白细胞介素-11结缔组织生长因子对乳腺癌骨转移的诊断价值分析

目的:研究白细胞介素-11（IL- 11）和结缔组织生长因子（CTGF）对乳腺癌的诊断价值,探索新的乳腺癌早期诊断的标志物。方法:对180 例经病理证实的乳腺癌及45例其他癌骨转移患者的外周血标本进行研究,以20例健康女性外周血标本作对照,应用酶联免疫法定量检测血中IL- 11与CTGF的含量。结果:IL- 11在乳腺癌骨转移组、未发生骨转移组与正常对照组之间差异均有统计学意义（P<0.05）,在乳腺癌骨转移组明显升高,而CTGF在各组间比较差异无统计学意义（P>0.05）。 两两进行比较发现IL- 11在乳腺癌骨转移组明显升高（P<0.05）,但在乳腺癌未发生骨转移组与健康对照组比较差异无统计学意义（P>0.05）。IL- 11在乳腺癌骨转移中的水平与其他肿瘤骨转移的表达水平相比差异有统计学意义（P<0.05）。 IL- 11与乳腺癌骨转移患者的年龄、骨痛程度及骨转移程度密切相关（P<0.05）。 结论:IL- 11的定量检测有助于乳腺癌骨转移的诊断,有望成为乳腺癌骨转移的血清标志物。      

RELATIONSHIP BETWEEN EXPRESSIONS OF P38 PROTEIN IN HUMAN BREAST CARCINOMA AND LYMPH NODES METASTASIS

Objective： To detect the change of p38 protein expression and investigate the relationship of p38 and lymph nodes metastasis in human breast carcinomas. Methods： Sixty breast cancer cases were checked by S-P immunohistochemistry technique and 30 breast cancer cases were examined by Western Blot. Results： Immunohistochemical results showed that p38 protein was observed in breast cancer and normal cytoplasm. P-p38 was positive in nucleus in breast cancer. P38 protein expressed positively in 29 out of 38 patients who had lymph nodes metastasis （positive rate 76.3%） and in 9 out of 22 patients who had no lymph nodes metastasis （positive rate 40.9%）. There was a significant difference between these two groups （P〈0.01）. The positive rate of p-p38 in patients who had lymph nodes metastasis was 68.4%, and the positive rate in patients who had no metastasis was 36.4%, and there was a significant difference between these two groups （P〈0.05）. The result of western blot showed that the protein contents of p38 and p-p38 in patients with metastasis was higher than those in patients without metastasis （P〈0.05）. P38 and p-p38 protein expressions had relation with clinical pathological grades in breast cancer, higher in grade Ⅲ than in grade Ⅰ, Ⅱ （P〈0.05）, while had no relation with patients＇ age and tumor size （P〉0.05）. Conclusion： p38 and p-p38 protein expressions had relationship with lymph nodes metastasis and the levels of p38 and p-p38 protein expression in groups with lymph nodes metastasis were higher than in groups without lymph nodes metastasis. P38 and p-p38 protein expressions had relationship with clinical grades and had no relationship with patients＇ age and tumor size.     

Metastasis and its Related Factors in Female Breast Cancer Patients in Kerman,Iran

Background: Metastasis is important in survival and the quality of life of female breast cancer patients. This study was run in order to investigate metastasis and its related factors in female breast cancer patients in Kerman province from 2005 to 2015. The aim of this study was to investigate the factors associated with secondary metastasis in female breast cancer patients in the largest province of Iran (Kerman). Materials and Methods: In this case-control study, medical records of women diagnosed with breast cancer between the years of 2005 to 2015 were studied. Among them, 200 breast cancer patients with secondary metastasis were randomly selected as cases and 400 patients without metastasis were selected as the control group. Backward logistic regression, chi-square test, t-test and Mann-Whitney-U test were performed for comparing the two groups in SPSS 22. Results: Disease stage at diagnosis was significantly associated with secondary metastasis (p<0.001). Female patients with stage III breast cancer at the time of diagnosis had a higher chance OR=9.11 (CI 95%=2.99-27.76) of metastasis than women with stage 0 and 1 at diagnosis. Also, patients from rural areas had a higher chance for metastasis OR=1.89 (CI 95%=1.04-3.41). Other factors such as age, tumor size, tumor grade at diagnosis, hormone receptor status of estrogen and progesterone and Her-2 showed no significant association with metastasis (p>0.05). Conclusion: Stage at diagnosis and the residential location of patients were the most important factors related to secondary metastasis. These results emphasize the importance of early diagnosis, adequate education and awareness for breast cancer screening.     

