Bone integrity and bone metastases in breast cancer

Individuals with a history of early-stage breast cancer may be at increased risk of osteoporosis related to adjuvant therapy, and those with metastatic breast cancer may experience skeletal-related complications from the cancer affecting the bone. Maintaining bone strength is critical in the care of both early- and late-stage breast cancer patients because fractures are associated with morbidity and mortality. This article reviews the maintenance of bone integrity in women with breast cancer.     

Bone marrow metastases without cortical bone involvement in breast cancer patients.

Bone marrow involvement by breast carcinoma in the absence of demonstrable bone lesions is unusual. We report six patients with medullary tumor without demonstration of cortical bone abnormality on scan or radiographs. This represents 2.8% of 213 patients with breast cancer in which bone marrow examination was performed and 6.2% of those in which marrow involvement was demonstrated.     

Bone metastases from breast cancer treated with calcitonin. Case report

A case of bone metastases from breast cancer is reported. After 6 months of therapy with calcitonin, the skeletal radiological examination showed an evident change in the roentgenographic pattern of a large metastasis of the left femur. A possible relationship between the calcitonin treatment and the radiological change is discussed.     

Bone metastases in primary operable breast cancer. The role of serial scintigraphy

In 1978 and 1979, 1060 Danish patients with primary operable breast cancer were bone-scanned for osseous metastases before entering a nationwide therapeutical trial. A re-reading group interpreted the scans produced in 12 participating hospitals. As a consequence standardized guide-lines for interpretation were agreed upon from 1979. The frequency of positive bone scans suggesting bone metastases fell abruptly from 1978 to 1979, as read both locally and by the re-reading group. As measured statistically the difference between the interpretation of the local and the re-reading groups remained unchanged. Of the 1060 patients 760 were followed by repeated pre-scheduled scans 6 and 12 months after surgery until any kind of recurrence was diagnosed. Only 37 of the 760 patients (4.9%) developed bone metastases verified by radiology or autopsy during the first 2 yr after surgery. A single positive scan, especially performed 6 or 12 months after surgery, as well as two or three scans repeatedly staying or becoming positive increase significantly the risk of developing bone metastases within 12 months after the latest scan. In 13 of the 37 patients with otherwise subsequently proven bone metastases the latest scan(s) were negative. It is concluded that a fixed schedule of repeated bone scans in patients with breast cancer is not warranted.     

胰腺癌骨转移

目的探讨胰腺癌骨转移的诊断与治疗。方法回顾性分析1999年至2003年间胰腺癌骨转移病例2例。结果经X线、B超、CT、ECT,淋巴细胞rDNA分析,肿瘤细胞学检查、肿瘤标记物检测等方法确诊。1例女性胰腺低分化腺癌,术后2年胸椎及右骶髂骨转移,接受放疗后半年后死亡;1例男性胰腺癌伴胸腰椎骨转移,在行梗阻性黄疸内引流术后1个月因肺部感染,呼吸衰竭死亡,尚未能接受对骨转移灶的治疗。结论影像学检查是发现骨转移瘤的主要方法。胰腺癌骨转移,预后差,除对原发肿瘤治疗外,应积极治疗骨转移灶以延长此类晚期患者的生存期及提高生活质量。     

Brain metastases in breast cancer

Despite therapeutic advances, the development of breast cancer brain metastases (BCBM) is still the harbinger of a dismal prognosis. Patient outcomes vary depending on factors, including tumor phenotype, extent of disease within and outside the brain, as well as patient performance status. Treatment includes surgery, radiation therapy and systemic therapy determined by patient and tumor characteristics. Despite these approaches, novel treatments are needed and there is growing interest in systemic therapies. However, the efficacy of pharmacologic agents is hampered by poor penetration of drugs across the blood–brain barrier. Therefore, there is a pressing need for a greater understanding of the natural history of BCBM to guide the development of further therapies. This review analyzes prognosis and treatment of BCBM by tumor phenotype and discusses ongoing research into new therapies.     

