title: Bone mineral density in premenopausal women treated for node-positive early breast cancer with 2 years of goserelin or 6 months of cyclophosphamide, methotrexate and 5-fluorouracil (CMF).
abstract: The purpose of this study was to compare changes in bone mineral density (BMD) in premenopausal patients with node-positive early breast cancer treated with goserelin (Zoladex) or cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Patients ( n=1640) were randomized to goserelin (3.6 mg every 28 days for 2 years) or CMF (sixx28-day cycles) treatment. In a protocoled sub-study involving 96 patients from eight centers (goserelin: n=53; CMF: n=43), lumbar spine (L2-L4) and femoral neck BMD were assessed by dual X-ray absorptiometry at baseline and then annually for 3 years. At the end of the 2-year goserelin-treatment period, mean BMD losses for goserelin-treated and CMF-treated patients were -10.5% and -6.5% ( P=0.0005) for lumbar spine and -6.4% and -4.5% ( P=0.04) for femoral neck, respectively. At 3 years, partial recovery of BMD was observed in goserelin recipients. In contrast, mean BMD losses for the CMF group indicated persistent BMD loss. No significant differences in BMD were observed between groups at the 3-year assessment of the spine or femoral neck. In the CMF group, based on amenorrhea status at 48 weeks, BMD losses at the lumbar spine were greater for amenorrheic than non-amenorrheic patients. Ovarian suppression resulting in amenorrhea was closely related to BMD loss in both treatment groups. Overall, patients who received CMF did not show recovery of BMD throughout follow-up, whereas partial recovery was observed 1 year after cessation of goserelin therapy, associated with the return of ovarian function in the majority of patients.
authors.affiliation: Department of Nuclear Medicine, Guy's, Kings and St Thomas' Hospital Medical School, SE1 9RT, London, UK. ignac.fogelman@kcl.ac.uk
authors.forename: I
authors.initials: I
authors.lastname: Fogelman
authors.forename: G M
authors.initials: GM
authors.lastname: Blake
authors.forename: R
authors.initials: R
authors.lastname: Blamey
authors.forename: M
authors.initials: M
authors.lastname: Palmer
authors.forename: W
authors.initials: W
authors.lastname: Sauerbrei
authors.forename: M
authors.initials: M
authors.lastname: Schumacher
authors.forename: D
authors.initials: D
authors.lastname: Serin
authors.forename: A
authors.initials: A
authors.lastname: Stewart
authors.forename: W
authors.initials: W
authors.lastname: Wilpshaar
mesh_terms: D000328:Adult; D000568:Amenorrhea / Q000139:chemically induced; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D005272:Femur Neck / Q000187:drug effects / Q000503:physiopathology; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D017273:Goserelin / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000503:physiopathology; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D017697:Premenopause / Q000187:drug effects* / Q000502:physiology
chemical_list: D018931:Antineoplastic Agents, Hormonal; D017273:Goserelin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate