Monitoring Of Breast Cancer Patients Research Articles

Independent Prognostication and Therapy Monitoring of Breast Cancer Patients by Dna/Rna Typing of Minimal Residual Cancer Cells

Clinical relevance, purification techniques and molecular characterization of minimal residual cancer cells (MRCC) is a controversial topic in the literature. An analytical concept including a novel isolation procedure and a panel of tests for DNA and RNA typing of MRCCs is described and clinically evaluated in this paper. The purification procedure exploiting the physical characteristics of MRCCs shows superior performance leading to > 50% pure and viable tumor cells. Proof of the presence and purity of MRCCs in an isolated sample is given by multiparametric DNA typing (amplifications, mutations, losses of heterozygosity). On the basis of the proven presence of MRCCs tumor-relevant mRNAs can be adequately analyzed by normalized quantitative real-time RT-PCR. The molecular characterization of MRCCs isolated from blood of breast cancer patients could have a strong clinical impact on prognostication, drug targeting and therapy monitoring.

CA 15-3 and CA 27-29 serum markers in monitoring breast cancer patients

CA 15-3 and CA 27-29 serum markers in monitoring breast cancer patients

Quantification of MUC1 in breast cancer patients: A method comparison study

Objective: To compare the performance of four serum assays for the quantification of MUC1 in breast cancer patients. Study design: A total of 282 serum samples were evaluated with two automated (Boehringer Mannheim Enzymun-Test® CA 15-3 and Chiron ACS™ BR) and two manual assays (Centocor CA 15-3® radioimmunoassay [RIA] and Biomira Truquant® BR RIA™). Sera were obtained from healthy controls ( n=50), patients with benign ( n=25) and malignant breast disease ( n=77) and patients with other malignancies ( n=69). In addition, sera from pregnant women ( n=56) and patients with liver cirrhosis ( n=5) were included. Results: Intraassay coefficients of variation (C.V.s) were highest for the manual Centocor CA 15-3 assay (7.4% for values below 50 kU/l and 8.1% for values above 180 kU/l). Interassay C.V.s were highest for the manual Truquant BR assay (11.7% for the lower concentration values and 18.6% for the higher concentration values). False positive rates ranged between 0% for the Centocor CA 15-3 RIA and 14% for the ACS BR assay (cut-off: 30 kU/l). In monitoring breast cancer patients all four assays show similar patterns, although absolute MUC1 values found may differ up to 50%. Conclusion: For monitoring purposes all assays perform equally well, however, automated assays show lower inter- and intraassay variability, especially in the higher value range. Therefore we recommend the use of the same, automated, assay for quantification of MUC1 during the follow-up of breast cancer patients.

A seminested RT-PCR assay for HER2/neu: Initial validation of a new method for the detection of disseminated breast cancer cells

Initial validation of a seminested reverse transcription-polymerase chain reaction (RT-PCR) assay for HER2/neu for use in detecting circulating tumor cells in the peripheral blood or bone marrow of breast cancer patients is described. RT-PCR assays for other epithelial markers, including the cytokeratins and carcinoembryonic antigen frequently lack specificity, sensitivity, or both. Thus, there is a need for an assay that is both sensitive and specific to be used to monitor breast cancer patients for micrometastatic or minimal residual disease. Assay conditions were optimized using the MCF7 breast cancer cell line and the Raji B-cell lymphoma cell line. The assay can detect as little as 3 mg of MCF7 RNA within a background of 3 mg of Raji RNA. The assay was positive in 12 of 12 breast tumors. None of the 33 peripheral blood or stem cell samples form patients without evidence of breast cancer were positive. Peripheral blood from 17 breast cancer patients was collected immediately before surgery and evaluated. The assay was positive in five of six patients with Stage II, four of eight patients with Stage I and one of three patients with Stage 0 disease. The seminested HER2/neu RT-PCR assay compares favorably with RT-PCR assays for other epithelial cell markers in terms of both sensitivity and specificity as a method to detect disseminated breast cancer cells. In breast cancer patients, the higher the disease stage, the more frequently was the assay positive.

Program for Genetic Monitoring of Breast Cancer Patients and Their Families

Limiting the success of breast cancer surgery in Bulgaria, sometimes diagnosis is very late. Genetic markers for breast cancer are not well known to the surgeons and they are not available for practical use. Appropriate psychological support is not available in every case, because the psychologists are not well informed about clinical and genetic aspects of the illness. There have been limited investigations of familial breast cancer in Bulgaria by the Department of Medical Genetics in Sofia, the National Oncological Center and the Clinic for Thoracic Surgery. There are observations concerning the clonality and chromosomal abnormalities in breast cancer. The Institute of Genetics, BAS, has introduced a model system for screening of the p53 tumor suppressor gene. However, many surgical clinics in the country are not included in the program for familial breast cancer. We have proposed a National Genetic Program for familial breast cancer, which will help the introduction of genetic markers for breast cancer, genetic counselling of the ill person and their family as well as psychological and social support. Abstract

