To evaluate CA 15-3, a new breast cancer associated antigen, and to compare it with carcinoembryonic antigen (CEA), all patients presenting with breast cancer had preoperative and serial (3-monthly) postoperative levels measured. Of 124 patients with primary breast cancer, 23% had an elevated CA 15-3 (greater than 25 units/ml) while 11% had an elevated CEA (greater than 5 ng/ml) (p = not significant). Neither marker was an indicator of spread to regional lymph nodes in primary breast cancer. In 45 recurrences of breast cancer, CA 15-3 was elevated at the time of first recurrence in 58% while CEA was elevated in 47% (p = not significant). Of 17 patients with locoregional recurrence alone, none had a CA 15-3 above 40 units/ml while 11 of 12 with synchronous locoregional and distant recurrence had a CA 15-3 level greater than 40 units/ml (chi 2: 21.36, p less than 0.0001). This study shows that CA 15-3, like CEA, is of little clinical value in primary breast cancer. CA 15-3, however, is an accurate indicator (overall accuracy, 97%) of synchronous distant metastases in patients with locoregional recurrence from breast cancer. This information has important implications for further investigation and management of such patients.

Antigens, Tumor-Associated, Carbohydrate↗

PubMedDate not supplied

Cancer metastasis: biological and clinical aspects.

The main cause of morbidity and mortality in cancer is the formation of distant metastases. While alterations in c-oncogenes, tumour suppressor genes and DNA repair enzymes are the key molecules involved in carcinogenesis, increased expression of proteases, motility factors and altered expression of adhesion molecules are causally involved in metastasis. The proteases mediating metastasis include urokinase plasminogen activator, cathepsin B, D and L and various matrix metalloproteinases. Certain proteases involved in metastasis (e.g., urokinase plasminogen activator) have been shown to be strong and independent prognostic markers for a variety of cancers. Finally, molecules involved in cancer spread are potential targets for new forms of anti-metastatic therapies.

Cell Adhesion Molecules↗

PubMedDate not supplied

Measurement of the stability of T-2 toxin in aqueous solution.

Studies were undertaken to determine unambiguously the stability of T-2 toxin in deuterated phosphate-buffered saline solutions in the pD range 5-12. No decomposition was observed after 1 year in samples between pD 5.0 and 6.7; above pD6.7, degradation proceeded via sequential cleavage of the ester side chains to form the series HT-2 toxin to T-2 triol to T-2 tetraol. A transient species believed to be an internal transesterification product of T-2 triol was also detected. Proton NMR was found to be a finely discriminatory technique for the observation and characterization of these species. It was possible for the first time to observe "in real time" the mixture of species, to model the multistage kinetics involved in their interconversion, and to obtain a set of rate constants. The kinetics of the breakdown of T-2 toxin at pD 11.2 were investigated. All reactions were found to be pseudo-first-order with half-lives of 5.4 and 11.7 h for T-2 toxin and HT-2 toxin, respectively. By extrapolation of these results, the half-life of T-2 toxin under quasi-physiological conditions (pD 7.4) was estimated to be about 4 years: this estimate is in broad agreement with the behavior observed in the stability study. Given this remarkable stability of T-2 toxin under pseudophysiological conditions, it was concluded that the contribution of nonenzymatic degradation to the detoxification of T-2 toxin and its metabolites is almost certainly negligible.

Drug Stability↗

PubMedDate not supplied

CA125 in ovarian cancer: European Group on Tumor Markers guidelines for clinical use.

CA125 is currently the most widely used tumor marker for ovarian epithelial cancer. The aim of this article is to provide guidelines for the routine clinical use of CA125 in patients with ovarian cancer. Due to lack of sensitivity for stage I disease and lack of specificity, CA125 is of little value in the detection of early ovarian cancer. At present, therefore, CA125, either alone or in combination with other modalities, cannot be recommended for screening for ovarian cancer in asymptomatic women outside the context of a randomized controlled trial. Preoperative levels in postmenopausal women, however, may aid the differentiation of benign and malignant pelvic masses. Serial levels during chemotherapy for ovarian cancer are useful for assessing response to treatment. Although serial monitoring following initial chemotherapy can lead to the early detection of recurrent disease, the clinical value of this lead-time is unclear. CA125 is the ovarian cancer marker against which new markers for this malignancy should be judged.

Biomarkers, Tumor↗

PubMedDate not supplied

CA 15-3: a prognostic marker in breast cancer.

