title: Patient-reported outcomes with adjuvant exemestane versus tamoxifen in premenopausal women with early breast cancer undergoing ovarian suppression (TEXT and SOFT): a combined analysis of two phase 3 randomised trials.
abstract: BACKGROUND
  The combined efficacy analysis of the TEXT and SOFT trials showed a significant disease-free survival benefit with exemestane plus ovarian function suppression (OFS) compared with tamoxifen plus OFS. We present patient-reported outcomes from these trials.
  
  
  METHODS
  Between Nov 7, 2003, and April 7, 2011, 4717 premenopausal women with hormone-receptor positive breast cancer were enrolled in TEXT or SOFT to receive unmasked adjuvant treatment with 5 years of exemestane plus OFS or tamoxifen plus OFS. Gonadotropin-releasing hormone analogue triptorelin, bilateral oophorectomy, or bilateral ovarian irradiation were used to achieve OFS. Chemotherapy use was optional. Randomisation with permuted blocks was done with the International Breast Cancer Study Group's internet-based system and was stratified by chemotherapy use and status of lymph nodes. Patients completed a quality of life (QoL) form comprising several global and symptom indicators at baseline, every 6 months for 24 months, and then every year during years 3 to 6. Differences in the change of QoL from baseline between the two treatments were tested at 6 months, 24 months, and 60 months with mixed-models for repeated measures for each trial with and without chemotherapy and overall. The analysis was by intention to treat. At the time of analysis, the median follow-up was 5·7 years (IQR 3·7-6·9); treatment and follow-up of patients continue. The trials are registered with ClinicalTrials.gov, as NCT00066703 (TEXT) and NCT00066690 (SOFT).
  
  
  RESULTS
  Patients on tamoxifen plus OFS were more affected by hot flushes and sweats over 5 years than were those on exemestane plus OFS, although these symptoms improved. Patients on exemestane plus OFS reported more vaginal dryness, greater loss of sexual interest, and difficulties becoming aroused than did patients on tamoxifen plus OFS; these differences persisted over time. An increase in bone or joint pain was more pronounced, particularly in the short term, in patients on exemestane plus OFS than patients on tamoxifen plus OFS. Changes in global QoL indicators from baseline were small and similar between treatments over the 5 years.
  
  
  CONCLUSIONS
  Overall, from a QoL perspective, there is no strong indication to favour either exemestane plus OFS or tamoxifen plus OFS. The distinct effects of the two treatments on the burden of endocrine symptoms need to be addressed with patients individually.
  
  
  BACKGROUND
  Pfizer, International Breast Cancer Study Group, and US National Cancer Institute.
authors.affiliation: International Breast Cancer Study Group Coordinating Center and Bern University Hospital, Inselspital, Bern, Switzerland. Electronic address: juerg.bernhard@ibcsg.org.
authors.forename: Jürg
authors.initials: J
authors.lastname: Bernhard
authors.affiliation: International Breast Cancer Study Group Statistical Center, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Weixiu
authors.initials: W
authors.lastname: Luo
authors.affiliation: International Breast Cancer Study Group Coordinating Center, Bern, Switzerland.
authors.forename: Karin
authors.initials: K
authors.lastname: Ribi
authors.affiliation: Division of Medical Senology, European Institute of Oncology and International Breast Cancer Study Group, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Colleoni
authors.affiliation: Dana-Farber Cancer Institute and Alliance for Clinical Trials in Oncology, Boston, MA, USA.
authors.forename: Harold J
authors.initials: HJ
authors.lastname: Burstein
authors.affiliation: Medical Oncology, Osp Papa Giovanni XXIII and International Breast Cancer Study Group, Bergamo, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Tondini
authors.affiliation: Medical Oncology, Ospedale di Circolo and Fondazione Macchi, and International Breast Cancer Study Group, Varese, Italy.
authors.forename: Graziella
authors.initials: G
authors.lastname: Pinotti
authors.affiliation: Medical Oncology, Centro di Riferimento Oncologico, and International Breast Cancer Study Group, Aviano, Italy.
authors.forename: Simon
authors.initials: S
authors.lastname: Spazzapan
authors.affiliation: Breast Center, Kantonsspital St Gallen, Swiss Group for Clinical Cancer Research (SAKK), and International Breast Cancer Study Group, St Gallen, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruhstaller
authors.affiliation: Department of Oncology, University Hospital of Udine, University of Udine and International Breast Cancer Study Group, Udine, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Puglisi
authors.affiliation: Oncology Unit, Salvatore Maugeri Foundation, and International Breast Cancer Study Group, Pavia, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pavesi
authors.affiliation: Surgical Oncology, Breast Services, Tata Memorial Hospital, and International Breast Cancer Study Group, Mumbai, India.
authors.forename: Vani
authors.initials: V
authors.lastname: Parmar
authors.affiliation: International Breast Cancer Study Group Statistical Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: Meredith M
authors.initials: MM
authors.lastname: Regan
authors.affiliation: Institute of Oncology of Southern Switzerland, Swiss Group for Clinical Cancer Research, and International Breast Cancer Study Group, Lugano Viganello, Switzerland.
authors.forename: Olivia
authors.initials: O
authors.lastname: Pagani
authors.affiliation: University of Chicago Medical Center and Alliance for Clinical Trials in Oncology, Chicago, IL, USA.
authors.forename: Gini F
authors.initials: GF
authors.lastname: Fleming
authors.affiliation: Peter MacCallum Cancer Center, St Vincent's Hospital, University of Melbourne, Melbourne and Australia and New Zealand Breast Cancer Trials Group, Newcastle, NSW, Australia, and International Breast Cancer Study Group.
authors.forename: Prudence A
authors.initials: PA
authors.lastname: Francis
authors.affiliation: International Breast Cancer Study Group Statistical Center, Frontier Science and Technology Research Foundation, Boston, MA, USA.
authors.forename: Karen N
authors.initials: KN
authors.lastname: Price
authors.affiliation: International Breast Cancer Study Group and University of Sydney, Sydney, NSW, Australia.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Coates
authors.affiliation: International Breast Cancer Study Group Statistical Center, Dana-Farber Cancer Institute, Harvard Medical School, Harvard School of Public Health, Frontier Science and Technology Research Foundation, Boston, MA, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gelber
authors.affiliation: Program for Breast Health (Senology), European Institute of Oncology, Milan, Italy; International Breast Cancer Study Group, Bern, Switzerland.
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
authors.affiliation: Tom Baker Cancer Centre and National Cancer Institute of Canada Clinical Trials Group, Calgary, AB, Canada.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Walley
mesh_terms: D000284:Administration, Oral; D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D055088:Early Detection of Cancer; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D010053:Ovary / Q000187:drug effects*; D017697:Premenopause / Q000502:physiology; D011788:Quality of Life; D018570:Risk Assessment; D057566:Self Report; D016019:Survival Analysis; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen