Clinical significance of serum c-erbB-2 protein in patients with primary breast cancer

We measured serum c-erbB-2 protein concentration in 167 patients with primary breast cancer. The rate of positive results was 6%. The positivity rate of serum c-erbB-2 protein did not differ among stages I, II, IIIa and IIIb. However the positivity rate on stage IV was 50% (3/6) and significantly higher than the other stages (p=0.0006). The rate of;positive results correlated significantly with lymph node status (p=0.0037). We concluded that the level of serum c-erbB-2 protein reflected the malignant characteristics of primary breast cancer and its measurement may be useful for a preoperative evaluation of primary breast cancer.     

Antibody microarray profiling reveals individual and combined serum proteins associated with pancreatic cancer

We used antibody microarrays to probe the associations of multiple serum proteins with pancreatic cancer and to explore the use of combined measurements for sample classification. Serum samples from pancreatic cancer patients (n = 61), patients with benign pancreatic disease (n = 31), and healthy control subjects (n = 50) were probed in replicate experiment sets by two-color, rolling circle amplification on microarrays containing 92 antibodies and control proteins. The antibodies that had reproducibly different binding levels between the patient classes revealed different types of alterations, reflecting inflammation (high C-reactive protein, alpha-1-antitrypsin, and serum amyloid A), immune response (high IgA), leakage of cell breakdown products (low plasma gelsolin), and possibly altered vitamin K usage or glucose regulation (high protein-induced vitamin K antagonist-II). The accuracy of the most significant antibody microarray measurements was confirmed through immunoblot and antigen dilution experiments. A logistic-regression algorithm distinguished the cancer samples from the healthy control samples with a 90% and 93% sensitivity and a 90% and 94% specificity in duplicate experiment sets. The cancer samples were distinguished from the benign disease samples with a 95% and 92% sensitivity and an 88% and 74% specificity in duplicate experiment sets. The classification accuracies were significantly improved over those achieved using individual antibodies. This study furthered the development of antibody microarrays for molecular profiling, provided insights into the nature of serum-protein alterations in pancreatic cancer patients, and showed the potential of combined measurements to improve sample classification accuracy.     

Serum proteome profiling of primary breast cancer indicates a specific biomarker profile

Non-invasive biomarkers for early breast cancer detection are urgently needed, as the risk of recurrent morbidity and mortality is closely related to the stage of the disease at the time of primary surgery. Currently, there are no established clinical biomarkers for breast cancer. Evaluation of protein expression patterns in body fluids using proteomic technologies can be used to discover new biomarkers for the detection of breast cancer. The aim of this study was to identify a biomarker signature identifying primary non-metastatic breast cancer and healthy controls. We screened 91 serum samples including 45 breast cancer patients and 46 healthy women using a proteomic approach. We found 14 biomarkers whose combination detects breast cancer patients from non-cancer controls with a sensitivity of 89% and specificity of 67%. Five biomarkers were comparable with previously identified proteins from published data using similar approaches. This biomarker panel allows accurate discrimination between breast cancer and healthy individuals. In addition, it could distinguish subgroups of breast cancer based on patterns of several specific biomarkers. Further validation of biomarkers could potentially facilitate the early diagnosis of breast cancer as an aid to imaging diagnostics.     

Antibody drug conjugates for patients with breast cancer

The receptor-based classification of breast cancer predicts its optimal therapy. Hormone Receptor (HR) positive breast cancer is treated with endocrine therapy, and HER2+ disease is treated with HER2-targeted therapy. Triple negative breast cancer (TNBC), defined as tumors lacking HR and HER2, represents an aggressive subtype of breast cancer associated with poor prognosis. Development of targeted therapy for this subtype has been challenging since TNBC usually lacks targetable genomic alterations. However, the advent of antibody drug conjugates (ADC) to target antigens overexpressed in breast cancer has opened the door to a new class of breast cancer therapeutics. In this review, we describe the current FDA-approved ADC therapies for breast cancer, including sacituzumab govitecan, as well as agents currently in advanced stages of investigation. In addition, we review the potential therapeutic application of ADCs across different breast cancer subtypes. In the future, therapeutic advances in ADCs targeting different antigens could redefine the current receptor-based classification of breast cancer.     

Prognostic significance of serum IgE levels in primary breast cancer

Summary Serum IgE was measured in presurgical sera from 166 nonallergic women admitted to a comprehensive, multidisciplinary study of primary, operable breast cancer. During the follow-up period, which averaged 48 months, there were 71 recurrences. Patients were divided into two groups: those with IgE levels greater than the geometric mean value of 24 I.U. and those with levels less than the mean. The rate of tumor recurrence was significantly greater for the IgE > 24 group (p<0.03). IgE remained a significant prognostic indicator when evaluated by Cox regression analysis in conjunction with other known prognostic factors including: number of positive lymph nodes, clinical stage, menopausal status, estrogen receptor status, mitotic grade, tumor diameter, breast feeding history, and age of patient (p<0.015). IgE was not correlated with any of these known prognostic factors in individual analyses. We conclude that serum IgE level is a significant, independent prognostic indicator in primary breast cancer. Address for reprints: Dr H. Ownby, Michigan Cancer Foundation, 110 East Warren Avenue, Detroit, MI 48201, USA.     

Antibody production in cultured blood lymphocytes from breast cancer patients

Peripheral blood lymphocytes from female patients with early breast cancer were examined before surgery for their ability to develop a primary antibody response in vitro against sheep red blood cells in soft agar cultures containing autologous plasma. After 6 days incubation, foci of proliferating hemolysin-forming cells surrounded by a lytic area were detected on the surface of the plates and counted with a dissection microscope; this response was antigen-dependent and antigen-specific. We applied this assay to a group of women suffering from early breast cancer and devoid of distant metastases. From our data, it appears that if all the patients are grouped together, cancer-bearing women produce somewhat fewer (P less than 0.05) haemolytic foci than healthy controls. However, division of the cancer patients into two subgroups, according to the TNM pretreatment clinical classification of regional lymph nodes, generated an interesting finding: N1 patients (N1b or N1a) produced definitely fewer foci than N0 patients, and the difference was highly statistically significant (P less than 0.001). The depression of anti sheep red blood cell antibody production observed in N1 patients was unrelated to the presence or absence of metastatic growth in their regional lymph nodes.     

双侧原发性乳腺癌的预后因素分析

目的:探讨双侧原发性乳腺癌(bilat eralprimarybreastcancer,BPBC)的生存结果 及其预后因素。方法:对1970年1月～2000 年12月我院收治的54例BPBC的临床资料进 行回顾性分析。结果:同时性和异时性BPBC 分别为16例和38例。同时性和异时性BPBC (从第二侧癌确诊起计算生存率)的5年总生存 率分别为49.1%和54.0%,8年总生存率分别 为32.1%和33.1%,两组比较差异无统计学意 义,P=0.5193;双侧腋窝淋巴结阴性、一侧阳 性和双侧阳性患者的5年总生存率分别为 75.6%、43.8%和28.9%,8年总生存率分别 65.5%、32.9%和0,总体比较差异有统计学意 义,P=0.0023;第一侧癌0～ⅡA期患者的5 年和8年总生存率分别为64.5%和51.6%, ⅡB～Ⅲ期者分别为38.6%和19.3%,两组比 较差异有统计学意义,P=0.0409;第二侧癌 0～ⅡA期患者的5年和8年总生存率分别为 60.9%和50.9%,ⅡB～Ⅲ期者分别为37.9% 和0,两组比较差异有统计学意义,P=0.021 3;在异时性BPBC中,间隔时间1～2年、2～5 年和>5年者的5年总生存率分别为52.6%、 58.7%%和85.7%,8年总生存率分别为 36.2%、42.2%和61.2%,总体比较差异有统 计学意义,P=0.0412。结论:同时性和异时性 BPBC的生存率结果相似。单因素分析表明双 侧腋窝淋巴结状况和第一、二侧癌的     

双侧原发性乳腺癌的预后因素分析

目的：探讨双侧原发性乳腺癌（bilateral primary breast cancer，BPBC）的生存结果及其预后因素。方法：对1970年1月～2000年12月我院收治的54例BPBC的临床资料进行回顾性分析。结果：同时性和异时性BPBC分别为16例和38例。同时性和异时性BPBC（从第二侧癌确诊起计算生存率）的5年总生存率分别为49．1％和54．0％，8年总生存率分别为32．1％和33．1％，两组比较差异无统计学意义，P=0．5193；双侧腋窝淋巴结阴性，一侧阳性和双侧阳性患者的5年总生存率分别为75．6％、43.8％和28.9％，8年总生存率分别65．5％、32．9％和0，总体比较差异有统计学意义，P=0．0023；第一侧癌0～ⅡA期患者的5年和8年总生存率分别为64．5％和51．6％，ⅡB～Ⅲ期者分别为38．6％和19．3％，两组比较差异有统计学意义，P=0．0409；第二侧癌0～ⅡA期患者的5年和8年总生存率分别为60．9％和50．9％，ⅡB～Ⅲ期者分别为37．9％和0，两组比较差异有统计学意义，P=0．0213；在异时性BPBC中，间隔时间1～2年、2～5年和〉5年者的5年总生存率分别为52．6％、58．7％％和85．7％，8年总生存率分别为36．2％、42．2％和61．2％，总体比较差异有统计学意义，P=0．0412。结论：同时性和异时性BPBC的生存率结果相似。单因素分析表明双侧腋窝淋巴结状况和第一、二侧癌的病理分期是影响BPBC生存率的主要因素，两侧癌发生的间隔时间〉5年者的预后比同时性或间隔时间在5年以内者好。多因素分析表明双侧腋窝淋巴结阴性是独立的预后因素。     

乳腺、卵巢双原发癌9例临床分析

目的总结乳腺、卵巢癌双原发癌患者的临床病理特征,并讨论其可能原因及防治策略。 方法回顾性分析2010年1月至2016年12月间重庆医科大学附属第二医院及四川省绵阳市中心医院收治的9例乳腺、卵巢双原发癌患者的临床资料。随访时间为24～312个月,中位随访时间为120个月。 结果9例患者中,6例首发乳腺癌,2例首发卵巢癌,1例为同时性乳腺、卵巢双原发癌。2例患者进行了BRCA基因检测,1例患者存在BRCA1基因突变。9例患者乳腺首发临床症状均为乳房包块;卵巢首发症状中6例为腹胀,2例为阴道异常流血,1例为卵巢肿物。有乳腺标本免疫组织化学检测结果的5例患者中,ER均阴性表达,其中4例为三阴性乳腺癌。9例患者均进行了乳腺癌根治术,并全部接受了化疗,有3例患者术后进行了放射治疗,1例患者术后接受了他莫昔芬内分泌治疗,无患者接受抗HER-2治疗。9例患者中除1例患者拒绝卵巢手术外,其余8例患者均进行了卵巢癌全面分期手术,9例患者均接受了静脉化疗,3例患者接受了腹腔灌注化疗,无患者接受放射治疗。9例患者的中位发病年龄为46岁(36～51岁),中位发病间隔时间为93个月(0～300个月),确诊第二癌后的中位无进展生存时间为19个月(7～22个月)。7例患者发生卵巢癌复发转移,随访期间3例患者死亡。6例无家族史者发生两癌的中位间隔时间为122个月,3例有家族史者发生两癌的中位间隔时间为21个月;3例患者发生首发癌时年龄<45岁,其发生第二原发癌的中位间隔时间为258个月,6例患者发生首发癌时年龄≥45岁,其发生第二原发癌的中位间隔时间为36个月。 结论乳腺、卵巢双原发癌患者的首发起病年龄较小,诊断卵巢癌时多已出现明显临床症状,有家族史的患者两癌的间隔时间明显缩短。患者的治疗以手术和化疗为主。     

双侧原发性乳腺癌年轻患者临床特征与诊治探讨

目的 双侧原发性乳腺癌(bilateral primary breast cancer,BPBC)虽然是一种少见类型乳腺癌,但在我国患病人数仍很可观,而且我国乳腺癌发病年龄趋于年轻化,直接影响了患者的治疗效果.本研究旨在探讨年轻双侧BPBC的临床病理特征、诊断、综合治疗及预后.方法 对天津医科大学肿瘤医院2005-01 01-2008-12-31收治的15例≤40岁(30～40岁)BPBC患者的临床资料进行回顾性分析,并与同期118例非年轻(＞40岁)BPBC患者进行对比.结果 年轻BPBC占同期全部BPBC的11.3％,年轻与非年轻BPBC的临床特征进行比较发现,年轻BPBC患者初潮年龄早,生育次数少,第二原发癌处于病理学分期Ⅱ期的患者比例高,以上特征差异均有统计学意义,P＜0.05.年轻BPBC与非年轻BPBC的5年无病生存率分别为71.1％和84.9％,差异无统计学意义,P=0.335;5年总生存率分别为73.3％和87.2％,差异无统计学意义,P=0.487.结论 年轻BPBC作为一种特殊类型的BPBC,与非年轻BPBC的临床病理特征上存在明显差异,这导致了二者预后的不同,但这种差异无统计学意义.单侧年轻乳腺癌术后患者为发生对侧乳腺癌的高危人群,应加强随访,以期做到早发现、早诊断、早治疗,改善预后.     

乳腺癌皮下腺体切除联合一期植入物乳房重建59例临床分析

目的探讨不同乳腺癌皮下腺体切除联合一期植入物乳房重建手术方法的安全性和美容效果。 方法回顾性分析2008年1月至2016年12月在解放军总医院第一医学中心接受皮下腺体切除联合一期植入物乳房重建的59例乳腺癌患者临床资料。59例患者采取2种分组方式：(1)根据乳房切除方式不同，分为保留乳房皮肤的皮下腺体切除术(SSM)与保留乳头、乳晕复合体的皮下腺体切除术(NSM) 2组；(2)根据乳房重建方式不同，分为"一步法"或"两步法"2组。采用秩和检验或Fisher确切概率法分别比较2组乳房切除方式和2组重建方式的并发症和美容效果。采用Kaplan-Meier法进行患者生存分析。 结果33.9%(20/59)患者行SSM，66.1%(39/59)患者行NSM；44.1%(26/59)患者行"一步法"重建，55.9%(33/59)患者行"两步法"重建。30.5%(18/59)患者同时行对侧乳腺预防性皮下腺体切除术加植入物重建术。中位随访71个月(范围：27～133个月)，失访12例。随访的47例患者中术后假体移位发生率为10.6%(5/47)，包膜挛缩和假体破裂发生率均为4.3%(2/47)。21.3%(10/47)患者最终取出植入物。不同乳房切除方式的并发症发生率和植入物取出率差异无统计学意义(P＝0.697、0.716)；不同重建方式的并发症发生率和植入物取出率差异无统计学意义(P＝0.449、1.000)。死亡2例，余45例患者术后美容效果评分的优良率为73.3%(33/45)，不同乳房切除方式和不同重建方式的术后美容效果评分比较差异无统计学意义(P＝0.296、1.000)。患者是否同时行对侧预防性皮下腺体切除及植入物重建术的美容效果评分比较差异也无统计学意义(P＝0.571)。患者的OS率为95.7%(45/47)，DFS率为89.4%(42/47)。 结论乳腺癌皮下腺体切除联合一期植入物乳房重建术后总体生存情况良好，不管采用哪种乳房切除方式或重建方式，术后不良事件与并发症发生率均较低，可达到预期的临床疗效，并获得良好的美容效果。     

Collagen IV levels are elevated in the serum of patients with primary breast cancer compared to healthy volunteers

Collagen IV is a major component of the vascular basement membrane and may be a marker of angiogenesis. Serum levels of this protein are elevated in some human cancers. Our objectives were to compare collagen IV levels in the serum of breast cancer patients and healthy women and to examine changes during preoperative chemotherapy. Sera from 51 patients with stage II-III breast cancer and 55 healthy controls were analysed. Collagen IV level was measured by a commercially available sandwich enzyme link immunoassay. Baseline serum levels were compared between cancer patients and healthy women and paired pre- and post-chemotherapy measurements were also performed in 39 patients who received preoperative chemotherapy and were correlated with response to therapy. The median serum collagen IV concentration was significantly higher in cancer patients (166 microg l(-1)) than in healthy women (115 microg l(-1)), P<0.001. Chemotherapy induced a significant further increase in serum collagen IV (167 microg l(-1) prechemo vs 206 microg l(-1) postchemo, P=0.001). There were no correlations between baseline collagen IV levels and response to therapy, age, clinical stage or HER2 status. In conclusion, patients with breast cancer have elevated levels of collagen IV compared to healthy women and collagen IV levels increase further during chemotherapy.     

早期乳腺癌患者血清的蛋白质组学研究

目的研究早期乳腺癌患者、良性乳腺疾病患者、正常健康志愿者血清蛋白质组表达图谱的差异,寻找和确定乳腺癌特征性血清标志物。方法获取研究对象血清标本,将血清标本进行双向电泳（2-DE）,电泳后经考马斯亮蓝染色和ImageMaster双向电泳软件分析进行数字化匹配与对比,确认差异蛋白质点。将有意义的差异蛋白点胶内胰蛋白酶酶解,经基质辅助激光解析电离飞行时间质谱（MALDI-TOF）鉴定,获得的肽图和氨基酸序列经过SWISSPROT数据库检索分析后,识别鉴定各个蛋白质。结果早期乳腺癌患者、良性乳腺疾病患者及正常健康志愿者各10例的血清经双向凝胶电泳软件分析,共找到21个差异表达的蛋白质点;21个差异蛋白质点经质谱分析鉴定出13个差异蛋白质,结合数据库查询结果,考虑在乳腺癌中高表达的蛋白质α1-抗胰蛋白酶及低表达的凝溶胶蛋白可能成为乳腺癌早期诊断的潜在标记物。结论早期乳腺癌患者与良性乳腺疾病患者及正常健康志愿者相比,在血清蛋白质组成分中存在差异。找到的这13种差异蛋白质为进一步完善乳腺癌血清学早期诊断及鉴别诊断指标提供了参考依据,尤其α1-抗胰蛋白酶和凝溶胶蛋白对乳腺癌早期诊断意义显著。     

乳腺癌患者血清抗核抗体的表达

目的 了解乳腺癌患者血清抗核抗体阳性率、细胞内定位及免疫荧光图形特点,探索抗核抗体作为肿瘤标志物的可能性.方法 收集2008年11月至2009年12月山东省威海市文登中心医院收治的97例女性乳腺癌,其中有腋窝淋巴结转移53例,无转移44例,52例女性乳腺良性肿瘤患者的术前血液标本,56例健康女性血液样本作为对照,应用间接免疫荧光法（IIF）检测血清中抗核抗体.统计分析用χ2检验,若P〈0.05.再进行两两比较.结果 抗核抗体阳性率分别为对照组16.1%（9/56）,良性肿瘤组21.2%（11/52）,乳腺癌未转移组45.4%（20/44）,乳腺癌转移组43.4%（23/53）,4组比较差异有统计学意义（χ2=16.369,P=0.001）.两两比较显示乳腺癌未转移组、乳腺癌转移组抗核抗体阳性率高于对照组（χ2=10.332,P=0.001;χ2=9.803,P=0.002）.对照组、良性肿瘤组、乳腺癌组三组间的抗核抗体、抗核质抗体阳性率比较,差异有统计学意义（χ2=16.321、7.902,P=0.000、0.019）,抗胞质抗体阳性率比较差异无统计学意义（χ2=5.995,P=0.050）.乳腺癌组与对照组的抗核抗体、抗核质抗体差异有统计学意义（χ2=12.636、5.972,P=0.000、0.015）,抗胞质抗体差异无统计学意义（χ2=4.473,P=0.034）.乳腺癌组与良性肿瘤组相比,抗核抗体差异有统计学意义（χ2=7.869,P=0.005）,抗核质抗体、抗胞质抗体差异无统计学意义（χ2=3.829、2.514,P=0.051、0.113）.乳腺癌转移组与未转移组抗核抗体、抗核质抗体、抗胞质抗体比较,差异无统计学意义（χ2=0.041、1.607、1.861,P〉0.050）.四组间血清抗核质抗体的比较差异有统计学意义（χ2=9.900,P=0.019）.结论 乳腺癌患者血清的抗核抗体与健康人生理性抗核抗体不同,有助于深入认识乳腺癌患者自身免疫现象,以供临床参考.     

Applications of microarray technology in breast cancer research

Microarrays provide a versatile platform for utilizing information from the Human Genome Project to benefit human health. This article reviews the ways in which microarray technology may be used in breast cancer research. Its diverse applications include monitoring chromosome gains and losses, tumour classification, drug discovery and development, DNA resequencing, mutation detection and investigating the mechanism of tumour development.     

Second primary cancers in breast cancer patients in Slovenia

Data from the Cancer Registry of Slovenia were used in a cohort studyto determine whether the incidence of second primary cancers in patients withfirst primary breast cancer differs from the incidence expected in thegeneral population. Special interest was given to long-term survivors. Theexpected numbers of second primary cancers were calculated by multiplying thenumber of appropriate person-years at risk by the corresponding age-andcalendar-period-specific cancer incidence rates for women in Slovenia. Therisk of a second primary cancer was expressed as the standardized incidenceratio (SIR). Of the 8,917 patients newly diagnosed in the period 1961-85 andfollowed-up to the end of 1994, 547 (6.2 percent) developed second primarycancers, whereas 410 (4.7 percent) were expected (SIR = 1.3, 95 percentconfidence interval [CI] = 1.2-1.4). The risk was higher among youngerpatients. In long-term survivors, the risk was increased significantly forsecond primary cancer of th e breast (SIR = 1.4, CI = 1.1-1.7), lung cancer(SIR = 1.6, CI = 1.1-2.3), melanoma (SIR = 2.7, CI = 1.5-4.4) andnon-melanoma skin cancers (SIR = 2.0, CI = 1.6-2.4), corpus uteri cancer (SIR= 1.6, CI = 1.2-2.1), ovarian cancer (SIR = 2.3, CI = 1.7-3.0), and thyroidcancer (SIR = 2.5, CI = 1.2-4.6). Our results confirm the findings of severalcohort studies carried out in Europe, the United States, and Japan,indicating that breast cancer patients should be monitored carefully for theoccurrence of second primary cancers.     

Serial serum MCA measurements in the follow-up of breast cancer patients

Mucin-like carcinoma-associated antigen (MCA) was serially assayed in 58 women with histologically proven breast cancer after their treatment for primary disease. MCA sensitivity and specificity were 87.5% and 76.9%, respectively, and the positive predictive value 82.4%. 10 patients had elevated MCA and no evidence of disease (NED) during their follow-up, of whom 4 finally developed overt metastases. The 4 had a mean (S.D.) MCA value of 46.48 (18.26) U/ml during the lead time, versus 18.76 (2.69) U/ml in the other 6, who are still at high risk for developing overt metastases. Raised levels of MCA in patients with NED create a dilemma of “treat” versus “wait and see”. Early treatment of patients with serially uprising MCA levels should be evaluated in a prospective randomised study to assess its ability to prevent or delay the development of overt metastatic disease and influence survival.     

24-hour CA 15/3 serum concentrations in patients with primary and metastasizing breast cancer

Serum determinations of tumor-associated antigens in breast cancer patients are utilized for detection of metastases as well as prediction of treatment response. That is critically dependent on the validity of single daily marker determination. In our study in patients suffering from primary or metastatic breast cancer we could demonstrate fluctuations of antigens detected with the two monoclonal antibodies 115D8 and DF3 (CA-15/3) during a 24 h observation period. Beside methodical inaccuracies those fluctuating serum concentrations might be related to biological phenomena. However, on basis of our data no intra- or interindividual rhythms could be exhibited.