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

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Date

2021-12-16

Authors

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 K L

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Massachusetts Medical Society
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Abstract

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.).

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Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
Breast Neoplasms
Chemotherapy, Adjuvant
Female
Gene Expression Profiling
Humans
Middle Aged
Neoplasm Recurrence, Local
Premenopause
Prospective Studies
Receptors, Steroid

DeCS Terms

Recurrencia
Quimioterapia
Terapéutica
Supervivencia sin enfermedad
Neoplasias de la mama
Quimioterapia adyuvante
Ganglios linfáticos
Neoplasias
Pronóstico
Genes

CIE Terms

Keywords

Antineoplastic Agents, Hormonal, Disease-Free Survival, Lymphatic Metastasis, Premenopause, Receptor, ErbB-2, Reverse Transcriptase Polymerase Chain Reaction

Citation

Kalinsky K, Barlow WE, Gralow JR, Meric-Bernstam F, Albain KS, Hayes DF, et al. 21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer. N Engl J Med. 2021 Dec 16;385(25):2336-2347