title: Goserelin, as an ovarian protector during (neo)adjuvant breast cancer chemotherapy, prevents long term altered bone turnover.
abstract: BACKGROUND
  The Ovarian Protection Trial In Premenopausal Breast Cancer Patients "OPTION" trial (NCT00427245) was a prospective, multicenter, randomised, open label study evaluating the frequency of primary ovarian insufficiency (POI) at 12 months in women randomised to 6-8 cycles of (neo)adjuvant chemotherapy (CT) +/- goserelin (G). Here we report the results of a secondary endpoint analysis of the effects of CT+/-G on markers of bone turnover.
  
  
  METHODS
  Serum for bone alkaline phosphatase (BALP) and urine for N-terminal telopeptide (NTX) were collected at baseline, 6, 12, 18, 24 and 36 months. Changes in median levels of bone turnover markers were evaluated for the overall population, according to age stratification at randomisation (≤40 vs >40 years) and with exploratory analysis according to POI rates at 12 months.
  
  
  RESULTS
  In the overall population, there was a significant increase in NTX at 6 months compared to baseline in patients treated with CT+G (40.81 vs 57.82 p=0.0074) with normalisation of levels thereafter. BALP was significantly increased compared to baseline at 6 months and 12 months in those receiving CT+G, but normalised thereafter. BALP remained significantly higher compared to baseline at 12, 24 and 36 months in patients receiving CT, resulting in a significant difference between treatment groups at 36 months (CT+G 5.845 vs CT 8.5 p=0.0006). These changes were predominantly seen in women >40 years. Women with POI at 12 months showed altered bone formation compared to baseline levels for a longer duration than women who maintained menses.
  
  
  CONCLUSIONS
  Addition of G to CT increases bone turnover during treatment with normalisation after cessation of treatment suggesting G may offer sufficient ovarian protection against CT induced POI to negate longstanding altered bone turnover associated with POI.
authors.affiliation: Academic Unit of Clinical Oncology, Weston Park Hospital, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Wilson
authors.affiliation: Mellanby Centre for Bone research, Sheffield Medical School, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Fatma
authors.initials: F
authors.lastname: Gossiel
authors.affiliation: Imperial College, London, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Leonard
authors.affiliation: MRC Centre for Reproductive Health, Queens Medical Research Centre, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Anderson
authors.affiliation: Ninewells Hospital and Medical School, Ward 32, University of Dundee, Dundee, United Kingdom.
authors.forename: Douglas J A
authors.initials: DJ
authors.lastname: Adamson
authors.affiliation: Imperial College, London, United Kingdom.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Thomas
authors.affiliation: Academic Unit of Clinical Oncology, Weston Park Hospital, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Coleman
keywords: Bone turnover markers; Breast cancer; Chemotherapy; Goserelin; Primary ovarian insufficiency