唑来膦酸对内分泌治疗绝经前乳腺癌患者所致骨丢失的效果观察

目的：观察唑来膦酸对戈舍瑞林与芳香化酶抑制剂联合治疗绝经前转移性乳腺癌患者所致骨丢失的临床效果和安全性,为临床应用提供参考。方法收集90例在我院乳腺科接受戈舍瑞林联合芳香化酶抑制剂治疗的绝经前转移性乳腺癌患者的临床资料,分为三组,A 组（30例）和 B 组（30例）在戈舍瑞林联合芳香化酶抑制剂治疗的同时使用唑来膦酸,疗程分别为5年和2年;C 组（30例）在戈舍瑞林联合芳香化酶抑制剂治疗期间未使用唑来膦酸。所有患者通过双能 X 线骨密度测量仪检测各时间点各组骨密度值,使用视觉模拟评分法进行肢体骨痛评定,观察记录骨质疏松性骨折的发生率。结果随访60个月,A 组患者各时间点骨密度均较 C 组升高（P ＜0．05）：A组患者在治疗第48,60个月骨密度较 B 组患者升高（P ＜0．05）：四肢疼痛视觉模拟评分 A 组低于 B 组和 C 组（P ＜0．05）：A 组患者骨质疏松性骨折的发生率显著低于 B 组和 C 组（P ＜0．05）。结论绝经前转移性乳腺癌患者行戈舍瑞林联合芳香化酶抑制剂治疗期间,早期足疗程应用唑来膦酸可减少骨量丢失和相关骨折发生,缓解骨痛。     

来曲唑和他莫昔芬治疗绝经后妇女早期乳腺癌的疗效比较

芳香化酶抑制剂来曲唑能够有效治疗转移性乳腺癌,在内分泌敏感性乳腺癌的绝经后妇女患者中,与他莫昔芬比较,来曲唑作为辅助治疗能够更有效地降低癌症复发的危险,特别是远端位置的复发。BIG1-98试验采用随机双盲法比较来曲唑和他莫昔芬对类固醇激素受体阳性的乳腺癌绝经后妇女进     

芳香化酶抑制剂治疗乳腺癌的研究进展及临床评价

目的:介绍芳香化酶抑制剂的研究进展,评价其在乳腺癌治疗中的应用及临床价值.方法:查阅近期国内、外相关文献进行整理、分析、总结.结果与结论:芳香化酶抑制剂用于绝经后晚期乳腺癌和早期乳腺癌术后辅助治疗的地位已经确立.新一代芳香化酶抑制剂与早期芳香化酶抑制剂相比,其疗效和抑制作用均有显著差异,这与其临床疗效较好有一致性.     

乳腺癌内分泌药物治疗的研究进展

乳腺癌是严重影响妇女身心健康甚至危及生命的恶性肿瘤之一。传统的乳腺癌内分泌治疗药物是作用于雌激素环节的雌激素受体调节剂、芳香化酶抑制剂,但芳香化酶抑制剂的选择性较差,有中度的治疗相关毒性,如高血脂、骨丢失、肝脂肪化等,因此需要开发具有组织选择性、高效低毒的芳香化酶抑制剂。此外,新型的甾体硫酸酯酶抑制剂也已成为有效的激素依赖性乳腺癌(HDBC)治疗药物,氨基磺酸酯基团被证实是这类药物中的药效团。本文综述了芳香化酶抑制剂和硫酸酯酶抑制剂的研究进展。     

来曲唑治疗晚期乳腺癌的临床分析

来曲唑是第3代芳香化酶抑制剂,大量临床研究表明,其对于绝经后激素依赖型晚期乳腺癌有较好疗效,且药物不良反应小,患者易于耐受。我院2008年5月-2010年5月采用来曲唑治疗晚期乳腺癌患者21例,疗效满意,现报道如下。1资料与方法     

ADR风向标

乳腺癌的生长和扩散通常依赖于雌激素,因此阻断雌激素是治疗乳腺癌的一个重要策略。芳香化酶抑制剂可通过抑制芳香化酶来阻断非卵巢组织中雌激素的合成,使绝经后妇女的雌激素水平下降超过97%,因此成为激素受体阳性乳腺癌的辅助内分泌治疗的重要选择之一。但是最近一项研究发现该药可增加心血管风险,建议缩短其使用时间。     

芳香化酶抑制剂——转移性肿瘤治疗的突破

国际乳腺组织（BIG）1-98协作组调查发现芳香化酶抑制剂来曲唑（letrozole）对绝经后早期乳腺癌妇女的辅助治疗效果较他奠昔芬（tamoxifen）更好，经中位数为期28．5个月的随访，来曲唑组5年复发率较他莫昔芬组降低3．4％，并可降低远端复发和对侧乳腺癌的发生率，尤其对接受化疗而未接受放疗具有淋巴结转移的患者疗效显著。     

乳腺癌内分泌治疗研究进展

内分泌治疗用于乳腺癌已有100多年的历史,具有疗效确实、耐受性良好的特点,已在各期激素受体阳性乳腺癌的辅助治疗中占据重要地位。目前,三苯氧胺仍是绝经前患者的标准用药,绝经后患者则首选芳香化酶抑制剂。本文就近年来进行的多个大宗临床试验,对乳腺癌内分泌治疗研究进展做一综述。     

辅助化疗、内分泌治疗对绝经后乳腺癌患者骨密度的影响

目的 研究辅助化疗、内分泌治疗对绝经后乳腺癌患者骨密度及骨丢失的影响.方法 收集2013年6月至2015年10月在本院诊断为绝经后乳腺癌患者共50例,分别在患者外科术后、接受常规化疗前及常规化疗完全结束后,内分泌AI治疗1年后,采用双能X线骨密度测量仪测量腰椎L2～L4及右股骨颈的骨密度.比较常规化疗前与常规化疗后,常规化疗后与AI治疗1年后腰椎及股骨颈的骨密度是否存在差异.结果 常规化疗后患者腰椎及股骨颈的骨密度较常规化疗前显著降低,其差异具有统计学意义;AI治疗1年后腰椎和股骨颈的骨密度较常规化疗后的骨密度显著降低,其差异具有统计学意义.结论 辅助化疗及内分泌治疗可不同程度的影响绝经后乳腺癌患者的骨代谢、降低骨密度,早期采用干预措施对预防骨丢失及骨质疏松是非常必要的.     

第三代芳香化酶抑制剂临床应用的常见不良反应

芳香化酶抑制剂在解救和辅助治疗乳腺癌方面，均显示出不逊于三苯氧胺的临床疗效．该类药物毒性反应成为人们关注的主要问题。近期资料显示芳香化酶抑制剂对血管、子宫的毒副作用明显少于三苯氧胺，而对血脂、骨丢失的影响较三苯氧胺明显，但该类药物的治疗相关毒性多为轻中度．均可很好处理。由于芳香化酶抑制剂应用时间尚短．其远期毒性还需进一步临床评价。     

唑来膦酸联合来曲唑治疗对绝经期乳腺癌术后生命质量的改善

探讨唑来膦酸联合来曲唑改善绝经期乳腺癌术后生命质量的治疗效果。方法：49例绝经期乳腺癌术后患者随机分为2组,观察组23例联合应用唑来膦酸和来曲唑,对照组26例单纯口服来曲唑。于术后6,12个月检测两组患者的骨密度（BMD）和血清骨特异性碱性磷酸酶（BALP）、I型胶原c端肽（CTX）,VAS评分镇痛效果,乳腺癌治疗功能评价系统（FACT-B）生命质量评分等指标并作比较。结果：观察组骨密度和FACT—B生命质量评分较对照组改善明显（P〈0．05或0．01）,观察组6,12个月时VAS评分、血清BALP水平、CTX含量等指标均较对照组明显减低（P〈0．05）。病变远处转移发生率两组差异无统计学意义（P〉0．05）。结论：唑来膦酸能有效改善来曲唑引起骨量丢失等不良反应,调高镇痛效果减低骨折风险发生提高患者生命质量。．     

唑来膦酸与替勃龙治疗绝经后骨质疏松疗效比较及对骨折的预防作用

目的比较唑来膦酸与替勃龙治疗绝经后骨质疏松的临床疗效及对骨折的预防作用。方法将本院诊治的128例绝经后骨质疏松患者随机分入唑来膦酸组与替勃龙组,两组患者均接受骨化三醇、钙剂治疗,唑来膦酸组患者同时接受唑来膦酸5 mg/年静脉注射,替勃龙组患者接受替勃龙2.5 mg/d,口服。用药后2年比较两组髋部及腰椎骨密度变化、血清Ⅰ型前胶原肽（CTX）、骨碱性磷酸酶（BALP）及不良反应发生情况。结果两组治疗后2年腰椎L1-L4和髋部区、股骨颈、大转子骨密度均显著增加（P〈0.05）,唑来膦酸组L1-L4骨密度增加显著优于替勃龙组（P〈0.05）;治疗后两组CTX及BALP均显著下降,唑来膦酸组CTX显著低于替勃龙组（P〈0.05）;唑来膦酸组与替勃龙组新发骨折发生率分别为4.5%和8.1%,两组比较差异无统计学意义（P〉0.05）;唑来膦酸组不良反应发生率为19.7%,替勃龙组为11.3%,两组均未发生严重不良反应。结论唑来膦酸与替勃龙治疗绝经后骨质疏松均可获得理想的临床疗效,唑来膦酸组腰椎骨质密度增加更为显著,患者治疗依从性好。     

绝经后妇女骨关节炎合并骨质疏松症的临床治疗研究

目的观察玻璃酸钠联合唑来膦酸治疗绝经后妇女骨关节炎伴骨质疏松症的疗效。方法将98例确诊为骨关节炎伴骨质疏松症的患者随机平均分为2组,A组为对照组,关节腔内注射玻璃酸钠2.5 mL,每周1次,5周1个疗程;B组为试验组,除了使用玻璃酸钠外,加用唑来膦酸（密固达）治疗,对患者进行膝关节功能评分、VAS、BMD,结果进行统计分析。结果膝关节功能评分2组间差异无统计学意义（P〉0.05）,膝关节疼痛缓解B组优于A组（P〈0.05）,骨密度检测A组治疗前后无明显变化,B组较治疗前明显增加（P〈0.05）。结论采用膝关节腔内注射玻璃酸钠加唑来膦酸治疗绝经后妇女骨关节炎伴骨质疏松症患者,效果良好。     

Pharmacotherapies to manage bone loss-associated diseases: a quest for the perfect benefit-to-risk ratio

In this review, benefits and side-effects of current and emerging therapies to treat and prevent pathological bone loss are described. Bisphosphonates are the antiresorptive compounds most widely used in the treatment of bone-loss associated diseases. They are generally well-tolerated although have recently been associated with osteonecrosis of the jaw and other complications. Therapies modulating estrogen receptor activation are indicated in the prevention and treatment of either breast cancer or osteoporosis in postmenopausal women. Thus, hormone replacement therapy is effective in prevention of osteoporosis, but its long-term use can increase the risk of breast cancer, stroke and embolism. Tamoxifen benefits all stages of breast cancer, but its use may lead to uterine cancer and thromboembolism. Raloxifene is approved in prevention of breast cancer and treatment of postmenopausal osteoporosis, but its use can increase the risk of fatal stroke. Aromatase inhibitors are superior to tamoxifen at advanced stages of disease and as adjuvants, but their use increase fracture incidence. Fulvestrant is as effective as aromatase inhibitors in the treatment of advanced breast cancer and does not cause bone fractures. Another antiresorptive available for the treatment of postmenopausal osteoporosis, Paget's disease and hypercalcemia is calcitonin, which also exhibits analgesic effects. A promising antiresorptive agent currently in clinical trials is denosumab. Aditional therapies for osteoporosis that decrease fracture risk consist of PTH-like anabolic agents and the dual action bone agent strontium ranelate. Antiseptics and antibiotics are used extensively in periodontal disease intervention to target bacterial biofilm, although host-directed therapies are also being developed.     

Anticancer activity of bisphosphonates in breast cancer

Despite progress in surgical and adjuvant therapy, a subset of patients with early stage breast cancer experience disease recurrence and/or distant metastases. Disseminated tumor cells (DTCs) in the bone marrow are believed to be the source of late relapses in bone and other tissues. Bone is the most common site of breast cancer metastasis, and agents that modify the bone microenvironment could therefore affect the disease course. Bisphosphonates are an effective bone-targeted therapeutic option for preventing cancer treatment- induced bone loss (CTIBL) in pre- and postmenopausal women with breast cancer. Bisphosphonates inhibit osteoclast-mediated bone resorption, thereby inhibiting the release of growth factors necessary to promote cancer cell growth, differentiation, and tumor formation in bone. Preclinical and clinical data also suggest anticancer synergy between cytotoxic chemotherapy agents and bisphosphonates. Recent trials of zoledronic acid in the adjuvant setting in breast cancer have demonstrated reduced disease recurrence in bone and other sites. Currently, several ongoing clinical trials are evaluating whether antiresorptives can inhibit disease recurrence and the development of bone metastases from breast cancer. Based on recent data, the role of bisphosphonates in the breast cancer setting is expected to expand in the future. With recent changes to treatment guidelines, routine use of bisphosphonates to prevent bone loss during adjuvant therapy is likely to become standard practice, especially for patients receiving endocrine therapy. Furthermore, the use of zoledronic acid to reduce the risk of recurrence is emerging based on ongoing clinical research.     

Single annual injectable treatment for postmenopausal osteoporosis

BACKGROUND: Several treatments for postmenopausal osteoporosis have become available over the last decade, but adherence to treatment is inadequate and the prevention of non-vertebral fracture by those medications is still modest. METHODS: We have performed a literature search regarding treatment with zoledronic acid in postmenopausal women. RESULTS: In the Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Pivotal Fracture Trial, involving 7765 postmenopausal women with low bone mineral density or with prevalent vertebral fracture, women taking zoledronic acid had a 70% vertebral fracture relative risk reduction and a 41% relative risk reduction for hip fracture, at 3 years, compared to placebo. In the HORIZON Recurrent Fracture Trial, 2127 patients (76% were women) were randomized to receive either zoledronic acid or a placebo after sustaining an initial hip fracture. After a median follow-up of 1.9 years, a relative risk reduction of 35% of clinical fractures was observed. Death from all causes was reduced by 28% in the zoledronic acid group. Zoledronic acid was generally safe in those trials, although a slightly increased rate of severe atrial fibrillations was observed in the HORIZON Prevention Fracture Trial, although not in the HORIZON Recurrent Fracture Trial. The clinical significance of this remains unclear. CONCLUSION: Yearly zoledronic acid presents a new option for the treatment of postmenopausal osteoporosis, with the perspective of improving the long-term persistence of therapy because of its once-a-year regimen.     

Denosumab: in the prevention of skeletal-related events in patients with bone metastases from solid tumours

Denosumab, a fully human monoclonal antibody, binds to the receptor activator of nuclear factor-κB ligand (RANKL) and thereby inhibits RANKL-mediated bone resorption. In various individual countries, subcutaneous denosumab is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumours (featured indication), and/or for the treatment of postmenopausal osteoporosis and/or of cancer treatment-induced bone loss in prostate or breast cancer patients. In three, pivotal, double-blind, multinational trials in adult patients with cancer-related bone metastases (total n?>?5700), including trials in patients with advanced breast or prostate cancer, subcutaneous denosumab (120 mg every 4 weeks) was shown to be noninferior to intravenous zoledronic acid (4 mg every 4 weeks), as determined by the median time to first on-study skeletal-related event (primary endpoint) at the time of the primary analysis (≈34 or 41 months). Denosumab treatment was superior to zoledronic acid in terms of the primary endpoint in two trials in patients with breast cancer or prostate cancer, based on secondary superiority analyses. In a third trial in patients with solid tumours excluding breast or prostate cancer, superiority of denosumab treatment versus zoledronic acid treatment was not demonstrated. The tolerability profile of denosumab was manageable in patients with bone metastases from solid tumours. Osteonecrosis of the jaw occurred in 1.8% and 1.3% of patients in the denosumab and zoledronic acid groups during the primary treatment phase; the incidence after approximately 4 additional months of denosumab treatment was 2.2%.     

Is zoledronic acid an anticancer drug?

Background: Zoledronic acid is used to prevent the bone loss associated with antioestrogen treatments in subjects with breast cancer. Preclinical studies suggest that zoledronic acid may have anticancer activity in its own right. This anticancer possibility with zoledronic acid has not been investigated extensively in clinical trials. Objectives/methods: This evaluation is of a large clinical trial that investigated the effect of zoledronic acid on cancer outcomes in premenopausal women with breast cancer. Results: The trial showed that after ～ 4 years, 94.0% of subjects who were treated with zoledronic acid were disease-free compared with 90.8% of those not treated with zoledronic acid. Recurrence survival was a secondary end point; this occurred in 94.0% with, and 90.9% without, zoledronic acid treatment. Conclusions: Zoledronic acid does have anticancer activity in premenopausal women with cancer.     

Zoledronic acid: a review of its use in the treatment of osteoporosis

Zoledronic acid (Aclasta; Reclast), a third-generation nitrogen-containing bisphosphonate, is the first once-yearly treatment to have been approved for use in patients with postmenopausal osteoporosis or at high risk of fracture. Intravenous zoledronic acid 5 mg once yearly is effective in reducing the risk of several types of fracture in patients with postmenopausal osteoporosis or recent low-trauma hip fracture. Moreover, improvements in bone mineral density (BMD) and reductions in markers of bone turnover are also generally observed. Zoledronic acid is generally well tolerated. Additional comparative data are required to definitively position zoledronic acid with respect to other agents. In the meantime, intravenous zoledronic acid 5 mg once yearly is a convenient and effective treatment option that may have an advantage over some other agents, for which adherence to treatment regimens is a recognized problem.     

Zoledronic acid for cancer therapy-induced and postmenopausal bone loss

Background: Cancer therapy-induced bone loss (CTIBL) and bone loss in postmenopausal (PMW) increase fracture risk. Objective: To review the efficacy and safety of zoledronic acid (ZA) for prevention and treatment of CTIBL and postmenopausal bone loss. Methods: Using PubMed, a search of the English language literature (January 1950 to November 2007) was performed to identify articles evaluating ZA in CTIBL patients without bone metastases and for postmenopausal bone loss; articles were reviewed and evaluated. Results/conclusion: Intermittent administration of ZA increases BMD, decreases bone turnover markers, and is well tolerated in both cancer patients without bone metastases and osteopenic/osteoporotic PMW. In osteopenic/osteoporotic PMW, ZA also decreases fracture rates and prevents second fractures. The optimal regimens in these populations are unknown.