title: Phase III comparison of tamoxifen versus tamoxifen plus ovarian function suppression in premenopausal women with node-negative, hormone receptor-positive breast cancer (E-3193, INT-0142): a trial of the Eastern Cooperative Oncology Group.
abstract: OBJECTIVE
  The effects of ovarian function suppression (OFS) on survival and patient-reported outcomes were evaluated in a phase III trial in which premenopausal women were randomly assigned to tamoxifen with or without OFS.
  
  
  METHODS
  Premenopausal women with axillary node-negative, hormone receptor-positive breast cancer tumors measuring ≤ 3 cm were randomly assigned to tamoxifen alone versus tamoxifen plus OFS; adjuvant chemotherapy was not permitted. Primary end points were disease-free survival (DFS) and overall survival (OS). Secondary end points included toxicity and patient-reported outcomes. Patient-reported outcome data included health-related quality of life, menopausal symptoms, and sexual function. These were evaluated at baseline, 6 months, 12 months, and then annually for up to 5 years after registration.
  
  
  RESULTS
  In all, 345 premenopausal women were enrolled: 171 on tamoxifen alone and 174 on tamoxifen plus OFS. With a median follow-up of 9.9 years, there was no significant difference between arms for DFS (5-year rate: 87.9% v 89.7%; log-rank P = .62) or OS (5-year rate: 95.2% v 97.6%; log-rank P = .67). Grade 3 or higher toxicity was more common in the tamoxifen plus OFS arm (22.4% v 12.3%; P = .004). Patients treated with tamoxifen plus OFS had more menopausal symptoms, lower sexual activity, and inferior health-related quality of life at 3-year follow-up (P < .01 for all). Differences diminished with further follow-up.
  
  
  CONCLUSIONS
  When added to tamoxifen, OFS results in more menopausal symptoms and sexual dysfunction, which contributes to inferior self-reported health-related quality of life. Because of early closure, this study is underpowered for drawing conclusions about the impact on survival when adding OFS to tamoxifen.
authors.affiliation: Amye J. Tevaarwerk, University of Wisconsin, Madison, WI; Molin Wang, Harvard University; Fengmin Zhao, Dana-Farber Cancer Institute, Boston, MA; John H. Fetting, Johns Hopkins University, Baltimore, MD; David Cella and Lynne I. Wagner, Northwestern University, Chicago, IL; Silvana Martino, Angeles Clinic and Research Institute, Santa Monica, CA; James N. Ingle, Mayo Clinic, Rochester, MN; Joseph A. Sparano, Montefiore Medical Center, Bronx, NY; Lawrence J. Solin, Albert Einstein Medical Center, Philadelphia, PA; William C. Wood, Emory University, Atlanta, GA; and Nicholas J. Robert, Virginia Cancer Specialists, Fairfax, VA. at4@medicine.wisc.edu.
authors.forename: Amye J
authors.initials: AJ
authors.lastname: Tevaarwerk
authors.affiliation: Amye J. Tevaarwerk, University of Wisconsin, Madison, WI; Molin Wang, Harvard University; Fengmin Zhao, Dana-Farber Cancer Institute, Boston, MA; John H. Fetting, Johns Hopkins University, Baltimore, MD; David Cella and Lynne I. Wagner, Northwestern University, Chicago, IL; Silvana Martino, Angeles Clinic and Research Institute, Santa Monica, CA; James N. Ingle, Mayo Clinic, Rochester, MN; Joseph A. Sparano, Montefiore Medical Center, Bronx, NY; Lawrence J. Solin, Albert Einstein Medical Center, Philadelphia, PA; William C. Wood, Emory University, Atlanta, GA; and Nicholas J. Robert, Virginia Cancer Specialists, Fairfax, VA.
authors.forename: Molin
authors.initials: M
authors.lastname: Wang
authors.affiliation: Amye J. Tevaarwerk, University of Wisconsin, Madison, WI; Molin Wang, Harvard University; Fengmin Zhao, Dana-Farber Cancer Institute, Boston, MA; John H. Fetting, Johns Hopkins University, Baltimore, MD; David Cella and Lynne I. Wagner, Northwestern University, Chicago, IL; Silvana Martino, Angeles Clinic and Research Institute, Santa Monica, CA; James N. Ingle, Mayo Clinic, Rochester, MN; Joseph A. Sparano, Montefiore Medical Center, Bronx, NY; Lawrence J. Solin, Albert Einstein Medical Center, Philadelphia, PA; William C. Wood, Emory University, Atlanta, GA; and Nicholas J. Robert, Virginia Cancer Specialists, Fairfax, VA.
authors.forename: Fengmin
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Amye J. Tevaarwerk, University of Wisconsin, Madison, WI; Molin Wang, Harvard University; Fengmin Zhao, Dana-Farber Cancer Institute, Boston, MA; John H. Fetting, Johns Hopkins University, Baltimore, MD; David Cella and Lynne I. Wagner, Northwestern University, Chicago, IL; Silvana Martino, Angeles Clinic and Research Institute, Santa Monica, CA; James N. Ingle, Mayo Clinic, Rochester, MN; Joseph A. Sparano, Montefiore Medical Center, Bronx, NY; Lawrence J. Solin, Albert Einstein Medical Center, Philadelphia, PA; William C. Wood, Emory University, Atlanta, GA; and Nicholas J. Robert, Virginia Cancer Specialists, Fairfax, VA.
authors.forename: John H
authors.initials: JH
authors.lastname: Fetting
authors.affiliation: Amye J. Tevaarwerk, University of Wisconsin, Madison, WI; Molin Wang, Harvard University; Fengmin Zhao, Dana-Farber Cancer Institute, Boston, MA; John H. Fetting, Johns Hopkins University, Baltimore, MD; David Cella and Lynne I. Wagner, Northwestern University, Chicago, IL; Silvana Martino, Angeles Clinic and Research Institute, Santa Monica, CA; James N. Ingle, Mayo Clinic, Rochester, MN; Joseph A. Sparano, Montefiore Medical Center, Bronx, NY; Lawrence J. Solin, Albert Einstein Medical Center, Philadelphia, PA; William C. Wood, Emory University, Atlanta, GA; and Nicholas J. Robert, Virginia Cancer Specialists, Fairfax, VA.
authors.forename: David
authors.initials: D
authors.lastname: Cella
authors.affiliation: Amye J. Tevaarwerk, University of Wisconsin, Madison, WI; Molin Wang, Harvard University; Fengmin Zhao, Dana-Farber Cancer Institute, Boston, MA; John H. Fetting, Johns Hopkins University, Baltimore, MD; David Cella and Lynne I. Wagner, Northwestern University, Chicago, IL; Silvana Martino, Angeles Clinic and Research Institute, Santa Monica, CA; James N. Ingle, Mayo Clinic, Rochester, MN; Joseph A. Sparano, Montefiore Medical Center, Bronx, NY; Lawrence J. Solin, Albert Einstein Medical Center, Philadelphia, PA; William C. Wood, Emory University, Atlanta, GA; and Nicholas J. Robert, Virginia Cancer Specialists, Fairfax, VA.
authors.forename: Lynne I
authors.initials: LI
authors.lastname: Wagner
authors.affiliation: Amye J. Tevaarwerk, University of Wisconsin, Madison, WI; Molin Wang, Harvard University; Fengmin Zhao, Dana-Farber Cancer Institute, Boston, MA; John H. Fetting, Johns Hopkins University, Baltimore, MD; David Cella and Lynne I. Wagner, Northwestern University, Chicago, IL; Silvana Martino, Angeles Clinic and Research Institute, Santa Monica, CA; James N. Ingle, Mayo Clinic, Rochester, MN; Joseph A. Sparano, Montefiore Medical Center, Bronx, NY; Lawrence J. Solin, Albert Einstein Medical Center, Philadelphia, PA; William C. Wood, Emory University, Atlanta, GA; and Nicholas J. Robert, Virginia Cancer Specialists, Fairfax, VA.
