Clinical evaluation of the Elecsys CA 15-3 test in breast cancer patients

The aim of the present study was to evaluate the clinical performance of the CA 15-3 assay on Elecsys systems in an international multicenter study (11 centers). A total of 1326 single samples (272 apparently healthy individuals, 34 pregnant women, 308 benign diseases, 273 cancers other than breast, 439 breast cancer) and 538 serial samples of 98 breast cancer patients during follow-up were analyzed. 95% of values in healthy individuals were below 25 kU/L, and 88% in benign breast diseases, respectively. In malignant breast disease at primary diagnosis the value distribution of Elecsys CA 15-3, sensitivity at 95% specificity, as well as the areas under the curve in ROC analysis were clearly correlated to tumor stages: UICC I to IV 88 to 25% of values < 25 kU/L, sensitivity 7 to 78%, areas under the curve 0.53 to 0.94. During follow-up, sensitivity/specificity for detection of recurrences were 90%/71%. In metastatic disease clinical progression/response to therapy were indicated in 91%/78% of patients at a specificity of 92%/78%. The findings indicate that the Elecsys CA 15-3 assay is very suitable in routine work for detection of recurrences as well as for therapy control in metastatic breast cancer.     

乳腺癌手术前后血清CA15-3和CEA水平与病理参数的相关性研究

目的探讨乳腺癌患者手术前后血清中CA15-3和CEA水平与病理参数的相关性。方法随机选择2012年6月至2014年7月南通市第四人民医院外科和南通市肿瘤医院肿瘤科共计267例乳腺癌患者为研究对象,采用电化学发光免疫分析法检测所有患者术前一周、术后1月血清中CA15-3和CEA水平,并分析CA15-3和CEA水平与乳腺癌患者临床病理参数的相关性。结果 267例乳腺癌患者术前一周血清中CA15-3和CEA水平分别为35.6±11.41U/ml和8.9±3.4ng/ml,术后1月分别为20.1±9.23U/ml和4.1±1.7ng/ml,P0.05,差异具有统计学意义;Ⅲ和Ⅳ期癌症患者的CA15-3和CEA阳性表达率均明显高于Ⅰ和Ⅱ期,肿瘤有多处转移的CA15-3和CEA阳性表达率明显高于1处转移的,术后复发患者的CA15-3和CEA阳性表达率高于没有复发患者,P0.05,差异均具有统计学意义;采用不同手术类型患者术后CA15-3和CEA阳性表达率无显著性差异,P0.05。结论乳腺癌患者血清中CA15-3和CEA水平与癌症TNM分期、转移、术后复发具有相关性,便于及时诊断术后癌症转移复发。     

Relationship of serum HER-2/neu and serum CA 15-3 in patients with metastatic breast cancer

BACKGROUND: Serum HER-2/neu antigen concentrations have been reported to correlate with increased tumor volume in patients with breast cancer. We measured serum CA 15-3, a surrogate marker of disease burden, and correlated serum CA 15-3 with serum HER-2/neu and analyzed the association of both markers with clinical outcomes. METHODS: Pretreatment serum samples from 566 patients were retrospectively analyzed from 2 phase III clinical trials of estrogen receptor-positive (ER(+)), ER(-)/progesterone receptor-positive, or ER status unknown metastatic breast cancer patients randomized in two similar studies to receive second-line hormone therapy with either megestrol acetate or an aromatase inhibitor (fadrozole). The extracellular domain of the HER-2/neu (c-erbB-2) oncogene and serum CA 15-3 were measured by ELISA on the Bayer Immuno 1. RESULTS: Serum HER-2/neu protein was increased in 168 patients (30%), and CA 15-3 was increased in 337 (60%) patients. Serum CA 15-3 and HER-2/neu were weakly correlated (r = 0.39; P <0.0001). The clinical benefit (complete responses plus partial responses plus stable disease) of endocrine therapy was significantly lower in patients with increased serum HER-2/neu. When adjusted for serum HER-2/neu, serum CA 15-3 was not predictive of response rates. The median time to progression was shorter in patients with increased serum HER-2/neu (89 days) compared with patients with normal serum HER-2/neu (176 days). Survival was significantly shorter in patients with increased serum HER-2/neu (513 vs 869 days; P <0.0001) or increased serum CA 15-3 (689 vs 939 days; P <0.0001). This observation was confirmed by multivariate analysis. CONCLUSIONS: Serum HER-2/neu is a significant independent predictive and prognostic factor in hormone receptor-positive metastatic breast cancer, even when adjusted for tumor burden as measured by CA 15-3. The combination of increased serum HER-2/neu and increased serum CA 15-3 predicts a worse prognosis than does increased CA 15-3 alone.     

癌胚抗原与糖类抗原15-3联合检测在乳腺癌诊断中的价值

[目的]探讨癌胚抗原（CEA）与糖类抗原15-3（CA15-3）联合检测对乳腺癌的诊断价值.[方法]采用电化学发光分析法检测118例乳腺癌患者,63例乳腺良性疾病患者,60例正常对照者的血清CEA、CA15-3水平.[结果]①CEA单独检测诊断乳腺癌的灵敏度、特异度、阳性预测值、阴性预测值、诊断准确度分别为34.7%、96.7%、91.1%、60.7%、66.4%.②CA15-3单独检测诊断乳腺癌的灵敏度、特异度、阳性预测值、阴性预测值、诊断准确度分别为61.0%、95.1%、92.3%、71.8%、78.4%.③CEA与CA15-3联合检测诊断乳腺癌的灵敏度、特异度、阳性预测值、阴性预测值、诊断准确度分别为78.0%、92.7%、91.1%、81.4%、85.5%.[结论]单独检测CEA或CA15-3诊断乳腺癌的灵敏度均较低,采用平行试验联合检测CEA与CA15-3大大提高乳腺癌的诊断灵敏度.     

乳腺癌患者血清CA15-3检测的临床价值

目的探讨血清CA15-3测定在乳腺癌诊断、监测及术后复发转移中的临床应用价值。方法采用酶联免疫吸附法检测182例乳腺癌、85例乳腺良性疾病与100例正常健康体检女性的血清CA15-3水平。结果CA15-3在诊断乳腺良性疾病与乳腺癌Ⅰ,Ⅱ期时,差异无显著性(P>0.05),而在乳腺癌晚期及复发或转移乳腺癌患者中CA15-3水平显著高于无复发或无转移乳腺癌患者(P<0.05)。结论血清CA15-3监测乳腺癌的术后复发或转移、预测复发转移具有重要的意义。     

CA 15-3 and carcinoembryonic antigen in the clinical evaluation of breast cancer

The individual and combined value of CA 15-3 and carcinoembryonic antigen (CEA) as breast cancer tumor markers was investigated in longitudinal studies. Patients included women at high risk for recurrence after primary therapy or undergoing treatment for metastatic disease. During follow-up, recurrent disease was documented in 33 of 39 (85%) patients including 11 with local recurrence and 22 with distant metastases. At the time recurrence was first documented by objective criteria 23 of 33 (70%) of the patients presented with abnormal CA 15-3 levels (>36.7 U/ml) compared with 19/33 (58%) with abnormal CEA levels (5 ng/ml). Tumor marker elevations predominated in patients with advanced disease indicating that CA 15-3 and CEA are not reliable for the detection of early breast cancer. Both markers were helpful in monitoring therapeutic response since antigen levels correlated closely with disease status.     

血清CEA和CA15-3水平对乳腺癌化疗疗效及预后评估的价值分析

目的探讨血清CEA和CA15-3水平对乳腺癌化疗疗效及预后评估的价值。方法回顾性分析2011年5月至2012年6月荆州市第一人民医院肿瘤科收治的63例乳腺癌晚期患者作为乳腺癌组,根据存活情况将其分为存活组(n=42例)和死亡组(n=21例),采用荧光免疫法检测血清CEA和CA15-3水平,随访4年,统计分析所有患者生存预后情况。结果Ⅳ期乳腺癌患者血清CEA和CA15-3水平明显高于Ⅲ期,差异有统计学意义(P0.05);CEA、CA15-3、CEA和CA15-3表达阴性组化疗有效率明显高于阳性组,差异有统计学意义(P0.05);所有患者随访1~4年,平均随访时间3.63年,最终有42例存活4年以上,CEA阳性组患者4年生存率(55.26%)明显低于阴性组(84.00%),差异有统计学意义(P0.05),CA15-3阳性组患者4年生存率(52.78%)明显低于阴性组(85.19%),差异有统计学意义(P0.05),CEA和CA15-3阳性组患者4年生存率(52.38%)明显低于阴性组(95.24%),差异有统计学意义(P0.05);存活组化疗前血清CEA和CA15-3水平明显低于死亡组,差异有统计学意义(P0.05)。结论检测乳腺癌患者化疗前血清CEA和CA15-3水平可为化疗疗效及预后评估提供可参考数据。     

Recombinant vaccinia virus encoding human MUC1 and IL2 as immunotherapy in patients with breast cancer

Polymorphic epithelial mucin, encoded by the MUC1 gene, is present at the apical surface of glandular epithelial cells. It is over-expressed and aberrantly glycosylated in most breast tumors, resulting in an antigenically distinct molecule and a potential target for immunotherapy. This transmembrane protein, when produced by tumor cells, is often cleaved into the circulation, where it is detectable as a tumor marker (CA 15.3) by various antibodies, allowing for early detection of recurrences and evaluation of treatment efficacy. The objective of the current study was to examine the clinical and environmental safety and immunogenicity of a live recombinant vaccinia virus expressing the human MUC1 and IL2 genes (VV TG5058), referred to here as TG1031. The study was an open-label phase 1 and 2 trial in nine patients with advanced inoperable breast cancer recurrences to the chest wall. The patients were vaccinated intramuscularly with a single dose of TG1031; three patients were treated at each of three progressive dose levels ranging from 5x10(5) to 5x10(7) plaque-forming units. A boost injection at their original dose level was administered in patients responding immunologically, clinically, or both. Vaccination resulted in no significant clinical adverse effects, and there was no environmental contamination by live TG1031. All patients had been vaccinated as children, and patients treated at the highest dose level mounted a significant anti-vaccinia antibody response. None of the nine patients had a significant increase in MUC1-specific antibody titers after one single injection, whereas five patients had a detectable increase in vaccinia virus antibody titers. Peripheral blood mononuclear cells of one patient at the intermediate dose level showed a proliferative response to in vitro culture with vaccinia virus, with a stimulation index of 6. A second patient treated at the intermediate dose level had a stimulation index of 7 to MUC1 peptide and of 14 after a boost injection. This patient had a concomitant decrease in carcinoembryonic antigen serum levels and remained clinically stable for 10 weeks. Evidence of MUC1-specific cytotoxic T lymphocytes was detected in two patients. Immunohistochemical analysis revealed an increase in T memory cells (CD45RO) in tumor biopsies after vaccination. The absence of serious adverse events, together with the documentation of immune stimulations in vivo, warrant the further use of TG1031 in immunotherapy trials of breast cancer.     

卵泡抑素、MUC1基因在乳腺癌患者血清中的表达及其临床意义

目的 研究乳腺癌患者血清中卵泡抑素（FS）和黏蛋白MUC1表达与肿瘤的发生发展与转移的关系及其临床意义.方法 采集60例乳腺疾病入院患者的血清样本,其中乳腺癌40例,乳腺良性疾病20例,分别采用ELISA法和CanAgMUC1检测试剂盒检测其血清中FS和MUC1含量.结果 在40例乳腺癌患者血清中FS和MUC1的血清含量分别为（3.75±1.32） ng/ml和（37.63±23.22） U/ml,FS和MUC1的阳性率分别为32.50％和47.50％,均明显高于对照组（P＜0.01）,乳腺癌患者FS和MUC1血清含量和阳性率与组织学分级、肿瘤大小、腋窝淋巴结转移有关（P＜0.01或P＜0.05）.结论 FS、MUC1与肿瘤发生、发展、生物学特征以及转移密切相关,联合检测这些指标有利于乳腺癌的早期诊断以及预后判断.     

High preoperative CA 15-3 concentrations predict adverse outcome in node-negative and node-positive breast cancer: study of 600 patients with histologically confirmed breast cancer

BACKGROUND: CA 15-3 is the most widely used serum marker in breast cancer. Currently, its main uses are in the surveillance of patients with diagnosed disease and monitoring the treatment of patients with advanced disease. METHODS: Preoperative CA 15-3 concentrations were measured prospectively in 600 patients with histologically confirmed breast cancer. Marker concentrations were related to patient outcome by both univariate and multivariate analysis. RESULTS: After a median follow-up of 6.27 years, patients with high preoperative concentrations of CA 15-3 (>30 units/L) had a significantly shorter overall survival pattern than those with low concentrations. As a prognostic factor, CA 15-3 was independent of tumor size, axillary node status, and patient age. As well as being prognostic in the total population of patients, CA 15-3 also predicted outcome in different subgroups of patients, including those with both node-negative and node-positive disease, those who were both estrogen receptor (ER)-negative and ER-positive, and those younger and older that 50 years of age. CA 15-3 was also predictive of outcome irrespective of the type of adjuvant therapy administered, i.e., whether adjuvant hormone therapy, adjuvant chemotherapy, or radiotherapy was administered. CONCLUSION: Assay of CA 15-3 is a relatively inexpensive, convenient, and noninvasive method for evaluating prognosis in newly diagnosed breast cancer patients.     

保留乳头乳晕乳腺癌术后即刻乳房再造15例

目的探讨保留乳头乳晕乳腺癌改良根治术后即刻采用背阔肌乳房再造的可行性。方法 2007年5月~2010年1月,对15例年龄为31~45岁(平均38岁)的乳腺癌患者行保留乳头乳晕乳腺癌改良根治术后即刻采用背阔肌乳房再造。对手术时间、术后并发症和美学效果进行评估。结果平均手术时间270 min,再造乳房全部成活,无严重的并发症发生。美容效果优良13例、尚好2例,无外形差的病例。5例术后出现背部供区血清肿,2例乳头部分坏死。术后所有患者对乳房形态均满意。结论对早期乳腺癌行保留乳头乳晕乳腺癌改良根治术后即刻采用背阔肌乳房再造是可行的。该方法操作简便,术后并发症少,再造乳房形态良好,它同时满足了肿瘤治疗和形体美容两个方面的要求,是早期乳腺癌患者一种安全有效的手术方式。     

CA 15-3: Uses and limitation as a biomarker for breast cancer

CA 15-3 which detects soluble forms of MUC-1 protein is the most widely used serum marker in patients with breast cancer. Its main use is for monitoring therapy in patients with metastatic disease. In monitoring therapy in this setting, CA 15-3 should not be used alone but measured in conjunction with diagnostic imaging, clinical history and physical examination. CA 15-3 is particularly valuable for treatment monitoring in patients that have disease that cannot be evaluated using existing radiological procedures. CA 15-3 may also be used in the postoperative surveillance of asymptomatic women who have undergone surgery for invasive breast cancer. In this setting, serial determination can provide median lead-times of 5–6 months in the early detection of recurrent/metastatic breast cancer. It is unclear however, whether administering systemic therapy based on this lead-time improves patient outcome. Consequently, expert panels disagree on the utility of regularly measuring CA 15-3 in the postoperative surveillance of asymptomatic women following a diagnosis of breast cancer. The main limitation of CA 15-3 as a marker for breast cancer is that serum levels are rarely increased in patients with early or localized disease.     

ER、PR、VEGF、CA15-3、CA125和CEA水平在乳腺癌预后判断中的临床意义

目的:探讨乳腺癌预后判断中ER、PR的表达情况及VEGF、CA15-3、CA125和CEA水平的临床意义.方法:86例乳腺癌患者行手术治疗,术后标记ER与PR,统计表达情况和随访情况;同时检测VEGF、CA15-3、CA125和CEA水平,并与40例正常对照组指标比较,分析其与临床分期、复发转移情况及治疗效果的关系.结果:22例ER和PR均表达阴性.随访后,“双阴性”患者进展(PD) 13例,稳定(SD)9例.乳腺癌组VEGF阳性率随临床分期(Ⅰ～Ⅳ)依次升高,淋巴结转移患者阳性率明显高于无转移者(P＜0.05).Ⅲ、Ⅳ期患者CA15-3、CA125和CEA水平显著高于Ⅰ、Ⅱ期和对照组,淋巴结转移患者明显高于无转移者(P＜0.05).复发者各项指标显著高于无复发者(P＜0.05).结论:联合检测ER、PR表达情况及VEGF、CA15-3、CA125和CEA水平有一定意义,可以指导乳腺癌诊疗工作.     

血清TK1、TPS、CA15-3联合检测在乳腺癌诊断中的临床价值

目的 探讨血清胸苷激酶1(TK1)、特异性组织多肽抗原(TPS)、糖类抗原15-3(CA15-3)联合检测在乳腺癌诊断中的临床价值.方法 采用免疫印迹-增强化学发光法对乳腺癌组(69例)、乳腺良性疾病组(52例)、健康对照组(48例)血清TK1进行检测,采用酶联免疫吸附试验(ELISA)对血清TPS进行检测,采用化学发光法对血清CA15-3进行检测,并对检验结果进行统计学分析.结果 乳腺癌患者血清TK1、TPS、CA15-3水平均显著高于乳腺良性疾病组与健康对照组(P＜0.01),3项指标联合检测的敏感性显著高于单项检测或2项联合检测(P＜0.05).结论检测血清TK1、TPS、CA15-3水平,对乳腺癌的诊断具有重要的价值,3种标志物联合检测能明显提高乳腺癌诊断的敏感性.     

乳腺癌14-3-3 sigma基因表达及其临床意义

目的 探讨乳腺癌14—3—3sigma基因表达及其临床意义。方法 采用RT—PCR和western—blot方法,分别对40例乳腺癌患者肿瘤组织和18例乳腺良性病变的乳腺组织,半定量检测14—3—3sigma基因的表达情况。结果 40例乳腺癌患者中,有35例（35／40,87．5％）没有检测出14—3—3sigma mRNA;western—blot也证明,40例中有32例14—3—3sigma蛋白表达缺失（32／40,80．0％）,两种试验同时阴性的有31例（77．5％）,另各有2例低表达。而在18例乳腺良性病变的患者,RT—PCR和western—blot均检测出14—3—3sigma基因表达。结论 14—3—3sigma基因表达缺失或低表达是乳腺癌的经常性事件,研究乳腺癌14—3—3sigma基因表达情况,可为乳腺癌的诊断提供实验室依据。     

Monocyte chemoattractant protein-1 in spinal tuberculosis: -362G/C genetic variant and protein levels in Chinese patients

The objective of the study is to explore the possible association of the monocyte chemoattractant protein (MCP)-1-362G/C genetic polymorphism and plasma levels of MCP-1 in patients with spinal tuberculosis (TB). The MCP-1-362G/C (rs2857656) polymorphism and blood levels of MCP-1 in patients with spinal TB and healthy subjects were evaluated and compared. Three hundred thirty-two patients and 336 healthy subjects were genotyped using polymerase chain reaction and Sanger DNA sequencing technology. MCP-1 plasma levels were measured by a solid-phase enzyme-linked immunosorbent assay. When comparisons were made between patients and controls, the frequency of the MCP-1-362*C minor allele (55.4% versus 47.5%, P = 0.004, odds ratio [OR] = 1.376, 95% confidence interval [CI]: 1.109–1.706) and the carriers of the MCP-1-362*C allele (80.7% versus 71.4%, P = 0.005, OR = 1. 657, 95% CI: 1.167–2.403) were over-represented in patients. The mean MCP-1 plasma level in spinal TB patients was significantly higher than in controls (154.44 ± 68.81 pg/mL versus 36.69 ± 21.71 pg/mL, t = –5.85, P < 0.001). The patients with the CC genotype had the highest MCP-1 level (150.63 ± 73.89 pg/mL), followed by those with the GC genotype (108.63 ± 52.09 pg/mL, t = 2.351, P = 0.022) and GG (91.29 ± 54.31 pg/mL, t = 3.091, P = 0.003) homozygotes. We report the association of the -362G/C genetic polymorphism and increased plasma levels of MCP-1 in patients with spinal TB and nominate the -362*C minor allele as a risk factor for spinal TB in the Chinese population.     

Combined inpatient rehabilitation and spa therapy for breast cancer patients: effects on quality of life and CA 15-3

The present study investigated the changes of quality of life, mood, and the tumor marker CA 15-3 associated with a 3-week inpatient breast cancer rehabilitation program incorporating spa therapy. One hundred forty-nine women, 32 to 82 years, participated in the study 3 to 72 months after breast cancer surgery. Quality of life (QoL, EORTC QLQ-C30), anxiety, and depression (HADS) were measured 2 weeks before, at the end, and 6 months after rehabilitation; CA 15-3 at the beginning, end, and at 6 months follow-up. Patients received an individualized rehabilitation program incorporating manual lymph drainage, exercise therapy, massages, psychological counseling, relaxation training, carbon dioxide baths, and mud packs. Quality of life and mood improved significantly, the greatest short-term improvements found for mood-related aspects of quality of life, the most lasting improvements found for physical complaints (eg, fatigue). Also, the tumor marker CA 15-3 declined significantly to follow-up. Patient characteristics, as well as the time since surgery, moderated rehabilitation outcome to a limited extent. Older patients, nonobese patients, patients with a greater lymphedema, and patients with an active coping style showed slightly greater improvements. Hot mud packs inducing hyperthermia did not affect CA 15-3. In conclusion, the combination of inpatient rehabilitation with spa therapy provides a promising approach for breast cancer rehabilitation.     

KU004 induces G1 cell cycle arrest in human breast cancer SKBR-3 cells by modulating PI3K/Akt pathway

KU004 is a newly synthesized compound which has been demonstrated possessing potent anti-cancer activities through targeting the highly-expressed protein HER2 on the surface of the cells. In this study, we investigated the potential roles of KU004 in the induced-cell cycle arrest in human breast cancer SK-BR-3 cells. KU004 could not only inhibit the proliferation of SK-BR-3 in a concentration-dependent manner but also induce G1 phase arrest in SK-BR-3 cells. The western blot results showed KU004 decreased the expression of cyclin D, CDK-4, p-Rb708/780, and up-regulated the p21. In order to verify whether KU004 takes the anti-tumor effect thought the regulation of PI3K/Akt pathway, we used western blot to detect the expression of protein Akt, Her2, p-Akt and p-Her2. Our results shown that after KU004 treatment, the amount of p-Akt and p-Her2 decreased but the total amount of Akt and Her2 remained unchanged. In conclusion, these results provide a framework for further exploration of KU004 as a novel chemotherapeutic for human breast tumors by modulating PI3K/Akt pathway.     

Elevated plasma TGF-beta1 levels correlate with decreased survival of metastatic breast cancer patients

BACKGROUND: The role of circulating TGF-beta(1) in prognosis of breast cancer (BC) was investigated with an intention to define TGF-beta(1)-dependent high risk and low risk subsets of patients. METHODS: Fifty three BC patients of all clinical stages and 37 healthy donors (HD) were analyzed for plasma TGF-beta(1) by the TbetaRII receptor-based Quantikine TGF-beta(1) ELISA kit. RESULTS: The plasma TGF-beta(1) level of Stage I/II disease (median: 0.94 ng/ml; n=10)) remained close to HD (median: 1.30 ng/ml; n=37; p>0.1). In contrast, Stage III/IV disease (median: 2.34 ng/ml; n=43) exhibited highly significant TGF-beta(1) elevation (p<0.001) relative to HD. Further analysis revealed that TGF-beta(1) increase was predominantly attributed to Stage IV, metastatic disease patients (Q3=4.23 ng/ml) rather than to the group Stage III/IV (Q3=3.58 ng/ml). Using the plasma TGF-beta(1) concentration of 3.00 ng/ml as the cut-off value, two subgroups of patients were formed. Overall 2-year survival of the first subgroup, having elevated plasma TGF-beta(1) (>3.00 ng/ml; n=10), was 10%. This was significantly decreased (p<0.05) compared to 52% survival observed for the second subgroup of patients with plasma TGFbeta(1) values close to HD (<3.00 ng/ml, n=19). CONCLUSION: We have performed a pilot study to determine the relationship between overall survival and TGF-beta(1) concentration in the blood of metastatic breast cancer patients. The survival was significantly reduced in the patients with elevated plasma TGF-beta(1) levels compared to that of the patients with plasma TGF-beta(1) levels close to normal. We propose that plasma TGF-beta(1) concentration may be a new tumour marker attributed to the presence of metastatic BC cells that may be used in selection of metastatic BC patients with poor prognosis.     

Cancer-associated antigen CA 15-3 in the diagnostics of breast tumours

The serum concentration of the new marker CA 15-3 was determined by a kit method, which is based on the use of two different monoclonal antibodies 115D8 and DF3, in a coated tube immunoradiometric technique. The mean CA 15-3 values in breast cancer patients (n = 40) were significantly higher than in patients with benign breast disease (n = 52, p less than 0.001) and in control subjects (n = 32, p less than 0.001). When we used the cut-off level 35 kU/l for CA 15-3, 0/32 of control subjects, 1/52 (2%) of patients with benign breast disease, 8/40 (20%) of all breast cancer patients, 6/19 (32%) of breast cancer patients with axillary nodal involvement and 1/1 of breast cancer patients with distant metastases were above this level. Among the same patients the CEA serum test was positive at a cut-off level of 5 micrograms/l in 7/40 (18%) cancer cases, and in 6/19 (32%) of cancer patients with nodal involvement. When we used the cut-off level 35 kU/l for CA 15-3 and 5 micrograms/l for CEA 1/52 (2%) of patients with benign breast disease, 10/40 (25%) of all breast cancer patients, 7/19 (37%) patients with axillary nodal involvement and 1/1 of breast cancer patients with distant metastases were positive in one or both of the tests. The serum CA 15-3 and CEA values were higher in patients with tumour size above 2 cm in diameter than in patients with smaller tumours (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)