Multicenter evaluation of the Bayer Immuno 1™ CA 15-3™ assay

We conducted a multicenter evaluation of the analytical and clinical features of the automated Bayer Immuno 1 CA 15-3 assay and compared assay performance to two manual tests. Results of the 10-day imprecision study of the Bayer Immuno 1 assay pooled across four evaluation sites and three lots of reagent produced total CV < or = 4%. Lot-to-lot reproducibility for 26 different lots of reagents and calibrators manufactured over a 2-year period was demonstrated (CV, 1.1%). Results for the Bayer Immuno 1 assay correlated well with the Biomira TRUQUANT BR 27.29 and Centocor CA 15-3 RIAs (r > or = 0.94). The upper limit of the reference interval for the Bayer Immuno 1 assay was 35.9 kilounits/L (35.9 units/mL); values were similar for all methods. Longitudinal monitoring of healthy women yielded assay values with an average CV of 11% and 21% for the Bayer Immuno 1 and Biomira assays, respectively. The Bayer Immuno 1 assay demonstrated the analytical features, intermethod correlation, and long-term performance characteristics that are essential for longitudinal monitoring of breast cancer patients.

Utility of CA 15-3 and CEA in monitoring breast cancer patients with bone metastases: Special emphasis on “spiking” phenomena

Objectives: CA 15-3 and CEA are considered useful tumor markers in monitoring breast cancer patients. This study was undertaken to specifically evaluate the transient elevations in these markers that are observed during systemic treatment for metastatic disease. This phenomenon has been termed “spiking.” Design and Methods: Serum tumor marker levels were investigated by enzyme immunoassay in 20 breast cancer patients without metastases and in 20 patients with bone metastases receiving systemic treatment. Results: Both CEA and CA 15-3 levels were significantly elevated in the patients with bone metastases. Serum CEA and CA 15-3 levels in patients with metastases displayed a transient, but significant, elevation days 15 and 30, respectively, after commencing systemic treatment, which returned to pretreatment levels on the 60th day. Conclusions: The spiking effect observed in the tumor marker levels should be carefully evaluated, and not be misdiagnosed as disease progression.

Clinical evaluation of potential usefulness of CEA, CA 15-3, and MCA in follow-up of breast cancer patients.

The potential usefulness of MCA, CA 15-3 and CEA in monitoring of breast cancer patients was evaluated in 135 female patients with histologically confirmed breast cancer. The patients were classified into two groups as follows: group of patients with no evidence of disease, NED; and group of patients with progressive disease, PD. In total, 2106 measurements of CEA, CA 15-3, and MCA were performed using an enzyme immunoassay. Serum levels of all three markers in the NED group differed significantly from those of patients with PD. The observed differences in the sensitivity and specificity of CEA, CA 15-3, and MCA tests were not significant. The serum concentrations of a particular marker correlated well with the concentrations of the other two markers, except when CEA was correlated with MCA or CA 15-3 in NED group patients. The elevation of tumor markers preceded by some 7 months the clinical evidence of dissemination, and marker levels reflected at a high percentage the response to therapy in PD patients. Therefore, this clinical study confirmed that MCA, CA 15-3 and also CEA are suited to discriminate between disease and disease-free periods, and also validated the usefulness of markers for treatment response monitoring.

Clinical value of CA 15-3, mucin-like carcinoma-associated antigen, tumor polypeptide antigen, and carcinoembryonic antigen in monitoring early breast cancer patients.

A total of 209 postsurgical breast cancer patients were prospectively monitored with simultaneous serum level estimations of CA 15,3, mucin-like carcinoma-associated antigen (MCA), tumor polypeptide antigen (TPA), and carcinoembryonic antigen (CEA); 141 (67.5%) were free of recurrence and 68 (32.5%) developed metastases during the follow-up. The mean values of tested tumor markers differed significantly in those with progressive disease compared with those free of disease recurrence. The sensitivity of tumor markers were CA 15-3, 68.2%; CEA, 34.1%; MCA, 72.7%; and TPA, 72.7%. The combination of CA 15-3 with TPA or MCA with TPA showed a trend for improved sensitivity of both markers (p = 0.06), with no specific loss of specificity (p = 0.11). The addition of CEA to CA 15-3 or MCA does not provide additional information for clinical evaluation. Patients with elevated tumor marker determinations had significantly shorter survival than those with values within the normal range. Two serial, progressively increasing values of tumor markers during the follow-up strongly predict recurrence. This study indicates that the comeasurement of CA 15-3 with TPA or MCA with TPA is justifiable in monitoring breast cancer patients postoperatively.

CA-549 serum levels in breast cancer monitoring.

CA-549 serum levels were assessed in 288 patients, 156 with early breast cancer (after surgery) and 132 with advanced breast cancer. CA-549 was abnormal (> 12 U/ml) in 25/156 patients (16%) without clinical signs of disease after surgery (median 9 U/ml), in 49/60 patients (82%) with disease in progression (P) (median 50 U/ml), in 19/27 patients (70%) with stationary disease (NC) (median 14 U/ml), in 25/33 patients (76%) with partial remission (PR) (median 18 U/ml) and in 4/12 patients (33%) with complete remission (CR) (median 9 U/ml). CA-549 serum levels correlated mainly with the extent of disease and secondarily with the prevalent metastatic site, higher values being observed in patients with visceral involvement (median 32.5 U/ml). CA-549 serum levels were also assessed in 51 patients at the start of treatment and at the time of objective evaluation: the results underline the concordance of CA-549 behavior with the clinical outcome in 71% of the cases. We conclude that CA-549 is a useful marker for monitoring breast cancer patients during the advanced stages of the disease.

Clinical value of a mucin-like carcinoma-associated antigen in monitoring breast cancer patients in comparison with CA 15-3

A new tumour marker, mucin-like carcinoma-associated antigen (MCA), was evaluated in 176 breast cancer patients classified either as free of tumour (NED, n = 141) or as having metastases (PD, n = 35). During the 5 year follow-up, 842 measurements of MCA and 363 measurements of CA 15-3 were done. MCA levels were significantly increased in the PD group ( P = 0.0001) but not in the NED group. The sensitivities of the MCA and the CA 15-3 assays were 84% and 78% and the specificities were 81% and 78%, respectively. The negative predictive value of 97% for MCA was significantly higher ( P = 0.0001) than the 88% for CA 15-3. Thus the MCA enzyme immunoassay is at least equivalent to the CA 15-3 test and is recommended in the assessment of metastatic spread or tumour recurrence in breast cancer patients.

A rational postoperative follow-up with carcinoembryonic antigen, tissue polypeptide antigen, and urinary hydroxyproline in breast cancer patients.

Breast cancer patients (n = 224) aged 28 to 81 were postoperatively followed up with serial determinations of carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), and urinary hydroxyproline (OHP). The clinical usefulness of these tumor markers to diagnose and monitor distant metastases was compared with that of the imaging techniques commonly used to monitor breast cancer patients (bone scanning [BS], liver echography [LE], chest radiograph, and skeletal radiograph). So far, 23 patients withdrew from the study, and distant metastases occurred in 33 patients. In 91% of the metastatic patients, constant elevation or progressive increase in serum CEA and/or TPA levels were the first pathologic findings of the relapse. Of the remaining 168 nonrelapsed patients, 122 were followed up longer than 24 months (43 +/- 17 months; mean +/- SD). In these 122 patients the false-positive results of CEA, TPA, and OHP were 0.8%, 2.4%, and 0%, respectively, when used simultaneously with clinical examination and the common laboratory examinations. BS and LE are the only imaging techniques that showed such a high sensitivity to be suitable in the postoperative follow-up of breast cancer patients. Nevertheless, because BS has a low specificity and is not harmless, it should be performed at longer intervals than tumor markers. Eventually, in the relapsed patients, TPA and OHP well reflected the response to treatment better than CEA and prevented useless radiologic examinations.

Ectopic production of placenta-"specific" tissue proteins (PP5 and PP11) by malignant breast tumors.

With use of an enzyme-bridge immunoperoxidase (PAP) technique, an immunohistochemical localization of the two new placenta-"specific" tissue proteins, PP5 and PP11, was investigated in 16 cases of breast cancer. PP5 was localized in the cytoplasm of breast cancer cells in 62.5% of cases examined and PP11, in 46.7%. Thus PP5 and PP11 may be markers for breast cancer and the detection of these proteins in sera from breast cancer patients may be more reliable and useful in the detection and monitoring of breast cancer patients than the determination of SP1, PP10, or PP12, other pregnancy "specific" proteins.

Immunologic monitoring in breast cancer patients receiving postoperative adjuvant chemotherapy.

A group of 17 patients, having undergone modified radical mastectomy for breast cancer, received 12 cycles of chemotherapy with methotrexate, 5-fluorouracil, and chlorambucil during 17 months. The number of circulating T and non T lymphocytes, as defined by E, EAC, and ME rosette formation, were reduced during treatment. The Non-T lymphocytes, however, were reduced to the highest relative extent. Relative phytohemagglutinin and mixed lymphocyte culture responses of the cells decreased, whereas purified protein derivative responses were unchanged. Serum concentrations of IgM were reduced, but IgA and IgG concentrations were unchanged or slightly increased. Antibody titres to morbilli and herpes simplex were not changed, whereas the antibody activity against cytomegalovirus (CMV) increased in several seropositive patients. None of these patients, however, developed signs of a CMV infection.