title: 21-Gene Recurrence Score and Locoregional Recurrence in Node-Positive/ER-Positive Breast Cancer Treated With Chemo-Endocrine Therapy.
abstract: The 21-gene recurrence score (RS) predicts risk of locoregional recurrence (LRR) in node-negative, estrogen receptor (ER)-positive breast cancer. We evaluated the association between RS and LRR in node-positive, ER-positive patients treated with adjuvant chemotherapy plus tamoxifen in National Surgical Adjuvant Breast and Bowel Project B-28.
  
  
  
  B-28 compared doxorubicin/cyclophosphamide (AC X 4) with AC X 4 followed by paclitaxel X 4. Tamoxifen was given to patients age 50 years or older and those younger than age 50 years with ER-positive and/or progesterone receptor-positive tumors. Lumpectomy patients received breast radiotherapy. Mastectomy patients received no radiotherapy. The present study includes 1065 ER-positive, tamoxifen-treated patients with RS assessment. Cumulative incidence functions and subdistribution hazard regression models were used for LRR to account for competing risks including distant recurrence, second primary cancers, and death from other causes. Median follow-up was 11.2 years. All statistical tests were one-sided.
  
  
  
  There were 80 LRRs (7.5%) as first events (68% local/32% regional). RS was low: 36.2%; intermediate: 34.2%; and high: 29.6%. RS was a statistically significant predictor of LRR in univariate analyses (10-year cumulative incidence of LRR = 3.3%, 7.2%, and 12.2% for low, intermediate, and high RS, respectively, P < .001). In multivariable regression analysis, RS remained an independent predictor of LRR (hazard ratio [HR] = 2.59, 95% confidence interval [CI] = 1.28 to 5.26, for a 50-point difference, P = .008) along with pathologic nodal status (HR = 1.91, 95% CI = 1.20 to 3.03, for four or more vs one to three positive nodes, P = .006) and tumor size (HR = 1.28, 95% CI = 1.05 to 1.55, for a 1 cm difference, P = .02).
  
  
  
  RS statistically significantly predicts risk of LRR in node-positive, ER-positive breast cancer patients after adjuvant chemotherapy plus tamoxifen. These findings can help in the selection of appropriate candidates for comprehensive radiotherapy.
authors.affiliation: Affiliations of authors: National Surgical Adjuvant Breast and Bowel Project (NSABP Legacy trials are now a part of the NRG Oncology portfolio), Pittsburgh, PA (EPM, SP, SRK, TBJ, BCL, DLW, NW); UF Health Cancer Center at Orland Health, Orlando, FL (EPM); NRG Oncology, Pittsburgh, PA (QL, GT, JHJ, JPC); University of Pittsburgh, Pittsburgh, PA (QL, GT, JHJ, JPC); Severance Biomedical Science Institute and Department of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea (SP); Genomic Health, Inc., Redwood City, CA (FLB, SMB, FJ, DBC, APS, SS); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (TBJ, DLW, NW); University of Pittsburgh Medical Center, Pittsburgh, PA (BCL).
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Mamounas
authors.affiliation: Affiliations of authors: National Surgical Adjuvant Breast and Bowel Project (NSABP Legacy trials are now a part of the NRG Oncology portfolio), Pittsburgh, PA (EPM, SP, SRK, TBJ, BCL, DLW, NW); UF Health Cancer Center at Orland Health, Orlando, FL (EPM); NRG Oncology, Pittsburgh, PA (QL, GT, JHJ, JPC); University of Pittsburgh, Pittsburgh, PA (QL, GT, JHJ, JPC); Severance Biomedical Science Institute and Department of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea (SP); Genomic Health, Inc., Redwood City, CA (FLB, SMB, FJ, DBC, APS, SS); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (TBJ, DLW, NW); University of Pittsburgh Medical Center, Pittsburgh, PA (BCL).
