Development and Validation of a Tool Integrating the 21-Gene Recurrence Score and Clinical-Pathological Features to Individualize Prognosis and Prediction of Chemotherapy Benefit in Early Breast Cancer

Abstract

PURPOSE The 21-gene recurrence score (RS) is prognostic for distant recurrence (DR) and predictive for chemotherapy benefit in early breast cancer, whereas clinical-pathological factors are only prognostic. Integration of genomic and clinical features offers the potential to guide adjuvant chemotherapy use with greater precision. METHODS We developed a new tool (RSClin) that integrates RS with tumor grade, tumor size, and age using a patient-specific meta-analysis including 10,004 women with hormone receptor–positive, human epidermal growth factor receptor 2–negative, and node-negative breast cancer who received endocrine therapy alone in the B-14 (n = 577) and TAILORx (n = 4,854) trials or plus chemotherapy in TAILORx (n = 4,573). Cox models for RSClin were compared with RS alone and clinical-pathological features alone using likelihood ratio tests. RSClin estimates of DR used a baseline risk with TAILORx event rates to reflect current medical practice. A patient-specific estimator of absolute chemotherapy benefit was computed using individualized relative chemotherapy effect from the randomized TAILORx and B-20 trials. External validation of risk estimation was performed by comparing RSClin estimated risk and observed risk in 1,098 women in the Clalit registry. RESULTS RSClin provides more prognostic information (likelihood ratio χ2) for DR than RS or clinical-pathological factors alone (both P < .001, likelihood ratio test). In external validation, the RSClin risk estimate was prognostic for DR risk in the Clalit registry ( P < .001) and the estimated risk closely approximated the observed 10-year risk (Lin concordance 0.962). The absolute chemotherapy benefit estimate ranges from 0% to 15% as the RS ranges from 11 to 50 using RSClin in a 55-year-old woman with a 1.5-cm intermediate-grade tumor. CONCLUSION The RSClin tool integrates clinical-pathological and genomic risk to guide adjuvant chemotherapy in node-negative breast cancer and provides more individualized information than clinical-pathological or genomic data alone.

A 95-gene signature stratifies recurrence risk of invasive disease in ER-positive, HER2-negative, node-negative breast cancer with intermediate 21-gene signature recurrence scores

“…The 95-gene signature classi cation was not signi cant among patients aged ≤ 50 years, which may be attributable to the small sample size of that population. Recently, Sparano et al showed that a new tool (RSCline), which integrates the 21-gene recurrence score and the clinicopathological features of histologic tumor grade, tumor size, and patient age at surgery, could provide more individualized estimation of survival bene t from adding adjuvant chemotherapy to endocrine therapy [14].…”

“…Time to recurrence (TTR) analysis TTR curve for patients with tumors classi ed as 95GC-L and as 95GC-H for populations with "intermediate" 21-gene signature assay RS (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25).…”

A 95-gene Signature Stratifies Recurrence Risk of Invasive Disease in ER-positive, HER2-negative, Node-negative Breast Cancer With Intermediate 21-gene Signature Recurrence Scores

“…Time to recurrence (TTR) analysis TTR curve for patients with tumors classi ed as 95GC-L and as 95GC-H for populations with "intermediate" 21-gene signature assay RS (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25).…”

Impact of Different Modules of 21-Gene Assay in Early Breast Cancer Patients

“…Correspondingly, the RS score was found to show different values of predicting the bene t of adding chemotherapy in subsets of different ages. The Trial Assigning Individualized Options for Treatment (TAILORx) categorized RS ranges as low-(< 11), intermediate- (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) or high-(> 25) risk subgroups and discovered that for the majority of population with RS < 25, endocrine therapy alone was noninferior to combined chemo-endocrine therapy. Of note, the interaction between age and RS was obvious.…”