Denosumab effect on bone mineral density and urinary-NTX in breast cancer patients receiving aromatase inhibitors.

INTRODUCTION: Aromatase inhibitors are used post-surgical intervention in postmenopausal patients with breast cancer. However, these drugs accelerate decline in bone mineral density (BMD), which is countered by use of denosumab, and the efficacy of the drug can be assessed by bone turnover markers. We investigated the effects of denosumab administration for 2 years on BMD and urinary N-telopeptide of type I collagen (u-NTX) levels in breast cancer patients treated with aromatase inhibitors. MATERIALS AND METHODS: This was a single-center retrospective study. Postoperative hormone receptor-positive breast cancer patients with low T-scores biannually received denosumab from the time of initiation of aromatase inhibitor therapy for 2 years. BMD was measured every 6 months, and u-NTX levels were assessed after 1 month and thereby every 3 months. RESULTS: The median patient age of the 55 patients included in this study was 69 (range: 51-90) years. BMD gradually increased in the lumbar spine and femoral neck and u-NTX levels were lowest at 3 months post-initiation of therapy. Patients were divided into two groups based on the change ratio of u-NTX 3 months post-denosumab administration. Of these, the group with higher change ratio showed a higher degree of BMD restoration in the lumbar spine and femoral neck 6 months post-denosumab treatment. CONCLUSION: Denosumab increased BMD in patients treated with aromatase inhibitors. The u-NTX level decreased soon after start of denosumab treatment, and its change ratio is predictive of improvement in BMD.

Utility of urinary type I collagen cross-linked N-telopeptide as a prognostic indicator in breast cancer patients with bone metastases.

BACKGROUND: Breast cancer patients with bone metastases are usually managed with bone modifying agents, such as zoledronic acid and denosumab, and some bone turnover markers (BTMs) have been recognized as prognostic indicators in such patients. Although several studies have demonstrated the validity of BTMs as prognostic markers in patients treated with zoledronic acid, few studies have reported the utility of BTMs with denosumab treatment. In this study, we evaluated whether urinary N-telopeptide of type I collagen (u-NTX) can be a prognostic indicator in patients treated with denosumab. METHODS: Thirty-six breast cancer patients newly diagnosed with bone metastases were evaluated retrospectively. Patients were treated with denosumab and anti-cancer drugs. u-NTX levels were measured 1 month before and after administration of denosumab, and the ratio of u-NTX levels before and after denosumab (change ratio) was assessed for its association with prognosis. RESULTS: Levels of u-NTX decreased after denosumab administration in all patients except for one. The median value of the u-NTX change ratio was 0.766. Based on the change ratio, patients were divided into either a "high group" (n = 18) or a "low group" (n = 18). The low group showed significantly shorter overall survival (OS) compared with the high group (low group 15.0 months; high group 54.0 months; P = 0.012). Multivariate analysis indicated that the "low group" was an independent prognostic factor for OS (P = 0.028). CONCLUSION: We demonstrated that the u-NTX change ratio in denosumab-treated breast cancer patients with bone metastases can be a prognostic marker.