title: Prognostic Impact of the Combination of Recurrence Score and Quantitative Estrogen Receptor Expression (ESR1) on Predicting Late Distant Recurrence Risk in Estrogen Receptor-Positive Breast Cancer After 5 Years of Tamoxifen: Results From NRG Oncology/National Surgical Adjuvant Breast and Bowel Project B-28 and B-14.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Norman
authors.initials: N
authors.lastname: Wolmark
authors.affiliation: 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.
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Mamounas
authors.affiliation: 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.
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Baehner
authors.affiliation: 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.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Butler
authors.affiliation: 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.
authors.forename: Gong
authors.initials: G
authors.lastname: Tang
authors.affiliation: 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.
authors.forename: Farid
authors.initials: F
authors.lastname: Jamshidian
authors.affiliation: 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.
authors.forename: Amy P
authors.initials: AP
authors.lastname: Sing
authors.affiliation: 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.
authors.forename: Steven
authors.initials: S
authors.lastname: Shak
authors.affiliation: 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.
authors.forename: Soonmyung
authors.initials: S
authors.lastname: Paik
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000032:analysis*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000209:etiology*; D011379:Prognosis; D012306:Risk; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D013629:Tamoxifen