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Effects of de-escalated bisphosphonate therapy on bone turnover biomarkers in breast cancer patients with bone metastases.

ABSTRACT: While de-escalation of bisphosphonates from 4 to 12-weekly dosing has been shown to be clinically non-inferior to standard dosing, there is evidence the de-escalation is associated with increased bone turnover biomarkers. Here we evaluated the effect of de-escalated dosing on a panel of biomarkers and determined their association with incidence of skeletal related events (SREs) in breast cancer patients with 'low risk' bone metastases. As part of a pilot randomized trial, women with baseline C-telopeptide levels <600 ng/L after >3 months of 3-4 weekly pamidronate were randomized to continue pamidronate every 4 weeks or de-escalation to 12-weekly treatment. Serum was analysed for bone biomarkers (C-telopeptide, N-telopeptide, bone-specific alkaline phosphatase, transforming growth factor-?, procollagen type 1 N-propeptide, activinA and bone sialoprotein) using ELISA. The associations between changes in biomarkers, pain scores and SREs were assessed by univariable logistic regression. Numerical increases in all biomarkers were observed between baseline and 12 weeks but were of higher magnitude in the de-escalated arm. Pain scores in the de-escalated treatment arm showed a greater magnitude of pain reduction from baseline to 12 weeks. Neither baseline levels nor changes in biomarkers from baseline to 12 weeks on treatment were associated with on study SREs. Baseline pain as measured by the FACT-BP was associated with increased risk of SRE. In conclusion, biomarkers of bone activity do not appear to predict for SREs in 'low risk' cohorts. However, baseline bone pain appears to be associated with SRE occurrence, a finding which warrants evaluation in larger cohorts.

SUBMITTER: Addison CL

PROVIDER: S-EPMC4194305 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Effects of de-escalated bisphosphonate therapy on bone turnover biomarkers in breast cancer patients with bone metastases.

Addison Christina L CL Pond Gregory R GR Zhao Huijun H Mazzarello Sasha S Vandermeer Lisa L Goldstein Robyn R Amir Eitan E Clemons Mark M

SpringerPlus 20141001

While de-escalation of bisphosphonates from 4 to 12-weekly dosing has been shown to be clinically non-inferior to standard dosing, there is evidence the de-escalation is associated with increased bone turnover biomarkers. Here we evaluated the effect of de-escalated dosing on a panel of biomarkers and determined their association with incidence of skeletal related events (SREs) in breast cancer patients with 'low risk' bone metastases. As part of a pilot randomized trial, women with baseline C-t ...[more]

PMID: 25332877

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Project description:Background: Previous studies have preliminarily identified the non-inferior efficacy for reducing skeletal-related event (SRE) rates between de-escalated (Q12w) and standard (Q3-4w) bone-targeting agents therapy in malignant tumor patients with bone metastases. In this study, we aim to make further efforts to analyze whether the de-escalated bisphosphonates (BPs) strategy is a suitable option by comprehensively retrieving and synthesizing state-of-the-art evidence. Methods: An extensive electronic search for randomized controlled trials (RCTs) comparing a BPs standard strategy with the de-escalated one in patients with bone metastases was performed up to June 2018. Outcomes of interest were general and found individual types of SRE, skeletal morbidity rate (SMR), bone pain, bone turnover biomarkers and adverse events (AEs). Continuous and dichotomous outcomes were summarized by the weighted mean difference (WMD) and risk ratio (RR), respectively, with 95% confidence intervals (CIs). Results: A total of eight studies, representing six unique trials (involving 3114 patients), were included. Pooled results indicated comparable efficacy on general SRE (RR 0.99, 95% CI 0.87-1.12; P = 0.86; I 2 = 0%) and SMR (WMD 0.00, 95% CI -0.02 -0.03; P = 0.81; I 2 = 0%). However, the rate of surgery involving bones was significantly higher in de-escalated group than standard group (RR 1.92, 95% CI 1.17-3.15; P = 0.01; I 2 = 0%) among individual types of SRE. Several trials also demonstrated increased levels of C-terminal or N-terminal telopeptide in de-escalated group. Meta-analyses for gastrointestinal disorders, dizziness and back pain showed significant reductions by 27% (RR 0.73, 95% CI 0.57-0.94; P = 0.01; I 2 = 0%), 48% (RR 0.52 95% CI 0.32-0.86; P = 0.01; I 2 = 0%), and 29% (RR 0.71, 0.51-0.99; P = 0.04; I 2 = 0%), respectively, compared to the standard therapy. Conclusion: For malignant tumor patients with bone metastases, a de-escalated BPs strategy is proved to have a better safety profile compared to standard dosing. Although the efficacy is generally comparable on SRE and SMR between the two dosing regimens, trials with long duration and large sample sizes are still warranted to make a solid judgment.

