title: Immediate versus delayed zoledronic acid for prevention of bone loss in postmenopausal women with breast cancer starting letrozole after tamoxifen-N03CC.
abstract: Postmenopausal women with breast cancer (BC) are at increased risk for bone loss. Bisphosphonates improve bone mineral density (BMD) in normal postmenopausal women. The purpose of this study was to determine if immediate treatment with zoledronic acid preserves BMD in postmenopausal women with BC starting letrozole after tamoxifen. Postmenopausal women with BC completing tamoxifen were treated with daily letrozole 2.5 mg/vitamin D 400 I.U., calcium 500 mg twice daily and were randomized to upfront or delayed zoledronic acid 4 mg every 6 months. Patients in the delayed arm were only given zoledronic acid if they developed a post-baseline BMD T score <-2.0 or had a fracture. The primary endpoint was the mean percent change in lumbar spine (LS) BMD at 1 year. About 558 women enrolled; 395 provided 1 year BMD data. The upfront arm experienced a mean change of +3.66% in LS BMD versus -1.66% for the delayed group (P < 0.001). Changes at the femoral neck/total hip were also greater for the upfront versus delayed arms (P < 0.001; P < 0.001) with differences persisting at 2 years. Patients in the delayed arm were more likely to experience a clinically meaningful 5% loss of BMD at all sites versus the upfront zoledronate group. Patients in the upfront arm were slightly more likely to report limb edema, fatigue, fever, nausea and jaw osteonecrosis(1%). Upfront zoledronic acid prevents bone loss in postmenopausal women with BC starting letrozole after tamoxifen.
authors.affiliation: Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA. hines.stephanie@mayo.edu
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Hines
authors.forename: Betty
authors.initials: B
authors.lastname: Mincey
authors.forename: Todor
authors.initials: T
authors.lastname: Dentchev
authors.forename: Jeff A
authors.initials: JA
authors.lastname: Sloan
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.forename: David B
authors.initials: DB
authors.lastname: Johnson
authors.forename: Paul L
authors.initials: PL
authors.lastname: Schaefer
authors.forename: Steve
authors.initials: S
authors.lastname: Alberts
authors.forename: Heshan
authors.initials: H
authors.lastname: Liu
authors.forename: Stephen
authors.initials: S
authors.lastname: Kahanic
authors.forename: Miroslaw A
authors.initials: MA
authors.lastname: Mazurczak
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Nikcevich
authors.forename: Charles L
authors.initials: CL
authors.lastname: Loprinzi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects; D015663:Osteoporosis, Postmenopausal / Q000139:chemically induced / Q000517:prevention & control*; D013629:Tamoxifen / Q000627:therapeutic use; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077211:Zoledronic Acid; D000077289:Letrozole