血清肿瘤标志物预测乳腺癌骨转移的价值

目的探讨血清肿瘤标志物预测乳腺癌骨转移的临床价值。方法应用化学发光免疫检测技术检测174例乳腺癌患者血清CA153、CA125、CEA、FER等四种肿瘤标志物,同时应用SPECT对所有患者行全身骨扫描检查,以明确有无骨转移。结果174例患者中55例临床诊断为乳腺癌骨转移。CA153、CA125、CEA、FER对诊断骨转移的阳性预测价值分别为68.0%(34/50),70.0%(14/20),88.9%(8/9),53.8%(14/26),阴性预测价值分别为86.2%(106/123),89.0%(130/146),73.2%(115/157),75.9%(85/112)。一种以上标志物同时阳性或阴性者,其阳性或阴性预测价值增加。结论CA153、CA125、CEA、FER具有预测乳腺癌骨转移的临床价值,联合检测CA153、CA125、CEA、FER能提高其预测乳腺癌骨转移的准确性。     

与乳腺癌相关的肿瘤标志物研究现状及评价

当前,肿瘤标志物的检测已从细胞水平深入到分子基因水平,在检测技术上,它将生物化学、核医学、免疫学、细胞学、病理学、分子生物学等诸多学科融合在一起,不仅使检测的项目有了大幅度的增加,而且检测的特异性和灵敏度也有很大的提高。     

乳腺癌转移复发肿瘤标志物研究进展

肿瘤标志物是指与肿瘤发生相关的物质，主要包括两部分：大分子蛋白质肿瘤标志物和基因肿瘤标志物，可用于肿瘤的早期发现、预后判断、定位和治疗。目前有多种肿瘤标志物与乳腺癌转移相关，但erbB-2可在20％－30％侵袭性乳腺癌患者中扩增表达，被认为是首选的肿瘤标志物，并成为抗乳腺癌治疗的靶点。研究认为，肿瘤的转移潜能与多药耐药（MDR）表型相关。因此从MDR相关基因和蛋白质中寻找肿瘤标志物，可成为克服乳腺癌转移的新策略。     

乳腺癌转移复发肿瘤标志物研究进展

肿瘤标志物是指与肿瘤发生相关的物质，主要包括两部分大分子蛋白质肿瘤标志物和基因肿瘤标志物，可用于肿瘤的早期发现、预后判断、定位和治疗。目前有多种肿瘤标志物与乳腺癌转移相关，但erb-2可在20％～30％侵袭性乳腺癌患者中扩增表达，被认为是首选的肿瘤标志物，并成为抗乳腺癌治疗的靶点。研究认为，肿瘤的转移潜能与多药耐药(MDR)表型相关。因此从MDR相关基因和蛋白质中寻找肿瘤标志物，可成为克服乳腺癌转移的新策略。     

肺腺癌骨转移患者血清肿瘤标志物的表达及意义

目的:探讨血清肿瘤标志物在晚期肺腺癌患者中的表达情况。方法:对2010年1月到2013年12月在我院住院治疗的64例肺腺癌骨转移患者的血清肿瘤标志物,进行回顾性分析,计算不同肿瘤标志物的阳性表达情况。结果:CEA、CA199、CA242、CA125、NSE和CY211在晚期肺腺癌中的阳性率分别为65.6%、40.6%、25.0%、73.4%、12.5%和43.8%,各组间阳性表达有统计学差异。联合检测的阳性率为90.6%。结论:不同肿瘤标志物在晚期肺癌骨转移患者血清中的表达是有差异的。CEA、CA199、CA125和CY211是肺腺癌诊断中较可靠的肿瘤标志指标。目前的血清肿瘤标志物检测对晚期肺癌诊断仍有一定的假阴性率,需结合临床及影像学检查进行综合判断。     

乳腺癌患者血清可溶性肿瘤标志物的临床价值研究

目的:探讨血清可溶性肿瘤标志物CEA、CA-153、ICAM-1、E-selection单项及联合检测在乳腺癌中的诊断价值.方法:选取不同临床分期乳腺癌患者130例.乳腺良性肿瘤患者30例,正常人群30例.通过酶联免疫吸附法(ELISA)测定各项指标血清浓度并进行比较.结果:乳腺癌CEA、CA-153、ICAM-1、E-selection血清浓度均显著高于良性肿瘤组及正常人群(P<0.01),且其血清浓度与肿瘤分期密切相关.在疾病进展的转移性乳腺癌中,各指标出现明显升高(P<0.01).CEA、CA-153、ICAM-1、E-selection单项检测对于乳腺癌的诊断敏感性较低.多指标联合检测可不同程度提高检测的敏感性,以含CA-153及E-selection组合最为显著.结论:E-selection、ICAM-1、CEA、CA-153均为乳腺癌重要的血清标志物,在肿瘤的发生、发展及转移过程中发挥重要的作用.对恶性肿瘤患者的多指标联合检测可在不显著降低特异性的基础上提高诊断的敏感性,为判断预后及监测病情提供重要价值.     

乳腺癌诊治中肿瘤标志物CA15-3的临床价值

目的：探讨CA15-3在乳腺癌诊治中的临床价值.方法：采用酶联免疫吸附法检测.结果：CA15-3在诊断乳腺良性疾病与乳腺癌时,差异无显著性（P＞0.05）;对62例乳腺癌进行观察,CA15-3在骨、肺转移及乳腺癌出现转移或复发时,阳性检测率较高,分别为85.71%、50%、100%,并且标志物浓度与转移、复发部位及病灶数目多少、浸润面积大小密切相关.结论：乳腺癌CA15-3浓度较高时,提示转移肿瘤存在且预后较差.     

乳腺癌新辅助化疗中肿瘤标志物检测的临床意义

目的检测肿瘤标志物在新辅助化疗乳腺癌中的表达,探讨新辅助化疗患者中ER、PR、c-erbB2和Ki67的表达及临床意义.方法用免疫组织化学法检测ER、PR、c-erbB2和Ki67在89例新辅助化疗乳腺癌组织中的表达状况,分析上述指标与化疗的关系.结果新辅助化疗总有效率89.9%,其中完全缓解CR32.6%,部分缓解PR57.3%,病理完全缓解pCR17.9%,疾病稳定SD10.5%,无恶化病例.ER/PR表达与疗效有关（P〈0.05）,c-erbB2、Ki67表达与化疗疗程无关.结论激素受体阴性者对新辅助化疗的敏感性较高,新辅助化疗肿瘤标志物的检测可以为临床评价疗效判断预后提供依据.     

乳腺癌标志物的临床意义

乳腺癌是妇女最常见的恶性肿瘤之一.近年来,乳腺癌发病率呈明显上升趋势,流行病学调查表明,25～35岁乳腺癌发病大幅增加,10年间平均增长速度高达10.7%.55～65岁为第二个发病高峰,在一些大中城市已跃居女性恶性肿瘤的首位或第二位,成为"女性之敌".与乳腺癌预后的有关因素除病期、病理类型、年龄及治疗方式方法之外,乳腺癌标志物的检测则可反映肿瘤的生物学特性,对指导治疗、辅助诊断、判断预后均有重要意义,越来越受到临床医师的重视.今将有关乳腺癌标志物的临床意义进行概述.     

乳腺癌相关血清肿瘤标志物的临床研究进展

癌胚抗原(CEA)、糖类抗原(CA)15-3、CA125等血清肿瘤标志物异常表达提示肿瘤的发生风险.CA15-3过表达被认为与乳腺癌的疾病进展有关,不同临床分期乳腺癌患者血清CA15-3的阳性检出率对诊断临床分期有显著优势,灵敏度和特异度均较高.但目前认为,某项血清肿瘤标志物单独检测对乳腺癌的阳性检出率较低,对早期筛查及诊断的意义不大,因此,多主张血清肿瘤标志物联合检测以对乳腺肿瘤进行早期筛查和早期诊断.本文对CEA、CA15-3、CA125等已在临床一定范围内得到应用的肿瘤标志物,以及新发现、潜在可能用于指导乳腺癌临床决策及治疗方案的肿瘤生物标志物与乳腺癌诊断、治疗及预后相关的临床研究进行综述.     

Bone metabolic markers in bone metastasis of breast cancer

Background. The efficacy and cost-performance benefit of radionuclide bone scintigraphy in monitoring metastatic bone activity remain controversial. Bone metabolic markers are now expected to play a role in the diagnosis and follow-up of bone metastasis. Methods. We investigated several bone metabolic markers in patients with breast cancer. We measured three metabolic markers of bone resorption: pyridinoline cross-linked carboxy terminal telopeptide (ICTP), C-telopeptides of type I collagen (CTx), and the free form of deoxypyridinoline (fDPD), and four metabolic markers of bone formation: procollagen I carboxy terminal peptide (PICP), total alkaline phosphatase (Al-p), bone-specific alkaline phosphatase (BAl-p), and osteocalcin (BGP) in 210 patients without and 268 patients with bone metastasis. Patients without bone metastasis were analyzed in terms of menstruation status. Patients with bone metastasis were analyzed in terms of bone metastatic burden and tumor lesion "condition" (ie, determination by X-ray and/or computed tomography and bone scan findings of new lesion, progression of disease, no change, improvement, and complete remission, according to the criteria of the International Unite Against Cancer). Results. In patients without bone metastasis, ICTP did not change with menopause. All markers other than ICTP were significantly elevated with menopause. In patients with bone metastasis, all markers, except for BGP, were significantly elevated according to metastatic bone tumor burden. Among the seven markers, ICTP showed the best receiver operating characteristic curves. ICTP also showed the best correlation to bone metastatic burden among the markers by Spearman's rank correlation coefficient. In patients stratified by "condition", ICTP, CTx, fDPD, Al-p, and BAl-p showed significant elevation in patients with progression, new lesion, and no change, while PICP and BGP showed only minimal elevation in those patients. Conclusion. Bone metabolic markers, particularly ICTP, appear to be valuable for the diagnosis of bone metastasis from breast cancer. Received: April 22, 1999 / Accepted: July 15, 1999     

The bisphosphonate incadronate for bone metastases of breast cancer

Background. Bisphosphonates are bone resorption inhibitors which are effective in the treatment of diseases of increased bone turnover, such as hypercalcemia of malignancy and osteolytic bone metastasis. The safety and efficacy of incadronate, a third-generation bisphosphonate, were evaluated in breast cancer patients with bone metastases. Methods. Fifteen breast cancer patients with bone metastasis were enrolled. Incadronate's safety, its effectiveness in relieving bone pain, and its effects on bone metabolic markers and a tumor marker were assessed in 8 patients treated with a 10-mg IV infusion once a week for 5 weeks (10 mg × 5), 3 patients treated with a single 20-mg IV infusion (20 mg × 1), and 4 patients treated with a 20-mg IV infusion once a week for 5 weeks (20 mg × 5). Pain assessment was performed only in the patients with the repeated infusion regimens. Results. All incadronate treatment regimens were administered without any serious adverse reactions. Minimal fever was noted in 6 patients, but it subsided without any treatment. Incadronate relieved bone pain in 10 of the 12 patients who received repeated infusions. Levels of bone resorption markers dropped transiently, but the decreases in the individual markers of bone resorption varied. Levels of bone formation markers did not change significantly. Levels of a tumor marker specific to breast cancer, carbohydrate antigen (CA)15-3 decreased in patients whose metastases were limited to bone. Conclusion. The third-generation bisphosphonate, incadronate, was administered safely at dosages of up to 20 mg once a week for 5 weeks. Incadronate reduced bone pain, bone resorption marker levels, and CA15-3 tumor marker levels in breast cancer patients with bone metastases. Received: November 9, 1999 / Accepted: March 6, 2000     

Evaluation of bone metabolic markers in breast cancer with bone metastasis

PURPOSE: In the present study, four bone metabolic markers were examined to clarify them meaning and clinical value in the detection of bone metastasis (BM) from breast cancer. METHODS: we examined serum carboxyterminal telopeptide of type I collagen (ICTP), tartrate resistant acid phosphatase (TRACP), total alkaline phosphatase (ALP) and urinary type I collagen cross-linked N-telopeptides (NTx) as potential markers. These bone markers were evaluated simultaneously in 156 breast cancer patients; 114 patients without metastasis (group A), 23 patients with BM (group B) and 19 patients with metastasis at sites other than bone (group C). RESULTS: The mean values of ICTP and TRACP in group B were significantly greater than those in group A. Group B consisted of the patients with varying degrees of BM and variation in their treatments. The patients in group B were divided into BM (+) and BM (++) according to hot spots in bone scan. ICTP and TRACP were elevated in BM (++) patients compared to BM (+) patients (p<0.05). The values of ICTP and TRACP of the twelve patients without treatment in group B were significantly higher than those in group A. In the treated patients of group B, the mean values of ICTP and TRACP were lower in responders and cases of stable disease than those with progression. NTx and ALP were inferior to ICTP and TRACP for clinical evaluation of BM. CONCLUSIONS: We confirmed that ICTP and TRACP might be useful markers for screening and monitoring BM in breast cancer.     

乳腺癌骨转移药物治疗的现状和进展

乳腺癌骨转移的发生率较高,应根据具体病情制订个体化的综合治疗方案,以减少或避免骨相关事件、延长患者的生存期、改善生活质量。其主要治疗手段包括抗肿瘤治疗、骨改良药物治疗、手术、放疗、止痛和支持治疗等。本文就乳腺癌骨转移的药物治疗作一综述。     

Clinical efficacy of bisphosphonate therapy for bone metastasis from breast cancer

Bisphosphonates inhibit osteoclastic bone resorption and are being used as treatment for bone metastases from breast cancer. Intravenous bisphosphonate therapy can significantly reduce skeletal related events (SREs) when administered concurrently with chemotherapy or endocrine therapy. In addition, intravenous bisphosphonate monotherapy is also able to alleviate cancer induced bone pain, and to improve bone metastases in some patients. Oral bisphosphonates are not routinely used for the treatment of bone metastases due to their low bioavailability. However, minodronate, a bisphosphonate 100-fold more potent than pamidronate, is now in phase II clinical studies in Japan, and may alter the role of oral bisphosphonates in the treatment of bone metastasis from breast cancer. The ASCO guidelines recommend that patients with osteolytic bone metastases be treated not with bisphosphonate monotherapy, but with concurrent bisphosphonate and systemic therapy. In addition, it is also recommended that current standards of care for cancer pain, analgesics and radiotherapy, should not be replaced with bisphosphonate therapy.     

乳腺癌骨转移和骨相关疾病临床诊疗专家共识(2008版)

乳腺癌骨转移在复发转移乳腺癌中的发生率为65%～75%.乳腺癌远处转移中,首发症状为骨转移者占27%～50%.骨痛、骨损伤、骨相关事件(skeletal related event,SRE)的发生及生活质量的降低是乳腺癌骨转移的常见并发症.SHE是指在临床试验中表明双膦酸盐类药物治疗失败的研究观察终点,一般定义为骨痛加剧或出现新的骨痛、病理性骨折、椎体压缩或变形、脊髓压迫、骨放疗、骨转移病灶进展及高钙血症等事件,是影响患者自主活动能力和生活质量的主要因素[1-3].     

Tumor microenvironment: driving forces and potential therapeutic targets for breast cancer metastasis

Distant metastasis to specific target organs is responsible for over 90% of breast cancer-related deaths, but the underlying molecular mechanism is unclear. Mounting evidence suggests that the interplay between breast cancer cells and the target organ microenvironment is the key determinant of organ-specific metastasis of this lethal disease.Here, we highlight new findings and concepts concerning the emerging role of the tumor microenvironment in breast cancer metastasis; we also discuss potential therapeutic intervention strategies aimed at targeting components of the tumor microenvironment.     

乳腺癌骨转移内分泌治疗与化疗的对比研究

目的　对比分析内分泌治疗与化疗对乳腺癌骨转移的疗效。方法　对 138例无内脏转移的乳腺癌骨转移患者 ,行 2 89例次单独内分泌治疗或化疗。结果　内分泌治疗与化疗的一线治疗有效率分别为 35 .4 %和 31.7% ,差异无显著性 (χ2 =0 .16 3,P =0 .6 87) ;全部治疗有效率分别为 2 7.1%和 2 5 .0 % ,差异无显著性 (χ2 =0 .15 9,P =0 .6 90 ) ;临床获益率分别为 4 3.9%和 36 .6 % ,差异无显著性(χ2 =0 .6 0 3,P =0 .4 37)。但内分泌治疗与化疗的二线治疗临床获益率分别为 4 7.8%和 2 4 .2 % ,全部治疗为 4 7.5 %和 2 7.7% ,差异均有显著性 (χ2 =4 .5 37,P =0 .0 33;χ2 =11.2 0 1,P =0 .0 0 1)。内分泌治疗和化疗患者的中位治疗失败时间 (TTF)为 5个月和 2个月 ,中位病变进展时间 (TTP)为 5个月和 2 .5个月 ,差异均有非常显著性 (P均 <0 .0 0 1)。结论　单独内分泌治疗和化疗均为乳腺癌骨转移的有效治疗手段 ,其中内分泌治疗优于化疗。     

乳腺癌骨髓转移特点及治疗方法探讨

目的探讨乳腺癌患者骨髓转移临床表现的特殊性、转移规律及治疗策略。方法回顾性分析62例女性乳腺癌骨髓转移患者的临床及随访资料,包括乳腺癌骨髓转移发生时间、激素受体状况等及不同治疗策略对预后的影响。24例联合化疗,25例单药化疗,13例未接受化疗。生存率用Kaplan—Meier方法计算,用Log—rank方法进行生存曲线比较。结果62例患者中位年龄39岁（30～71岁）,中位病程21个月（1～49个月）。雌激素受体（ER）和（或）孕激素受体（PR）阳性患者30例（48．4％）,阴性19例（30．6％）。发热14例（22．6％）和（或）血象的一系或三系降低34例（62．9％）是乳腺癌骨髓转移的常见表现。联合化疗和单药化疗中位生存期分别为10个月和16个月（QPH=7．38,P=0．0335）,未接受化疗者中位生存期仅1个月。骨髓转移发生偏晚,一般有多处转移尤其是骨转移的背景。结论骨髓穿刺有利于早期发现骨髓转移;骨髓转移晚期体质较弱,单药化疗可能是有效的治疗策略之一,与联合化疗组的患者相比具有生存优势。     

乳腺癌骨转移研究的新进展及展望——从机制到临床

乳腺癌骨转移是晚期乳腺癌患者严重的并发症之一.骨转移后出现的严重骨痛、病理性骨折等并发症,严重影响患者的生活质量并缩短其生存期.近年来,随着对乳腺癌骨转移机制以及肿瘤细胞与骨微环境之间相关调控网络的认知不断深入,许多新药的开发和应用使乳腺癌骨转移的治疗取得重大进展.现就乳腺癌骨转移机制及目前治疗研究进展进行综述.