Early detection of metastatic disease in asymptomatic breast cancer patients with whole-body imaging and defined tumour marker increase.

BACKGROUND: Follow-up care in breast cancer is still an issue of debate. Diagnostic methods are more sensitive, and more effective therapeutic options are now available. The risk of recurrence is not only influenced by tumour stage but also by the different molecular subtypes. This study was performed to evaluate the use of whole-body imaging combined with tumour marker monitoring for the early detection of asymptomatic metastatic breast cancer (MBC). METHODS: This analysis was performed as part of a follow-up study evaluating 813 patients with a median follow-up of 63 months. After primary therapy, all patients underwent tumour marker monitoring for CEA, CA 15-3 and CA 125 at 6-week intervals within an intensified diagnostic aftercare algorithm. A reproducible previously defined increase was considered as a strong indicator of MBC. From 2007 to 2010, 44 patients with tumour marker increase underwent whole-body magnetic resonance imaging and/or an FDG-PET/CT scan. Histological clarification and/or imaging follow-up were done. RESULTS: Metastases were detected in 65.9% (29/44) of patients, 13.6% (6/44) had secondary malignancies besides breast cancer and 20.5% (9/44) had no detectable malignancy. Limited disease was found in 24.1% (7/29) of patients. Median progression-free survival of MBC was 9.2 months and median overall survival was 41.1 months. The 3- and 5-year survival rates were 64.2% and 40.0%, respectively. CONCLUSIONS: A reproducible tumour marker increase followed by whole-body imaging is highly effective for early detection. By consequence, patients might benefit from earlier detection and improved therapeutic options with a prolonged survival.

Cytokeratin 19-fragments (CYFRA 21-1) as a novel serum biomarker for response and survival in patients with advanced pancreatic cancer.

BACKGROUND: CYFRA 21-1 serves as biomarker in several epithelial malignancies. However, its role in pancreatic cancer (PC) has not yet been investigated. METHODS: Within a prospective single-centre study serial blood samples were collected from patients with confirmed advanced PC. Pre-treatment values and weekly measurements of CYFRA 21-1, carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (assessed by Elecsys 2010, Roche Diagnostics) during palliative first-line chemotherapy were obtained. Biomarker data were correlated with objective response (determined by RECIST) as well as time to progression (TTP) and overall survival (OS) using uni- and multivariate analyses. RESULTS: Seventy-eight patients were included, 45% of these received treatment in prospective clinical trials. Median TTP was 3.9 months, median OS 7.7 months. Pre-treatment CYFRA 21-1 levels were significantly associated with performance status (P=0.0399) and stage of disease (P=0.0001). Marker values before chemotherapy and at the 2-month staging of all three markers were considered significant predictors for objective treatment response. Pre-treatment CYFRA 21-1 levels, as well as CA 19-9 values, could be applied to define subgroups (categorised by tertiles) with a different OS outcome (CYFRA: 14.8 vs 7.1 vs 4.8 months, CA 19-9: 14.2 vs 7.1 vs 5.2 months; P<0.0001). CYFRA 21-1 and CA 19-9 (both as categorised and as continuous variables) showed a highly significant correlation with TTP and OS at nearly all-time points assessed in univariate analysis. In multivariate analysis, only CYFRA 21-1 and performance status were independent predictors for OS. CONCLUSIONS: CYFRA 21-1 may serve as a valuable tool for monitoring treatment response and assessing prognosis in advanced PC.

Cytokeratin serum biomarkers in patients with colorectal cancer.

BACKGROUND: Circulating cytokeratins have shown to be important for management of patients with lung cancer. Here we investigated their role for differential diagnosis, therapy monitoring and prognosis in colorectal cancer (CRC). PATIENTS AND METHODS: Pretherapeutic levels of cytokeratin-19 fragments (CYFRA 21-1), carcino-embryonic antigen (CEA) and cancer antigen (CA) 19-9 were measured in 42 patients with CRC, 45 with benign colorectal diseases and 51 healthy controls. Furthermore, courses of CYFRA 21-1, tissue polypeptide antigen (TPA), tissue polypeptide specific antigen (TPS), M30-antigen, CEA and CA 19-9 were analyzed in prospectively collected sera of 15 patients with CRC during primary chemotherapy and were correlated with therapy response and overall survival (OS). RESULTS: Similar to CEA and CA 19-9, CYFRA 21-1 was significantly elevated in serum from patients with CRC (median 2.1 ng/ml) as compared with healthy (1.2 ng/ml; p<0.0001) and benign gastrointestinal controls (1.7 ng/ml; p=0.0178) and showed stage dependency in CRC (p=0.0118). CYFRA 21-1 correlated with CEA in benign diseases and CRC but not with CA 19-9. The best discrimination between healthy controls and patients with CRC was achieved by combination of CYFRA 21-1 and CA 19-9 (area under the curve; AUC=86.7%), while the combination of CEA and CA 19-9 discriminated best between benign diseases and CRC (AUC=73.9%). In CRC patients during primary chemotherapy, levels of cytokeratins CYFRA 21-1, TPA, TPS, CEA and CA 19-9 tended to be higher in patients with poor response to therapy and with poor prognosis. CONCLUSION: Cytokeratins are elevated in patients with CRC and show some association with response to primary therapy and prognosis.

