化疗对乳腺癌术后患者骨代谢的影响

目的:观察不同化疗药物对乳癌术后患者骨代谢的影响,为化疗引起的继发性骨代谢异常、骨质疏松及其并发症(骨痛和病理性骨折)的早期干预提供临床依据.方法:收集年龄在50岁以下接受化疗的乳癌术后患者120例,按不同的化疗方案T(艾素),ET(表阿霉素、艾素),ECT(表阿霉素、环磷酰胺、艾素)分为3组,每组30例.另外30例未接受化疗的乳腺癌患者为对照组.分别于治疗前、后用双能X线骨密度仪对腰椎及股骨近端行骨密度(BMD)测定,同时使用全自动生化仪器测定患者血清碱性磷酸酶(ALP)、尿钙(Ca),放免法测定骨钙素(BGP)等生化指标.结果:4组乳腺癌患者的腰椎、股骨BMD值、ALP、BGP、尿Ca等生化指标治疗前各项检测指标经方差分析显示均无显著性差异(均P>0.05);对照组治疗前后上述各项指标比较均无显著性差异(均P>0.05).化疗后3组病例分别与对照组比较腰椎BMD、股骨BMD指标均显著下降(均P<0.05),且3化疗组下降程度也存在明显差异(均P<0.05),3化疗组间生化指标比较,除T组与ET组ALP指标无明显变化外(P>0.1),其余指标均有显著性差异(均P＜0.001).结论:化疗药物对乳腺癌术后患者骨质代谢存在明显不良影响,表现为骨吸收增高,骨质丢失增多,术后联合应用化疗药物与单一用药比较可明显加重乳癌患者的骨质丢失程度,提示乳癌术后患者接受化疗会使继发性骨质疏松及其并发症(骨痛和病理性骨折)的风险因素增高,应给予早期干预.     

唑来膦酸钠对绝经后乳腺癌患者骨代谢影响结果分析

目的:通过观察唑来膦酸钠对绝经后乳腺癌患者骨代谢影响,探讨唑来膦酸钠在早期预防乳腺癌患者发生骨代谢障碍及抑制骨转移中的作用。方法:85例绝经后乳腺癌患者均手术治疗,且术后常规行6个疗程的化疗,无骨转移病例。对照组:28例化疗后接受中药治疗;来曲唑组:30例化疗后继续服用来曲唑2.5mg/d;来曲唑+唑来膦酸钠组:27例患者化疗后除服用来曲唑2.5mg/d外,使用唑来膦酸钠注射液4mg+生理盐水100ml,静脉滴注15min,每4周为1个疗程。6个月后应用双能X线骨密度仪对三组乳癌患者腰椎、股骨近端骨密度(BMD)进行测定,用SPETCT行全身核素骨显像检查,使用全自动生化仪器测定血清碱性磷酸酶(ALP)、血钙(Ca)、血磷(P)等生化指标,用免疫组化方法测定雌激素(E2),对三组患者治疗前后各项指标分析比较。结果:治疗后来曲唑组与对照组病人的BMD、E2、血清Ca、P指标比较,均明显降低(P<0.05)、ALP明显上高(P<0.05);来曲唑+唑来膦酸钠组与来曲唑组比较,BMD、血清Ca、P指标明显升高(P<0.05),ALP降低(P<0.05)、E2未见明显变化(P>0.05);来曲唑+唑来膦酸钠与对照组比较,ALP、E2指标明显降低(P<0.05),BMD明显升高(P<0.05),血清Ca、P未见明显变化(P>0.05)。与对照组比较唑来膦酸钠组的骨转移发生率明显降低(P<0.05)。结论:唑来膦酸钠对接受来曲唑治疗引起的骨代谢障碍早期防治疗效明显,且对骨转移发生有明显抑制作用。     

