title: A pilot study of estradiol followed by exemestane for reversing endocrine resistance in postmenopausal women with hormone receptor-positive metastatic breast cancer.
abstract: BACKGROUND
  Endocrine resistance is a frequent complication, and strategies to reverse it are a high research priority for metastatic breast cancer (MBC) that is hormone receptor positive. Preclinical data suggest re-exposure to estrogen induces tumor regression in tamoxifen-resistant tumors. We conducted a pilot study to determine whether short-term estradiol exposure would reverse endocrine resistance and resensitize tumors
  
  
  METHODS
  Postmenopausal women with estrogen receptor-positive MBC whose disease had progressed after receiving at least one prior endocrine therapy were eligible for the study. Patients were initially treated with 6 mg/day estradiol, and those who had not progressed after 3 months were then switched to exemestane.
  
  
  RESULTS
  Thirteen patients were evaluable for toxicity and response. No grade 3 or 4 toxicities were observed. Of the 13 patients who initiated estradiol therapy, 6 patients (46%) had not experienced disease progression at month 3 and were switched to exemestane. On exemestane, disease progression was documented in five patients, with one having stable disease as best response. Median progression-free survival for all patients was 4.8 months (range: 0.6-9.5 months).
  
  
  CONCLUSIONS
  Treatment with an estrogen prior to resuming antiestrogen treatments was not effective at reversing hormone resistance; however, low-dose estradiol treatment had measurable clinical activity with minimal toxicity and should be considered as a therapeutic option for hormone-refractory MBC.
authors.affiliation: University of Arizona Cancer Center, Tucson, Arizona, USA pchalasani@uacc.arizona.edu.
authors.forename: Pavani
authors.initials: P
authors.lastname: Chalasani
authors.affiliation: University of Arizona Cancer Center, Tucson, Arizona, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Stopeck
authors.affiliation: University of Arizona Cancer Center, Tucson, Arizona, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Clarke
authors.affiliation: University of Arizona Cancer Center, Tucson, Arizona, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Livingston
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004958:Estradiol / Q000009:adverse effects / Q000627:therapeutic use*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D005260:Female; D006801:Humans; D008875:Middle Aged; D010865:Pilot Projects; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D000970:Antineoplastic Agents; D020847:Estrogen Receptor Modulators; D011960:Receptors, Estrogen; D004958:Estradiol; C056516:exemestane