Increased alpha-fetoprotein receptor in the serum of patients with early-stage breast cancer.

The alpha-fetoprotein (afp) receptor (recaf) is an oncofetal antigen found in most types of cancer. Using a competitive radioimmunoassay, we measured the concentration of serum recaf in three sets of samples.Set 1 was blind and consisted of 119 normal subjects, 43 breast cancer patients (stages i and ii), and 20 patients with benign breast conditions. In this set, the assay discriminated normal from cancer samples with a receiver operating characteristic for the area under the curve (ROC(AUC)) of 0.983; with 95% specificity and 93% sensitivity at a cut-off of 4.6 K (arbitrary) recaf units; and with 72% sensitivity and 100% specificity at a cut-off of 7.3 K units. At 7.3 K units, the specificity for benign breast conditions was 85%, and the sensitivity was 72% (ROC(AUC) was 0.773). Carcinoembryonic antigen and cancer antigen 15-3 respectively showed 39% and 41% sensitivity, with 95% specificity in comparisons of normal with cancer samples, and 34% and 44% sensitivity, with 85% specificity in comparisons of benign with cancer samples. Set 2 consisted of 353 normal, 30 benign, and 64 cancer samples (stages ii and iii). The recaf assay sensitivity in discriminating normal from cancer samples was 97%, with 97% specificity. Benign compared with cancer samples showed 87% sensitivity, with 97% specificity. Set 3 included only 40 normal and 40 cancer samples. The assay sensitivity was 89%, with 100% specificity. Sets 2 and 3 were not tested with carcinoembryonic antigen and cancer antigen 15-3.These results strongly suggest that the recaf assay could be used for detecting breast cancer in its early stages.

Detection of prostate cancer with complexed PSA and complexed/total PSA ratio - is there any advantage?

OBJECTIVE: To evaluate the performance of total PSA (tPSA), the free/total PSA ratio (f/tPSA), complexed PSA (cPSA) and the complexed/total PSA ratio (c/tPSA) in prostate cancer detection. METHODS: Frozen sera of 442 patients have been analysed for tPSA, free PSA (fPSA) and cPSA. 131 patients had prostate cancer and 311 patients benign prostatic hyperplasia. RESULTS: Differences in the distribution of the biomarkers were seen as follows: tPSA, cPSA and c/tPSA were significantly higher in the PC group, and f/tPSA was significantly higher in the BPH group. In the tPSA-range of 0-4 ng/ml none of the biomarkers showed a significant difference in the distribution between both groups. In the tPSA-ranges of 0-10 ng/ml, 2-10 ng/ml, 4-10 ng/ml and <10 ng/ml, f/tPSA showed the highest specificity at high sensitivtities, followed by c/tPSA, cPSA, and tPSA, respectively. In tPSA-ranges greater than 10 ng/ml, cPSA offered the best discriminatory ability. CPSA compared to tPSA offered better specificity at high sensitivities in all tPSA-ranges. CONCLUSION: F/tPSA offers the best ability to distinguish between both groups in lower tPSA-ranges, followed by c/tPSA. CPSA compared to tPSA offers a better ability to discriminate between both groups in all PSA-ranges and could be used as an initial test for PC.

Significance of serum CA125 and TPS antigen levels for determination of overall survival after three chemotherapy courses in ovarian cancer patients during long-term follow-up.

