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Biomedical subjects

J F Robertson

Publications and source records attributed to J F Robertson.

193 records · Page 11Linked to original sources
PubMedDate not supplied

The role of blood tumor marker measurement (using a biochemical index score and c-erbB2) in directing chemotherapy in metastatic breast cancer.

The role of blood tumor markers in monitoring response in advanced breast cancer is established in endocrine therapy and standard chemotherapy. This study examines marker levels in patients receiving new chemotherapy regimens. Thirty patients were recruited into two multicenter trials in which docetaxel-based regimens were used in 15 patients. The other 15 received doxorubicin-based regimens. Biochemical response calculated from a score using CA15.3, CEA and ESR was compared with UICC response. Marker changes at 2, 4 and 5 months correlated with UICC response at 3, 4(1/2) and 6 months, respectively (p < 0.03). Eleven patients achieved both clinical/radiological and biochemical response at the end of treatment; markers had not yet returned to below cutoffs in seven, suggesting a possible advantage to continue chemotherapy. No patient showed a biochemical response whilst judged clinically/radiologically progressive. Nineteen patients had progressed either clinically/radiologically or biochemically at six months; of these, eight showed progression assessed earlier by markers so that a median of four cycles of chemotherapy could have been saved. Measurements of serum c-erbB2 showed a correlation with tissue c-erbB2 staining in the primary tumor (p < 0.003). Among the patients with positive tissue staining, sequential changes in serum c-erbB2 completely paralleled initial response.

Biomarkers, Tumor↗
PubMedDate not supplied

Analysis of the temporal compressibility of breast tumour marker assays: development of a "near patient" assay.

The aim of this study was to investigate whether immunoassays for circulating MUC1 antigen in breast cancer could be compressed in time so that serum level results would be made available during the time of the patient's visit to clinic. Two assays were used: -The EMCA (Euro DPC) is a liquid phase immunoassay and the ELSA CA15-3 (CIS) is a double determinant solid phase immunoradiometric assay. The effects of shortened incubation times were investigated by assaying standards and unknown samples and comparing the results with those using the standard kit protocols. The binding kinetics of the monoclonal antibodies employed in the assays were analysed separately. We conclude that the EMCA assay can be shortened to 35 min and we have attributed this to the fast binding kinetics inherent in a liquid phase assay. This shortened assay may produce the basis for a useful "near patient" assay. By comparison, the solid phase ELSA CA15-3 assay cannot be compressed without loss in assay performance.

Antibodies, Monoclonal↗
PubMedDate not supplied

Oestrogen and progesterone receptors as prognostic variables in hormonally treated breast cancer.

This study directly compares ER status and PgR status of primary tumour tissue measured by enzyme immunoassays for prediction of response to therapy and survival in 99 women with breast cancer treated by hormone therapy. ER and PgR status alone both correlated with response to therapy (p = 0.002 and p = 0.02 respectively), time to progression (p < 0.0001 and p = 0.003 respectively) and survival (p < 0.001 and p = 0.01 respectively). 67% of tumours ER(+)/PgR(+) showed responsive or static disease compared to 25% of tumours ER(-)/PgR(-). Tumours of mixed phenotype (i.e. ER(+)/PgR(-) and ER(-)/PgR(+)) showed an intermediate response rate of 46%. Similar findings were observed when tumour phenotype was compared with overall survival. Combining ER and PgR allows more accurate prediction of clinical outcome but does not aid in selecting individual patients for endocrine therapy.

Adult↗
PubMedDate not supplied

c-erbB-2 in serum of patients with breast cancer.

c-erbB-2 is an oncoprotein which is overexpressed in some breast cancers. Recently it has been established that the extracellular domain of c-erbB-2 is shed into the serum of patients with breast cancer. There appears to be no association between tumor stage and extracellular domain of c-erbB-2 (c-erbB-2/ECD): c-erbB-2/ECD seems to correlate with patient prognosis whatever the stage of disease. The data also suggest that c-erbB-2/ECD may be useful in monitoring for tumor recurrence and in predicting resistance to hormonal therapy, but not as useful in predicting response to chemotherapy. This may relate to the power of this marker to reflect disease burden, which has an overwhelmingly negative impact on outcome.

