Zoledronic acid effectively prevents aromatase inhibitor- associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: Z-fast study 36-month follow-up results

Adam M. Brufsky, Linda D. Bosserman, Richard R. Caradonna, Barbara B. Haley, C. Michael Jones, Halle C F Moore, Lixian Jin, Ghulam M. Warsi, Solveig G. Ericson, Edith A. Perez

Research output: Contribution to journalArticle

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Abstract

Background: Postmenopausal women with breast cancer receiving adjuvant aromatase inhibitors (AIs) are at risk for accelerated bone loss and subsequent fractures. The ongoing Zometa-Femara Adjuvant Synergy Trial (Z-FAST) is evaluating the efficacy and safety of zoledronic acid in preventing such bone loss. Patients and Methods: In this multicenter study, postmenopausal women with early hormone receptor-positive breast cancer receiving adjuvant letrozole were randomized to receive up-front or delayed-start zoledronic acid (ZA; 4 mg intravenously every 6 months) for 5 years. Delayed-start ZA was administered if the lumbar spine (LS) or total hip (TH) T score fell below -2.0 or a nontraumatic fracture occurred. The primary endpoint was to compare the change from baseline in LS bone mineral density (BMD) between groups at month 12; secondary endpoints, measured at other predetermined timepoints, included comparing changes in TH BMD, LS BMD, and markers of bone turnover, fracture incidence, and time to disease recurrence. Herein, we report the results of the 36-month interim analysis. Results: Overall, 301 patients were randomized to each group. At month 36, the absolute difference in mean LS and TH BMDs between the up-front and delayed groups was 6.7% and 5.2%, respectively (P < .0001 for both). Although this study was not designed to show antifracture efficacy, the incidence of fractures was slightly higher in the delayed group (up-front, 17 [5.7%] vs. delayed, 19 [6.3%]) but not statistically significant (P = .8638). Pyrexia (27 [9%] vs. 6 [2%]; P = .0002) and bone pain (39 [13%] vs. 20 [6.7%]; P = .01) were more common in up-front patients; cough (13 [4.3%] vs. 27 [9%]; P = .03) was more common in delayed patients. No severe renal dysfunction or confirmed cases of osteonecrosis of the jaw were reported. Disease recurrence was reported in 9 up-front (3.0%) and 16 delayed (5.3%) patients (Kaplan-Meier analysis, P = .127), with an absolute decrease of 2.3%. Conclusion: Up-front ZA more effectively prevents AI-associated bone loss in postmenopausal women with early breast cancer than delaying therapy until substantial bone loss or fracture occurs.

Original languageEnglish (US)
Pages (from-to)77-85
Number of pages9
JournalClinical Breast Cancer
Volume9
Issue number2
DOIs
StatePublished - 2009

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letrozole
zoledronic acid
Aromatase Inhibitors
Postmenopausal Osteoporosis
Breast Neoplasms
Spine
Bone Density
Bone and Bones
Hip
Pelvic Bones
Recurrence
Osteonecrosis
Bone Remodeling
Bone Fractures
Incidence
Kaplan-Meier Estimate
Jaw
Cough
Multicenter Studies
Fever

Keywords

  • Bisphosphonates
  • Bone mineral density
  • Bone-specific alkaline phosphatase
  • N-telopeptide
  • T score

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Zoledronic acid effectively prevents aromatase inhibitor- associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole : Z-fast study 36-month follow-up results. / Brufsky, Adam M.; Bosserman, Linda D.; Caradonna, Richard R.; Haley, Barbara B.; Jones, C. Michael; Moore, Halle C F; Jin, Lixian; Warsi, Ghulam M.; Ericson, Solveig G.; Perez, Edith A.

In: Clinical Breast Cancer, Vol. 9, No. 2, 2009, p. 77-85.

