21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer Academic Article uri icon

  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All


  • 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.


    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.


    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.


    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.).


  • Kalinsky, Kevin
  • Barlow, William E
  • Gralow, Julie R
  • Meric-Bernstam, Funda
  • Albain, Kathy S
  • Hayes, Daniel F
  • Lin, Nancy U
  • Perez, Edith A
  • Goldstein, Lori J
  • Chia, Stephen KL
  • Dhesy-Thind, Sukhbinder
  • Rastogi, Priya
  • Alba, Emilio
  • Delaloge, Suzette
  • Martin, Miguel
  • Kelly, Catherine M
  • Ruiz-Borrego, Manuel
  • Gil-Gil, Miguel
  • Arce-Salinas, Claudia H
  • Brain, Etienne GC
  • Lee, Eun-Sook
  • Pierga, Jean-Yves
  • Bermejo, Begoña
  • Ramos-Vazquez, Manuel
  • Jung, Kyung-Hae
  • Ferrero, Jean-Marc
  • Schott, Anne F
  • Shak, Steven
  • Sharma, Priyanka
  • Lew, Danika L
  • Miao, Jieling
  • Tripathy, Debasish
  • Pusztai, Lajos
  • Hortobagyi, Gabriel N

publication date

  • December 16, 2021

has subject area