The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

The 70-gene MammaPrint (MP) assay revealed a statistically significant benefit from extended letrozole therapy in patients with low-risk, hormone receptor–positive (HR+) breast cancer, according to research presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

Priya Rastogi, MD, of NSABP/NRG Oncology and the UPMC Hillman Cancer Center in Pittsburgh, Pennsylvania, outlined the utility of the assay to identify low- and high-risk patients who are likely to benefit from the extended therapy with the aromatase inhibitor, letrozole based on findings from the randomized phase 3 NSABP B-42 trial ( Identifier: NCT00382070).

A total of 1866 patients from the trial with known MP results were classified based on the 70-gene signature: 706 patients (38%) were defined as high risk (MP-H; MP score ≤0.000), 1160 patients were low-risk (MP-L; MP score > 0.000). Low-risk patients were further subclassified: 252 patients (22%) were ultralow risk (MP-UL; MP score >0.355) and patients were low risk but not ultralow risk (MP-LNUL; MP score >0.000, ≤0.355). The MP-LNUL represented 48.7% of the total translational MP cohort.

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At baseline, the distribution of patient and tumor characteristics were similar between the different cohorts except for HER2 status. The primary endpoint was distant recurrence (DR) and the secondary endpoints were disease-free survival (DFS) and breast cancer–free interval (BCFI).

Overall, extended letrozole therapy had a more profound survival benefit in the MP cohort compared with the rest of the B-42 cohort. In the MP-L cohort, letrozole had a statistically significant benefit on DR (hazard ratio [HR], 0.43; 95% CI, 0.25-0.74, P =.002) but not in the MP-H cohort (HR, 0.65; 95% CI, 0.34-1.24, P =.19; interaction P =.38).

Extended letrozole therapy  had a statistically significant improvement in the DFS in the MP-L cohort, but not in the MP-H cohort (interaction P= .015). A similar trend of statistically significant improvement in BCFI was observed in the MP-L with extended letrozole therapy, but not in the MP-H cohort (interaction P= .006). The treatment by risk group interaction was significantly better for DFS and BCFI, but not for DR. Within the low-risk cohorts, the benefit was stronger in MP-LNUL than in MP-UL. There was statistically significant benefit with extended letrozole therapy in MP-LNUL but not in MP-UL for DR, DFS, and BCFI.

“These results have clinical implications for the utility of MP in patient selection for extended endocrine therapy,” said Dr Rastogi. She added, “Further confirmation in similar datasets of extended endocrine therapy would be important. Future analyses of the B-42 MP translational cohort incorporating clinical-pathologic characteristics, such as lymph node status, could further optimize patient selection”.

Disclosure: This research was funded by the U.S. National Institutes of Health, Novartis, and Agendia. Several study authors declared affiliations with the pharmaceutical industry. Please see the original article for a full list of authors’ affiliations.

Read more of Cancer Therapy Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.


Rastogi P, Bandos H, Lucas PC, et al. Utility of the 70-gene MammaPrint assay for prediction of benefit from extended letrozole therapy (ELT) in the NRG Oncology/NSABP B-42 trial. J Clin Oncol. 2021;39:(suppl 15; abstr 502). doi:10.1200/JCO.2021.39.15_suppl.502