Bone metabolism and quality-of-life of postmenopausal women with invasive breast cancer receiving neoadjuvant hormonal therapy: Sub-analyses from celecoxib anti-aromatase neoadjuvant (CAAN) trial

Louis W.C. Chow, Adrian Y.S. Yip, W. P. Chu, Wings T.Y. Loo, Masakazu Toi

Research output: Contribution to journalArticle

  • 5 Citations

Abstract

Objective: Anti-aromatase therapy is important in the treatment of breast cancer in postmenopausal women but they have effects on the bone mineral density (BMD) and osteoporosis. Cyclooxygenase-2 (COX-2) inhibitors have been shown to be effective in chemoprevention in animal and clinical studies. A proof of principle study was performed to investigate the efficacy of combing anti-aromatase therapy (exemestane) and COX-2 inhibitors neoadjuvantly. The changes in the BMD, bone turnover proteins and quality-of-life (QoL) were analyzed and presented here. Method: 82 postmenopausal patients with histologically confirmed invasive hormone-sensitive breast cancers were included for the neoadjuvant therapy (NHT). 30 patients received exemestane (EXE) 25 mg daily and celecoxib (CXB) 400 mg twice daily (group A), 24 patients received EXE 25 mg daily (group B) and 28 patients received letrozole (LET) 2.5 mg daily (group C). The same assigned treatment was intended to continue for 2 years to study the changes in the bone metabolism. BMD of 48 patients were analyzed; 23 belongs to group A, 10 to group B and 15 to group C. The serum bone turnover proteins bone-specific alkaline phosphatase (BAP) and carboxyterminal crosslinked telopeptide of type I collagen (ICTP), were measured with commercially available test kits before treatment, 3 months and 15 months after treatment. Functional Assessment of Cancer Therapy core questionnaire (FACT-G) with its additional breast cancer subscale were performed at baseline, 4, 8, and 12 weeks after NHT. Result: Difference between groups (p = 0.007) for BMD at femur was significant. The changes of BMD in group B patients were significantly greater than patients in group A (p = 0.011, CI = 0.063-0.437), and group C (p = 0.003, CI = 0.146-0.620). The mean BAP increased from baseline in group B patients but decreased from baseline in group C patients at 3 months and 15 months. No statistical significance was found in the FACT-G scores and FACT-B scores among different groups at baseline, week 4, week 8 and week 12 after NHT. The Breast Cancer Subscale scores in group A patients were significantly higher than that of group C patients (p = 0.021). After 4 weeks of NHT, negative changes of FACT-B and FACT-G scores were found in group B and C patients, but there were positive changes in group A patients. Significant differences of FACT-B score (p = 0.008) and FACT-G score (p = 0.019) were observed at that time point. Article from the Special issue on Targeted Inhibhitors.

LanguageEnglish (US)
Pages112-119
Number of pages8
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume125
Issue number1-2
DOIs
StatePublished - May 1 2011

Fingerprint

Celecoxib
Neoadjuvant Therapy
Aromatase
Metabolism
Bone
Quality of Life
exemestane
Breast Neoplasms
Bone and Bones
Minerals
Bone Density
letrozole
Cyclooxygenase 2 Inhibitors
Alkaline Phosphatase
Bone Remodeling
Functional assessment
Therapeutics

Keywords

  • Aromatase inhibitor
  • Bone metabolism
  • Breast cancer
  • Cyclooxygenase-2 inhibitors
  • Neoadjuvant
  • Quality-of-life

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

Cite this

@article{2c9e1ce9de7a4f349fc1359bfb675433,
title = "Bone metabolism and quality-of-life of postmenopausal women with invasive breast cancer receiving neoadjuvant hormonal therapy: Sub-analyses from celecoxib anti-aromatase neoadjuvant (CAAN) trial",
abstract = "Objective: Anti-aromatase therapy is important in the treatment of breast cancer in postmenopausal women but they have effects on the bone mineral density (BMD) and osteoporosis. Cyclooxygenase-2 (COX-2) inhibitors have been shown to be effective in chemoprevention in animal and clinical studies. A proof of principle study was performed to investigate the efficacy of combing anti-aromatase therapy (exemestane) and COX-2 inhibitors neoadjuvantly. The changes in the BMD, bone turnover proteins and quality-of-life (QoL) were analyzed and presented here. Method: 82 postmenopausal patients with histologically confirmed invasive hormone-sensitive breast cancers were included for the neoadjuvant therapy (NHT). 30 patients received exemestane (EXE) 25 mg daily and celecoxib (CXB) 400 mg twice daily (group A), 24 patients received EXE 25 mg daily (group B) and 28 patients received letrozole (LET) 2.5 mg daily (group C). The same assigned treatment was intended to continue for 2 years to study the changes in the bone metabolism. BMD of 48 patients were analyzed; 23 belongs to group A, 10 to group B and 15 to group C. The serum bone turnover proteins bone-specific alkaline phosphatase (BAP) and carboxyterminal crosslinked telopeptide of type I collagen (ICTP), were measured with commercially available test kits before treatment, 3 months and 15 months after treatment. Functional Assessment of Cancer Therapy core questionnaire (FACT-G) with its additional breast cancer subscale were performed at baseline, 4, 8, and 12 weeks after NHT. Result: Difference between groups (p = 0.007) for BMD at femur was significant. The changes of BMD in group B patients were significantly greater than patients in group A (p = 0.011, CI = 0.063-0.437), and group C (p = 0.003, CI = 0.146-0.620). The mean BAP increased from baseline in group B patients but decreased from baseline in group C patients at 3 months and 15 months. No statistical significance was found in the FACT-G scores and FACT-B scores among different groups at baseline, week 4, week 8 and week 12 after NHT. The Breast Cancer Subscale scores in group A patients were significantly higher than that of group C patients (p = 0.021). After 4 weeks of NHT, negative changes of FACT-B and FACT-G scores were found in group B and C patients, but there were positive changes in group A patients. Significant differences of FACT-B score (p = 0.008) and FACT-G score (p = 0.019) were observed at that time point. Article from the Special issue on Targeted Inhibhitors.",
keywords = "Aromatase inhibitor, Bone metabolism, Breast cancer, Cyclooxygenase-2 inhibitors, Neoadjuvant, Quality-of-life",
author = "Chow, {Louis W.C.} and Yip, {Adrian Y.S.} and Chu, {W. P.} and Loo, {Wings T.Y.} and Masakazu Toi",
year = "2011",
month = "5",
day = "1",
doi = "10.1016/j.jsbmb.2010.12.018",
language = "English (US)",
volume = "125",
pages = "112--119",
journal = "Journal of Steroid Biochemistry and Molecular Biology",
issn = "0960-0760",
publisher = "Elsevier Limited",
number = "1-2",

}

TY - JOUR

T1 - Bone metabolism and quality-of-life of postmenopausal women with invasive breast cancer receiving neoadjuvant hormonal therapy

T2 - Journal of Steroid Biochemistry and Molecular Biology

AU - Chow, Louis W.C.

AU - Yip, Adrian Y.S.

AU - Chu, W. P.

AU - Loo, Wings T.Y.

AU - Toi, Masakazu

PY - 2011/5/1

Y1 - 2011/5/1

N2 - Objective: Anti-aromatase therapy is important in the treatment of breast cancer in postmenopausal women but they have effects on the bone mineral density (BMD) and osteoporosis. Cyclooxygenase-2 (COX-2) inhibitors have been shown to be effective in chemoprevention in animal and clinical studies. A proof of principle study was performed to investigate the efficacy of combing anti-aromatase therapy (exemestane) and COX-2 inhibitors neoadjuvantly. The changes in the BMD, bone turnover proteins and quality-of-life (QoL) were analyzed and presented here. Method: 82 postmenopausal patients with histologically confirmed invasive hormone-sensitive breast cancers were included for the neoadjuvant therapy (NHT). 30 patients received exemestane (EXE) 25 mg daily and celecoxib (CXB) 400 mg twice daily (group A), 24 patients received EXE 25 mg daily (group B) and 28 patients received letrozole (LET) 2.5 mg daily (group C). The same assigned treatment was intended to continue for 2 years to study the changes in the bone metabolism. BMD of 48 patients were analyzed; 23 belongs to group A, 10 to group B and 15 to group C. The serum bone turnover proteins bone-specific alkaline phosphatase (BAP) and carboxyterminal crosslinked telopeptide of type I collagen (ICTP), were measured with commercially available test kits before treatment, 3 months and 15 months after treatment. Functional Assessment of Cancer Therapy core questionnaire (FACT-G) with its additional breast cancer subscale were performed at baseline, 4, 8, and 12 weeks after NHT. Result: Difference between groups (p = 0.007) for BMD at femur was significant. The changes of BMD in group B patients were significantly greater than patients in group A (p = 0.011, CI = 0.063-0.437), and group C (p = 0.003, CI = 0.146-0.620). The mean BAP increased from baseline in group B patients but decreased from baseline in group C patients at 3 months and 15 months. No statistical significance was found in the FACT-G scores and FACT-B scores among different groups at baseline, week 4, week 8 and week 12 after NHT. The Breast Cancer Subscale scores in group A patients were significantly higher than that of group C patients (p = 0.021). After 4 weeks of NHT, negative changes of FACT-B and FACT-G scores were found in group B and C patients, but there were positive changes in group A patients. Significant differences of FACT-B score (p = 0.008) and FACT-G score (p = 0.019) were observed at that time point. Article from the Special issue on Targeted Inhibhitors.

AB - Objective: Anti-aromatase therapy is important in the treatment of breast cancer in postmenopausal women but they have effects on the bone mineral density (BMD) and osteoporosis. Cyclooxygenase-2 (COX-2) inhibitors have been shown to be effective in chemoprevention in animal and clinical studies. A proof of principle study was performed to investigate the efficacy of combing anti-aromatase therapy (exemestane) and COX-2 inhibitors neoadjuvantly. The changes in the BMD, bone turnover proteins and quality-of-life (QoL) were analyzed and presented here. Method: 82 postmenopausal patients with histologically confirmed invasive hormone-sensitive breast cancers were included for the neoadjuvant therapy (NHT). 30 patients received exemestane (EXE) 25 mg daily and celecoxib (CXB) 400 mg twice daily (group A), 24 patients received EXE 25 mg daily (group B) and 28 patients received letrozole (LET) 2.5 mg daily (group C). The same assigned treatment was intended to continue for 2 years to study the changes in the bone metabolism. BMD of 48 patients were analyzed; 23 belongs to group A, 10 to group B and 15 to group C. The serum bone turnover proteins bone-specific alkaline phosphatase (BAP) and carboxyterminal crosslinked telopeptide of type I collagen (ICTP), were measured with commercially available test kits before treatment, 3 months and 15 months after treatment. Functional Assessment of Cancer Therapy core questionnaire (FACT-G) with its additional breast cancer subscale were performed at baseline, 4, 8, and 12 weeks after NHT. Result: Difference between groups (p = 0.007) for BMD at femur was significant. The changes of BMD in group B patients were significantly greater than patients in group A (p = 0.011, CI = 0.063-0.437), and group C (p = 0.003, CI = 0.146-0.620). The mean BAP increased from baseline in group B patients but decreased from baseline in group C patients at 3 months and 15 months. No statistical significance was found in the FACT-G scores and FACT-B scores among different groups at baseline, week 4, week 8 and week 12 after NHT. The Breast Cancer Subscale scores in group A patients were significantly higher than that of group C patients (p = 0.021). After 4 weeks of NHT, negative changes of FACT-B and FACT-G scores were found in group B and C patients, but there were positive changes in group A patients. Significant differences of FACT-B score (p = 0.008) and FACT-G score (p = 0.019) were observed at that time point. Article from the Special issue on Targeted Inhibhitors.

KW - Aromatase inhibitor

KW - Bone metabolism

KW - Breast cancer

KW - Cyclooxygenase-2 inhibitors

KW - Neoadjuvant

KW - Quality-of-life

UR - http://www.scopus.com/inward/record.url?scp=79957678145&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79957678145&partnerID=8YFLogxK

U2 - 10.1016/j.jsbmb.2010.12.018

DO - 10.1016/j.jsbmb.2010.12.018

M3 - Article

VL - 125

SP - 112

EP - 119

JO - Journal of Steroid Biochemistry and Molecular Biology

JF - Journal of Steroid Biochemistry and Molecular Biology

SN - 0960-0760

IS - 1-2

ER -