唑来膦酸钠对绝经后乳腺癌患者骨代谢影响结果分析

目的：通过观察唑来膦酸钠对绝经后乳腺癌患者骨代谢影响,探讨唑来膦酸钠在早期预防乳腺癌患者发生骨代谢障碍及抑制骨转移中的作用。方法：85例绝经后乳腺癌患者均手术治疗,且术后常规行6个疗程的化疗,无骨转移病例。对照组：28例化疗后接受中药治疗;来曲唑组：30例化疗后继续服用来曲唑2．5mg／d;来曲唑＋唑来膦酸钠组：27例患者化疗后除服用来曲唑2．5mg／d外,使用唑来膦酸钠注射液4mg＋生理盐水100ml,静脉滴注15min,每4周为1个疗程。6个月后应用双能x线骨密度仪对三组乳癌患者腰椎、股骨近端骨密度（BMD）进行测定,用SPETCT行全身核素骨显像检查,使用全自动生化仪器测定血清碱性磷酸酶（ALP）、血钙（Ca）、血磷（P）等生化指标,用免疫组化方法测定雌激素（E2）,对三组患者治疗前后各项指标分析比较。结果：治疗后来曲唑组与对照组病人的BMD、E2、血清Ca、P指标比较,均明显降低（P〈0．05）、ALP明显上高（P〈0．05）;来曲唑＋唑来膦酸钠组与来曲唑组比较,BMD、血清Ca、P指标明显升高（P〈0．05）,ALP降低（P〈0．05）、E2未见明显变化（P〉0．05）;来曲唑＋唑来膦酸钠与对照组比较,ALP、E2指标明显降低（P〈0．05）,BMD明显升高（P〈0．05）,血清Ca、P未见明显变化（P〉0．05）。与对照组比较唑来膦酸钠组的骨转移发生率明显降低（P〈0．05）。结论：唑来膦酸钠对接受来曲唑治疗引起的骨代谢障碍早期防治疗效明显,且对骨转移发生有明显抑制作用。     

Chemotherapy for breast cancer (Review)

The use of cytotoxic chemotherapy in both advanced and early stage breast cancer has made significant progress in the last 10 years with several landmark studies identifying clear survival benefits for newer therapies. In spite of these developments the optimal approach for any specific patient can not be determined from a literature review or decision-making algorithm alone. Treatment choices are predominantly based on practice determined by individual or collective experience and the historical development of treatment within a locality. The improvement in the understanding of the molecular biological basis of breast cancer provides possible targets for novel therapies. Personalised therapies for breast cancer based on the molecular characteristics of the tumour could improve the risk: benefit ratio of current therapies. Increased improvements in the use of a panel of biomarkers will thus not only move us towards tailored therapies but will also spare a group of patients that do not benefit from adjuvant chemotherapy. At the same time a better understanding of tumour biology will also streamline the development of new regimens for those who are unlikely to benefit from existing drugs. This review will focus on the evidence for the use of chemotherapy and highlight advances in chemotherapy treatments with the addition of new and novel drugs marching into our clinics as standard treatments based on evidence from clinical trials and from a better understanding of tumour biology that has transformed the outlook in breast cancer in both the adjuvant and metastatic setting.     

乳腺癌骨扫描诊断骨转移特点分析

目的 :了解乳腺癌骨转移的特点。方法 :通过对 93例乳腺癌骨转移患者的骨扫描结果进行回顾性分析 ,了解乳腺癌骨转移的特点。结果 :乳腺癌患者骨转移表现以异常放射性浓集灶为主 ,部分患者也可表现为放射性稀疏缺损区。骨转移病灶以脊柱及肋骨为最多 ,占 80 % ;颅骨、胸骨、骨盆及四肢骨约占 2 0 %。浸润性导管癌最多 ,占 3 5 5 % ;腺癌其次 ,占 2 5 8% ;髓样癌占 12 9% ;黏液癌仅占 4 3 %。结论 :乳腺癌患者骨转移表现以异常放射性浓集灶为主 ,部分患者也可表现为放射性稀疏缺损区 ;浸润性导管癌和腺癌骨转移率高于髓样癌和黏液癌     

Mechanisms of preferential metastasis of breast cancer to bone - (Review)

Breast cancer frequently and preferentially spreads to bone. Once breast cancer colonizes bone, it is essentially incurable. The cellular and molecular mechanisms by which breast cancer selectively metastasizes to bone remain largely unknown. Elucidation of these mechanisms should lead to the development of effective and specific therapeutic strategies for bone metastasis of breast cancer.     

