Norman Wolmark1, Eleftherios P Mamounas2, Frederick L Baehner1, Steven M Butler1, Gong Tang1, Farid Jamshidian1, Amy P Sing1, Steven Shak1, Soonmyung Paik1. 1. Norman Wolmark, Eleftherios P. Mamounas, and Soonmyung Paik, National Surgical Adjuvant Breast and Bowel Project Operations Center; Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Gong Tang, University of Pittsburgh; and Gong Tang, NRG Oncology, Pittsburgh, PA; Eleftherios P. Mamounas, UF Health Cancer Center at Orlando Health, Orlando, FL; Frederick L. Baehner, Steven M. Butler, Farid Jamshidian, Amy P. Sing, and Steven Shak, Genomic Health, Redwood City, and Frederick L. Baehner, University of California, San Francisco, San Francisco CA; and Soonmyung Paik, Yonsei University College of Medicine, Seoul, Korea. 2. Norman Wolmark, Eleftherios P. Mamounas, and Soonmyung Paik, National Surgical Adjuvant Breast and Bowel Project Operations Center; Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital; Gong Tang, University of Pittsburgh; and Gong Tang, NRG Oncology, Pittsburgh, PA; Eleftherios P. Mamounas, UF Health Cancer Center at Orlando Health, Orlando, FL; Frederick L. Baehner, Steven M. Butler, Farid Jamshidian, Amy P. Sing, and Steven Shak, Genomic Health, Redwood City, and Frederick L. Baehner, University of California, San Francisco, San Francisco CA; and Soonmyung Paik, Yonsei University College of Medicine, Seoul, Korea. terry.mamounas@orlandohealth.com.
Abstract
PURPOSE: We determined the utility of the 21-Gene Recurrence Score (RS) in predicting late (> 5 years) distant recurrence (LDR) in stage I and II breast cancer within high and low-ESR1-expressing groups. PATIENTS AND METHODS: RS was assessed in chemotherapy/tamoxifen-treated, estrogen receptor (ER) -positive, node-positive National Surgical Adjuvant Breast and Bowel Project B-28 patients and tamoxifen-treated, ER-positive, node-negative B-14 patients. The association of the RS with risk of distant recurrence (DR) 0 to 5 years and those at risk > 5 years was assessed. An ESR1 expression cut point was optimized in B-28 and tested in B-14. RESULTS: Median follow-up was 11.2 years for B-28 and 13.9 years for B-14. Of 1,065 B-28 patients, 36% had low (< 18), 34% intermediate (18 to 30), and 30% high (≥ 31) RS. Of 668 B-14 patients, 51% had low, 22% intermediate, and 27% high RS. Median ESR1 expression by reverse transcriptase polymerase chain reaction was: B-28, 9.7 normalized expression cycle threshold units (CT) and B-14, 10.7 CT. In B-28, RS was associated with DR 0 to 5 years (log-rank P < .001) and > 5 to 10 years (log-rank P = .02) regardless of ESR1 expression. An ESR1 expression cut point of 9.1 CT was identified in B-28. It was validated in B-14 patients for whom the RS was associated with DR in years 5 to 15: 6.8% (95% CI, 4.4% to 10.6%) versus 11.2% (95% CI, 6.2% to 19.9%) versus 16.4% (95% CI, 10.2% to 25.7%) for RS < 18, RS 18 to 30, and RS ≥ 31, respectively (log-rank P = .01). CONCLUSION: For LDR, RS is strongly prognostic in patients with higher quantitative ESR1. Risk of LDR is relatively low for patients with low RS. These results suggest the value of extended tamoxifen therapy merits evaluation in patients with intermediate and high RS with higher ESR1 expression at initial diagnosis.
PURPOSE: We determined the utility of the 21-Gene Recurrence Score (RS) in predicting late (> 5 years) distant recurrence (LDR) in stage I and II breast cancer within high and low-ESR1-expressing groups. PATIENTS AND METHODS: RS was assessed in chemotherapy/tamoxifen-treated, estrogen receptor (ER) -positive, node-positive National Surgical Adjuvant Breast and Bowel Project B-28patients and tamoxifen-treated, ER-positive, node-negative B-14patients. The association of the RS with risk of distant recurrence (DR) 0 to 5 years and those at risk > 5 years was assessed. An ESR1 expression cut point was optimized in B-28 and tested in B-14. RESULTS: Median follow-up was 11.2 years for B-28 and 13.9 years for B-14. Of 1,065 B-28patients, 36% had low (< 18), 34% intermediate (18 to 30), and 30% high (≥ 31) RS. Of 668 B-14patients, 51% had low, 22% intermediate, and 27% high RS. Median ESR1 expression by reverse transcriptase polymerase chain reaction was: B-28, 9.7 normalized expression cycle threshold units (CT) and B-14, 10.7 CT. In B-28, RS was associated with DR 0 to 5 years (log-rank P < .001) and > 5 to 10 years (log-rank P = .02) regardless of ESR1 expression. An ESR1 expression cut point of 9.1 CT was identified in B-28. It was validated in B-14patients for whom the RS was associated with DR in years 5 to 15: 6.8% (95% CI, 4.4% to 10.6%) versus 11.2% (95% CI, 6.2% to 19.9%) versus 16.4% (95% CI, 10.2% to 25.7%) for RS < 18, RS 18 to 30, and RS ≥ 31, respectively (log-rank P = .01). CONCLUSION: For LDR, RS is strongly prognostic in patients with higher quantitative ESR1. Risk of LDR is relatively low for patients with low RS. These results suggest the value of extended tamoxifen therapy merits evaluation in patients with intermediate and high RS with higher ESR1 expression at initial diagnosis.
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