Pigment epithelium-derived factor (PEDF) inhibits breast cancer metastasis by down-regulating fibronectin

Pigment epithelium-derived factor (PEDF) plays an important role in the tumor growth and metastasis inhibition. It has been reported that PEDF expression is significantly reduced in breast cancer, and associated with disease progression and poor patient outcome. However, the exact mechanism of PEDF on breast cancer metastasis including liver and lung metastasis remains unclear. The present study aims to reveal the impact of PEDF on breast cancer. The orthotopic tumor mice model inoculated by MDA-MB-231 cells stably expressing PEDF or control cells was used to assess liver and lung metastasis of breast cancer. In vitro, migration and invasion experiments were used to detect the metastatic abilities of MDA-MB-231 and SKBR3 breast cancer cells with or without overexpression of PEDF. The metastatic-related molecules including EMT makers, fibronectin, and p-AKT and p-ERK were detected by qRT-PCR, Western blot, and Fluorescent immunocytochemistry. PEDF significantly inhibited breast cancer growth and metastasis in vivo and in vitro. Mechanically, PEDF inhibited breast cancer cell migration and invasion by down-regulating fibronectin and subsequent MMP2/MMP9 reduction via p-ERK and p-AKT signaling pathways. However, PEDF had no effect on EMT conversion in the breast cancer cells which was usually involved in cancer metastasis. Furthermore, the study showed that laminin receptor mediated the down-regulation of fibronectin by PEDF. These results reported for the first time that PEDF inhibited breast cancer metastasis by down-regulating fibronectin via laminin receptor/AKT/ERK pathway. Our findings demonstrated PEDF as a dual effector in limiting breast cancer growth and metastasis and highlighted a new avenue to block breast cancer progression.     

KAI1/CD82在原发性乳腺癌中的表达及其临床意义

目的:探讨KAI1/CD82在乳腺癌中的表达及其临床意义。方法:采用RT-PCR和免疫组化方法对69例原发性乳腺癌组织、癌旁组织和区域淋巴结组织中KAI1 mRNA和CD82蛋白的表达进行研究。结果:在69例原发性乳腺癌中,癌旁组织中KAI1基因在区域淋巴结转移阴性组和区域淋巴结转移阳性组的mRNA表达无显著性差异(P>0.05)。癌组织和区域淋巴结组织中KAI1基因在区域淋巴结转移阴性组和区域淋巴结转移阳性组的mRNA表达有显著差异(P<0.05)。CD82表达与临床病理类型以及PR表达无相关性(P>0.05),而与临床分期、组织学分级、区域淋巴结转移、远处转移、ER表达有相关性(P<0.05)。结论:KAI1/CD82的表达与乳腺癌的转移及某些临床病理因素有关,具有一定的临床指导意义。     

Loco-regional cancer therapy for hepatic metastasis

We undertook a clinical evaluation of chemotherapy for hepatic metastasis of gastric, colorectal and breast cancer. Between 1980 and 1989, chemotherapy for hepatic metastasis of gastric cancer was performed in 96 cases. Between 1973 and 1989, chemotherapy for hepatic metastasis of colorectal cancer and breast cancer was performed in 40 and 14 cases. Results: (1) In hepatic metastasis of gastric cancer, the 50% survival period was 149 days in local injection therapy, 132 days in arterial infusion therapy and 117 days with no chemotherapy. There was no significant difference in the survival period in gastric cancer. (2) In hepatic metastasis of colorectal cancer, the 50% survival period was 445 days in arterial infusion therapy, 206 days in local injection therapy and 96 days with no chemotherapy. The survival period with hepatic metastasis of colorectal cancer that had undergone chemotherapy was longer than for no chemotherapy. (3) In hepatic metastasis of breast cancer, arterial infusion therapy was more effective, and the survival period was prolonged significantly.     