乳腺癌新辅助化疗的乳房肿物体表定位膜定位

目的探讨乳房肿物体表定位膜（简称乳房尺膜）标记法在乳腺癌新辅助化疗中乳腺肿瘤病灶定位的应用价值。方法对120例乳腺癌患者新辅助化疗前同时采用乳房尺膜对乳腺肿瘤病灶的位置和边界进行标记。对于非隆起性乳腺肿瘤病灶,将尺膜直接贴在乳房上,正向标记;对于边界不清楚的肿瘤病灶在超声引导下确定边界。对于隆起性乳腺肿瘤病灶,尺膜贴在肿瘤病灶以外的正常乳房皮肤上,反向标记。应用TEC方案2个疗程后再次标记,结合超声、钼靶及核磁共振结果综合判断临床疗效,决定手术或改为TP方案继续化疗。术前复位第一次标记结果,按标记的乳腺肿瘤病灶的位置和边界手术。结果完全缓解26例,部分缓解76例,稳定10例,进展8例。其中,完全缓解的24例按尺膜标记的肿瘤病灶位置和边界行保乳手术,部分缓解的18例按尺膜标记的肿瘤病灶位置及残余肿瘤病灶边界外1．5～2．0cm行保乳手术;其余78例,按尺膜标记的肿瘤病灶边界,行简化根治术,其中局部晚期皮缘不充足的13例,采用腹部全厚游离皮瓣覆盖创面。结论乳腺癌新辅助化疗的肿瘤病灶定位应用乳房尺膜法准确且无创,有效节省了肿瘤病灶周围正常的乳腺组织及皮肤,患者依从性好,明显优于传统的坐标法、体表纹身法以及金属标志物法。乳房尺膜标记法操作简单,尺膜价格低廉,便于普及和推广。     

Up-regulation of bone marrow stromal protein 2 (BST2) in breast cancer with bone metastasis

Background  

Bone metastases are frequent complications of breast cancer. Recent literature implicates multiple chemokines in the formation of bone metastases in breast cancer. However, the molecular mechanism of metastatic bone disease in breast cancer remains unknown. We have recently made the novel observation of the BST2 protein expression in human breast cancer cell lines. The purpose of our present study is to investigate the expression and the role of BST2 in bone metastatic breast cancer.     

骨唾液酸蛋白与乳腺癌骨转移相关性的研究进展

多项研究已证实骨唾液酸蛋白(BSP)与乳腺癌骨转移具有相关性,而目前研究的热点是BSP诱导乳腺癌骨转移的具体作用机制及参与BSP基因表达调控的因子种类,这将为今后研究治疗骨转移相应靶向药物提供直接理论依据。同时将BSP与其他骨代谢指标如OPN、TRACP5b、NTx、PTHrP等联合检测可提高乳癌骨转移高风险人群筛选的精确性,并且这些因子可以作为乳腺癌的独立预后因素。     

Neoadjuvant (preoperative) chemotherapy for breast cancer

Despite recent developments in the treatment of breast cancer, metastatic breast cancer remains an incurable disease. Postoperative adjuvant treatment may improve the survival of a subgroup of node positive, Stage II breast cancer patients, but the proportion of failures is still high. Preoperative adjuvant chemotherapy, an example of a new approach in scheduling of available agents, is based on sound theoretical and experimental principles. In this report, the authors summarize the background data on the rationale for preoperative adjuvant chemotherapy and present preliminary results of this study in which preoperative treatment starting with one course of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) was given to newly diagnosed patients with breast cancer. Analysis of the first 43 patients given such treatment has shown that the side effects were comparable to those seen in patients treated with conventional postoperative chemotherapy, and that the delay time between diagnosis and starting chemotherapy has been substantially reduced compared to the historic group of patients. Additional aspects of this study include the introduction of fine-needle aspiration as the only diagnostic method for obtaining the tissue diagnosis of breast cancer, as well as a more intensive interaction between the surgeons from private practice and the oncology institute.     

Trastuzumab (herceptin) for early-stage breast cancer

Breast cancer patients who have HER2 gene amplification and, consequently, protein overexpression, generally show an aggressive course with short disease-free and overall survivals. Trastuzumab, a humanized monoclonal antibody against the extracellular domain of HER2 protein, has been shown to benefit patients who have HER2-positive metastatic breast cancer, and recently, the results of five adjuvant trials involving more than 13,000 women have been released. Here, the authors summarize the main results and outline the differences among these trials, which have demonstrated an important role of trastuzumab in the treatment of women who have HER2-overexpressing/amplified early breast cancer.     

Autologous bone marrow transplantation for breast cancer.

There will be an estimated 180,000 new cases of breast cancer this year with 46,000 deaths. Adjuvant chemotherapy is now firmly established as a valuable modality in breast cancer, improving both disease-free and overall survival in appropriate patients. Unfortunately, chemotherapy has yielded little improvement in the survival of patients with metastatic breast cancer.     