Research output: Contribution to journalArticle

Brufsky, Adam M. ; Bosserman, Linda D. ; Caradonna, Richard R. ; Haley, Barbara B. ; Jones, C. Michael ; Moore, Halle C F ; Jin, Lixian ; Warsi, Ghulam M. ; Ericson, Solveig G. ; Perez, Edith A. / Zoledronic acid effectively prevents aromatase inhibitor- associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole : Z-fast study 36-month follow-up results. In: Clinical Breast Cancer. 2009 ; Vol. 9, No. 2. pp. 77-85.
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abstract = "Background: Postmenopausal women with breast cancer receiving adjuvant aromatase inhibitors (AIs) are at risk for accelerated bone loss and subsequent fractures. The ongoing Zometa-Femara Adjuvant Synergy Trial (Z-FAST) is evaluating the efficacy and safety of zoledronic acid in preventing such bone loss. Patients and Methods: In this multicenter study, postmenopausal women with early hormone receptor-positive breast cancer receiving adjuvant letrozole were randomized to receive up-front or delayed-start zoledronic acid (ZA; 4 mg intravenously every 6 months) for 5 years. Delayed-start ZA was administered if the lumbar spine (LS) or total hip (TH) T score fell below -2.0 or a nontraumatic fracture occurred. The primary endpoint was to compare the change from baseline in LS bone mineral density (BMD) between groups at month 12; secondary endpoints, measured at other predetermined timepoints, included comparing changes in TH BMD, LS BMD, and markers of bone turnover, fracture incidence, and time to disease recurrence. Herein, we report the results of the 36-month interim analysis. Results: Overall, 301 patients were randomized to each group. At month 36, the absolute difference in mean LS and TH BMDs between the up-front and delayed groups was 6.7{\%} and 5.2{\%}, respectively (P < .0001 for both). Although this study was not designed to show antifracture efficacy, the incidence of fractures was slightly higher in the delayed group (up-front, 17 [5.7{\%}] vs. delayed, 19 [6.3{\%}]) but not statistically significant (P = .8638). Pyrexia (27 [9{\%}] vs. 6 [2{\%}]; P = .0002) and bone pain (39 [13{\%}] vs. 20 [6.7{\%}]; P = .01) were more common in up-front patients; cough (13 [4.3{\%}] vs. 27 [9{\%}]; P = .03) was more common in delayed patients. No severe renal dysfunction or confirmed cases of osteonecrosis of the jaw were reported. Disease recurrence was reported in 9 up-front (3.0{\%}) and 16 delayed (5.3{\%}) patients (Kaplan-Meier analysis, P = .127), with an absolute decrease of 2.3{\%}. Conclusion: Up-front ZA more effectively prevents AI-associated bone loss in postmenopausal women with early breast cancer than delaying therapy until substantial bone loss or fracture occurs.",
keywords = "Bisphosphonates, Bone mineral density, Bone-specific alkaline phosphatase, N-telopeptide, T score",
author = "Brufsky, {Adam M.} and Bosserman, {Linda D.} and Caradonna, {Richard R.} and Haley, {Barbara B.} and Jones, {C. Michael} and Moore, {Halle C F} and Lixian Jin and Warsi, {Ghulam M.} and Ericson, {Solveig G.} and Perez, {Edith A.}",
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T1 - Zoledronic acid effectively prevents aromatase inhibitor- associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole

T2 - Z-fast study 36-month follow-up results

AU - Brufsky, Adam M.

AU - Bosserman, Linda D.

AU - Caradonna, Richard R.

AU - Haley, Barbara B.

AU - Jones, C. Michael

AU - Moore, Halle C F

AU - Jin, Lixian

AU - Warsi, Ghulam M.

AU - Ericson, Solveig G.

AU - Perez, Edith A.

PY - 2009

Y1 - 2009

N2 - Background: Postmenopausal women with breast cancer receiving adjuvant aromatase inhibitors (AIs) are at risk for accelerated bone loss and subsequent fractures. The ongoing Zometa-Femara Adjuvant Synergy Trial (Z-FAST) is evaluating the efficacy and safety of zoledronic acid in preventing such bone loss. Patients and Methods: In this multicenter study, postmenopausal women with early hormone receptor-positive breast cancer receiving adjuvant letrozole were randomized to receive up-front or delayed-start zoledronic acid (ZA; 4 mg intravenously every 6 months) for 5 years. Delayed-start ZA was administered if the lumbar spine (LS) or total hip (TH) T score fell below -2.0 or a nontraumatic fracture occurred. The primary endpoint was to compare the change from baseline in LS bone mineral density (BMD) between groups at month 12; secondary endpoints, measured at other predetermined timepoints, included comparing changes in TH BMD, LS BMD, and markers of bone turnover, fracture incidence, and time to disease recurrence. Herein, we report the results of the 36-month interim analysis. Results: Overall, 301 patients were randomized to each group. At month 36, the absolute difference in mean LS and TH BMDs between the up-front and delayed groups was 6.7% and 5.2%, respectively (P < .0001 for both). Although this study was not designed to show antifracture efficacy, the incidence of fractures was slightly higher in the delayed group (up-front, 17 [5.7%] vs. delayed, 19 [6.3%]) but not statistically significant (P = .8638). Pyrexia (27 [9%] vs. 6 [2%]; P = .0002) and bone pain (39 [13%] vs. 20 [6.7%]; P = .01) were more common in up-front patients; cough (13 [4.3%] vs. 27 [9%]; P = .03) was more common in delayed patients. No severe renal dysfunction or confirmed cases of osteonecrosis of the jaw were reported. Disease recurrence was reported in 9 up-front (3.0%) and 16 delayed (5.3%) patients (Kaplan-Meier analysis, P = .127), with an absolute decrease of 2.3%. Conclusion: Up-front ZA more effectively prevents AI-associated bone loss in postmenopausal women with early breast cancer than delaying therapy until substantial bone loss or fracture occurs.

AB - Background: Postmenopausal women with breast cancer receiving adjuvant aromatase inhibitors (AIs) are at risk for accelerated bone loss and subsequent fractures. The ongoing Zometa-Femara Adjuvant Synergy Trial (Z-FAST) is evaluating the efficacy and safety of zoledronic acid in preventing such bone loss. Patients and Methods: In this multicenter study, postmenopausal women with early hormone receptor-positive breast cancer receiving adjuvant letrozole were randomized to receive up-front or delayed-start zoledronic acid (ZA; 4 mg intravenously every 6 months) for 5 years. Delayed-start ZA was administered if the lumbar spine (LS) or total hip (TH) T score fell below -2.0 or a nontraumatic fracture occurred. The primary endpoint was to compare the change from baseline in LS bone mineral density (BMD) between groups at month 12; secondary endpoints, measured at other predetermined timepoints, included comparing changes in TH BMD, LS BMD, and markers of bone turnover, fracture incidence, and time to disease recurrence. Herein, we report the results of the 36-month interim analysis. Results: Overall, 301 patients were randomized to each group. At month 36, the absolute difference in mean LS and TH BMDs between the up-front and delayed groups was 6.7% and 5.2%, respectively (P < .0001 for both). Although this study was not designed to show antifracture efficacy, the incidence of fractures was slightly higher in the delayed group (up-front, 17 [5.7%] vs. delayed, 19 [6.3%]) but not statistically significant (P = .8638). Pyrexia (27 [9%] vs. 6 [2%]; P = .0002) and bone pain (39 [13%] vs. 20 [6.7%]; P = .01) were more common in up-front patients; cough (13 [4.3%] vs. 27 [9%]; P = .03) was more common in delayed patients. No severe renal dysfunction or confirmed cases of osteonecrosis of the jaw were reported. Disease recurrence was reported in 9 up-front (3.0%) and 16 delayed (5.3%) patients (Kaplan-Meier analysis, P = .127), with an absolute decrease of 2.3%. Conclusion: Up-front ZA more effectively prevents AI-associated bone loss in postmenopausal women with early breast cancer than delaying therapy until substantial bone loss or fracture occurs.

KW - Bisphosphonates

KW - Bone mineral density

KW - Bone-specific alkaline phosphatase

KW - N-telopeptide

KW - T score

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