Bone metabolic markers in bisphosphonate therapy for skeletal metastases in patients with breast cancer

The use of bisphosphonates for skeletal metastasis of breast cancer is now well established. Although clinical judgement for treating skeletal metastasis is based on symptoms and imaging studies, accurate or quantitative means are few. Various bone metabolic markers have been developed and these were evaluated in patients with metastasis to bone. Bone metabolic markers, especially resorption markers, have been shown to be a good tool for the monitoring the response to therapy for skeletal metastasis. This is also true for bisphosphonate treatment for skeletal metastasis. Bone metabolic markers are produced by different mechanisms. There are some different classes of resorption markers; tartrate-resistant acid phosphatase (TRAP) is secreted by osteoclast, N- and C-terminal cross-linking telopeptide of type I collagen (NTx and CTx) are the degradation the products of type I collagen, mainly produced by cathepsin K, and pyridinoline cross-linked carboxyl-terminal telopeptides of type I collagen (I CTP) is also a degradation product of type I collagen, by matrix metalloproteases. Even though bone resorption markers are a good tool to monitor response to bisphosphonate therapy, there remains the question of which class of bone resorption markers is best suited to the task.     

Bone metastases in primary operable breast cancer. The role of a yearly scintigraphy

In 231 patients with primary operable breast cancer bone scintigraphies were performed yearly from the second of the 6th year until recurrence irrespective of localization was diagnosed, another cancer was detected, or the patient refused further follow-up or died. During the observation period (from 2 up to 7 years after surgery) 13 patients (5.6%) had bone metastases verified by X-ray or histology within 12 months after the last bone scintigraphy. The scintigraphy was positive in only 7 of these patients. The yearly incidence of bone metastases varied between 0.6 and 2.6%. Due to this low incidence and a low cost/benefit, we conclude that a fixed schedule of repeated scintigraphies in primary operable breast cancer patients otherwise free of apparent disease is not justified.     

乳腺癌腋窝淋巴结跳跃式转移的临床病理研究

目的 探讨乳腺癌腋窝淋巴结跳跃式转移与患者临床病理特征的关系及其对预后的影响.方法 回顾性分析1502例行完全腋窝淋巴结清除术乳腺癌患者的临床资料,观察腋窝淋巴结跳跃式转移的发生规律,分析其与患者临床病理特征的关系及对预后的影响.结果 有淋巴结转移者814例,其中腋窝淋巴结跳跃式转移者119例,占14.6%;跳跃式转移中,最常见的是从第Ⅰ、Ⅱ水平跳过第Ⅲ水平至腋尖,发生率为5.2%.跳跃式转移的发生与患者的年龄、肿瘤大小、临床分期以及雌激素受体状态均无关(均P＞0.05).Ⅰ～Ⅱ期患者中,跳跃式转移组的10年无病生存率较非跳跃式转移组低(58.5%∶ 77.3%,P＝0.003);Ⅲ期患者中,两组的10年无病生存率差异无统计学意义(50.0%∶ 57.6%,P＝0.457).Cox多因素分析显示,肿块大小、淋巴结转移数目、淋巴结结外是否受侵及是否发生跳跃式转移,是影响患者预后的独立因素.结论 某些常见的临床病理指标尚不能准确地预测腋窝淋巴结跳跃式转移的发生;早期乳腺癌发生跳跃式转移者预后差,对其应坚持严格而规范的治疗.     

Interpectoral nodes metastases in breast cancer

Objective:To study interpectoral nodes metastasis rate in breast cancer and its clinical significance.Methods:171 female patients undergone surgery for breast cancer were reviewed,of whom the interpectoral nodes were SUbjected to pathological examination.Results:Interpectoral nodes were identified in 25.7% of the 171 female patients,and the interpectoral nodes metastasis rate was 9.9%.The patients with interpectoral nodes metastasis had larger tumor size,later TNM classification,higher axillary apical nodes metastasis rate and lower ER positive rate.Conclusion:Dissection of interpectoral nodes should be regard as routine clinical practice in modified radical mastectomy,and interpectoral nodes should be snbjected to pathological examination.     

CNS metastases in breast cancer.