Therapeutic targets for bone metastases in breast cancer

Breast cancer is prone to metastasize to bone. Once metastatic cells are in the bone marrow, they do not, on their own, destroy bone. Instead, they alter the functions of bone-resorbing (osteoclasts) and bone-forming cells (osteoblasts), resulting in skeletal complications that cause pathological fractures and pain. In this review, we describe promising molecular bone-targeted therapies that have arisen from recent advances in our understanding of the pathogenesis of breast cancer bone metastases. These therapies target osteoclasts (receptor activator of nuclear factor kB ligand, integrin αvβ3, c-Src, cathepsin K), osteoblasts (dickkopf-1, activin A, endothelin A) and the bone marrow microenvironment (transforming growth factor β, bone morphogenetic proteins, chemokine CXCL-12 and its receptor CXCR4). The clinical exploitation of these bone-targeted agents will provide oncologists with novel therapeutic strategies for the treatment of skeletal lesions in breast cancer.     

Targeted intra-operative radiotherapy (Targit): An innovative method of treatment for early breast cancer

Introduction:We believe that conservative treatment of earlybreast cancer may not require radiotherapy that encompasses the whole breast.We present here the clinico-pathological basis for this view, as well as anovel therapeutic approach that allows intra-operative radiotherapy to besafely and accurately delivered to the target tissues in a standard operatingtheatre. The rationale:Whole-organ analysis of mastectomy specimensreveals that 80% of occult cancer foci are situated remotefrom the index quadrant. In contrast, over 90% of localrecurrences after breast conservative therapy occur nearthe originaltumour, even when radiotherapy is not given. Therefore, the remote occultcancer foci may be clinically irrelevant and radiotherapy to the indexquadrant alone might be sufficient. A novel technique:The Photon Radiosurgery System (PRS) is aningenious portable electron-beam driven device that can typically deliverintra-operative doses of 5–20 Gy, respectively, to 1 cm and 0.2 cmfrom the tumour bed over about 22 min. The pliable breast tissue – thetarget – wraps around the source, providing perfect conformalradiotherapy. Being soft X-rays, the dose attenuates rapidly(1/r³), reducing distant damage. Results:In our pilot study of 25 patients (age 30–80 years,T = 0.42–4.0 cm), we replaced the routine post-operative tumour bedboost with targeted intra-operative radiotherapy.There have been no major complications and no patient has developed localrecurrence, although the median follow-up time is short, at 24 months. Conclusion:It is safe and feasible to deliver targetedintra-operative radiotherapy (Targit) for earlybreast cancer. We have begun a randomised trial – the first of its kind– comparingTargitwith conventional six-week course ofradiotherapy. If proven equivalent in terms of local recurrence and cosmesis,it could eliminate the need for the usual six-week course ofpost-operative radiotherapy.     

Breast-conserving therapy (BCT) for early-stage breast cancer

Several patient and tumor factors go into the decision process to determine whether a breast cancer patient is a good candidate for breast-conserving therapy. The patient must be seen by all disciplines before any therapeutic intervention. When used appropriately, breast-conserving therapy produces maximal disease control and improves quality of life in patients with early-stage breast cancer.     

乳腺癌骨转移患者溶骨性骨代谢指标与治疗效果的关系

目的 探讨特异性的溶骨性骨代谢指标血I型胶原吡啶交联羧基末端肽(sICTP)、尿I型胶原吡啶交联氨基末端肽(uNTx)和尿吡啶酚(uPyd)与乳腺癌骨转移患者治疗反应的关系.方法 应用酶联免疫吸附试验(ELISA),测定120例乳腺癌患者的sICTP、uNTx和uPyd,比较其在骨转移和无骨转移患者中浓度的差别,并对乳腺癌骨转移患者进行随访,比较患者治疗前后sICTP、uNTx和aPyd指标与治疗效果的关系.结果 骨转移组患者的sICTP、uNTx和uPyd水平均明显高于无骨转移组(P<0.01),56例乳腺癌骨转移患者的sICTP、uNTx和uPyd指标间两两相关(均r>0.5,P<0.01).获得随访的45例乳腺癌骨转移患者中,临床受益组25例,sICTP、uNTx和uPyd治疗3个月后明显下降(P=0.025,P<0.001,P<0.001).病情进展组20例,治疗3个月后,sICTP、uNTx和uPyd无明显变化(P>0.05);而病情进展后,sICTP、uNTx和uPyd明显升高(P=0.011,P=0.002,P=0.002).Logistic回归分析结果显示,uPyd和uNTx治疗后降低的患者治疗收益的概率增加(OR=17.0,P=0.019;OR=16.7,P=0.015),而治疗后sICTP指标下降与治疗受益无关(P=0.841).结论 sICTP、uNTx和uPyd可作为乳腺癌骨转移患者评价疗效和转归监测的辅助指标.