Project description:Bone metastasis is a major cause of morbidity within solid tumours of the breast, prostate, lung and kidney. Metastasis to the skeleton is associated with a wide range of complications including bone fractures, spinal cord compression, hypercalcaemia and increased bone pain. Improved treatments for bone metastasis, such as the use of anti-bone resorptive bisphosphonate agents, within post-menopausal women have improved disease-free survival; however, these treatments are not without side effects. There is thus a need for biomarkers, which will predict the risk of developing the spread to bone within these cancers. The application of molecular profiling techniques, together with animal model systems and engineered cell-lines has enabled the identification of a series of potential bone-metastasis biomarker molecules predictive of bone metastasis risk. Some of these biomarker candidates have been validated within patient-derived samples providing a step towards clinical utility. Recent developments in multiplex biomarker quantification now enable the simultaneous measurement of up to 96 micro-RNA/protein molecules in a spatially defined manner with single-cell resolution, thus enabling the characterisation of the key molecules active at the sites of pre-metastatic niche formation as well as tumour-stroma signalling. These technologies have considerable potential to inform biomarker discovery. Additionally, a potential future extension of these discoveries could also be the identification of novel drug targets within cancer spread to bone. This chapter summarises recent findings in biomarker discovery within the key bone metastatic cancers (breast, prostate, lung and renal cell carcinoma). Tissue-based and circulating blood-based biomarkers are discussed from the fields of genomics, epigenetic regulation (micro-RNAs) and protein/cell-signalling together with a discussion of the potential future development of these markers towards clinical development.

Project description:Background For elderly patients with breast cancer, the treatment strategy is still controversial. In China, preoperative axillary lymph node needle biopsy is not widely used, resulting in many patients receiving axillary lymph node dissection (ALND) directly. Our study aims to determine whether local and systemic therapy can be safely de-escalated in elderly breast cancer. Methods Patients aged ≥70 years were retrospectively enrolled from our institution’s medical records between May 2013 and July 2021. Groups were assigned according to local and systemic treatment regimens, and stratified analysis was performed by molecular subtypes. Univariate and multivariate survival analyses were used to compare the effects of different regimens on relapse-free survival (RFS). Results A total of 653 patients were enrolled for preliminary data analysis, and 563 patients were screened for survival analysis. The mean follow-up was 19 months (range, 1–82 months). Axillary lymph node metastases were pathologically confirmed in only 2.1% of cN0 cases and up to 97.1% of cN+ cases. In the aspect of breast surgery, RFS showed no significant difference between mastectomy and BCS group (p = 0.3078). As for axillary surgery, patients in the ALND group showed significantly better RFS than those in the sentinel lymph node biopsy (SLNB) group among pN0 patients (p = 0.0128). Among these cases, the proportion of cN+ in ALND was significantly higher than that in SLNB (6.4% vs. 0.4%, p = 0.002), which meant axillary lymph nodes (ALNs) of ALND patients were larger in imaging and more likely to be misdiagnosed as metastatic. With regard to adjuvant therapy, univariate and multivariate analyses showed that RFS in different comprehensive adjuvant regimens were similar especially among hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)− subgroup where patients who did not receive any adjuvant therapy accounted for 15.7% (p > 0.05). Conclusions It is feasible to reduce some unnecessary local or systemic treatments for elderly breast cancer patients, especially in HR+/HER2− subtype. Multiple patient-related factors should be considered when making treatment plans.

Dataset Information

Effects of de-escalated bisphosphonate therapy on bone turnover biomarkers in breast cancer patients with bone metastases.

Publications

Effects of de-escalated bisphosphonate therapy on bone turnover biomarkers in breast cancer patients with bone metastases.

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