Role of 21- gene recurrence score in patients age ≥70 with T1N0 ER/PR+ HER2- breast cancer treated with breast-conserving surgery and endocrine therapy.
Authors: Chevli Neil Chandrabhan , Haque Waqar , Tran Kevin Thomas , Farach Andrew M. , Schwartz Mary R. , Geyer Charles E. , Hatch Sandra S. , Butler E. Brian , Teh Bin S. 
Published: June 2021

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Background: Based on the results of the CALGB 9343 trial, patients age ≥70 with T1N0 ER/PR+ HER2- breast cancer who are treated with breast conserving surgery (BCS) and endocrine therapy (ET) are candidates for omission of radiotherapy (RT). This trial predated the 21- gene RT-PCR recurrence score (RS) test, which is an assay now available for patients with hormone receptor positive, HER2 negative, node negative breast cancer to determine who will benefit from chemotherapy. Whether the RS can predict for patients most likely to benefit from radiation therapy (RT) following BCS has not been previously examined. The purpose of this study was to use a large database of patients age ≥70 with T1N0 ER/PR+ HER2- disease to determine if RS could predict who would benefit from RT following BCS. Methods: The National Cancer Database (NCDB) was queried (2004-2017) for female patients age ≥70 with pT1N0 ER+ PR+ HER2- breast cancer treated with BCS and ET and who had an available RS. Patients were stratified based on their RS (low risk [LR] = 1-10, intermediate risk [IR] = 11-25, high risk [HR] = 26-99). For survival analysis, propensity score matching (PSM) was conducted overall and for each group to create 1:1 matched cohorts of patients who received radiotherapy and patients who did not. Kaplan-Meier analysis with log-rank testing was used to evaluate overall survival (OS). Univariable (UVA) and multivariable (MVA) analysis were conducted using Cox proportional hazard models to determine which clinical and treatment factors were prognostic for OS. Results: A total of 13,614 patients met the selection criteria: 3,840 in the LR cohort, 8,383 in the IR cohort, and 1,391 in the HR cohort. A total of 79% received RT: 77% in the LR cohort, 79% in the IR cohort, and 85% in the HR cohort. Because PSM could not be efficiently performed in the HR cohort alone, the IR and HR cohort were merged (IRHR) for matching. After PSM, overall the 5-year OS was 90% for those who received RT and 88% for those who did not (p = 0.03). The 5-year OS in the LR cohort was 89% for those who received RT and 89% for those who did not (p = 0.517). In the IRHR cohort, the 5-year OS was 93% for those who received RT and 88% for those who did not (p = 0.004). On MVA in the overall cohort, RT (p = 0.037) was predictive of improved OS while increasing age (p < 0.001) and CDCC comorbidity score (p < 0.001) were predictive of worse OS. On MVA in the LR cohort, RT (p = 0.602) was not predictive of improved OS. However, on MVA in the IRHR cohort, RT (p = 0.004) was a positive prognostic factor for OS. Conclusions: This is the first study investigating the role of RS in this subset of patients eligible for omission of radiotherapy. There is an OS benefit with the use of RT in patients with IRHR RS, but not in patients with LR RS. Pending prospective evaluation, assessment of RS in this older subset of patients is recommended with consideration of RT when RS is ≥11.