PURPOSE OF INVESTIGATION: To evaluate the prognostic significance for overall survival rate for the marker combination TPS and CA125 in ovarian cancer patients after three chemotherapy courses during long-term clinical follow-up. METHODS: The overall survival of 212 (out of 213) ovarian cancer patients (FIGO Stages I-IV) was analyzed in a prospective multicenter study during a 10-year clinical follow-up by univariate and multivariate analysis. RESULTS: In patients with ovarian cancer FIGO Stage I (34 patients) or FIGO Stage II (30 patients) disease, the univariate and multivariate analysis of the 10-year overall survival data showed that CA125 and TPS serum levels were not independent prognostic factors. In the FIGO Stage III group (112 patients), the 10-year overall survival was 15.2%; while in the FIGO Stage IV group (36 patients) a 10-year overall survival of 5.6% was seen. Here, the tumor markers CA125 and TPS levels were significant prognostic factors in both univariate and multivariate analysis (p < 0.0001). In a combined FIGO Stage III + FIGO Stage IV group (60 patients with optimal debulking surgery), multivariate analysis demonstrated that CA125 and TPS levels were independent prognostic factors. For patients in this combined FIGO Stage III + IV group having both markers below respective discrimination level, 35.3% survived for more than ten years, as opposed to patients having one marker above the discrimination level where the 10-year survival was reduced to 10% of the patients. For patients showing both markers above the respective discrimination level, none of the patients survived for the 10-year follow-up time. CONCLUSION: In FIGO III and IV ovarian cancer patients, only patients with CA 125 and TPS markers below the discrimination level after three chemotherapy courses indicated a favorable prognosis. Patients with an elevated level of CA 125 or TPS or both markers after three chemotherapy courses showed unfavorable prognosis.

Comparison of CT colonography, colonoscopy, sigmoidoscopy and faecal occult blood tests for the detection of advanced adenoma in an average risk population.

BACKGROUND AND AIMS: This prospective trial was designed to compare the performance characteristics of five different screening tests in parallel for the detection of advanced colonic neoplasia: CT colonography (CTC), colonoscopy (OC), flexible sigmoidoscopy (FS), faecal immunochemical stool testing (FIT) and faecal occult blood testing (FOBT). METHODS: Average risk adults provided stool specimens for FOBT and FIT, and underwent same-day low-dose 64-multidetector row CTC and OC using segmentally unblinded OC as the standard of reference. Sensitivities and specificities were calculated for each single test, and for combinations of FS and stool tests. CTC radiation exposure was measured, and patient comfort levels and preferences were assessed by questionnaire. RESULTS: 221 adenomas were detected in 307 subjects who completed CTC (mean radiation dose, 4.5 mSv) and OC; 269 patients provided stool samples for both FOBT and FIT. Sensitivities of OC, CTC, FS, FIT and FOBT for advanced colonic neoplasia were 100% (95% CI 88.4% to 100%), 96.7% (82.8% to 99.9%), 83.3% (95% CI 65.3% to 94.4%), 32% (95% CI 14.9% to 53.5) and 20% (95% CI 6.8% to 40.7%), respectively. Combination of FS with FOBT or FIT led to no relevant increase in sensitivity. 12 of 45 advanced adenomas were smaller than 10 mm. 46% of patients preferred CTC and 37% preferred OC (p<0.001). CONCLUSIONS: High-resolution and low-dose CTC is feasible for colorectal cancer screening and reaches sensitivities comparable with OC for polyps >5 mm. For patients who refuse full bowel preparation and OC or CTC, FS should be preferred over stool tests. However, in cases where stool tests are performed, FIT should be recommended rather than FOBT.

Relapse and survival in early-stage ovarian cancer.

OBJECTIVE: To analyze the prognostic influence of patient characteristics, diagnostic markers or therapeutic procedures in women diagnosed with early ovarian cancer based on relapse and survival in long term follow-up. MATERIALS AND METHODS: All women diagnosed and treated for early ovarian cancer at our institution between 1992 and 2006 were included in this retrospective study. Patient characteristics, clinical data including operative procedure, serum markers, stage and histology at first diagnosis as well as follow-up data were analyzed with regard to survival times and relapse rates. RESULTS: Altogether, 116 patients were included. Mean follow-up time was 7.0 +/- 3.3 years (range 2-14 years). Histology revealed a serous tumor in 64.7% (75/116), mucinous in 19.0% (22/116) and endometiroid tumors in 7.8% (9/116) of all cases. TNM classification was pT1a in 49.1% (57/116), pT1b in 6% (7/116), pT1c in 32.8% (38/116) and pT2a in 12.1% (14/116). Lymph node involvement (N1) was found in 3.4% of all patients. 17 deaths and 17 relapses (each 14.7%) were documented during follow-up time with a mean time to recurrence of 3.3 +/- 2.1 years (range 1-7 years). The general 1-, 2-, 5- and 10-year survival rates were 99, 95.7 and 88.9 and 81.0%, respectively. Patients with tumor stage pT1a and pT1b had a significantly better survival (P = 0.0003) and significantly lower risk of recurrence (P = 0.0138) compared to higher tumor stages. Moreover, patients who experienced recurrent disease or presented with ascites at primary diagnosis had a significantly worse overall survival (recurrence: hazard ratio 0.17, 95% confidence interval 0.0155-0.2182, P = 0.0001; ascites: HR 2.84, CI 1.1919-10.1131, P = 0.0225). The risk for recurrent disease was significantly elevated for patients with low grade (G3) tumors (P = 0.0330). Interestingly, there was neither a worse survival rate nor a higher relapse rate for patients with primary laparoscopic surgical access. CONCLUSION: Patients with early ovarian cancer stage pT1c and pT2a or low grade tumor have to be monitored closely in oncologic follow-up as they bare a significant risk for disease recurrence. Ascites at primary diagnosis, pT1c or pT2a tumor stage or recurrent disease are associated with a poor survival even in early ovarian cancer.

Clinical relevance of tumor markers for the control of chemotherapy.

This presentation is based on our experience with tumor marker monitoring of surgery therapy and chemotherapy effects. The control of chemotherapy is one of the most important problems in oncological practice. The correlation between the clinical status of the patient and tumor size changes, based on the results of different imaging methods, has been the most important and most frequently used method. However, the therapy effect has been recently assessed by markers of the biological activity of the tumor. Using tumor markers for the assessment of the effect of surgery therapy is already part of routine practice in many different types of cancer. Pre-operative and post-operative values of tumor markers are essential for a proper evaluation. However, tumor marker monitoring of the effect of radiotherapy and chemotherapy has been used very rarely, mostly only for research purposes. Besides monitoring by classical tumor markers, monitoring by markers of angiogenesis and apoptosis seem to be promising for the assessment of chemotherapy effect. Measurement of circulating cancer cells by means of mRNA also seems to be intriguing for therapy effect control and monitoring of the course of disease. Unfortunately, the routine use of these methods has been applied in only a few institutes worldwide. A completely different situation has been observed in palliative treatment. In most cases, changes of serum levels of tumor markers correlate with therapy effect. Thus, the effect of treatment on tumor proliferation can be successfully estimated by decreasing tumor marker levels.

Changes of thymidine kinase (TK) during adjuvant and palliative chemotherapy.

UNLABELLED: Thymidine kinase is involved in nucleic acid synthesis and is, therefore, considered to be an important proliferation tumor marker. For this reason, we monitored this marker in the course of colorectal cancer chemotherapy. MATERIALS AND METHODS: We examined thymidine kinase (TK) levels in 30 patients with colorectal cancer who underwent adjuvant or palliative chemotherapy (CHT schemes). The condition for being included in the study was a minimum of 3 cycles of chemotherapy. TK was always assessed with radio-receptor analysis, before and after every chemotherapy cycle, together with other tumor markers. RESULTS: From the monitored tumor markers, only TK changed typically in the course of chemotherapy. In adjuvant chemotherapy, it was mostly low at the beginning of the cycle and its values usually increased considerably at the end. On the other hand, in palliative chemotherapy the dynamics of TK varied mainly depending on the effect of the therapy. Other tumor markers showed nonstandard behavior and minimal correlation with TK changes. CONCLUSION: Thymidine kinase seems to be a suitable parameter for monitoring the effect of adjuvant and palliative chemotherapy in colorectal cancer.

Markers of cellular adhesion in diagnosis and therapy control of colorectal carcinoma.

AIM: Early diagnosis of the progressive tumor disease and control of the effect of therapy in colorectal carcinoma are most frequently performed by monitoring CEA or CA 19-9 tumor markers. Their clinical application is, however, limited. The aim of our study was to demonstrate the contribution of adhesive molecule assessment to the early diagnosis of progression. We also wanted to find out if changes in the levels of cellular adhesion parameters correlate with the effect of antitumor therapy. MATERIALS AND METHODS: Intercellular cell adhesive molecule-1 (ICAM-1) and Vascular cell adhesive molecule-1 (VCAM-1) were assessed using the ELISA method, and the results were correlated with CEA and CA 19-9 tumor markers. Three hundred and sixty-four patients with colorectal carcinoma in Dukes' stages B-D were monitored. The results were processed with the SAS 6.2. statistical program and Statistica. RESULTS: In 92 patients with first clinical progression (occurrence of distant metastases irrespective of localization), significantly increased ICAM-1 and VCAM-1 values were demonstrated. In ROC evaluation of curves, we also demonstrated high sensitivity of adhesive molecules against both the control healthy group (n =89) and the no evidence of disease group (NED) (n=183). Adhesive molecule levels were closely connected with the type and course of therapy and are presented in the form of case reports. CONCLUSION: Soluble adhesive molecules are a prospective parameter both for the early diagnosis of progression and for control of the effect of therapy. There is a need for a large-scale study, preferably multicentric, which would verify the suitability of introducing cellular adhesion parameter assessment into routine practice.

[Tumor markers--how they should be applied]. / Nur der gezielte Einsatz bringt Vorteile für den Patienten. Tumormarker gehören nicht zum Routine-Check-up.

Determination of a tumor marker is currently not suitable method for screening purpose (exception: PSA and thyroglobulin). Tumor marker determination cannot be employed to exclude the presence of a tumor. Prior to surgery, however, such determination is desirable, and in the case of germ cell tumors even mandatory. Postoperatively, or after termination of adjuvant chemotherapy and/or radiotherapy, determination of tumor markers as an individual baseline is necessary for the further disease course. During the course of the disease and for follow-up care, the kinetic development of tumor factors is, in comparison with the individual baseline values, of decisive importance. However, in order to ensue correct interpretation it is important to use the same test system.

Therapy control in oncology by circulating nucleosomes.

The courses of circulating nucleosomes in the serum of patients with various solid tumors correlate with the clinical outcome after chemo- and radiotherapy. Already during the initial phase of treatment they showed considerable alterations consisting of a rapid increase followed by a decrease during the first therapeutic week. Among patients with advanced lung cancer undergoing chemotherapy, those patients who responded to therapy exhibited less pronounced increases and more complete decreases compared to those patients with insufficient response. In addition, response to therapy was correlated with stronger decreases of the precyclic baseline values from cycle 1 to 2 and from cycle 1 to 3. Thus, circulating nucleosomes are a valuable tool for the early prediction of therapeutic efficacy and can help to modulate therapy strategies early and on an individual basis.

Apoptotic markers in cancer.

In cancer, apoptotic processes occur both spontaneously and induced by antitumor therapies. Qualitative and quantitative changes in cancer cell death along with proliferative alterations are essential determinants in the pathogenesis and progression of malignant disease and its responsiveness to therapy. Besides detecting apoptosis by invasive means in tumor tissue, apoptotic products can be quantified in the circulation. Although circulating apoptotic products usually lack organ and tumor specificity, they contribute in the assessment of disease extent or aggressiveness. The ease of drawing blood facilitates the serial measurement of circulating apoptotic markers to monitor antitumor treatment and predict early response to therapy. This review describes the features of apoptotic and necrotic cell death along with the role the balance between the rates of cell death and cell proliferation plays in the progression of malignancy. The intracellular pathways mediating apoptosis are next summarized. The focus then shifts to the apoptotic markers found in the circulation and their diagnostic, prognostic, predictive, and management utility in cancer.

Effects of single-dose irradiation on bronchial epithelium: a comparison of BEAS 2B cell monolayers, human organ cultures, and Goettinger minipigs.

To assess the effects of radiation on bronchial epithelium, BEAS 2B cells cultured as monolayers and human bronchial epithelium cultured as organ cultures were exposed to single doses of 0, 10 and 30 Gy. The lactate dehydrogenase in the supernatant of the BEAS 2B cells increased markedly 24 h after irradiation, whereas in the organ cultures only a minor increase was found after 48 h. The nucleosomes in the supernatant of the BEAS 2B cells showed a massive increase in response to irradiation, whereas in the organ cultures no change could be seen. The number of BEAS 2B cells was dramatically diminished after 96 h, whereas in the organ cultures a smaller decrease was observed no earlier than 21 days after irradiation. To assess the effects of brachytherapy in bronchial epithelium in vivo, brachytherapy with 30 Gy was performed in Goettinger minipigs, and histological sections of the bronchi were analyzed for morphological alterations and cell numbers. After 2 weeks, only slight cell damage was observable, and after 3 weeks, moderate morphological changes and decreased cell numbers were found. However, after 8 weeks, the epithelium had nearly regained its normal structure. We conclude that the bronchial epithelium has a remarkably high radioresistance and that organ cultures, but not monolayers of BEAS 2B cells, reflect the effects of radiation in vivo.

Are serial CA 19-9 kinetics helpful in predicting survival in patients with advanced or metastatic pancreatic cancer treated with gemcitabine and cisplatin?

BACKGROUND: Serial kinetics of serum CA 19-9 levels have been reported to reflect response and survival in patients with pancreatic cancer undergoing surgery, radiotherapy, and chemotherapy. We prospectively studied serial kinetics of serum CA 19-9 levels of patients with locally advanced or metastatic disease treated with gemcitabine and cisplatin. PATIENTS AND METHODS: Enrolled in the study were 87 patients (female/male = 26/61; stage III/IV disease = 24/63). Patients received gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 plus cisplatin 50 mg/m(2) on days 1 and 15, every 4 weeks. Serum samples were collected at the onset of chemotherapy and before the start of a new treatment cycle (day 28). RESULTS: 77 of 87 patients (88.5%) with initially elevated CA 19-9 levels were included for evaluation. According to imaging criteria, 4 (5.2%) achieved a complete remission and 11 (14.3%) achieved partial remission, yielding an overall response rate of 19.5%. 43 (55.8%) patients were CA 19-9 responders, defined by a > or = 50% decrease in CA 19-9 serum levels within 2 months after treatment initiation. Except for one, all patients who had responded by imaging criteria (n = 14) fulfilled the criterion of a CA 19-9 responder. Despite being characterized as non-responders by CT-imaging criteria (stable/progressive disease), 29 patients were classified as CA 19-9 responders (positive predictive value 32.5%). Independent of the response evaluation by CT, CA 19-9 responders survived significantly longer than CA 19-9 nonresponders (295 d; 95% CI: 285-445 vs. 174 d; 95% CI: 134-198; p = 0.022). CONCLUSION: CA 19-9 kinetics in serum serve as an early and reliable indicator of response and help to predict survival in patients with advanced pancreatic cancer receiving effective treatment with gemcitabine and cisplatin.

[Treatment monitoring, recurrence detection, prognosis. Here's where tumor markers make good sense]. / Therapie überwachen, Rezidiv erkennen, Prognose abschätzen. Hier liegen die wahren Stärken von Tumormarkern.

Of the growing group of cancer biomarkers, circulating humoral tumour markers (TM) are the longest-known subgroup of substances with protein, lipid, glycolipid or carbohydrate structure, that can be used as probes for identifying the origin, growth and therapy-related debulking of a tumor. Relevant TM are well-defined and easy to determine, and disturbing factors and statistical characteristics well-known. They are most commonly used not so much for early detection, localization and diagnosis, but for treatment monitoring, detection of recurrence and, latterly, also for outcome prediction. Their particular value lies in their supporting role in invasive imaging or endoscopic procedures. In some cases, they may also prolong the intervals between for such procedures.

Serum CEA and CA 15-3 as prognostic factors in primary breast cancer.

In the present study, we investigated the association of the serum levels of the tumour markers carcinoembryonic antigen and cancer antigen 15-3 with disease free survival and death from disease in 1046 women with breast cancer without metastases at the time of primary diagnosis in relation to age and the established prognostic factors tumour size, lymph node status, histological grading and hormone receptor status. We found that elevated pre-operative serum marker values were correlated with early relapse (cancer antigen 15-3; P=0.0003) and death from disease (carcinoembryonic antigen, cancer antigen 15-3; P=0.0001 both) in univariate analyses. By comparing pre- and post-operative values we found a decline in values post-surgery. In those patients where marker levels of carcinoembryonic antigen decreased more than 33%, a significantly higher risk for relapse and death from disease (both P=0.0001) in univariate analyses was observed. In multivariate analysis this decrease of carcinoembryonic antigen proved to be an independent prognostic factor. The results for cancer antigen 15-3 were comparable to carcinoembryonic antigen in univariate analyses but showed no significance in multivariate analysis. In this study the post-operative decrease of the serum tumour marker carcinoembryonic antigen was a strong independent prognostic factor for disease free survival and death from disease in breast cancer patients.