title: Relationship between specific adverse events and efficacy of exemestane therapy in early postmenopausal breast cancer patients.
abstract: BACKGROUND
  Many adverse events (AEs) associated with aromatase inhibitors (AIs) involve symptoms related to the depletion of circulating estrogens, and may be related to efficacy. We assessed the relationship between specific AEs [hot flashes (HF) and musculoskeletal AEs (MSAE)] and survival outcomes in Dutch and Belgian patients treated with exemestane (EXE) in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. Additionally, the relationship between hormone receptor expression and AEs was assessed.
  
  
  METHODS
  Efficacy end points were relapse-free survival (RFS), overall survival (OS) and breast cancer-specific mortality (BCSM), starting at 6 months after starting EXE treatment. AEs reported in the first 6 months of treatment were included. Specific AEs comprised HF and/or MSAE. Landmark analyses and Cox proportional hazards models assessed survival differences up to 5 years.
  
  
  RESULTS
  A total of 1485 EXE patients were included. Patients with HF had a better RFS than patients without HF [multivariate hazard ratio (HR) 0.393, 95% confidence interval (CI) 0.19-0.813; P = 0.012]. The occurrence of MSAE versus no MSAE did not relate to better RFS (multivariate HR 0.677, 95% CI 0.392-1.169; P = 0.162). Trends were maintained for OS and BCSM. Quantitative hormone receptor expression was not associated with specific AEs.
  
  
  CONCLUSIONS
  Some AEs associated with estrogen depletion are related to better outcomes and may be valuable biomarkers in AI treatment.
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden.
authors.forename: D B Y
authors.initials: DBY
authors.lastname: Fontein
authors.affiliation: Department of Medical Oncology, Leiden University Medical Center, Leiden.
authors.forename: D
authors.initials: D
authors.lastname: Houtsma
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden.
authors.forename: E T M
authors.initials: ETM
authors.lastname: Hille
authors.affiliation: Department of Medical Oncology, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam.
authors.forename: C
authors.initials: C
authors.lastname: Seynaeve
authors.affiliation: Department of Medical Statistics, Leiden University Medical Center, Leiden.
authors.forename: H
authors.initials: H
authors.lastname: Putter
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden.
authors.forename: E
authors.initials: E
authors.lastname: Meershoek-Klein Kranenbarg
authors.affiliation: Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: Guchelaar
authors.affiliation: Department of Medical Oncology, Leiden University Medical Center, Leiden.
authors.forename: H
authors.initials: H
authors.lastname: Gelderblom
authors.affiliation: St Augustinus Hospital, Wilrijk.
authors.forename: L Y
authors.initials: LY
authors.lastname: Dirix
authors.affiliation: UZ Gasthuisberg, Leuven, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Paridaens
authors.affiliation: Ontario Institute for Cancer Research, Toronto, Canada; Department of Pathology, University of Edinburgh, Edinburgh, UK.
authors.forename: J M S
authors.initials: JMS
authors.lastname: Bartlett
authors.affiliation: Department of Medical Oncology, Leiden University Medical Center, Leiden.
authors.forename: J W R
authors.initials: JWR
authors.lastname: Nortier
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden. Electronic address: c.j.h.van_de_velde@lumc.nl.
authors.forename: C J H
authors.initials: CJH
authors.lastname: van de Velde
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000009:adverse effects* / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D017698:Postmenopause; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; C056516:exemestane