乳腺癌组织中P38、VEGF表达与其淋巴结转移及预后的关系

目的 探讨乳腺癌组织中P38、VEGF表达与其淋巴结转移及预后的关系.方法 选取经病理证实为乳腺癌患者88例为研究对象.采用SP法检测P38、VEGF蛋白在乳腺癌组织中的表达,应用COX回归模型,探讨P38、VEGF表达与乳腺癌预后的关系.结果 88例患者中P38阳性表达67例,阴性21例;VEGF阳性56例 阴性32例.所有患者均随访到2016年1月31日,以死亡或肿瘤转移、复发为终点事件,出现终点事件的患者17例;P38、VEGF在Ⅲ期乳腺癌组织中表达水平明显高于Ⅰ、Ⅱ期,而与患者年龄、肿瘤大小无明显相关性.复发及转移患者中P38、VEGF阳性率明显高于无转移和复发者,差异显著,具有统计学意义,P<0.05;多因素分析提示:肿瘤分期(P=0.01)、P38阳性(P=0.001)、VEGF阳性(P=0.02)是乳腺癌患者转移或复发的独立危险因素.结论 P38、VEGF阳性表达患者的转移及复发率高,P38、VEGF阳性是患者转移及复发的独立风险因素.     

A case of advanced breast cancer with meningeal carcinomas and orbital metastasis successfully treated with multi-disciplinary therapy

We report a case of advanced breast cancer with meningeal metastasis and orbital metastasis (T4bN3cM1, Stage IV) achieving a significant improvement in QOL by multi-disciplinary therapy. The patient was a 51-year-old woman who had headaches and an ulcerative breast lump with meningeal metastasis and orbital metastasis. A core needle biopsy for breast tumor led to a diagnosis of an invasive ductal carcinoma positive for HER2/neu protein expression. She received 9 cycles of weekly trastuzumab and radiation therapy for meningeal metastasis and orbital metastasis. Although the size of breast tumor, orbital metastasis lesion, and meningeal metastasis lesion exhibited no change, clinical symptoms were improved. One year later, she received paclitaxel so that the sensitivity of HER2/neu dropped. However, the tumor markers relapsed and we then changed paclitaxel to TS-1. Eighteen-months later, she had no neurological symptoms. Multi disciplinary therapy can improve patient's QOL and the clinical outcomes in Stage IV advanced breast cancer.     

TSGF指引Ⅱ期乳腺癌术后二线化疗的对比研究

目的探讨以恶性肿瘤特异性生长因子(tumor specific growth factor,TSGF)指引Ⅱ期乳腺癌术后二线化疗对减少乳腺癌术后复发或转移的作用。方法入组病例每月复查TSGF,符合治疗条件者(治疗组)即开始二线化疗(紫杉醇单药治疗)。与对照组比较2年内出现复发或转移的病例数。结果治疗组在4次化疗期间均未见复发或转移,而在2年内出现复发或转移共3例;对照组出现复发或转移共17例,两组比较差异有统计学意义(P<0.05)。结论采用TSGF定期检测的方式指引Ⅱ期乳腺癌二线化疗可以降低复发或转移率,从而进一步提高乳腺癌的治疗效果。     

Esophageal metastasis of breast carcinoma

Esophageal metastasis from primary breast cancer is an unusual manifestation. We recently treated a patient with dysphagia, whose breast cancer had been treated in the distant past. A 70-year-old woman had been followed regularly in our outpatient clinic for 14 years after her primary breast cancer treatment, with no apparent tumor recurrence. After 2 years absence, she consulted our clinic with progressive dysphagia. Contrast esophagography and endoscopic examination with ultrasonography revealed a protruding submucosal tumor that was histopathologically diagnosed as esophageal metastasis of breast cancer. Radiation therapy involving a total of 60 Gy in combination with aromatase inhibitor was given. The patient’s dysphagia was greatly relieved, concomitant with marked improvement of the stenotic lesion on imaging. Since treatment for recurrent breast cancer is generally palliative, systemic (chemo- and/or endocrine-) therapy in combination with radiotherapy is the first-line option for esophageal metastasis of breast cancer.     