CA 15-3 (also known as MUC1) is the most widely used serum marker in breast cancer. MUC1 is a large transmembrane glycoprotein which is frequently overexpressed and aberrantly glycosylated in cancer. Physiologically, MUC1 appears to play a role in cell adhesion and the high levels present in cancer may be causally involved in metastasis. At present the main uses of CA 15-3 are in preclinically detecting recurrent breast cancer and monitoring the treatment of patients with advanced breast cancer. In a prospective study of 368 patients we show that patients with high preoperative levels of CA 15-3 (>30.4 U/mL) had a worse outcome than patients with low levels of the marker. In multivariate analysis CA 15-3 as a prognostic marker was independent of both tumor size and nodal status. Furthermore, in multivariate analysis the prognostic impact of CA 15-3 was stronger than that of tumor size and at least as strong as nodal status. CA 15-3 may thus be the first independent prognostic serum marker in breast cancer.

Breast Neoplasms↗

PubMedDate not supplied

The clinical value of CEA and CA 15-3 in breast cancer management.

The value of tumour-associated antigens CEA and CA 15-3 was studied in patients with breast cancer over a 4-year period. A total of 252 patients with primary or recurrent disease had available and corresponding CEA and CA 15-3 values at diagnosis and during follow-up and were studied in detail. Preoperative and three-monthly serial postoperative levels were measured in each patient. Ten of 11 patients presenting with primary and concurrent metastatic disease had elevated CA 15-3 levels (> 25 I.U./ml) as compared to 6 with CEA (> 5 ng/ml). Fourty-seven patients developed locoregional recurrence of which 15 had concurrent metastatic disease. CA 15-3 was elevated in 14 cases while CEA in 11. Of 32 patients with locoregional recurrence alone, 18 later developed metastatic disease at a mean follow-up time of 17.5 months. There was a significant correlation between CA 15-3 value at locoregional recurrence and time to subsequent metastasis (r = 0.-0.57, P = 0.0133). CEA was elevated in 64%, CA 15-3 in 87% and either marker in 94% of 87 patients diagnosed with metastatic disease. Of 53 patients with serial markers and metastatic disease, 72% (38/53) had rising CA 15-3 levels prior to diagnosis with a mean lead time of 9.9 months. Use of CEA in conjunction improved lead time detection to 83%. This study demonstrates that CA 15-3 is superior to CEA at detecting metastatic disease at initial presentation and during follow-up. Use of CEA in conjunction with CA 15-3 improves the detection of systemic disease.

Bone Neoplasms↗

PubMedDate not supplied

High levels of cathepsin B predict poor outcome in patients with breast cancer.

Cathepsin B (CB) is a thiol-stimulated protease implicated in cancer invasion and metastasis. Other proteases involved in cancer spread such as urokinase-type plasminogen activator (uPA) and cathepsin D have previously been shown to be prognostic markers in breast cancer. CB was assayed by ELISA in 193 patients with primary breast cancer. CB levels were significantly higher in both primary and metastatic breast tumors than in fibroadenomas (p = 0.0001). In the primary carcinomas, CB levels showed no significant correlation with either nodal status, tumor size or estrogen receptor (ER) status. Patients with primary breast cancers containing high levels of CB had a significantly shorter disease-free interval (p = 0.01, chi-square = 6.61) and overall survival (p = 0.014, chi-square = 6.08) than patients with low levels of the protease. However, in multivariate analysis, using nodal status, tumor size, ER status and urokinase plasminogen activator (uPA), CB was not an independent prognostic marker. In contrast, nodal status, ER status and uPA were prognostic in multivariate analysis. In conclusion, CB, like certain other proteases implicated in cancer metastasis, correlates with poor outcome in patients with breast cancer. These results thus support the evidence from model systems linking CB to cancer spread. Inhibition of CB expression or activity might therefore be exploited for anti-metastatic therapies.

Biomarkers, Tumor↗

PubMedDate not supplied

Detection of estrogen receptor-beta mRNA in breast cancer using RT-PCR.

The estrogen receptor (ER) is the most useful marker currently available for breast cancer, being used both to predict response to therapy and assess prognosis. Recently, a new form of the ER, known as ER-beta, was identified. In this preliminary study we show that ER-beta mRNA was expressed less frequently in breast cancers than ER-alpha. ER-alpha but not ER-beta levels correlated with ER protein as determined by ELISA. We conclude that ER-beta is expressed in approximately 50% of breast cancers but it does not appear to be detected by a widely available ELISA.

Biomarkers, Tumor↗