In an analysis from the NRG Oncology/NSABP B-42 trial reported in the Journal of Clinical Oncology, Priya Rastogi, MD, and colleagues found that the 70-gene MammaPrint assay findings did not predict the distant recurrence benefit of extended letrozole therapy vs placebo in patients with early-stage, hormone receptor–positive breast cancer. However, a significant predictive ability of MammaPrint was observed for secondary outcome measures.
Priya Rastogi, MD
Study Details
In the trial, 1,866 patients randomly assigned to receive extended letrozole therapy (n = 916) or placebo (n = 950) were eligible for the MammaPrint analysis. In total, 564 patients in the extended letrozole therapy group and 596 patients in the placebo group had MammaPrint low-risk status (MP-LR), and 352 and 354, respectively, had MammaPrint high-risk status (MP-HR). MP-LR tumors were further categorized as ultra–low-risk (MP-UL) or low non–ultra-low risk (MP-LNUL).
The primary outcome measure was distant recurrence.
Key Findings
There was no statistically significant difference in extended letrozole therapy benefit vs placebo in terms of distant recurrence between MP-LR and MP-HR patients (interaction P = .38). Rates of distant recurrence for extended letrozole therapy vs placebo at 10 years were 3.5% vs 7.2% (hazard ratio [HR] = 0.43, P = .002) among patients with MP-LR and 4.9% vs 7.3% (HR = 0.65, P = .19) among those with MP-HR.
The 10-year extended letrozole therapy benefit vs placebo was significant for disease-free survival (20.3% vs 28.1%, HR = 0.67, P < .001) and breast cancer–free interval (8.4% vs 15.4%, HR = 0.51, P < .001) among patients with MP-LR status and not significant for disease-free survival (28.8% vs 27.2%, HR = 1.00, P = .55) or breast cancer–free interval (14.6% vs 11.6%, HR = 1.15, P = .53) among patients with MP-HR status. The P values for interaction were significant for both outcomes: P = .015 for disease-free survival and P = .006 for breast cancer–free interval.
In exploratory analyses, the 10-year extended letrozole therapy benefit vs placebo was significant among 908 patients with MP-LNUL tumors for distant recurrence (difference = 4.0%), disease-free survival (9.5%), and breast cancer–free interval (7.9%). The 10-year benefit of extended letrozole therapy vs placebo among 252 patients with MP-UL tumors was not significant for distant recurrence (3%), disease-free survival (1.8%), or breast cancer–free interval (4.1%).
The investigators concluded, “The primary hypothesis of predictive ability of MammaPrint on distant recurrence was not confirmed. However, the secondary outcomes demonstrated MammaPrint was predictive of extended letrozole therapy response and identified a subset of patients with early-stage, hormone receptor–positive breast cancer (MP-LR) with improved outcomes from extended letrozole therapy. These data could have important clinical implications in patient selection beyond clinical risk assessment for extended endocrine therapy.”
Dr. Rastogi, of UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute, Korea Health Technology R&D Project, Agendia, Inc, and others. For full disclosures of the study authors, visit ascopubs.org.