A case of local recurrent breast cancer with complete response to combination of systemic chemotherapy and topical use of adriamycin ointment

A Case of local recurrent breast cancer in a 45-year-old female with complete response to Combination of chemotherapy and topical administration of Adriamycin is reported. The patient had left mastectomy for breast cancer in 1978, and then right mastectomy for breast cancer in 1987. Two years later, she was readmitted to our hospital with right neck lymph node metastasis and local recurrence at right chest wall. Neck lymph node metastasis was treated with irradiation with good response. On the other hand, Adriamycin ointment was applied to recurrent cancer on the right chest. The cancer was gradually diminished in size. Seventy-eight days after treatment, the local chest wall with cancer was resected. Histologically, the entire resected tissue showed no viable cancer cells and Adriamycin concentration in the tissue was extraordinary high (ten to forty fold over on systemic chemotherapy). Adriamycin ointment may be an alternative treatment of choice for local recurrent breast cancer.     

Implication of video assisted thoracoscopic surgery in the diagnosis of pulmonary metastasis of breast cancer

Purpose  To determine pulmonary metastasis, video assisted thoracoscopic surgery (VATS) was performed on the patients who had undergone breast cancer surgery. Patients and Methods p Nineteen patients with a history of breast cancer underwent VATS, because of subsequent abnormal pulmonary shadows on chest computed tomograms (CT). All patients were suspected to have pulmonary metastasis from breast cancer.   Results  The VATS procedure showed 10 (52%) patients to have pulmonary metastasis, but, 9 (48%) had primary lung cancers or benign lesions. In the patients of pulmonary metastasis, 7 had nodular lesions (5 had a single nodule and 2 had two nodules with a median diameter of 8.5 mm), and 3 patients had pleural dissemination. The follow-up period of the patients with pulmonary metastasis ranged from 3 to 28 months. Three patients died of brain metastasis and respiratory failure, 3 suffered recurrence and 4 were free from disease after VATS. Conclusion  VATS was useful for distinguishing small metastatic lesions from other diseases and a minimally invasive surgical approach in the follow-up of breast cancer patients suspected of pulmonary metastasis.     

EVALUATION OF THE PROGNOSTIC VALUE OF nm23 GENE EXPRESSION IN BREAST CANCER

Mortality of breast cancer is almost due to subsequent metastases, but the micrometastasis is difficult to be detected. Early diagnosis of distant metastasis is a key to improve prognosis of breast cancer. The nm23 gene is a putative metastasis suppressor gene originally identified in murine melanoma cells. The purpose of this study was to investigate the relationship between nm23 gene expression (mRNA and protein) and distant metastasis of breast cancer. MATERIALS AND METHODS Pati…     

乳腺癌内乳淋巴结活检的临床研究

背景与目的:内乳淋巴结(intemal mammary node,IMN)是乳腺癌重要的转移途径之一,其状况将影响乳腺癌患者的分期、治疗、预后及疗效评价,本研究旨在探讨内乳前哨淋巴结活检(intemal mammary sentinel node biopsy,IMSNB)和经肋间IMN第Ⅰ～Ⅳ肋间活检、以及IMN微转移灶检测在临床应用的意义.方法:在行常规乳腺癌切除术中,采用核素示踪法经肋间隙行IMSNB,然后对患侧第Ⅰ～Ⅳ肋间的IMN均行活检(经肋间隙,非扩大根治术),所有IMN均行常规单一切面HE染色病理检查,阴性病例的IMN采用多层切片加免疫组化的方法检测微转移.结果:全组38例病人中发现内乳前哨淋巴结(internal mammary sentinel node,IMSN)17例,占44.7%,均成功行IMSNB,其中4例IMSN常规病理阳性,1例IMSN发现微转移,2例发现孤立的肿瘤细胞群,10例为阴性,均与对应病例经第Ⅰ～Ⅳ肋间IMN活检的病理结果一致;无发现IMSN 21例,占55.3%,经第Ⅰ～Ⅳ肋间IMN活检,常规病理阳性5例,阴性16例,未发现微转移.结论:对发现IMSN者,IMSN能够准确评价IMN状况,但对无发现IMSN者,尤其是对IMN转移可能性大者,应经肋间隙行IMN第Ⅰ～Ⅳ肋间活检,以减少假阴性的发生;多层切片加免疫组化技术有助于IMN微转移灶的检出.     

Study on the safety of rapid infusion and the efficacy of incadronate against bone metastasis of breast cancer]

To assess the safety of rapid infusion of incadronate and its efficacy against bone metastasis of breast cancer, we conducted a trial using incadronate therapy for breast cancer patients with bone metastasis. Of the 12 patients, 6 had undergone pamidronate or alendronate therapy. Rapid infusion of incadronate consisted of administration of 10 mg incadronate diluted in 100 ml saline in 30 minutes, and was repeated every two weeks. Each patient underwent 2 to 20 incadronate administrations. With the incadronate therapy, no patients showed hypocalcemia, but 3 patients showed asymptomatic hypophosphoremia. Of the 11 patients with bone pain, 5 patients (45%) experienced pain relief. A decrease in tumor marker levels in serum was found in 5 (56%) of the 9 patients with elevated marker levels. The side effects of incadronate administration were general fatigue (25%), pyrexia (17%) and transient pain increase (17%), but no renal dysfunction was found. In conclusion, rapid infusion of incadronate was a safe treatment and the incadronate therapy was effective against bone metastasis of breast cancer.     

305例三阴乳腺癌患者的临床特征及预后因素分析

背景与目的:三阴乳腺癌(triple-negative breast cancer)指雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)和HER2/neu均无表达的乳腺癌,被认为是一种独立的临床病理类型,以侵袭性强、预后较差为主要特征的乳腺癌。本研究目的在于分析三阴乳腺癌的临床特征和影响预后的因素。方法:收集2000年1月至2004年12月中山大学肿瘤防治中心收治的经病理组织学证实、有完整随访资料的1280例可手术乳腺癌患者的临床资料,经病理学检查证实ER、PR和HER2/neu均为阴性的三阴乳腺癌305例(23.8%)。回顾性分析三阴乳腺癌患者的临床特征、复发及生存情况。结果:本组乳腺癌患者中有23.8%(305/1280)是三阴乳腺癌,多见于年轻患者,诊断时肿块较大、局部淋巴结阳性者较多,有乳腺癌家族史的患者较多。截止至2007年6月,三阴乳腺癌组患者中位随访时间为52个月(28～89个月),有234例患者出现复发及转移,94例已死亡。三阴乳腺癌组局部复发率与非三阴乳腺癌患者相比无显著性差异;但三阴乳腺癌患者远处转移发生率显著增高,主要表现肺转移(HR=4.41,P<0.001)和肝转移(HR=2.13,P=0.006)发生率高。生存分析显示,三阴乳腺癌患者的5年无病生存率和总生存率分别为73.7%和88.5%,均显著低于非三阴乳腺癌患者(80.8%和92.8%,P=0.025,P=0.010)。多因素分析显示,肿块大小和淋巴结状况是影响三阴乳腺癌预后的两个主要因素。结论:三阴乳腺癌在乳腺癌中占有约1/4的比例。这些患者往往年轻、有乳腺癌家族史、肿块较大、淋巴结阳性多。三阴乳腺癌容易出现肺转移和肝转移,这可能是导致三阴乳腺癌预后较差的重要原因。     

乳腺癌患者血清CYFRA21-1检测的临床价值

目的 :检测乳腺癌患者血清中CYFRA2 1 1水平 ,探讨其在乳腺癌的术前诊断和术后随访监测中的应用价值。方法 :采用放免法测定 34例乳腺良性疾病患者术前、4 7例乳腺癌患者术前和术后 4周及 56例乳腺癌术后随访患者的血清CYFRA2 1 1水平 ,进行对照分析。结果 :乳腺良性疾病无 1例阳性 ;乳腺癌术前阳性率仅 2 1% ,但两者血清CYFRA2 1 1水平有明显差异 ;4 7例乳腺癌患者手术前与术后 4周血清CYFRA2 1 1水平相比有显著差异 ;56例乳腺癌患者术后随访 8例转移复发者中 6例阳性 ,无转移复发者均阴性 ,转移复发者血清CYFRA2 1 1水平较无转移复发者明显增高 ,两者相比差异有极显著性。结论 :血清CYFRA2 1 1检测对乳腺癌特异性高 ,但对乳腺癌术前诊断价值不大 ,对乳腺癌转移复发的监测有非常重要意义。     

Association of matrix metalloproteinase-8 gene variation with breast cancer prognosis

Animal and cell studies indicate an inhibitory effect of matrix metalloproteinase-8 (MMP8) on tumorigenesis and metastasis. We investigated whether MMP8 gene variation was associated with breast cancer metastasis and prognosis in humans. We first studied nine tagging single nucleotide polymorphisms (SNP) in the MMP8 gene in 140 clinically and pathologically well-characterized breast cancer patients. Four of the SNPs were found to be associated with lymph node metastasis, the most pronounced being a promoter SNP (rs11225395) with its minor allele (T) associating with reduced susceptibility to lymph node metastasis (P = 0.02). This SNP was further evaluated for association with cancer relapse and survival among a cohort of approximately 1,100 breast cancer patients who had been followed for cancer recurrence and mortality for a median of 7.1 years. The T allele was associated with reduced cancer relapse and greater survival, particularly among patients with earlier stage cancer. Among patients of tumor-node-metastasis stage 0 to II, the adjusted hazard ratio of disease-free survival was 0.7 [95% confidence interval (95% CI), 0.5-0.9] for patients carrying T allele compared with those homozygous for the C allele (P = 0.02). In vitro experiments showed that the T allele had higher promoter activity than the C allele in breast cancer cells. Electrophoretic mobility shift assays showed binding of nuclear proteins to the DNA sequence at the SNP site of the T allele but not that of the C allele. The data suggest that MMP8 gene variation may influence breast cancer prognosis and support the notion that MMP8 has an inhibitory effect on cancer metastasis.     

Expression of neuronal protein synuclein gamma gene as a novel marker for breast cancer prognosis

Synucleins are emerging as central players in the fundamental neural processes and in the formation of pathologically insoluble deposits characteristic of neurodegenerative diseases. However, synuclein γ (SNCG), previously identified as a breast cancer specific gene (BCSG1), is also highly expressed in breast carcinomas, but not expressed in normal or benign breast tissues. We analyzed SNCG gene expression in 93 clinical breast specimens and associated it with clinical outcome. Overall SNCG mRNA expression was detectable in 36% breast cancers. However, 81% of stage III/IV breast cancers were positive for SNCG expression, while only 15% of stage I/II breast cancers were positive for SNCG expression. In contrast, SNCG was undetectable in benign breast lesions. Expression of SNCG in the primary tumor also significantly associated with lymph node involvement and metastasis. There was no significant correlation between SNCG gene expression and age, menstruation, and status of ER, PR, PCNA, and HER-2. Patients whose tumors expressed SNCG had a significantly shorter DFS and a high probability of death when compared with those whose tumors did not express SNCG. The hazard ratio of metastasis or recurrence according to the SNCG status was 4.515 (95% CI, 1,188–17.154; P = 0.027). Cox multivariate analysis showed that SNCG had independent prognostic significance above and beyond conventional variables. This study suggests that the expression of SNCG is an independent predictive marker for recurrence and metastasis in breast cancer progression. SNCG is expected to be a useful marker for breast cancer progression and a potential target for breast cancer treatment.