Breast Neoplasms↗
PubMedDate not supplied

c-erbB-2 expression in primary breast cancer.

c-erbB-2 is an oncoprotein which is overexpressed in up to 40% of primary breast cancers. c-erbB-2 overexpression is a bad prognostic factor in patients with lymph node-positive disease. Unfortunately, there has been no agreement to date on whether c-erbB-2 overexpression is of prognostic significance in patients with lymph node-negative disease. c-erbB-2 overexpression is correlated with the absence of estrogen receptor expression in a number of publications. Correlation between c-erbB-2 overexpression and hormone sensitivity in the clinical setting is less well established and is the focus of ongoing studies. Both preclinical and clinical studies support an association between c-erbB-2 receptor overexpression and resistance to alkylating agents. In contrast, the data for c-erbB-2 and anthracyclines should be viewed in a slightly different manner. Anthracyclines appear to have a greater therapeutic effect in c-erbB-2-positive disease which may be dose sensitive. In c-erbB-2-negative disease not only is the therapeutic effect reduced but there does not appear to be any improved response to higher doses of anthracyclines. The data for c-erbB-2 and the taxanes is still not clear enough to provide any definite conclusions. If there is a correlation it would at present appear to be between paclitaxel and response rates, but this needs to be confirmed in larger studies. Few studies have looked at changes in c-erbB-2 on therapy. Those that have seem to show no significant change on either tamoxifen or chemotherapy.

Breast Neoplasms↗
PubMedDate not supplied

Local excision of ampullary carcinoma.

Pancreaticoduodenectomy is widely and reasonably regarded as the treatment of choice for ampullary carcinoma. Reported cases of local excision are few and mainly involve elderly, poor risk patients. Eight patients with ampullary carcinoma treated by local excision are presented. None of these patients who had local excision were considered unfit for pancreaticoduodenectomy. There were two post-operative deaths (25%). Median survival was 57 months with 44% five year actuarial survival. Three of the patients who survived the local excision subsequently developed recurrent disease. If local excision is performed some form of biliary bypass may be advisable.

Adult↗
PubMedDate not supplied

Serum tissue polypeptide specific antigen (TPS) in breast cancer patients: comparison with CA 15.3 and CEA.

Pre-treatment TPS serum levels from patients with Stage IV breast cancer (n = 66) (1386.0 +/- 3504.5) were significantly higher (p < 0.0001), than normal controls (n = 47), (75.5 +/- 111.5 U/L), benign breast disease patients (n = 84) (58.5 +/ 57.1 U/L), and breast cancer patients with Stage I/II (n = 79) (52.7 +I- 49.5U/L) or Stage III disease (n = 57) (166.7 +/- 218.8). Analysis of sequentially obtained samples from Stage IV patients during endocrine treatment showed TPS alone or in combination with CEA and CA 15.3 was less accurate in predicting response than the combination of CEA with CA 15.3. In this study TPS did not usefully add to the established marker combination of CEA and CA 15.3.

Biomarkers, Tumor↗
PubMedDate not supplied

Interactions between oestradiol and danazol on the growth of gastrointestinal tumour cells.

The gastrointestinal tumour cell lines, MKN45G and C146 possessed oestrogen receptors (ER) of affinities 1.8 x 10(-8) and 5.2 x 10(-9) M respectively. C146 and MKN45G had enhanced proliferation in the presence of oestradiol (10(-8) and 10(-10) M). Fifty-six percent (5/9) of primary gastric and colorectal tumours had their proliferation enhanced by oestradiol. The anti-steroidal drug, danazol, inhibited the basal growth of MKN45G (10 micrograms ml-1 45% of the untreated control), C146 (10 and 5 micrograms ml-1, 20 and 48% of control, respectively) and 3/9 GI primary tumours (10 micrograms ml-1). Danazol competed with 3 [H]-Oestradiol for binding to ER on MKN45G and C146, at concentrations from 10 to 1 micrograms ml-1.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

The significance of p53 autoantibodies in the serum of patients with breast cancer.

Serum p53 autoantibodies were studied in 82 patients with Stage 1 or 2 breast cancer using an ELISA assay. Tissue expression of p53 in these patients was also examined. High levels of serum p53 autoantibodies were detected in 48% (39/82) patients, while 23% (19/82) were tissue positive. Patients with high serum p53 autoantibodies levels were not significantly different to those with low levels with respect to, tissue p53, tumour grade, size, stage or oestrogen receptor status. Tissue immunoreactivity for p53 was significantly associated with tumour grade and negative oestrogen receptor status. Patients in both groups were followed for a median of over five years but the presence of p53 autoantibodies in serum was not prognostic with respect to disease free interval or survival. In this study detection of p53 autoantibodies in serum does not correlate with any of the usual tumour related prognostic factors, nor does it correlate with clinical outcome.

Antibodies, Neoplasm↗
PubMedDate not supplied

Evaluation of the IMMULITE BR-MA and CEA assays and comparison with immunoradiometric assays for CA15-3 and CEA in breast cancer.

This study was designed to evaluate the performance of a new automated assay system, the IMMULITE Automated Immunoassay Analyzer in comparison with more commonly used IRMA assays for measuring circulating tumour marker levels in breast cancer patients. The assays investigated measure the MUC1 mucin (CA15-3 antigen) or CEA. Serum samples from breast cancer patients with various stages of disease and from a group of normal individuals were analysed. Significant correlations were found between tumour marker levels measured using the IMMULITE BR-MA and the CA15-3 assays and between levels measured using the two CEA assay formats. Levels of IMMULITE BR-MA and CEA correlated with stage of disease suggesting that both are markers of tumour burden Levels in Stage III breast cancer patients were found to be significantly higher than those of normals using the IMMULITE system but not the IRMA assays. This would suggest a role for the automated system in the monitoring of breast cancer at an earlier stage than that at which tumour markers are routinely used. Elevated marker levels did not correspond to any particular site of metastasis however, a greater proportion of patients with multiple sites of metastasis had elevated levels compared with those with secondary disease at a single site. We conclude that the IMMULITE Automated Immunoassay Analyzer is of value in the routine surveillance of tumour marker levels.

Automation↗
PubMedDate not supplied

Male breast cancer: pathological and immunohistochemical features.

BACKGROUND: male breast cancer is uncommon and studies regarding the potential clinical relevance of the histopathological and immunohistochemical features are infrequently reported. MATERIALS AND METHODS: We investigated the biological characteristics of forty-one male patients with invasive breast cancer by assessing histopathological and multiple immunohistochemical features. RESULTS: The majority were no special type (ductal) (37/41), lobular cancer was not seen. 73% were histological grade 3, 93% were positive for oestrogen receptor and 73% for progesterone receptor. The proportion of cancers positive for c-ebB-2 (45%), EGFR (20%), p53 (58%), MiB1 (40%), NCRC11 (78%), were similar to reports for female breast cancer. Nonsignificant associations between poor survival outcome and grade 3 tumours, and positive tissue staining for MiB1 and p53 were seen. CONCLUSION: While there ar similarities in the biological features of breast cancer in males and females, some differences were identified. Male breast cancer is more likely to be grade 3 tumours and hormone receptor positive.

Biomarkers, Tumor↗
PubMedDate not supplied

C-erbB2 expression predicts response to preoperative chemotherapy for locally advanced breast cancer.

BACKGROUND: Previous work suggests that the presence of c-erbB2 oncoprotein immunostaining and the proliferation rate of tumours, may be relevant to chemo-sensitivity in breast cancer. PATIENTS AND METHODS: To investigate this we assessed pretreatment biopsies from 50 patients with locally advanced breast cancer for expression of c-erbB2 and MIB1 (proliferative marker) in relation to clinical response after 3 months preoperative chemotherapy. RESULTS: Objective response was significantly more likely (22/30, 73%) for tumours negative for c-erbB2 membrane staining, compared to positively staining tumours (6/20, 30%, p = 0.0025). The percentage of cells staining positively for MIB1 was not predictive of response (p = 0.56). CONCLUSIONS: This study has shown an increased likelihood of response to preoperative chemotherapy for breast cancers negative for c-erbB2 staining. Previous studies have shown that c-erbB2 immunostaining can correlate with either chemo-resistance or chemo-response. We postulate that this conflict may be due to differences in the type of chemotherapy administered. This raises the possibility of biological markers being use to assist in the selection of the type of chemotherapy regimen administered to particular tumour biological phenotype.

Antigens, Nuclear↗