Bone mineral density in breast cancer patients treated with adjuvant letrozole, tamoxifen, or sequences of letrozole and tamoxifen in the BIG 1-98 study (SAKK 21/07)

Ann Oncol. 2012 Jun;23(6):1474-81. doi: 10.1093/annonc/mdr448. Epub 2011 Oct 14.


Background: The risk of osteoporosis and fracture influences the selection of adjuvant endocrine therapy. We analyzed bone mineral density (BMD) in Swiss patients of the Breast International Group (BIG) 1-98 trial [treatment arms: A, tamoxifen (T) for 5 years; B, letrozole (L) for 5 years; C, 2 years of T followed by 3 years of L; D, 2 years of L followed by 3 years of T].

Patients and methods: Dual-energy X-ray absorptiometry (DXA) results were retrospectively collected. Patients without DXA served as control group. Repeated measures models using covariance structures allowing for different times between DXA were used to estimate changes in BMD. Prospectively defined covariates were considered as fixed effects in the multivariable models.

Results: Two hundred and sixty-one of 546 patients had one or more DXA with 577 lumbar and 550 hip measurements. Weight, height, prior hormone replacement therapy, and hysterectomy were positively correlated with BMD; the correlation was negative for letrozole arms (B/C/D versus A), known osteoporosis, time on trial, age, chemotherapy, and smoking. Treatment did not influence the occurrence of osteoporosis (T score < -2.5 standard deviation).

Conclusions: All aromatase inhibitor regimens reduced BMD. The sequential schedules were as detrimental for bone density as L monotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bone Density / drug effects*
  • Breast Neoplasms / drug therapy*
  • Female
  • Hip / diagnostic imaging
  • Hip / pathology
  • Humans
  • Letrozole
  • Lumbar Vertebrae / diagnostic imaging
  • Lumbar Vertebrae / pathology
  • Middle Aged
  • Multivariate Analysis
  • Nitriles / administration & dosage
  • Osteoporosis / chemically induced
  • Osteoporosis / diagnostic imaging
  • Postmenopause
  • Radiography
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Tamoxifen / administration & dosage
  • Triazoles / administration & dosage


  • Nitriles
  • Triazoles
  • Tamoxifen
  • Letrozole