TY - JOUR
T1 - 21-gene assay to inform chemotherapy benefit in node-positive breast cancer
AU - Kalinsky, Kevin
AU - Barlow, William E.
AU - Gralow, Julie R.
AU - Meric-Bernstam, Funda
AU - Albain, Kathy S.
AU - Hayes, Daniel F.
AU - Lin, Nancy U.
AU - Perez, Edith A.
AU - Goldstein, Lori J.
AU - Chia, Stephen K.L.
AU - Dhesy-Thind, Sukhbinder
AU - Rastogi, Priya
AU - Alba, Emilio
AU - Delaloge, Suzette
AU - Martin, Miguel
AU - Kelly, Catherine M.
AU - Ruiz-Borrego, Manuel
AU - Gil-Gil, Miguel
AU - Arce-Salinas, Claudia H.
AU - Brain, Etienne G.C.
AU - Lee, Eun Sook
AU - Pierga, Jean Yves
AU - Bermejo, Begoña
AU - Ramos-Vazquez, Manuel
AU - Jung, Kyung Hae
AU - Ferrero, Jean Marc
AU - Schott, Anne F.
AU - Shak, Steven
AU - Sharma, Priyanka
AU - Lew, Danika L.
AU - Miao, Jieling
AU - Tripathy, Debasish
AU - Pusztai, Lajos
AU - Hortobagyi, Gabriel N.
N1 - Funding Information:
RxPONDER was sponsored by the National Cancer Institute (NCI) Cancer Therapy Evaluation Program and coordinated by SWOG, with participation from the UNICANCER Breast Group, the Grupo Español de Investigación en Cáncer de Mama, and other federally funded groups, including the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network Cancer Research Group, the Alliance for Clinical Trials in Oncology, NRG Oncology, and the Canadian Cancer Trials Group. The trial was conducted at 632 sites in nine countries.
Funding Information:
Funded by the National Cancer Institute and others; RxPONDER ClinicalTrials.gov number, NCT01272037.
Funding Information:
Supported by grants from the National Cancer Institute (U10CA180888, U10CA180819, U10CA180820, U10CA180821, U10CA180868, U10CA180863, UG1CA2333247, UG1CA233329, UG1CA233160, UG1CA233180, UG1CA239767, UG1CA233337, P30CA015704, and P30CA006927) and by the Susan G. Komen for the Cure Research Program, the Hope Foundation for Cancer Research, the Breast Cancer Research Foundation, and Genomic Health.
Publisher Copyright:
© 2021 Massachusetts Medical Society.
PY - 2021/12/16
Y1 - 2021/12/16
N2 - 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.
AB - 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.
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U2 - 10.1056/NEJMoa2108873
DO - 10.1056/NEJMoa2108873
M3 - Article
C2 - 34914339
AN - SCOPUS:85121901181
SN - 0028-4793
VL - 385
SP - 2336
EP - 2347
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 25
ER -