# 21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer

Source: https://onco.cc/key-papers/paper-rxponder-n-engl-j-med-2021/  
OnCo record `paper-rxponder-n-engl-j-med-2021` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Published report from the RxPONDER trial registered as NCT01272037, in New England Journal of Medicine (2021), chosen as the most cited paper whose own text cites the registry id.

## Summary

Background: The recurrence score based on the 21-gene breast-cancer assay has been clinically useful in predicting a chemotherapy benefit in hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary lymph-node-negative breast cancer. In women with positive lymph-node disease, the role of the recurrence score with respect to predicting a benefit of adjuvant chemotherapy is unclear.

Methods: In a prospective trial, we randomly assigned women with hormone-receptor-positive, HER2-negative breast cancer, one to three positive axillary lymph nodes, and a recurrence score of 25 or lower (scores range from 0 to 100, with higher scores indicating a worse prognosis) to endocrine therapy only or to chemotherapy plus endocrine (chemoendocrine) therapy. The primary objective was to determine the effect of chemotherapy on invasive disease-free survival and whether the effect was influenced by the recurrence score. Secondary end points included distant relapse-free survival.

Results: A total of 5083 women (33.2% premenopausal and 66.8% postmenopausal) underwent randomization, and 5018 participated in the trial. At the prespecified third interim analysis, the chemotherapy benefit with respect to increasing invasive disease-free survival differed according to menopausal status (P = 0.008 for the comparison of chemotherapy benefit in premenopausal and postmenopausal participants), and separate prespecified analyses were conducted. Among postmenopausal women, invasive disease-free survival at 5 years was 91.9% in the endocrine-only group and 91.3% in the chemoendocrine group, with no chemotherapy benefit (hazard ratio for invasive disease recurrence, new primary cancer [breast cancer or another type], or death, 1.02; 95% confidence interval [CI], 0.82 to 1.26; P = 0.89). Among premenopausal women, invasive disease-free survival at 5 years was 89.0% with endocrine-only therapy and 93.9% with chemoendocrine therapy (hazard ratio, 0.60; 95% CI, 0.43 to 0.83; P = 0.002), with a similar increase in distant relapse-free survival (hazard ratio, 0.58; 95% CI, 0.39 to 0.87; P = 0.009). The relative chemotherapy benefit did not increase as the recurrence score increased.

Conclusions: Among premenopausal women with one to three positive lymph nodes and a recurrence score of 25 or lower, those who received chemoendocrine therapy had longer invasive disease-free survival and distant relapse-free survival than those who received endocrine-only therapy, whereas postmenopausal women with similar characteristics did not benefit from adjuvant chemotherapy. (Funded by the National Cancer Institute and others; RxPONDER ClinicalTrials.gov number, NCT01272037.).

Indexed on Europe PMC as PubMed record 34914339 (DOI 10.1056/nejmoa2108873). Its abstract cites the registry id NCT01272037, which is how it was matched to this trial; no figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: New England Journal of Medicine
- Year: 2021
- DOI: 10.1056/nejmoa2108873
- Authors: Kalinsky K, Barlow WE, Gralow JR, et al.
- What it means: This is the paper Europe PMC returns for registry id NCT01272037 with the most citations, so it is the natural first reading for anyone following the RxPONDER trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Caveats: Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.

## Sources

- N Engl J Med 2021: https://doi.org/10.1056/nejmoa2108873
- PubMed: https://pubmed.ncbi.nlm.nih.gov/34914339/
- Europe PMC: https://europepmc.org/article/MED/34914339
- ClinicalTrials.gov NCT01272037: https://clinicaltrials.gov/study/NCT01272037

## Connected records

- trials: [RxPONDER (SWOG S1007)](https://onco.cc/trials/rxponder/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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