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Affiliations of authors: National Surgical Adjuvant Breast and Bowel Project (NSABP Legacy trials are now a part of the NRG Oncology portfolio), Pittsburgh, PA (EPM, SP, SRK, TBJ, BCL, DLW, NW); UF Health Cancer Center at Orland Health, Orlando, FL (EPM); NRG Oncology, Pittsburgh, PA (QL, GT, JHJ, JPC); University of Pittsburgh, Pittsburgh, PA (QL, GT, JHJ, JPC); Severance Biomedical Science Institute and Department of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea (SP); Genomic Health, Inc., Redwood City, CA (FLB, SMB, FJ, DBC, APS, SS); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (TBJ, DLW, NW); University of Pittsburgh Medical Center, Pittsburgh, PA (BCL).
authors.forename: Soonmyung
authors.initials: S
authors.lastname: Paik
authors.affiliation: Affiliations of authors: National Surgical Adjuvant Breast and Bowel Project (NSABP Legacy trials are now a part of the NRG Oncology portfolio), Pittsburgh, PA (EPM, SP, SRK, TBJ, BCL, DLW, NW); UF Health Cancer Center at Orland Health, Orlando, FL (EPM); NRG Oncology, Pittsburgh, PA (QL, GT, JHJ, JPC); University of Pittsburgh, Pittsburgh, PA (QL, GT, JHJ, JPC); Severance Biomedical Science Institute and Department of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea (SP); Genomic Health, Inc., Redwood City, CA (FLB, SMB, FJ, DBC, APS, SS); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (TBJ, DLW, NW); University of Pittsburgh Medical Center, Pittsburgh, PA (BCL).
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Baehner
authors.affiliation: Affiliations of authors: National Surgical Adjuvant Breast and Bowel Project (NSABP Legacy trials are now a part of the NRG Oncology portfolio), Pittsburgh, PA (EPM, SP, SRK, TBJ, BCL, DLW, NW); UF Health Cancer Center at Orland Health, Orlando, FL (EPM); NRG Oncology, Pittsburgh, PA (QL, GT, JHJ, JPC); University of Pittsburgh, Pittsburgh, PA (QL, GT, JHJ, JPC); Severance Biomedical Science Institute and Department of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea (SP); Genomic Health, Inc., Redwood City, CA (FLB, SMB, FJ, DBC, APS, SS); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (TBJ, DLW, NW); University of Pittsburgh Medical Center, Pittsburgh, PA (BCL).
authors.forename: Gong
authors.initials: G
authors.lastname: Tang
authors.affiliation: Affiliations of authors: National Surgical Adjuvant Breast and Bowel Project (NSABP Legacy trials are now a part of the NRG Oncology portfolio), Pittsburgh, PA (EPM, SP, SRK, TBJ, BCL, DLW, NW); UF Health Cancer Center at Orland Health, Orlando, FL (EPM); NRG Oncology, Pittsburgh, PA (QL, GT, JHJ, JPC); University of Pittsburgh, Pittsburgh, PA (QL, GT, JHJ, JPC); Severance Biomedical Science Institute and Department of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea (SP); Genomic Health, Inc., Redwood City, CA (FLB, SMB, FJ, DBC, APS, SS); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (TBJ, DLW, NW); University of Pittsburgh Medical Center, Pittsburgh, PA (BCL).
authors.forename: Jong-Hyeon
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Affiliations of authors: National Surgical Adjuvant Breast and Bowel Project (NSABP Legacy trials are now a part of the NRG Oncology portfolio), Pittsburgh, PA (EPM, SP, SRK, TBJ, BCL, DLW, NW); UF Health Cancer Center at Orland Health, Orlando, FL (EPM); NRG Oncology, Pittsburgh, PA (QL, GT, JHJ, JPC); University of Pittsburgh, Pittsburgh, PA (QL, GT, JHJ, JPC); Severance Biomedical Science Institute and Department of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea (SP); Genomic Health, Inc., Redwood City, CA (FLB, SMB, FJ, DBC, APS, SS); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (TBJ, DLW, NW); University of Pittsburgh Medical Center, Pittsburgh, PA (BCL).
authors.forename: S Rim
authors.initials: SR
authors.lastname: Kim
authors.affiliation: Affiliations of authors: National Surgical Adjuvant Breast and Bowel Project (NSABP Legacy trials are now a part of the NRG Oncology portfolio), Pittsburgh, PA (EPM, SP, SRK, TBJ, BCL, DLW, NW); UF Health Cancer Center at Orland Health, Orlando, FL (EPM); NRG Oncology, Pittsburgh, PA (QL, GT, JHJ, JPC); University of Pittsburgh, Pittsburgh, PA (QL, GT, JHJ, JPC); Severance Biomedical Science Institute and Department of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea (SP); Genomic Health, Inc., Redwood City, CA (FLB, SMB, FJ, DBC, APS, SS); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (TBJ, DLW, NW); University of Pittsburgh Medical Center, Pittsburgh, PA (BCL).
