title: Long-Term Safety of Letrozole and Gonadotropin Stimulation for Fertility Preservation in Women With Breast Cancer.
abstract: There has been increased attention to the issue of fertility preservation (FP). We aimed to investigate the long-term safety of FP via controlled ovarian stimulation with letrozole supplementation (COSTLES) prior to breast cancer treatment.
  
  
  
  This is a prospective, nonrandomized, controlled study conducted between the years 2002 and 2014. A total of 337 women diagnosed with stage 3 or less invasive breast cancer were enrolled during a FP consultation before chemotherapy. Of those, 120 elected to undergo COSTLES for FP prior to chemotherapy (FP group). The remaining 217 patients did not undergo any FP procedure and served as the controls.
  
  
  
  The primary end point was cancer recurrence defined as the detection of locoregional tumor (chest wall, regional nodal disease), distant metastases, or contralateral invasive breast cancer.
  
  
  
  The baseline characteristics at enrollment were similar between the FP and control groups except for the less frequent lymph node involvement (P = .02) in the former. The mean follow-up after diagnosis was 5.0 years in the FP group and 6.9 years in the control group. In the FP group, the hazard ratio for recurrence after ovarian stimulation was 0.77 (95% confidence interval 0.28–2.13), and the survival was not compromised compared with controls (P = .61). Neither BRCA gene mutation status (P = .57) nor undergoing FP before or after breast surgery (P = .44) affected survival outcomes in the FP group. Likewise, none of the tumor characteristics including the estrogen receptor status affected the survival rates after the COSTLES.
  
  
  
  COSTLES is unlikely to cause a substantially increased recurrence risk in breast cancer during the 5 years after diagnosis.
authors.affiliation: Division of Reproductive Medicine, Fertility Preservation, and Infertility (J.K., V.T., K.O.), Department of Obstetrics and Gynecology, New York Medical College, Valhalla, New York 10595; Innovation Institute for Fertility Preservation (J.K., V.T., K.O.), New York, New York 10570; Department of Obstetrics and Gynecology (V.T.), Yeni Yuzyil University School of Medicine, GOP Hospital, Istanbul, Turkey; and Department of Obstetrics and Gynecology (J.K.), Cha Gangnam Hospital, Cha University, Seoul 135-081, Korea.
authors.forename: Jayeon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Division of Reproductive Medicine, Fertility Preservation, and Infertility (J.K., V.T., K.O.), Department of Obstetrics and Gynecology, New York Medical College, Valhalla, New York 10595; Innovation Institute for Fertility Preservation (J.K., V.T., K.O.), New York, New York 10570; Department of Obstetrics and Gynecology (V.T.), Yeni Yuzyil University School of Medicine, GOP Hospital, Istanbul, Turkey; and Department of Obstetrics and Gynecology (J.K.), Cha Gangnam Hospital, Cha University, Seoul 135-081, Korea.
authors.forename: Volkan
authors.initials: V
authors.lastname: Turan
authors.affiliation: Division of Reproductive Medicine, Fertility Preservation, and Infertility (J.K., V.T., K.O.), Department of Obstetrics and Gynecology, New York Medical College, Valhalla, New York 10595; Innovation Institute for Fertility Preservation (J.K., V.T., K.O.), New York, New York 10570; Department of Obstetrics and Gynecology (V.T.), Yeni Yuzyil University School of Medicine, GOP Hospital, Istanbul, Turkey; and Department of Obstetrics and Gynecology (J.K.), Cha Gangnam Hospital, Cha University, Seoul 135-081, Korea.
authors.forename: Kutluk
authors.initials: K
authors.lastname: Oktay
mesh_terms: D000328:Adult; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D005260:Female; D005298:Fertility / Q000187:drug effects*; D059247:Fertility Preservation; D006062:Gonadotropins / Q000627:therapeutic use*; D006801:Humans; D000077289:Letrozole; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009570:Nitriles / Q000627:therapeutic use*; D010062:Ovulation Induction; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D047072:Aromatase Inhibitors; D006062:Gonadotropins; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole