title: Incidence and predictors of ovarian function recovery (OFR) in breast cancer (BC) patients with chemotherapy-induced amenorrhea (CIA) who switched from tamoxifen to exemestane.
abstract: BACKGROUND
  Aromatase inhibitors (AIs) may promote ovarian function recovery (OFR). True incidence, predictors and impact on the outcome of OFR are unknown.
  
  
  METHODS
  We carried out a prospective study to assess ovarian function in estrogen receptor (ER)-positive BC patients on tamoxifen who had at least 2 years of chemotherapy-induced amenorrhea (CIA) and postmenopausal E2 levels. Patients switched to exemestane and underwent a series of investigations including vaginal ultrasound, antimullerian hormone, follicle stimulating hormone (FSH), and E2. E2 measurements were made using a clinical assay (direct) and a highly sensitive (indirect) immunoassay for comparison.
  
  
  RESULTS
  Both E2 assays (indirect versus direct) showed a similar incidence of OFR 32% (95% CI 19.5-44.5) versus 30% (95% CI 17.7-42.3) and median time to OFR 5.4 months (95% CI 1.2-9.6) versus 6.0 months (95% CI 4.8-7.1).On multivariate analysis, the mean age at the start of exemestane treatment was the only marker associated with probability of OFR (OR: 0.44, 0.24-0.78; P = 0.006). According to a receiver operating characteristic (ROC) analysis, age <48 years predicted for OFR (sensitivity: 59%; 1-specificity: 17%; AUC: 0.796; P = 0.001). Patients with OFR had higher mean E2 levels (43.6 versus 5.76 pmol/l; P = 0.001) and a reduced disease-free survival [DFS; HR 9.3 (95% CI 3.3-48.0; P = 0.04)] than those without it.
  
  
  CONCLUSIONS
  Even with a clinical and biochemical profile compatible with menopause, switching from tamoxifen to an AI should be avoided in patients <48 with CIA.
authors.affiliation: Department of Medical Oncology, Royal Marsden Hospital, London, UK. angelgz@comv.es
authors.forename: A
authors.initials: A
authors.lastname: Guerrero
authors.forename: J
authors.initials: J
authors.lastname: Gavilá
authors.forename: E
authors.initials: E
authors.lastname: Folkerd
authors.forename: B
authors.initials: B
authors.lastname: Ortiz
authors.forename: F
authors.initials: F
authors.lastname: Martínez
authors.forename: A
authors.initials: A
authors.lastname: García
authors.forename: M A
authors.initials: MA
authors.lastname: Climent
authors.forename: V
authors.initials: V
authors.lastname: Guillem
authors.forename: A
authors.initials: A
authors.lastname: Ruíz
mesh_terms: D000328:Adult; D000568:Amenorrhea / Q000139:chemically induced* / Q000401:mortality / Q000503:physiopathology; D000730:Androstadienes / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects* / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D057915:Drug Substitution; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008598:Menstruation / Q000187:drug effects; D008875:Middle Aged; D010053:Ovary / Q000187:drug effects / Q000503:physiopathology*; D011446:Prospective Studies; D012372:ROC Curve; D020127:Recovery of Function; D013629:Tamoxifen / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D013629:Tamoxifen; D004958:Estradiol; C056516:exemestane