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The MammaPrint (MP) genetic assay identified a group of patients with hormone receptor-positive early-stage breast cancer who might benefit most from extended letrozole therapy (ELT), but it was not the group researchers thought it would be.

An analysis of patients from the NSABP B-42 trial found no significant difference in the primary endpoint of 10-year distant recurrence rate between letrozole or placebo in patients categorized as MP high-risk or low-risk, reported Priya Rastogi, MD, of the University of Pittsburgh Medical Center Hillman Cancer Center and NRG Oncology/NSABP Foundation, and colleagues.

However, as they reported in an exploratory analysis in the , there was a significant benefit for 10-year distant recurrence in 908 patients classified as "low but not ultra-low" risk.

Furthermore, there was no benefit for the secondary endpoints of disease-free survival and breast cancer-free interval for patients identified as high-risk, as the researchers had hypothesized. Instead, they found significant benefits for these endpoints in low-risk patients.

"The primary hypothesis of predictive ability of MP on distant recurrence was not confirmed," the researchers concluded. "However, the secondary outcomes demonstrated MP was predictive of ELT response and identified a subset of patients with early-stage hormone receptor–positive breast cancer ... with improved outcomes from ELT. These data could have important clinical implications in patient selection beyond clinical risk assessment for extended endocrine therapy."

Rastogi elaborated on the findings and the implications in the following interview.

Why do you think your study found benefits for endpoints in low-risk and ultra-low-risk patients, but not high-risk patients as you had hypothesized?

Rastogi: For women with MP-high risk tumors, most recurrences occur in the first 5 years after diagnosis, during which they significantly benefit from endocrine therapy. These patients may have intrinsic decreased sensitivity to hormone therapy and did not benefit from extended endocrine therapy, as evidenced by the results of this study.

Although information on adjuvant chemotherapy use was not collected in the NSABP B-42 trial, it is likely that more patients with MP-high risk tumors received adjuvant chemotherapy compared with patients with MP-low risk tumors, which may explain the similar recurrence rates between the two groups in the placebo arm.

Is there anything from this study that oncologists can apply right now in clinical practice, or is it necessary to await further studies?

Rastogi: At this time scores on the MP assay should not be used to select which patients with hormone receptor-positive early-stage breast cancer should receive shorter versus longer durations of endocrine treatment. These data raise the possibility that patients whose tumors score in the low-but-not-ultralow category may have the most benefit from prolonged treatment in terms of disease-free survival and breast cancer-free interval, but this requires further validation in other independent trials.

Is there anything else you want to make sure oncologists understand about this study or the MammaPrint assay?

Rastogi: This is one of the first studies to evaluate the MammaPrint assay to predict distant recurrence with extended endocrine therapy. Hormone receptor-positive early-stage breast cancer is associated with persistent long-term risk of recurrence. It is important to improve the identification of individual patients who would derive benefit from extended endocrine therapy.

This study suggests that a significant extended endocrine therapy benefit in NSABP B-42 could be dependent on genomic classification by MammaPrint.

Read the study here.