Bone mineral density and circulating biomarkers in the BIG 1-98 trial comparing adjuvant letrozole, tamoxifen and their sequences.
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.
Division of Medical Oncology, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy, andrea.decensi@galliera.it.
Andrea
A
Decensi
Zhuoxin
Z
Sun
Aliana
A
Guerrieri-Gonzaga
Beat
B
Thürlimann
Christina
C
McIntosh
Carlo
C
Tondini
Alain
A
Monnier
Mario
M
Campone
Marc
M
Debled
Astrid
A
Schönenberger
Khalil
K
Zaman
Harriet
H
Johansson
Karen N
KN
Price
Richard D
RD
Gelber
Aron
A
Goldhirsch
Alan S
AS
Coates
Stefan
S
Aebi
D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D015519:Bone Density / Q000187:drug effects*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D024042:Collagen Type I / Q000097:blood; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage*; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000097:blood; D010455:Peptides / Q000097:blood; D017698:Postmenopause / Q000097:blood; D011446:Prospective Studies; D013629:Tamoxifen / Q000008:administration & dosage*; D014230:Triazoles / Q000008:administration & dosage*
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D024042:Collagen Type I; D009570:Nitriles; D010455:Peptides; D014230:Triazoles; C052929:collagen type I trimeric cross-linked peptide; D013629:Tamoxifen; D015675:Osteocalcin; D000077289:Letrozole; D000469:Alkaline Phosphatase