title: Specific adverse events are associated with response to exemestane therapy in postmenopausal breast cancer patients: Results from the TEAMIIA study (BOOG2006-04).
abstract: OBJECTIVE
  In the adjuvant setting, specific adverse events (AEs) such as vasomotor symptoms (VMS) and musculoskeletal AEs are associated with relapse-free survival in aromatase inhibitor (AI)-treated patients. In the neoadjuvant setting, specific AEs may be associated with tumor response to AIs as well.
  
  
  METHODS
  Between 2007 and 2012, 107 patients participated in the prospective TEAMIIA trial, a prospective, phase II trial investigating 6 months of neoadjuvant exemestane in patients with strongly ER-positive breast cancer. Radiological response (≥30% decrease in tumor size) was studied in relation to VMSs and MSAEs. Pearson's Chi-Square tests and multivariate logistic regression analyses were used to evaluate of statistical significance (p < 0.05).
  
  
  RESULTS
  Out of 102 patients 26 patients (25.4%) experienced at least one episode of VMS and 27 patients (26.4%) experienced MSAE. Out of 240 reported adverse events, 71 were specific AEs (40 MSAEs, 31 VMSs). Radiological response was greater in patients who reported VMSs compared to patients who did not (70.8% vs. 49.3%, multivariate OR 2.91, 95% C.I. 1.03-8.26, P = 0.045). No significant advantage towards better response was observed in patients who experienced MSAEs (60.0% vs. 53.3%, univariate OR 1.33, 95% C.I. 0.53-3.38, P = 0.545).
  
  
  CONCLUSIONS
  VMSs are associated with tumor response to neoadjuvant exemestane and may be useful for predicting treatment outcomes of AI treatment at an early stage in patients treated with neoadjuvant AIs.
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: D B Y
authors.initials: DB
authors.lastname: Fontein
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands; Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: a.charehbili@lumc.nl.
authors.forename: A
authors.initials: A
authors.lastname: Charehbili
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J W R
authors.initials: JW
authors.lastname: Nortier
authors.affiliation: Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Putter
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: E Meershoek-Klein
authors.initials: EM
authors.lastname: Kranenbarg
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J R
authors.initials: JR
authors.lastname: Kroep
authors.affiliation: Department of Medical Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: S C
authors.initials: SC
authors.lastname: Linn
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: C J H
authors.initials: CJ
authors.lastname: van de Velde
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000009:adverse effects*; D047072:Aromatase Inhibitors / Q000009:adverse effects*; D018771:Arthralgia / Q000139:chemically induced; D001168:Arthritis / Q000139:chemically induced; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D018275:Carcinoma, Lobular / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D019584:Hot Flashes / Q000139:chemically induced*; D006801:Humans; D007592:Joint Diseases / Q000139:chemically induced; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008327:Mammography; D008408:Mastectomy; D008875:Middle Aged; D015999:Multivariate Analysis; D009140:Musculoskeletal Diseases / Q000139:chemically induced*; D063806:Myalgia / Q000139:chemically induced; D020360:Neoadjuvant Therapy; D016017:Odds Ratio; D010024:Osteoporosis / Q000139:chemically induced; D017698:Postmenopause; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D016896:Treatment Outcome; D016217:Ultrasonography, Mammary; D014666:Vasomotor System
chemical_list: D000730:Androstadienes; D047072:Aromatase Inhibitors; D011960:Receptors, Estrogen; C056516:exemestane
keywords: Adverse events; Aromatase inhibitors; Breast cancer; Hot flushes