Effects of adjuvant exemestane versus anastrozole on bone mineral density for women with early breast cancer (MA.27B): A companion analysis of a randomised controlled trial

Paul E. Goss, Dawn L. Hershman, Angela M. Cheung, James N. Ingle, Sundeep Khosla, Vered Stearns, Haji Chalchal, Kendrith Rowland, Hyman B. Muss, Hannah M. Linden, Judite Scher, Kathleen I. Pritchard, Catherine R. Elliott, Tanja Badovinac-Crnjevic, Jessica St Louis, Judith Anne W Chapman, Lois E. Shepherd

Research output: Contribution to journalArticle

Abstract

Background: Treatment of breast cancer with aromatase inhibitors is associated with damage to bones. NCIC CTG MA.27 was an open-label, phase 3, randomised controlled trial in which women with breast cancer were assigned to one of two adjuvant oral aromatase inhibitors-exemestane or anastrozole. We postulated that exemestane-a mildly androgenic steroid-might have a less detrimental effect on bone than non-steroidal anastrozole. In this companion study to MA.27, we compared changes in bone mineral density (BMD) in the lumbar spine and total hip between patients treated with exemestane and patients treated with anastrozole. Methods: In MA.27, postmenopausal women with early stage hormone (oestrogen) receptor-positive invasive breast cancer were randomly assigned to exemestane 25 mg versus anastrozole 1 mg, daily. MA.27B recruited two groups of women from MA.27: those with BMD T-scores of -2·0 or more (up to 2 SDs below sex-matched, young adult mean) and those with at least one T-score (hip or spine) less than -2·0. Both groups received vitamin D and calcium; those with baseline T-scores of less than -2·0 also received bisphosphonates. The primary endpoints were percent change of BMD at 2 years in lumbar spine and total hip for both groups. We analysed patients according to which aromatase inhibitor and T-score groups they were allocated to but BMD assessments ceased if patients deviated from protocol. This study is registered with ClinicalTrials.gov, NCT00354302. Findings: Between April 24, 2006, and May 30, 2008, 300 patients with baseline T-scores of -2·0 or more were accrued (147 allocated exemestane, 153 anastrozole); and 197 patients with baseline T-scores of less than -2·0 (101 exemestane, 96 anastrozole). For patients with T-scores greater than -2·0 at baseline, mean change of bone mineral density in the spine at 2 years did not differ significantly between patients taking exemestane and patients taking anastrozole (-0·92%, 95% CI -2·35 to 0·50 vs -2·39%, 95% CI -3·77 to -1·01; p=0·08). Respective mean loss in the hip was -1·93% (95% CI -2·93 to -0·93) versus -2·71% (95% CI -4·32 to -1·11; p=0·10). Likewise for those who started with T-scores of less than -2·0, mean change of spine bone mineral density at 2 years did not differ significantly between the exemestane and anastrozole treatment groups (2·11%, 95% CI -0·84 to 5·06 vs 3·72%, 95% CI 1·54 to 5·89; p=0·26), nor did hip bone mineral density (2·09%, 95% CI -1·45 to 5·63 vs 0·0%, 95% CI -3·67 to 3·66; p=0·28). Patients with baseline T-score of -2·0 or more taking exemestane had two fragility fractures and two other fractures, those taking anastrozole had three fragility fractures and five other fractures. For patients who had baseline T-scores of less than -2·0 taking exemestane, one had a fragility fracture and four had other fractures, whereas those taking anastrozole had five fragility fractures and one other fracture. Interpretation: Our results demonstrate that adjuvant treatment with aromatase inhibitors can be considered for breast cancer patients who have T-scores less than -2·0. Funding: Canadian Cancer Society Research Institute, Pfizer, Canadian Institutes of Health Research.

Original languageEnglish (US)
Pages (from-to)474-482
Number of pages9
JournalThe Lancet Oncology
Volume15
Issue number4
DOIs
StatePublished - 2014

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exemestane
Bone Density
Randomized Controlled Trials
Breast Neoplasms
Aromatase Inhibitors
Spine
Hip
anastrozole

ASJC Scopus subject areas

  • Oncology

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Effects of adjuvant exemestane versus anastrozole on bone mineral density for women with early breast cancer (MA.27B) : A companion analysis of a randomised controlled trial. / Goss, Paul E.; Hershman, Dawn L.; Cheung, Angela M.; Ingle, James N.; Khosla, Sundeep; Stearns, Vered; Chalchal, Haji; Rowland, Kendrith; Muss, Hyman B.; Linden, Hannah M.; Scher, Judite; Pritchard, Kathleen I.; Elliott, Catherine R.; Badovinac-Crnjevic, Tanja; St Louis, Jessica; Chapman, Judith Anne W; Shepherd, Lois E.

In: The Lancet Oncology, Vol. 15, No. 4, 2014, p. 474-482.

Research output: Contribution to journalArticle

Goss, PE, Hershman, DL, Cheung, AM, Ingle, JN, Khosla, S, Stearns, V, Chalchal, H, Rowland, K, Muss, HB, Linden, HM, Scher, J, Pritchard, KI, Elliott, CR, Badovinac-Crnjevic, T, St Louis, J, Chapman, JAW & Shepherd, LE 2014, 'Effects of adjuvant exemestane versus anastrozole on bone mineral density for women with early breast cancer (MA.27B): A companion analysis of a randomised controlled trial', The Lancet Oncology, vol. 15, no. 4, pp. 474-482. https://doi.org/10.1016/S1470-2045(14)70035-X
Goss, Paul E. ; Hershman, Dawn L. ; Cheung, Angela M. ; Ingle, James N. ; Khosla, Sundeep ; Stearns, Vered ; Chalchal, Haji ; Rowland, Kendrith ; Muss, Hyman B. ; Linden, Hannah M. ; Scher, Judite ; Pritchard, Kathleen I. ; Elliott, Catherine R. ; Badovinac-Crnjevic, Tanja ; St Louis, Jessica ; Chapman, Judith Anne W ; Shepherd, Lois E. / Effects of adjuvant exemestane versus anastrozole on bone mineral density for women with early breast cancer (MA.27B) : A companion analysis of a randomised controlled trial. In: The Lancet Oncology. 2014 ; Vol. 15, No. 4. pp. 474-482.
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title = "Effects of adjuvant exemestane versus anastrozole on bone mineral density for women with early breast cancer (MA.27B): A companion analysis of a randomised controlled trial",
abstract = "Background: Treatment of breast cancer with aromatase inhibitors is associated with damage to bones. NCIC CTG MA.27 was an open-label, phase 3, randomised controlled trial in which women with breast cancer were assigned to one of two adjuvant oral aromatase inhibitors-exemestane or anastrozole. We postulated that exemestane-a mildly androgenic steroid-might have a less detrimental effect on bone than non-steroidal anastrozole. In this companion study to MA.27, we compared changes in bone mineral density (BMD) in the lumbar spine and total hip between patients treated with exemestane and patients treated with anastrozole. Methods: In MA.27, postmenopausal women with early stage hormone (oestrogen) receptor-positive invasive breast cancer were randomly assigned to exemestane 25 mg versus anastrozole 1 mg, daily. MA.27B recruited two groups of women from MA.27: those with BMD T-scores of -2·0 or more (up to 2 SDs below sex-matched, young adult mean) and those with at least one T-score (hip or spine) less than -2·0. Both groups received vitamin D and calcium; those with baseline T-scores of less than -2·0 also received bisphosphonates. The primary endpoints were percent change of BMD at 2 years in lumbar spine and total hip for both groups. We analysed patients according to which aromatase inhibitor and T-score groups they were allocated to but BMD assessments ceased if patients deviated from protocol. This study is registered with ClinicalTrials.gov, NCT00354302. Findings: Between April 24, 2006, and May 30, 2008, 300 patients with baseline T-scores of -2·0 or more were accrued (147 allocated exemestane, 153 anastrozole); and 197 patients with baseline T-scores of less than -2·0 (101 exemestane, 96 anastrozole). For patients with T-scores greater than -2·0 at baseline, mean change of bone mineral density in the spine at 2 years did not differ significantly between patients taking exemestane and patients taking anastrozole (-0·92{\%}, 95{\%} CI -2·35 to 0·50 vs -2·39{\%}, 95{\%} CI -3·77 to -1·01; p=0·08). Respective mean loss in the hip was -1·93{\%} (95{\%} CI -2·93 to -0·93) versus -2·71{\%} (95{\%} CI -4·32 to -1·11; p=0·10). Likewise for those who started with T-scores of less than -2·0, mean change of spine bone mineral density at 2 years did not differ significantly between the exemestane and anastrozole treatment groups (2·11{\%}, 95{\%} CI -0·84 to 5·06 vs 3·72{\%}, 95{\%} CI 1·54 to 5·89; p=0·26), nor did hip bone mineral density (2·09{\%}, 95{\%} CI -1·45 to 5·63 vs 0·0{\%}, 95{\%} CI -3·67 to 3·66; p=0·28). Patients with baseline T-score of -2·0 or more taking exemestane had two fragility fractures and two other fractures, those taking anastrozole had three fragility fractures and five other fractures. For patients who had baseline T-scores of less than -2·0 taking exemestane, one had a fragility fracture and four had other fractures, whereas those taking anastrozole had five fragility fractures and one other fracture. Interpretation: Our results demonstrate that adjuvant treatment with aromatase inhibitors can be considered for breast cancer patients who have T-scores less than -2·0. Funding: Canadian Cancer Society Research Institute, Pfizer, Canadian Institutes of Health Research.",
author = "Goss, {Paul E.} and Hershman, {Dawn L.} and Cheung, {Angela M.} and Ingle, {James N.} and Sundeep Khosla and Vered Stearns and Haji Chalchal and Kendrith Rowland and Muss, {Hyman B.} and Linden, {Hannah M.} and Judite Scher and Pritchard, {Kathleen I.} and Elliott, {Catherine R.} and Tanja Badovinac-Crnjevic and {St Louis}, Jessica and Chapman, {Judith Anne W} and Shepherd, {Lois E.}",
year = "2014",
doi = "10.1016/S1470-2045(14)70035-X",
language = "English (US)",
volume = "15",
pages = "474--482",
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TY - JOUR

T1 - Effects of adjuvant exemestane versus anastrozole on bone mineral density for women with early breast cancer (MA.27B)

T2 - A companion analysis of a randomised controlled trial

AU - Goss, Paul E.

AU - Hershman, Dawn L.

AU - Cheung, Angela M.

AU - Ingle, James N.

AU - Khosla, Sundeep

AU - Stearns, Vered

AU - Chalchal, Haji

AU - Rowland, Kendrith

AU - Muss, Hyman B.

AU - Linden, Hannah M.

AU - Scher, Judite

AU - Pritchard, Kathleen I.

AU - Elliott, Catherine R.

AU - Badovinac-Crnjevic, Tanja

AU - St Louis, Jessica

AU - Chapman, Judith Anne W

AU - Shepherd, Lois E.

PY - 2014

Y1 - 2014

N2 - Background: Treatment of breast cancer with aromatase inhibitors is associated with damage to bones. NCIC CTG MA.27 was an open-label, phase 3, randomised controlled trial in which women with breast cancer were assigned to one of two adjuvant oral aromatase inhibitors-exemestane or anastrozole. We postulated that exemestane-a mildly androgenic steroid-might have a less detrimental effect on bone than non-steroidal anastrozole. In this companion study to MA.27, we compared changes in bone mineral density (BMD) in the lumbar spine and total hip between patients treated with exemestane and patients treated with anastrozole. Methods: In MA.27, postmenopausal women with early stage hormone (oestrogen) receptor-positive invasive breast cancer were randomly assigned to exemestane 25 mg versus anastrozole 1 mg, daily. MA.27B recruited two groups of women from MA.27: those with BMD T-scores of -2·0 or more (up to 2 SDs below sex-matched, young adult mean) and those with at least one T-score (hip or spine) less than -2·0. Both groups received vitamin D and calcium; those with baseline T-scores of less than -2·0 also received bisphosphonates. The primary endpoints were percent change of BMD at 2 years in lumbar spine and total hip for both groups. We analysed patients according to which aromatase inhibitor and T-score groups they were allocated to but BMD assessments ceased if patients deviated from protocol. This study is registered with ClinicalTrials.gov, NCT00354302. Findings: Between April 24, 2006, and May 30, 2008, 300 patients with baseline T-scores of -2·0 or more were accrued (147 allocated exemestane, 153 anastrozole); and 197 patients with baseline T-scores of less than -2·0 (101 exemestane, 96 anastrozole). For patients with T-scores greater than -2·0 at baseline, mean change of bone mineral density in the spine at 2 years did not differ significantly between patients taking exemestane and patients taking anastrozole (-0·92%, 95% CI -2·35 to 0·50 vs -2·39%, 95% CI -3·77 to -1·01; p=0·08). Respective mean loss in the hip was -1·93% (95% CI -2·93 to -0·93) versus -2·71% (95% CI -4·32 to -1·11; p=0·10). Likewise for those who started with T-scores of less than -2·0, mean change of spine bone mineral density at 2 years did not differ significantly between the exemestane and anastrozole treatment groups (2·11%, 95% CI -0·84 to 5·06 vs 3·72%, 95% CI 1·54 to 5·89; p=0·26), nor did hip bone mineral density (2·09%, 95% CI -1·45 to 5·63 vs 0·0%, 95% CI -3·67 to 3·66; p=0·28). Patients with baseline T-score of -2·0 or more taking exemestane had two fragility fractures and two other fractures, those taking anastrozole had three fragility fractures and five other fractures. For patients who had baseline T-scores of less than -2·0 taking exemestane, one had a fragility fracture and four had other fractures, whereas those taking anastrozole had five fragility fractures and one other fracture. Interpretation: Our results demonstrate that adjuvant treatment with aromatase inhibitors can be considered for breast cancer patients who have T-scores less than -2·0. Funding: Canadian Cancer Society Research Institute, Pfizer, Canadian Institutes of Health Research.

AB - Background: Treatment of breast cancer with aromatase inhibitors is associated with damage to bones. NCIC CTG MA.27 was an open-label, phase 3, randomised controlled trial in which women with breast cancer were assigned to one of two adjuvant oral aromatase inhibitors-exemestane or anastrozole. We postulated that exemestane-a mildly androgenic steroid-might have a less detrimental effect on bone than non-steroidal anastrozole. In this companion study to MA.27, we compared changes in bone mineral density (BMD) in the lumbar spine and total hip between patients treated with exemestane and patients treated with anastrozole. Methods: In MA.27, postmenopausal women with early stage hormone (oestrogen) receptor-positive invasive breast cancer were randomly assigned to exemestane 25 mg versus anastrozole 1 mg, daily. MA.27B recruited two groups of women from MA.27: those with BMD T-scores of -2·0 or more (up to 2 SDs below sex-matched, young adult mean) and those with at least one T-score (hip or spine) less than -2·0. Both groups received vitamin D and calcium; those with baseline T-scores of less than -2·0 also received bisphosphonates. The primary endpoints were percent change of BMD at 2 years in lumbar spine and total hip for both groups. We analysed patients according to which aromatase inhibitor and T-score groups they were allocated to but BMD assessments ceased if patients deviated from protocol. This study is registered with ClinicalTrials.gov, NCT00354302. Findings: Between April 24, 2006, and May 30, 2008, 300 patients with baseline T-scores of -2·0 or more were accrued (147 allocated exemestane, 153 anastrozole); and 197 patients with baseline T-scores of less than -2·0 (101 exemestane, 96 anastrozole). For patients with T-scores greater than -2·0 at baseline, mean change of bone mineral density in the spine at 2 years did not differ significantly between patients taking exemestane and patients taking anastrozole (-0·92%, 95% CI -2·35 to 0·50 vs -2·39%, 95% CI -3·77 to -1·01; p=0·08). Respective mean loss in the hip was -1·93% (95% CI -2·93 to -0·93) versus -2·71% (95% CI -4·32 to -1·11; p=0·10). Likewise for those who started with T-scores of less than -2·0, mean change of spine bone mineral density at 2 years did not differ significantly between the exemestane and anastrozole treatment groups (2·11%, 95% CI -0·84 to 5·06 vs 3·72%, 95% CI 1·54 to 5·89; p=0·26), nor did hip bone mineral density (2·09%, 95% CI -1·45 to 5·63 vs 0·0%, 95% CI -3·67 to 3·66; p=0·28). Patients with baseline T-score of -2·0 or more taking exemestane had two fragility fractures and two other fractures, those taking anastrozole had three fragility fractures and five other fractures. For patients who had baseline T-scores of less than -2·0 taking exemestane, one had a fragility fracture and four had other fractures, whereas those taking anastrozole had five fragility fractures and one other fracture. Interpretation: Our results demonstrate that adjuvant treatment with aromatase inhibitors can be considered for breast cancer patients who have T-scores less than -2·0. Funding: Canadian Cancer Society Research Institute, Pfizer, Canadian Institutes of Health Research.

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