individuals diagnosed with breast cancer," said William Audeh, MD, MS, chief medical officer at Agendia. The FLEX study has now enrolled more than 20,000 breast cancer patients and continues to contribute meaningful insights to breast cancer research.
