title: Patient-reported outcomes with anastrozole versus tamoxifen for postmenopausal patients with ductal carcinoma in situ treated with lumpectomy plus radiotherapy (NSABP B-35): a randomised, double-blind, phase 3 clinical trial.
abstract: BACKGROUND
  The NSABP B-35 trial compared 5 years of treatment with anastrozole versus tamoxifen for reducing subsequent occurrence of breast cancer in postmenopausal patients with ductal carcinoma in situ. This report assesses the effect of these drugs on quality of life and symptoms.
  
  
  METHODS
  The study was done at 333 hospitals in North America. Postmenopausal women with hormone-positive ductal carcinoma in situ treated by lumpectomy with clear resection margins and whole breast irradiation were randomly assigned to receive either tamoxifen (20 mg/day) or anastrazole (1 mg/day) for 5 years, stratified by age (<60 years vs ≥60 years). Patients and investigators were masked to treatment allocation. Patients completed questionnaires at baseline and every 6 months thereafter for 6 years. The primary outcomes were SF-12 physical and mental health component scale scores, and vasomotor symptoms (as per the BCPT symptom scale). Secondary outcomes were vaginal symptoms and sexual functioning. Exploratory outcomes were musculoskeletal pain, bladder symptoms, gynaecological symptoms, cognitive symptoms, weight problems, vitality, and depression. We did the analyses by intention to treat, including patients who completed questionnaires at baseline and at least once during follow-up. This study is registered with ClinicalTrials.gov, NCT00053898.
  
  
  RESULTS
  Between Jan 6, 2003, and June 15, 2006, 3104 patients were enrolled in the study, of whom 1193 were included in the quality-of-life substudy: 601 assigned to tamoxifen and 592 assigned to anastrozole. We detected no significant difference between treatment groups for: physical health scores (mean severity score 46·72 for tamoxifen vs 45·85 for anastrozole; p=0·20), mental health scores (52·38 vs 51·48; p=0·38), energy and fatigue (58·34 vs 57·54; p=0·86), or symptoms of depression (6·19 vs 6·39; p=0·46) over 5 years. Vasomotor symptoms (1·33 vs 1·17; p=0·011), difficulty with bladder control (0·96 vs 0·80; p=0·0002), and gynaecological symptoms (0·29 vs 0·18; p<0·0001) were significantly more severe in the tamoxifen group than in the anastrozole group. Musculoskeletal pain (1·50 vs 1·72; p=0·0006) and vaginal symptoms (0·76 vs 0·86; p=0·035) were significantly worse in the anastrozole group than in the tamoxifen group. Sexual functioning did not differ significantly between the two treatments (43·65 vs 45·29; p=0·56). Younger age was significantly associated with more severe vasomotor symptoms (mean severity score 1·45 for age <60 years vs 0·65 for age ≥60 years; p=0·0006), vaginal symptoms (0·98 vs 0·65; p<0·0001), weight problems (1·32 vs 1·02; p<0·0001), and gynaecological symptoms (0·26 vs 0·22; p=0·014).
  
  
  CONCLUSIONS
  Given the similar efficacy of tamoxifen and anastrozole for women older than age 60 years, decisions about treatment should be informed by the risk for serious adverse health effects and the symptoms associated with each drug. For women younger than 60 years old, treatment decisions might be driven by efficacy (favouring anastrozole); however, if the side-effects of anastrozole are intolerable, then switching to tamoxifen is a good alternative.
  
  
  BACKGROUND
  US National Cancer Institute, AstraZeneca Pharmaceuticals.
authors.affiliation: NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; University of California, Los Angeles, CA, USA. Electronic address: pganz@mednet.ucla.edu.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Ganz
authors.affiliation: NRG Oncology, Pittsburgh, PA, USA; Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Reena S
authors.initials: RS
authors.lastname: Cecchini
authors.affiliation: NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Department of Surgical Oncology, Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA, USA.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Julian
authors.affiliation: NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; The Jewish General Hospital, McGill University, Montréal, QC, Canada.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Margolese
authors.affiliation: NRG Oncology, Pittsburgh, PA, USA; Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Costantino
authors.affiliation: NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Vallow
authors.affiliation: NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Southwest Oncology Group, San Antonio, TX, USA; Department of Medicine, Loyola University Chicago Stritch School of Medicine, Chicago, IL, USA.
authors.forename: Kathy S
authors.initials: KS
authors.lastname: Albain
authors.affiliation: NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Alliance for Clinical Trials in Oncology/American College of Surgeons Oncology Group, Chicago, IL, USA; Nashville Breast Center, Nashville, TN, USA.
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Whitworth
authors.affiliation: NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Southwest Oncology Group, San Antonio, TX, USA; Eastern Cooperative Oncology Group/American College of Radiology Imaging Network, Philadelphia, PA, USA; Department of Hematology/Oncology, Banner MD Anderson Cancer Center, Gilbert, AZ, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Cianfrocca
authors.affiliation: NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Department of Hematology/Oncology, Magee Womens Hospital/University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Brufsky
authors.affiliation: NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Dayton Physicians, Dayton, OH, USA.
authors.forename: Howard M
authors.initials: HM
authors.lastname: Gross
authors.affiliation: NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Missouri Valley Cancer Consortium, Omaha, NE, USA.
authors.forename: Gamini S
authors.initials: GS
authors.lastname: Soori
authors.affiliation: NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Southeast Clinical Oncology Research Consortium National Cancer Institute Community Oncology Research Program, Winston Salem, NC, USA; Department of Hematology/Oncology, Forsyth Regional Cancer Center, Winston Salem, NC, USA.
authors.forename: Judith O
authors.initials: JO
authors.lastname: Hopkins
authors.affiliation: NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Department of Medical Oncology, Kaiser Permanente, Northern California Vallejo, CA, USA.
authors.forename: Louis
authors.initials: L
authors.lastname: Fehrenbacher
authors.affiliation: NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Department of Medical Oncology Colorado Cancer Research Program, Denver, CO, USA.
authors.forename: Keren
authors.initials: K
authors.lastname: Sturtz
authors.affiliation: NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Community Clinical Oncology Program, Christiana Care Health Systems, Wilmington, DE, USA.
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Wozniak
authors.affiliation: NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Atlanta Regional Community Clinical Oncology Program, Atlanta, GA, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Seay
authors.affiliation: NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; UF Health Cancer Center at Orlando Health, Orlando, FL, USA.
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Mamounas
authors.affiliation: NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Department of Surgical Oncology, Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA, USA.
authors.forename: Norman
authors.initials: N
authors.lastname: Wolmark
mesh_terms: D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage / Q000627:therapeutic use*; D017698:Postmenopause; D011788:Quality of Life; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use*; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole