Validity of bone marker measurements for monitoring response to bisphosphonate therapy with zoledronic acid in metastatic breast cancer

Aktas, Bahriye; Kasimir‐Bauer, Sabine; Lehmann, Nils; Tewes, Mitra

doi:10.3892/or.2013.2409

Cited by 11 publications

(7 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Mountzious et al (15) prospectively evaluated RANKL, OPG and CTX, and observed that none of these markers was capable of predicting response to bone. In a recent prospective study, Aktas et al observed that procollagen type I N propeptide and ICTP were the best indicators of bone disease respect to tumor routine markers for monitoring response to bisphosphonates in breast cancer patients (14).…”

Section: Discussionmentioning

confidence: 99%

“…Another potentially useful tool to aid clinicians in measuring bone response could be the use of circulating predictive markers. Although numerous markers have been evaluated for this purpose, including cross-linked C-terminal telopeptides of type I collagen (ICTP) and cross-linked N-terminal telopeptides of type I collagen (NTX), no really accurate markers have been identified to RANKL: A promising circulating marker for bone metastasis response (13)(14)(15)(16)(17). The present authors previously focused their attention on the molecules of the receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) axis that govern bone resorption and are involved in bone metastasis (18,19).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

RANKL: A promising circulating marker for bone metastasis response

et al. 2016

View full text Add to dashboard Cite

Abstract. Bone metastases are a frequent event in patients with solid tumors. Although great advances have been made in the treatment of these patients, the identification of novel, accurate indicators of bone response would greatly facilitate the clinical management of the disease. The receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) signaling pathway is significantly involved in bone metastasis formation. The main aim of the present study was to evaluate the role of circulating RANK, RANKL and OPG levels in predicting bone response. Marker accuracy was also compared with that of the conventional tumor marker N-terminal telopeptide of type I collagen (NTX). A prospective study was performed on 49 patients with bone metastases from breast, lung and prostate cancer, who were undergoing treatment with zoledronic acid. Patients were monitored for 1 year with blood tests, clinical evaluation and instrumental exams according to the response evaluation criteria of the University of Texas M. D. Anderson Cancer Center (Houston, TX, USA) and the Positron Emission Tomography Response Criteria in Solid Tumors. Circulating RANK/RANKL/OPG transcripts and NTX levels were evaluated by reverse transcription -quantitative polymerase chain reaction and immune enzymatic assay, respectively. The baseline RANKL levels differed significantly between responders and non-responders, whereas no differences in NTX levels were observed between the two groups. Receiver operating characteristic curve evaluation for all markers revealed that RANKL was the most accurate marker, with an area under the curve of 0.74 (95% confidence interval, 0.54-0.93). In addition, RANKL, which is the target of the novel monoclonal antibody denosumab, was the most accurate predictor of bone response in the present series of patients with bone metastases. Thus, the use of RANKL as a marker could potentially improve clinical practice, as current bone response evaluation is still somewhat problematic. IntroductionBone metastases are common in numerous solid cancers, including breast, prostate and lung cancer (1,2). In the USA, ~2/3 of patients who succumb to cancer each year have bone metastases, and ~20-25% of patients with neoplastic disease develop clinically evident bone metastases during the natural course of the disease (3,4).Bone metastases are responsible for high morbidity and reduced quality of life due to the frequent onset of clinical complications defined as skeletal-related events (SREs), which lead to a reduction in functional independence and quality of life, decrease survival rates and substantially increase healthcare costs (5,6).Bisphosphonates have improved the quality of life of patients with bone metastases from breast cancer by inducing both a reduction in SREs and in the risk of mortality (7). In particular, zoledronic acid (ZA), a potent third-generation nitrogen-containing bisphosphonate, has achieved widespread clinical use in the treatment of bone metastases from solid tumors (8-10). Denosumab, a ...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

RANKL: A promising circulating marker for bone metastasis response

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Elevation of ICTP occurs in bone loss due to myeloma (17), as well as other cancers causing bony metastases, including lung (18), breast (19) and prostate (20). Elevation of ICTP also occurs in rheumatoid disease (21), as it does with increased bone turnover secondary to coeliac disease (22).…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Accuracy of Bone Turnover Markers as a Screening Tool for Aseptic Loosening after Total Hip Arthroplasty

et al. 2015

View full text Add to dashboard Cite

Aseptic loosening is the most common cause of prosthesis failure after total hip arthroplasty (THA). We measured serum cross-linked carboxyterminal telopeptide of type I collagen (ICTP), tartrate-resistant acid phosphatase 5b (TRAP5b), dickkopf-1 (dkk-1) and sclerostin; and urinary α isomer of C-terminal cross-linked telopeptide of type I collagen (αCTX-I) to investigate their potential diagnostic value detecting aseptic loosening after THA. Biomarkers were measured in 24 subjects with aseptic loosening of THA versus 26 control subjects without loosening after THA. Serum ICTP in the loose group (7.04 ng/mL) was higher than controls (5.15 ng/mL), (p = 0.0007). ROC analysis demonstrated that a serum ICTP >5.5 ng/L had a sensitivity of 91% and specificity of 69% for detecting aseptic loosening (area under ROC curve = 0.77, p = 0.0001), resulting in a positive predictive value (PPV) of 73% and a negative predictive value (NPV) of 90%. Serum TRAP5b in the aseptic loosening group (4.17U/L) was higher than controls (3.44 U/L), (p = 0.03). A serum TRAP5b >2.46 U/L had sensitivity of 100% and a specificity of 31% to detect aseptic loosening (AUC 0.67, p = 0.031), resulting in a PPV of 57% and a NPV of 100%. Serum dkk-1, serum sclerostin and urinary αCTX-I were not elevated in subjects with aseptic loosening (p>0.05). Serum ICTP and TRAP5b show potential utility as screening biomarkers for excluding aseptic loosening, because of their ability to discriminate individuals without disease. Our finding of elevated ICTP, generated by the action of matrix metalloproteinases, suggests a role for this group of endopeptidases in aseptic loosening.

show abstract

“…More effective clinical predictors have been explored in medical field for many years, for comprehensively and accurately understanding the probability of postoperative recurrence and metastasis of breast cancer (Godfrey et al, 2013;Vermeulen et al, 2013;Zubeda et al, 2013). The tumor-related indicators in all individuals cannot be detected systemically and comprehensively due to limited economics and techniques, thereby, joint detection of specific tumor markers is of great importance (Wang et al, 2012;Aktas et al, 2013;Lawicki et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Expression and Significance of ER, PR, VEGF, CA15-3, CA125 and CEA in Judging the Prognosis of Breast Cancer

Zhang

Hu²,

Qian³

et al. 2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Objective: To explore the expression and significance of estrogen receptor (ER), progestrone receptor (PR), vascular endothelial growth factor (VEGF), CA15-3, CA125 and carcinoma embryonic antigen (CEA) expression in judging the prognosis of breast cancer. Materials and Methods: Sixty-five patients with breast cancer undergoing operations in the general surgery department were considered as the observation group, and 50 healthy outpatients of our hospital as the control group. Cubital venous blood was drawn in the morning from fasting patients in the two groups and chemiluminescence immunoassays were used to detect the levels of CA15-3, CA125 and CEA in serum. The follow-up duration was from 4 months to 2 years, and change in levels of the indicators was detected by dynamically drawing blood. After surgery, cancer tissue samples of patients in observation group remained on file (the non-recurrent patients were biopsied). Immunohistochemistry was applied to determine the expression of ER, PR and VEGF in tissue. Results: The effective rate of 12 patients with negative ER and PR expression was 33.3% in the observation group, being associated with prognosis to varying extents. Serum CA15-3, CA125 and CEA in the observation group were all significantly higher than in control group (p<0.01). With increase in pathological staging, levels of serum CA15-3, CA125 and CEA gradually increased (p<0.01). Levels in patients with lymph node metastasis were markedly higher than in those without (p<0.01). In addition, values with distal lymph node metastasis were notably higher than with adjacent lymph node metastasis (p<0.01). The postoperative follow-up results revealed that positive VEGF and levels of serum VEGF, CA15-3, CA125 and CEA in recurrence group were obviously higher than in non-recurrence group (p<0.01). Conclusions: Joint detection of ER and PR expression as well as levels of serum VEGF, CA15-3, CA125 and CEA is meaningful and can guide the diagnosis and treatment for breast cancer.

show abstract

Validity of bone marker measurements for monitoring response to bisphosphonate therapy with zoledronic acid in metastatic breast cancer

Cited by 11 publications

References 28 publications

RANKL: A promising circulating marker for bone metastasis response

RANKL: A promising circulating marker for bone metastasis response

Diagnostic Accuracy of Bone Turnover Markers as a Screening Tool for Aseptic Loosening after Total Hip Arthroplasty

Expression and Significance of ER, PR, VEGF, CA15-3, CA125 and CEA in Judging the Prognosis of Breast Cancer

Contact Info

Product

Resources

About