title: Extended therapy with letrozole and ovarian suppression in premenopausal patients with breast cancer after tamoxifen.
abstract: BACKGROUND
  In premenopausal women with breast cancer, standard adjuvant endocrine therapy has been 5 years of tamoxifen. This study sought to investigate the safety and feasibility of treating patients who remain premenopausal after adjuvant tamoxifen with gonadotropin-releasing hormone agonist (GnRH-a) concurrent with an aromatase inhibitor, mimicking the strategy that has proven effective in postmenopausal patients.
  
  
  METHODS
  This phase II single-arm clinical trial aimed to enroll 50 premenopausal women who had completed > 4.5 years of adjuvant tamoxifen for a 2-year course of leuprolide (7.5 mg intramuscularly monthly or 22.5 mg intramuscularly every 3 months) and letrozole (2.5 mg orally daily). Zoledronic acid (4 mg intravenously every 6 months) was offered optionally to help prevent bone loss.
  
  
  RESULTS
  Despite aggressive recruitment strategies at the 3 participating sites (including Dana-Farber Cancer Institute), poor accrual over 3.5 years ultimately led to early study closure after only 16 patients began therapy. Of the 16, 4 stopped treatment before 1 year, owing to toxicity; 5 completed 2 years of protocol-directed therapy; and 7 remained on treatment as of September 1, 2013, for an average of 53.5 weeks (SD, 17.2 weeks). Hot flashes, vaginal dryness, and pain were common toxicities.
  
  
  CONCLUSIONS
  Extended therapy with GnRH-a and an aromatase inhibitor (plus optional bisphosphonate) is associated with substantial side effects in premenopausal women who have already completed > 4.5 years of adjuvant tamoxifen. This study's poor accrual suggests that young women may not be highly motivated to pursue lengthier courses of endocrine therapy and that future studies of this approach may be challenging.
authors: Department of Oncology, Mayo Clinic, Rochester, MN. Electronic address: ruddy.kathryn@mayo.edu.
authors: Kathryn J
authors: KJ
authors: Ruddy
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors: Stephen D
authors: SD
authors: DeSantis
authors: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA.
authors: William
authors: W
authors: Barry
authors: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA.
authors: Hao
authors: H
authors: Guo
authors: Tufts University School of Medicine, Boston, MA.
authors: Caroline C
authors: CC
authors: Block
authors: Division of Medical Oncology, University of Colorado Denver, Denver, CO.
authors: Virginia
authors: V
authors: Borges
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors: Eric P
authors: EP
authors: Winer
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors: Ann H
authors: AH
authors: Partridge
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D007987:Gonadotropin-Releasing Hormone; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009570:Nitriles / Q000627:therapeutic use*; D010052:Ovariectomy; D017697:Premenopause; D011379:Prognosis; D015996:Survival Rate; D013629:Tamoxifen / Q000627:therapeutic use*; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D007987:Gonadotropin-Releasing Hormone; D000077289:Letrozole
keywords: Dyspareunia; Endocrine therapy; Hot flashes; Pain; Toxicity