title: Drug withdrawal in women with progressive metastatic breast cancer while on aromatase inhibitor therapy.
abstract: BACKGROUND
  Acquiring resistance to endocrine therapy is common in metastatic hormone-receptor-positive breast cancer (MBC). These patients most often transition either to next-line endocrine therapy or to systemic chemotherapy. However, withdrawal of endocrine therapy and observation as is selectively practiced in prostate cancer is another potential strategy for breast cancer patients.
  
  
  METHODS
  A prospective, single-arm phase II trial of aromatase inhibitor (AI) withdrawal was performed in women with MBC, who had disease progression on AI therapy. The primary objective was to estimate the clinical benefit rate (defined as complete or partial response, or stable disease for at least 24 weeks, by RECIST criteria). Participants were monitored clinically and radiographically off all therapy at 8, 16 and 24 weeks after treatment and every 12 weeks thereafter until disease progression.
  
  
  RESULTS
  Twenty-four patients (of 40 intended) were enrolled when the study was closed due to slow accrual. Clinical benefit rate overall was 46% (95% CI 26% to 67%). Median progression-free survival from time of AI withdrawal was 4 months. Two patients have remained progression free, off all treatment, for over 60 months.
  
  
  CONCLUSIONS
  Despite suboptimal patient accrual, our results suggest that selected patients with metastatic breast cancer progressing on AI therapy can experience disease stabilisation and a period of observation after AI withdrawal. A randomised phase II trial is planned.
authors.affiliation: Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico City, Mexico.
authors.forename: Y
authors.initials: Y
authors.lastname: Chavarri-Guerra
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, MA, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Higgins
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, MA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Szymonifka
authors.affiliation: Weill Cornell Medical College, New York, NY, USA.
authors.forename: T
authors.initials: T
authors.lastname: Cigler
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, MA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Liedke
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Partridge
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ligibel
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Come
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, MA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Finkelstein
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA, USA.
authors.forename: P D
authors.initials: PD
authors.lastname: Ryan
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, MA, USA.
authors.forename: P E
authors.initials: PE
authors.lastname: Goss
mesh_terms: D000328:Adult; D000368:Aged; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011446:Prospective Studies
chemical_list: D047072:Aromatase Inhibitors