authors.forename: Steven M
authors.initials: SM
authors.lastname: Butler
authors.affiliation: Affiliations of authors: National Surgical Adjuvant Breast and Bowel Project (NSABP Legacy trials are now a part of the NRG Oncology portfolio), Pittsburgh, PA (EPM, SP, SRK, TBJ, BCL, DLW, NW); UF Health Cancer Center at Orland Health, Orlando, FL (EPM); NRG Oncology, Pittsburgh, PA (QL, GT, JHJ, JPC); University of Pittsburgh, Pittsburgh, PA (QL, GT, JHJ, JPC); Severance Biomedical Science Institute and Department of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea (SP); Genomic Health, Inc., Redwood City, CA (FLB, SMB, FJ, DBC, APS, SS); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (TBJ, DLW, NW); University of Pittsburgh Medical Center, Pittsburgh, PA (BCL).
authors.forename: Farid
authors.initials: F
authors.lastname: Jamshidian
authors.affiliation: Affiliations of authors: National Surgical Adjuvant Breast and Bowel Project (NSABP Legacy trials are now a part of the NRG Oncology portfolio), Pittsburgh, PA (EPM, SP, SRK, TBJ, BCL, DLW, NW); UF Health Cancer Center at Orland Health, Orlando, FL (EPM); NRG Oncology, Pittsburgh, PA (QL, GT, JHJ, JPC); University of Pittsburgh, Pittsburgh, PA (QL, GT, JHJ, JPC); Severance Biomedical Science Institute and Department of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea (SP); Genomic Health, Inc., Redwood City, CA (FLB, SMB, FJ, DBC, APS, SS); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (TBJ, DLW, NW); University of Pittsburgh Medical Center, Pittsburgh, PA (BCL).
authors.forename: Diana B
authors.initials: DB
authors.lastname: Cherbavaz
authors.affiliation: Affiliations of authors: National Surgical Adjuvant Breast and Bowel Project (NSABP Legacy trials are now a part of the NRG Oncology portfolio), Pittsburgh, PA (EPM, SP, SRK, TBJ, BCL, DLW, NW); UF Health Cancer Center at Orland Health, Orlando, FL (EPM); NRG Oncology, Pittsburgh, PA (QL, GT, JHJ, JPC); University of Pittsburgh, Pittsburgh, PA (QL, GT, JHJ, JPC); Severance Biomedical Science Institute and Department of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea (SP); Genomic Health, Inc., Redwood City, CA (FLB, SMB, FJ, DBC, APS, SS); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (TBJ, DLW, NW); University of Pittsburgh Medical Center, Pittsburgh, PA (BCL).
authors.forename: Amy P
authors.initials: AP
authors.lastname: Sing
authors.affiliation: Affiliations of authors: National Surgical Adjuvant Breast and Bowel Project (NSABP Legacy trials are now a part of the NRG Oncology portfolio), Pittsburgh, PA (EPM, SP, SRK, TBJ, BCL, DLW, NW); UF Health Cancer Center at Orland Health, Orlando, FL (EPM); NRG Oncology, Pittsburgh, PA (QL, GT, JHJ, JPC); University of Pittsburgh, Pittsburgh, PA (QL, GT, JHJ, JPC); Severance Biomedical Science Institute and Department of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea (SP); Genomic Health, Inc., Redwood City, CA (FLB, SMB, FJ, DBC, APS, SS); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (TBJ, DLW, NW); University of Pittsburgh Medical Center, Pittsburgh, PA (BCL).
authors.forename: Steven
authors.initials: S
authors.lastname: Shak
authors.affiliation: Affiliations of authors: National Surgical Adjuvant Breast and Bowel Project (NSABP Legacy trials are now a part of the NRG Oncology portfolio), Pittsburgh, PA (EPM, SP, SRK, TBJ, BCL, DLW, NW); UF Health Cancer Center at Orland Health, Orlando, FL (EPM); NRG Oncology, Pittsburgh, PA (QL, GT, JHJ, JPC); University of Pittsburgh, Pittsburgh, PA (QL, GT, JHJ, JPC); Severance Biomedical Science Institute and Department of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea (SP); Genomic Health, Inc., Redwood City, CA (FLB, SMB, FJ, DBC, APS, SS); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (TBJ, DLW, NW); University of Pittsburgh Medical Center, Pittsburgh, PA (BCL).
