title: Ovarian Suppression With Triptorelin During Adjuvant Breast Cancer Chemotherapy and Long-term Ovarian Function, Pregnancies, and Disease-Free Survival: A Randomized Clinical Trial.
abstract: OBJECTIVE
  Whether the administration of luteinizing hormone-releasing hormone analogues (LHRHa) during chemotherapy is a reliable strategy to preserve ovarian function is controversial owing to both the lack of data on long-term ovarian function and pregnancies and the safety concerns about the potential negative interactions between endocrine therapy and chemotherapy.
  
  
  OBJECTIVE
  To evaluate long-term results of LHRHa-induced ovarian suppression during breast cancer chemotherapy.
  
  
  METHODS
  Parallel, randomized, open-label, phase 3 superiority trial conducted at 16 Italian sites. Between October 2003 and January 2008, 281 premenopausal women with stage I to III hormone receptor-positive or hormone receptor-negative breast cancer were enrolled. Last annual follow-up was June 3, 2014.
  
  
  METHODS
  Patients were randomized to receive adjuvant or neoadjuvant chemotherapy alone (control group) or chemotherapy plus triptorelin (LHRHa group).
  
  
  METHODS
  The primary planned end point was incidence of chemotherapy-induced early menopause. Post hoc end points were long-term ovarian function (evaluated by yearly assessment of menstrual activity and defined as resumed by the occurrence of at least 1 menstrual cycle), pregnancies, and disease-free survival (DFS).
  
  
  RESULTS
  A total of 281 women (median age, 39 [range, 24-45] years) were randomized. Median follow-up was 7.3 years (interquartile range, 6.3-8.2 years). The 5-year cumulative incidence estimate of menstrual resumption was 72.6% (95% CI, 65.7%-80.3%) among the 148 patients in the LHRHa group and 64.0% (95% CI, 56.2%-72.8%) among the 133 patients in the control group (hazard ratio [HR], 1.28 [95% CI, 0.98-1.68]; P = .07; age-adjusted HR, 1.48 [95% CI, 1.12-1.95]; P = .006). Eight pregnancies (5-year cumulative incidence estimate of pregnancy, 2.1% [95% CI, 0.7%-6.3%]) occurred in the LHRHa group and 3 (5-year cumulative incidence estimate of pregnancy, 1.6% [95% CI, 0.4%-6.2%]) in the control group (HR, 2.56 [95% CI, 0.68-9.60]; P = .14; age-adjusted HR, 2.40 [95% CI, 0.62-9.22]; P = .20). Five-year DFS was 80.5% (95% CI, 73.1%-86.1%) in the LHRHa group and 83.7% (95% CI, 76.1%-89.1%) in the control group (LHRHa vs control: HR, 1.17 [95% CI, 0.72-1.92]; P = .52).
  
  
  CONCLUSIONS
  Among premenopausal women with either hormone receptor-positive or hormone receptor-negative breast cancer, concurrent administration of triptorelin and chemotherapy, compared with chemotherapy alone, was associated with higher long-term probability of ovarian function recovery, without a statistically significant difference in pregnancy rate. There was no statistically significant difference in DFS for women assigned to triptorelin and those assigned to chemotherapy alone, although study power was limited.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier:NCT00311636.
authors.affiliation: Department of Medical Oncology, U.O. Oncologia Medica A, IRCCS AOU San Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Lambertini
authors.affiliation: Centro Coordinamento Sperimentazioni Cliniche, AOU Careggi and Istituto Toscano Tumori, Firenze, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Boni
authors.affiliation: U. O. Oncologia Medica I, Ospedale S. Chiara, Dipartimento di oncologia, dei trapianti e delle nuove tecnologie, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Michelotti
authors.affiliation: Oncology Department, Ospedale S.S. Trinità, Sora, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Gamucci
authors.affiliation: U. O. Oncologia Medica, Ospedale Civile, Sassari, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Scotto
authors.affiliation: S. C. Oncologia Medica, Ospedale Santa Maria della Misericordia, Perugia, Italy7U. O. C. Oncologia Medica, Ospedale Sacro Cuore-Don Calabria, Negrar-Verona, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Gori
authors.affiliation: S. C. di Oncologia, Azienda Ospedaliera S. Anna, Como, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Giordano
authors.affiliation: Dipartimento di Oncologia, Ospedale di Insegnamento S. Croce e Carle, Cuneo, Italy.
authors.forename: Ornella
authors.initials: O
authors.lastname: Garrone
authors.affiliation: Department of Medical Oncology, U. O. Sviluppo Terapie Innovative, IRCCS AOU San Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Levaggi
authors.affiliation: Department of Medical Oncology, U.O. Oncologia Medica A, IRCCS AOU San Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Poggio
authors.affiliation: Department of Medical Oncology, U. O. Sviluppo Terapie Innovative, IRCCS AOU San Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Giraudi
authors.affiliation: Department of Medical Oncology, U.O. Oncologia Medica A, IRCCS AOU San Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bighin
authors.affiliation: Department of Surgical Oncology, Chirurgia Senologica U1E, IRCCS AOU San Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Vecchio
authors.affiliation: Department of Medical Oncology, Clinica di Oncologia Medica, IRCCS AOU San Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, Genova.
authors.forename: Mario Roberto
authors.initials: MR
authors.lastname: Sertoli
authors.affiliation: Department of Medical Oncology, U.O. Oncologia Medica A, IRCCS AOU San Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Pronzato
authors.affiliation: Department of Medical Oncology, U. O. Sviluppo Terapie Innovative, IRCCS AOU San Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Del Mastro
mesh_terms: D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D017024:Chemotherapy, Adjuvant / Q000379:methods; D018572:Disease-Free Survival; D004347:Drug Interactions; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008186:Luteolytic Agents / Q000627:therapeutic use; D008597:Menstrual Cycle / Q000502:physiology; D008875:Middle Aged; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D018873:Pregnancy Rate; D017697:Premenopause / Q000187:drug effects; D020127:Recovery of Function; D017329:Triptorelin Pamoate / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D008186:Luteolytic Agents; D017329:Triptorelin Pamoate