authors.forename: Silvana
authors.initials: S
authors.lastname: Martino
authors.affiliation: Amye J. Tevaarwerk, University of Wisconsin, Madison, WI; Molin Wang, Harvard University; Fengmin Zhao, Dana-Farber Cancer Institute, Boston, MA; John H. Fetting, Johns Hopkins University, Baltimore, MD; David Cella and Lynne I. Wagner, Northwestern University, Chicago, IL; Silvana Martino, Angeles Clinic and Research Institute, Santa Monica, CA; James N. Ingle, Mayo Clinic, Rochester, MN; Joseph A. Sparano, Montefiore Medical Center, Bronx, NY; Lawrence J. Solin, Albert Einstein Medical Center, Philadelphia, PA; William C. Wood, Emory University, Atlanta, GA; and Nicholas J. Robert, Virginia Cancer Specialists, Fairfax, VA.
authors.forename: James N
authors.initials: JN
authors.lastname: Ingle
authors.affiliation: Amye J. Tevaarwerk, University of Wisconsin, Madison, WI; Molin Wang, Harvard University; Fengmin Zhao, Dana-Farber Cancer Institute, Boston, MA; John H. Fetting, Johns Hopkins University, Baltimore, MD; David Cella and Lynne I. Wagner, Northwestern University, Chicago, IL; Silvana Martino, Angeles Clinic and Research Institute, Santa Monica, CA; James N. Ingle, Mayo Clinic, Rochester, MN; Joseph A. Sparano, Montefiore Medical Center, Bronx, NY; Lawrence J. Solin, Albert Einstein Medical Center, Philadelphia, PA; William C. Wood, Emory University, Atlanta, GA; and Nicholas J. Robert, Virginia Cancer Specialists, Fairfax, VA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Sparano
authors.affiliation: Amye J. Tevaarwerk, University of Wisconsin, Madison, WI; Molin Wang, Harvard University; Fengmin Zhao, Dana-Farber Cancer Institute, Boston, MA; John H. Fetting, Johns Hopkins University, Baltimore, MD; David Cella and Lynne I. Wagner, Northwestern University, Chicago, IL; Silvana Martino, Angeles Clinic and Research Institute, Santa Monica, CA; James N. Ingle, Mayo Clinic, Rochester, MN; Joseph A. Sparano, Montefiore Medical Center, Bronx, NY; Lawrence J. Solin, Albert Einstein Medical Center, Philadelphia, PA; William C. Wood, Emory University, Atlanta, GA; and Nicholas J. Robert, Virginia Cancer Specialists, Fairfax, VA.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Solin
authors.affiliation: Amye J. Tevaarwerk, University of Wisconsin, Madison, WI; Molin Wang, Harvard University; Fengmin Zhao, Dana-Farber Cancer Institute, Boston, MA; John H. Fetting, Johns Hopkins University, Baltimore, MD; David Cella and Lynne I. Wagner, Northwestern University, Chicago, IL; Silvana Martino, Angeles Clinic and Research Institute, Santa Monica, CA; James N. Ingle, Mayo Clinic, Rochester, MN; Joseph A. Sparano, Montefiore Medical Center, Bronx, NY; Lawrence J. Solin, Albert Einstein Medical Center, Philadelphia, PA; William C. Wood, Emory University, Atlanta, GA; and Nicholas J. Robert, Virginia Cancer Specialists, Fairfax, VA.
authors.forename: William C
authors.initials: WC
authors.lastname: Wood
authors.affiliation: Amye J. Tevaarwerk, University of Wisconsin, Madison, WI; Molin Wang, Harvard University; Fengmin Zhao, Dana-Farber Cancer Institute, Boston, MA; John H. Fetting, Johns Hopkins University, Baltimore, MD; David Cella and Lynne I. Wagner, Northwestern University, Chicago, IL; Silvana Martino, Angeles Clinic and Research Institute, Santa Monica, CA; James N. Ingle, Mayo Clinic, Rochester, MN; Joseph A. Sparano, Montefiore Medical Center, Bronx, NY; Lawrence J. Solin, Albert Einstein Medical Center, Philadelphia, PA; William C. Wood, Emory University, Atlanta, GA; and Nicholas J. Robert, Virginia Cancer Specialists, Fairfax, VA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Robert
mesh_terms: D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008875:Middle Aged; D010053:Ovary / Q000187:drug effects*; D017697:Premenopause; D011788:Quality of Life; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013629:Tamoxifen / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen