Bone mineral density and circulating biomarkers in the BIG 1-98 trial comparing adjuvant letrozole, tamoxifen and their sequences

Andrea DeCensi, Zhuoxin Sun, Aliana Guerrieri-Gonzaga, Beat Thürlimann, Christina McIntosh, Carlo Tondini, Alain Monnier, Mario Campone, Marc Debled, Astrid Schönenberger, Khalil Zaman, Harriet Johansson, Karen N. Price, Richard D. Gelber, Aron Goldhirsch, Alan S. Coates, Stefan Aebi

Research output: Contribution to journalArticlepeer-review


The purpose of the study is to determine the effects of the BIG 1-98 treatments on bone mineral density. BIG 1-98 compared 5-year adjuvant hormone therapy in postmenopausal women allocated to four groups: tamoxifen (T); letrozole (L); 2-years T, 3-years L (TL); and 2-years L, 3-years T (LT). Bone mineral density T-score was measured prospectively annually by dual energy X-ray absorption in 424 patients enrolled in a sub-study after 3 (n = 150), 4 (n = 200), and 5 years (n = 74) from randomization, and 1 year after treatment cessation. Prevalence of osteoporosis and the association of C-telopeptide, osteocalcin, and bone alkaline phosphatase with T-scores were assessed. At 3 years, T had the highest and TL the lowest T-score. All arms except for LT showed a decline up to 5 years, with TL exhibiting the greatest. At 5 years, there were significant differences on lumbar T-score only between T and TL, whereas for femur T-score, differences were significant for T versus L or TL, and L versus LT. The 5-year prevalence of spine and femur osteoporosis was the highest on TL (14.5 %, 7.1 %) then L (4.3 %, 5.1 %), LT (4.2 %, 1.4 %) and T (4 %, 0). C-telopeptide and osteocalcin were significantly associated with T-scores. While adjuvant L increases bone mineral density loss compared with T, the sequence LT has an acceptable bone safety profile. C-telopeptide and osteocalcin are useful markers of bone density that may be used to monitor bone health during treatment. The sequence LT may be a valid treatment option in patients with low and intermediate risk of recurrence.

Original languageEnglish
Pages (from-to)321-329
Number of pages9
JournalBreast Cancer Research and Treatment
Issue number2
Publication statusPublished - 2014


  • Adjuvant drug therapy
  • Aromatase inhibitor
  • Bone density
  • Bone turnover
  • Breast cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Medicine(all)


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