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Julian
authors.affiliation: Affiliations of authors: National Surgical Adjuvant Breast and Bowel Project (NSABP Legacy trials are now a part of the NRG Oncology portfolio), Pittsburgh, PA (EPM, SP, SRK, TBJ, BCL, DLW, NW); UF Health Cancer Center at Orland Health, Orlando, FL (EPM); NRG Oncology, Pittsburgh, PA (QL, GT, JHJ, JPC); University of Pittsburgh, Pittsburgh, PA (QL, GT, JHJ, JPC); Severance Biomedical Science Institute and Department of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea (SP); Genomic Health, Inc., Redwood City, CA (FLB, SMB, FJ, DBC, APS, SS); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (TBJ, DLW, NW); University of Pittsburgh Medical Center, Pittsburgh, PA (BCL).
authors.forename: Barry C
authors.initials: BC
authors.lastname: Lembersky
authors.affiliation: Affiliations of authors: National Surgical Adjuvant Breast and Bowel Project (NSABP Legacy trials are now a part of the NRG Oncology portfolio), Pittsburgh, PA (EPM, SP, SRK, TBJ, BCL, DLW, NW); UF Health Cancer Center at Orland Health, Orlando, FL (EPM); NRG Oncology, Pittsburgh, PA (QL, GT, JHJ, JPC); University of Pittsburgh, Pittsburgh, PA (QL, GT, JHJ, JPC); Severance Biomedical Science Institute and Department of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea (SP); Genomic Health, Inc., Redwood City, CA (FLB, SMB, FJ, DBC, APS, SS); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (TBJ, DLW, NW); University of Pittsburgh Medical Center, Pittsburgh, PA (BCL).
authors.forename: D Lawrence
authors.initials: DL
authors.lastname: Wickerham
authors.affiliation: Affiliations of authors: National Surgical Adjuvant Breast and Bowel Project (NSABP Legacy trials are now a part of the NRG Oncology portfolio), Pittsburgh, PA (EPM, SP, SRK, TBJ, BCL, DLW, NW); UF Health Cancer Center at Orland Health, Orlando, FL (EPM); NRG Oncology, Pittsburgh, PA (QL, GT, JHJ, JPC); University of Pittsburgh, Pittsburgh, PA (QL, GT, JHJ, JPC); Severance Biomedical Science Institute and Department of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea (SP); Genomic Health, Inc., Redwood City, CA (FLB, SMB, FJ, DBC, APS, SS); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (TBJ, DLW, NW); University of Pittsburgh Medical Center, Pittsburgh, PA (BCL).
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Costantino
authors.affiliation: Affiliations of authors: National Surgical Adjuvant Breast and Bowel Project (NSABP Legacy trials are now a part of the NRG Oncology portfolio), Pittsburgh, PA (EPM, SP, SRK, TBJ, BCL, DLW, NW); UF Health Cancer Center at Orland Health, Orlando, FL (EPM); NRG Oncology, Pittsburgh, PA (QL, GT, JHJ, JPC); University of Pittsburgh, Pittsburgh, PA (QL, GT, JHJ, JPC); Severance Biomedical Science Institute and Department of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea (SP); Genomic Health, Inc., Redwood City, CA (FLB, SMB, FJ, DBC, APS, SS); Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (TBJ, DLW, NW); University of Pittsburgh Medical Center, Pittsburgh, PA (BCL).
authors.forename: Norman
authors.initials: N
authors.lastname: Wolmark
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D011237:Predictive Value of Tests; D018714:Radiotherapy, Adjuvant; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012189:Retrospective Studies; D012307:Risk Factors; D013629:Tamoxifen / Q000008:administration & dosage; D047368:Tumor Burden
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel