Effect of letrozole versus placebo on bone mineral density in women with primary breast cancer completing 5 or more years of adjuvant tamoxifen: A companion study to NCIC CTG MA.17

Edith A. Perez, Robert G. Josse, Kathleen I. Pritchard, James N. Ingle, Silvana Martino, Brian P. Findlay, Tamara N. Shenkier, Richard G. Tozer, Michael J. Palmer, Lois E. Shepherd, Shifang Liu, Dongsheng Tu, Paul E. Goss

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Abstract

Purpose: Aromatase inhibition depletes estrogen levels and may be associated with accelerated bone resorption. The National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) study MA.17B evaluated bone turnover markers and bone mineral density (BMD) in postmenopausal women randomly assigned to MA.17, a placebo-controlled trial of letrozole after standard adjuvant tamoxifen. Patients and Methods: Eligible women had a baseline BMD T score of at least 2.0 in either the hip or L2-4 spine; all received calcium 500 mg and vitamin D 400 U daily. Percentage change in BMD (L2-L4 spine and hip) at 12 and 24 months, rate of osteoporosis, and change in markers of bone formation (serum bone alkaline phosphatase) and resorption (serum C-telopeptide and urine N-telopeptide) at 6, 12, and 24 months were compared. Results: Two hundred twenty-six patients (122 letrozole, 104 placebo) were enrolled. Baseline characteristics were similar in the two groups, including BMD, median age of 60.7 years (81 % < 70 years), and median follow-up of 1.6 years. At 24 months, patients receiving letrozole had a significant decrease in total hip BMD (-3.6% v -0.71%; P = .044) and lumbar spine BMD (-5.35% v -0.70%; P = .008). Letrozole increased urine N-telopeptide at 6, 12, and 24 months (P = .054, < .001, and .016, respectively). No patient went below the threshold for osteoporosis in total hip BMD, whereas at the L2-L4 (posteroanterior view), more women became osteoporotic by BMD while receiving letrozole (4.1% v 0%; P = .064). Conclusion: After 5 years of adjuvant tamoxifen, subsequent letrozole causes a modest increase in bone resorption and reduction in bone mineral density in the spine and hip compared to placebo. Further follow-up is necessary to evaluate the long-term clinical implications of this difference.

Original languageEnglish (US)
Pages (from-to)3629-3635
Number of pages7
JournalJournal of Clinical Oncology
Volume24
Issue number22
DOIs
StatePublished - Aug 1 2006

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letrozole
National Cancer Institute (U.S.)
Tamoxifen
Bone Density
Canada
Placebos
Clinical Trials
Breast Neoplasms
Spine
Pelvic Bones
Hip
Bone Resorption
Osteoporosis
Urine
Bone and Bones
Aromatase
Bone Remodeling

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Effect of letrozole versus placebo on bone mineral density in women with primary breast cancer completing 5 or more years of adjuvant tamoxifen : A companion study to NCIC CTG MA.17. / Perez, Edith A.; Josse, Robert G.; Pritchard, Kathleen I.; Ingle, James N.; Martino, Silvana; Findlay, Brian P.; Shenkier, Tamara N.; Tozer, Richard G.; Palmer, Michael J.; Shepherd, Lois E.; Liu, Shifang; Tu, Dongsheng; Goss, Paul E.

In: Journal of Clinical Oncology, Vol. 24, No. 22, 01.08.2006, p. 3629-3635.

Research output: Contribution to journalArticle

Perez, EA, Josse, RG, Pritchard, KI, Ingle, JN, Martino, S, Findlay, BP, Shenkier, TN, Tozer, RG, Palmer, MJ, Shepherd, LE, Liu, S, Tu, D & Goss, PE 2006, 'Effect of letrozole versus placebo on bone mineral density in women with primary breast cancer completing 5 or more years of adjuvant tamoxifen: A companion study to NCIC CTG MA.17', Journal of Clinical Oncology, vol. 24, no. 22, pp. 3629-3635. https://doi.org/10.1200/JCO.2005.05.4882
Perez, Edith A. ; Josse, Robert G. ; Pritchard, Kathleen I. ; Ingle, James N. ; Martino, Silvana ; Findlay, Brian P. ; Shenkier, Tamara N. ; Tozer, Richard G. ; Palmer, Michael J. ; Shepherd, Lois E. ; Liu, Shifang ; Tu, Dongsheng ; Goss, Paul E. / Effect of letrozole versus placebo on bone mineral density in women with primary breast cancer completing 5 or more years of adjuvant tamoxifen : A companion study to NCIC CTG MA.17. In: Journal of Clinical Oncology. 2006 ; Vol. 24, No. 22. pp. 3629-3635.
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abstract = "Purpose: Aromatase inhibition depletes estrogen levels and may be associated with accelerated bone resorption. The National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) study MA.17B evaluated bone turnover markers and bone mineral density (BMD) in postmenopausal women randomly assigned to MA.17, a placebo-controlled trial of letrozole after standard adjuvant tamoxifen. Patients and Methods: Eligible women had a baseline BMD T score of at least 2.0 in either the hip or L2-4 spine; all received calcium 500 mg and vitamin D 400 U daily. Percentage change in BMD (L2-L4 spine and hip) at 12 and 24 months, rate of osteoporosis, and change in markers of bone formation (serum bone alkaline phosphatase) and resorption (serum C-telopeptide and urine N-telopeptide) at 6, 12, and 24 months were compared. Results: Two hundred twenty-six patients (122 letrozole, 104 placebo) were enrolled. Baseline characteristics were similar in the two groups, including BMD, median age of 60.7 years (81 {\%} < 70 years), and median follow-up of 1.6 years. At 24 months, patients receiving letrozole had a significant decrease in total hip BMD (-3.6{\%} v -0.71{\%}; P = .044) and lumbar spine BMD (-5.35{\%} v -0.70{\%}; P = .008). Letrozole increased urine N-telopeptide at 6, 12, and 24 months (P = .054, < .001, and .016, respectively). No patient went below the threshold for osteoporosis in total hip BMD, whereas at the L2-L4 (posteroanterior view), more women became osteoporotic by BMD while receiving letrozole (4.1{\%} v 0{\%}; P = .064). Conclusion: After 5 years of adjuvant tamoxifen, subsequent letrozole causes a modest increase in bone resorption and reduction in bone mineral density in the spine and hip compared to placebo. Further follow-up is necessary to evaluate the long-term clinical implications of this difference.",
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T1 - Effect of letrozole versus placebo on bone mineral density in women with primary breast cancer completing 5 or more years of adjuvant tamoxifen

T2 - A companion study to NCIC CTG MA.17

AU - Perez, Edith A.

AU - Josse, Robert G.

AU - Pritchard, Kathleen I.

AU - Ingle, James N.

AU - Martino, Silvana

AU - Findlay, Brian P.

AU - Shenkier, Tamara N.

AU - Tozer, Richard G.

AU - Palmer, Michael J.

AU - Shepherd, Lois E.

AU - Liu, Shifang

AU - Tu, Dongsheng

AU - Goss, Paul E.

PY - 2006/8/1

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N2 - Purpose: Aromatase inhibition depletes estrogen levels and may be associated with accelerated bone resorption. The National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) study MA.17B evaluated bone turnover markers and bone mineral density (BMD) in postmenopausal women randomly assigned to MA.17, a placebo-controlled trial of letrozole after standard adjuvant tamoxifen. Patients and Methods: Eligible women had a baseline BMD T score of at least 2.0 in either the hip or L2-4 spine; all received calcium 500 mg and vitamin D 400 U daily. Percentage change in BMD (L2-L4 spine and hip) at 12 and 24 months, rate of osteoporosis, and change in markers of bone formation (serum bone alkaline phosphatase) and resorption (serum C-telopeptide and urine N-telopeptide) at 6, 12, and 24 months were compared. Results: Two hundred twenty-six patients (122 letrozole, 104 placebo) were enrolled. Baseline characteristics were similar in the two groups, including BMD, median age of 60.7 years (81 % < 70 years), and median follow-up of 1.6 years. At 24 months, patients receiving letrozole had a significant decrease in total hip BMD (-3.6% v -0.71%; P = .044) and lumbar spine BMD (-5.35% v -0.70%; P = .008). Letrozole increased urine N-telopeptide at 6, 12, and 24 months (P = .054, < .001, and .016, respectively). No patient went below the threshold for osteoporosis in total hip BMD, whereas at the L2-L4 (posteroanterior view), more women became osteoporotic by BMD while receiving letrozole (4.1% v 0%; P = .064). Conclusion: After 5 years of adjuvant tamoxifen, subsequent letrozole causes a modest increase in bone resorption and reduction in bone mineral density in the spine and hip compared to placebo. Further follow-up is necessary to evaluate the long-term clinical implications of this difference.

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