title: New onset vasomotor symptoms but not musculoskeletal symptoms associate with clinical outcomes on extended adjuvant letrozole - Analyses from NCIC CTG MA.17.
abstract: OBJECTIVE
  New onset symptoms on adjuvant aromatase inhibitors for hormone receptor positive early breast cancer may associate with clinical outcomes. We performed this exploratory analysis of the association of new onset musculoskeletal (MSK) and vasomotor (VM) symptoms with clinical outcomes in the NCIC CTG MA.17 trial 5 years of extended adjuvant endocrine therapy with letrozole after tamoxifen.
  
  
  METHODS
  Symptoms were collected at baseline, 1, 6, and every 12 months on study. Multivariate Cox Models adjusting for age, nodal status, duration of tamoxifen and prior chemotherapy were used to compare disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) based on data collected before, and after, the unblinding between women with VM or MSK symptoms and those without.
  
  
  RESULTS
  Data post-unblinding showed new VM symptoms on extended letrozole significantly improved DFS and DDFS when occurring 1 month (DFS HR 0.52, 95% CI, 0.28-0.96; p = 0.04; DDFS HR 0.49, 95% CI, 0.24-0.99; p = 0.046) and 6 months (DFS HR 0.43, 95% CI, 0.24-0.78; p = 0.006; DDFS HR 0.44, 95% CI, 0.22-0.85; p = 0.02) after treatment initiation. Those with new VM symptoms at 12 months also had a significantly better DFS (HR 0.47, 95% CI 0.26, 0.84; P = 0.01) and a trend in improved DDFS. Only a trend to improved OS was found for those with VM symptoms 6 month after treatment. No significant improvement was found for those with new MSK symptoms at any time point or for any endpoint.
  
  
  CONCLUSIONS
  New onset VM symptoms with extended letrozole may be useful in predicting treatment benefit.
authors.affiliation: Department of Clinical Oncology, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil; Mãe de Deus Cancer Institute, Hospital Mãe de Deus, Porto Alegre, RS, Brazil; Brazilian Breast Cancer Study Group, Porto Alegre, RS, Brazil; Massachusetts General Hospital Cancer Center, Avon International Breast Cancer Research Program, Boston, MA, USA.
authors.forename: P E R
authors.initials: PE
authors.lastname: Liedke
authors.affiliation: Canadian Cancer Trials Group, Queen's University, Ontario, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Tu
authors.affiliation: Canadian Cancer Trials Group, Queen's University, Ontario, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Shepherd
authors.affiliation: Department of Hematology-Oncology, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico; Massachusetts General Hospital Cancer Center, Avon International Breast Cancer Research Program, Boston, MA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Chavarri-Guerra
authors.affiliation: Canadian Cancer Trials Group, Queen's University, Ontario, Canada; Sunnybrook Odette Cancer Center, University of Toronto, Toronto, ON, Canada.
authors.forename: K I
authors.initials: KI
authors.lastname: Pritchard
authors.affiliation: Kimmel Cancer Center at Johns Hopkins, Breast Cancer Program, Baltimore, MD, USA.
authors.forename: V
authors.initials: V
authors.lastname: Stearns
authors.affiliation: Canadian Cancer Trials Group, Queen's University, Ontario, Canada; Massachusetts General Hospital Cancer Center, Avon International Breast Cancer Research Program, Boston, MA, USA.
authors.forename: P E
authors.initials: PE
authors.lastname: Goss
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001342:Autonomic Nervous System Diseases / Q000209:etiology*; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy / Q000401:mortality*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D015999:Multivariate Analysis; D009140:Musculoskeletal Diseases / Q000209:etiology*; D009570:Nitriles / Q000008:administration & dosage*; D016016:Proportional Hazards Models; D013629:Tamoxifen / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage*; D014666:Vasomotor System / Q000503:physiopathology
chemical_list: D000970:Antineoplastic Agents; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole
keywords: Aromatase inhibitors; Breast cancer; Extended hormonal therapy; Letrozole; Musculoskeletal symptoms; Vasomotor symptoms