As systemic therapy of metastatic breast cancer improves, CNS involvement is becoming a more widespread problem. This article summarizes the current knowledge regarding the incidence, clinical presentation, diagnosis, prognosis, and treatment of CNS metastases in patients with breast cancer. When available, studies specific to breast cancer are presented; in studies in which many solid tumors were evaluated together, the proportion of patients with breast cancer is noted. On the basis of data from randomized trials and retrospective series, neurosurgery and stereotactic radiosurgery (SRS) may prolong survival in patients with single brain metastases. The treatment of multiple metastases remains controversial, as does the routine use of whole-brain radiotherapy (WBRT) after either surgery or SRS. Although it is widely assumed that chemotherapy is of limited benefit, data from case series and case reports suggest otherwise. WBRT, neurosurgery, SRS, and medical therapy each have a role in the treatment of CNS metastases; however, neurologic symptoms frequently are not fully reversible, even with appropriate therapy. Studies specifically targeted toward this group of patients are needed.     

Bone morphogenetic protein 7 in the development and treatment of bone metastases from breast cancer

Bone morphogenetic protein 7 (BMP7) counteracts the physiological epithelial-to-mesenchymal transition (EMT), a process that is indicative of epithelial plasticity. Because EMT is involved in cancer, we investigated whether BMP7 plays a role in breast cancer growth and metastasis. In this study, we show that decreased BMP7 expression in primary breast cancer is significantly associated with the formation of clinically overt bone metastases in patients with > or = 10 years of follow-up. In line with these clinical observations, BMP7 expression is inversely related to tumorigenicity and invasive behavior of human breast cancer cell lines. Moreover, BMP7 decreased the expression of vimentin, a mesenchymal marker associated with invasiveness and poor prognosis, in human MDA-MB-231 (MDA-231)-B/Luc(+) breast cancer cells under basal and transforming growth factor-beta (TGF-beta)-stimulated conditions. In addition, exogenous addition of BMP7 to TGF-beta-stimulated MDA-231 cells inhibited Smad-mediated TGF-beta signaling. Furthermore, in a well-established bone metastasis model using whole-body bioluminescent reporter imaging, stable overexpression of BMP7 in MDA-231 cells inhibited de novo formation and progression of osteolytic bone metastases and, hence, their metastatic capability. In line with these observations, daily i.v. administration of BMP7 (100 mug/kg/d) significantly inhibited orthotopic and intrabone growth of MDA-231-B/Luc(+) cells in nude mice. Our data suggest that decreased BMP7 expression during carcinogenesis in the human breast contributes to the acquisition of a bone metastatic phenotype. Because exogenous BMP7 can still counteract the breast cancer growth at the primary site and in bone, BMP7 may represent a novel therapeutic molecule for repression of local and bone metastatic growth of breast cancer.     

Ⅰ型胶原羧基端前肽和β胶原降解产物在乳腺癌骨转移诊断和随访中的价值

目的探讨Ⅰ型胶原羧基端前肽(PICP)和β胶原降解产物(β-CTx)在乳腺癌骨转移诊断和随访中的应用价值。方法将114例乳腺癌患者分为骨转移组(56例)和无骨转移组(对照组,58例)。对照组根据腋窝淋巴结转移情况分为p N0组(12例)、p N1组(15例)、p N2组(19例)和p N3组(12例),根据激素受体情况分为Lumina型组(30例)和非Lumina型组(28例)。分别测定114例患者血清中PICP和β-CTx的水平。结果骨转移组PICP和β-CTx的水平均高于对照组,差异有统计学意义(P<0.05)。对照组中,p N0组、p N1组、p N2组以及p N3组间的PICP和β-CTx水平比较,差异无统计学意义(P>0.05);非Lumina型组的PICP和β-CTx水平高于Lumina型组,差异有统计学意义(P<0.05)。对照组患者有7例无症状患者在随访过程中出现骨代谢指标异常升高,进一步检查发现有5例出现骨转移。结论骨代谢指标能够早于常规影像学检查提示骨转移的发生,在乳腺癌骨转移的诊断和远期随访中具有重要价值。     

Ocular metastases from breast cancer

Breast cancer is the most common cancer to metastasize to the eye. This is thought to be a rare occurrence but may be more common than thought. Two cases with eye metastases from breast cancer are presented to acquaint physicians with this entity. Other tumors that metastasize to the eye, the anatomic location of metastases in the eye, and the evaluation, treatment, and prognosis of breast cancer metastatic to the eye are discussed.