Biomedical subjects

Catherine Duggan

Publications and source records attributed to Catherine Duggan.

9 recordsLinked to original sources

PubMed2005

Expression of the breast cancer metastasis suppressor gene, BRMS1, in human breast carcinoma: lack of correlation with metastasis to axillary lymph nodes.

The BRMS1 (breast cancer metastasis suppressor 1) gene has been found to suppress metastasis in animal models without inhibiting primary tumor growth. The aim of this study was to measure expression of BRMS1 mRNA in a panel of human breast carcinomas and compare its expression with parameters of local dissemination such as tumor size and lymph node metastasis. We also compared expression of BRMS1 mRNA in normal breast tissue, fibroadenomas, primary breast cancers and axillary nodal metastases from primary breast cancers. BRMS1 mRNA was detected in 10/11 (90%) specimens of normal breast tissue, 12/16 (75%) fibroadenomas, 64/82 (78%) primary breast cancer and 11/15 (64%) lymph node metastases (p, NS). In the primary cancer, expression was independent of tumor size, tumor grade, metastasis to axillary nodes and hormone receptor status. Furthermore, similar levels of BRMS1 were found in normal breast tissue, primary breast carcinomas and lymph node metastases from primary breast cancer. Our results do not suggest a role for BRMS1 in suppressing metastasis to local lymph nodes in patients with breast cancer.

Axilla↗

PubMed2005

CT computer-optimized high-dose-rate brachytherapy with surface applicator technique for scar boost radiation after breast reconstruction surgery.

PURPOSE: Immediate breast reconstruction has become increasingly prevalent after mastectomy for breast cancer. Postoperative scar boost radiation for the reconstructed breast presents many planning challenges due to the shape, size, and curvature of the scar. High-dose-rate (HDR) surface applicator brachytherapy is a novel and effective method of delivering scar boost radiation. Two cases, one with a saline implant and one with a transverse rectus abdominis musculocutaneous flap reconstruction, illustrate the method and advantages of HDR optimization of surface applicators. METHODS AND MATERIALS: For 2 patients a mold of the breast was made with Aquaplast sheets. A reproducible system was used for arm positioning. Skin fiducials, including tattoos from external beam planning, were matched to fiducials on the mold. HDR catheters were sited on the mold at 1cm intervals, with the central catheter situated along the scar. Topographically, both scars demonstrated extreme curvature in both craniocaudal and mediolateral directions. A CT computer-optimized HDR plan was developed, with the reference dose prescribed at the skin surface. The dosimetry was compared to single-field and matched-field electron plans. RESULTS: This surface applicator technique provided a uniform skin dose of 100% to the entire clinical target volume (CTV) without hot spots in both patients. The patient position and surface applicator setup were consistently reproducible. The patients tolerated the treatment well with minimal skin erythema. In the single-field electron plan, skin dose was decreased to 50% at the periphery of the scar. Matching fields addressed this depth dose decrement, but resulted in large localized hot spots of more than 200% centrally in each field. CONCLUSION: CT computer-optimized HDR surface applicator brachytherapy provided a reproducible homogeneous method of treating highly curved scars on the reconstructed breast. Electron beam treatment would result in longer and more complex treatments yet still provide a less homogeneous dose than this surface applicator technique.

Brachytherapy↗

PubMed2004

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.

Adult↗

PubMed2003

Inherited and acquired risk factors for venous thromboembolic disease among women taking tamoxifen to prevent breast cancer.

PURPOSE: Venous thromboembolism (VTE) is of particular concern in women receiving tamoxifen in a chemopreventive setting. We investigate the association between acquired and inherited risk factors for VTE in the International Breast Cancer Intervention Study (IBIS-I) trial of tamoxifen prophylaxis for women at increased risk of breast cancer. METHODS: We used a nested case-control study design to investigate the role of tamoxifen and acquired risk factors in the risk of developing a VTE. RESULTS: Tamoxifen was associated with a significantly increased risk of developing a major VTE (odds ratio [OR], 2.1; 95% CI, 1.1 to 4.1). Women who had surgery, immobilization, or fracture in the previous month had a greatly increased risk of developing a major VTE (OR, 4.7; 95% CI, 2.2 to 10.1). Prothrombin and factor V Leiden mutations were found exclusively among control women: factor V Leiden in eight of 159 control women (5.0%) and the prothrombin mutation in three control women (1.9%). Thirty-five women with a VTE and a blood sample were negative for these mutations. The upper one-sided 97.5% CI for the OR of having either mutation was 1.87. Being overweight, smoking, or taking hormone replacement therapy was not associated with VTE in this study, but the CIs were wide. CONCLUSION: Tamoxifen and prior surgery, fracture, or immobilization were associated with a significantly increased risk of developing a VTE. Factor V Leiden and prothrombin mutations were not associated with thrombosis in this population.

Adult↗

PubMed2003

Expression of ADAM-9 mRNA and protein in human breast cancer.

The ADAMs (a disintegrin and metalloprotease) are membrane proteins containing both protease and adhesion domains and thus may be potentially important in cancer invasion and metastasis. The aim of our study was to investigate the distribution and potential clinical significance of ADAM-9 in breast cancer. ADAM-9 expression was measured using both reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. ADAM-9 mRNA was expressed more frequently in both breast carcinomas (72/110, 66%) and fibroadenomas (21/38, 55%) compared to normal breast tissue (6/25, 24%) (p = 0.0004, p = 0.028, respectively). Multiple forms of ADAM-9 protein were detected by Western blotting, i.e., at 124, 84 and 48 kDa under reducing conditions and at 115, 76, 55, 52 and 46 kDa under nonreducing conditions. The 84 and 55 kDa forms were detected more frequently in the primary cancers compared to normal breast tissue (p < 0.0001, p = 0.0002, respectively). In addition, relative levels of the 84 kDa mature form were significantly higher in the primary cancers than in the fibroadenomas (p = 0.003), while the reverse was found for the 124 kDa precursor form (p = 0.026). In the carcinomas, the 84 kDa form of ADAM-9 protein was expressed at higher levels in node-positive than node-negative cancers (p = 0.05) and correlated positively with HER-2/neu protein levels (r = 0.313, p = 0.016). This is the first report to describe expression of any ADAM in a large number of human carcinomas.

ADAM Proteins↗

PubMed2003

Radiotherapy and tamoxifen in women with completely excised ductal carcinoma in situ of the breast in the UK, Australia, and New Zealand: randomised controlled trial.

BACKGROUND: As a consequence of mammographic breast screening programmes, ductal carcinoma in situ is diagnosed with increasing frequency. Mastectomy for localised ductal carcinoma in situ is thought to be an over-treatment by many physicians, but there is much controversy as to whether complete local excision alone is sufficient. We aimed to assess the effectiveness of adjuvant radiotherapy and tamoxifen. METHODS: We used a 2x2 factorial design in a randomised controlled trial. Between May, 1990, and August, 1998, 1701 patients recruited from screening programmes were randomised to both treatments in combination or singly, or to none, or to either one (eg, radiotherapy) with an elective decision to give or to withhold the other (ie, in this case tamoxifen). Patients had complete surgical excision of the lesion confirmed by specimen radiography and histology. Patients have been followed up at least once a year. Median follow-up was 52.6 (range 2.4-118.3) months. Our primary endpoint was the incidence of ipsilateral invasive disease. FINDINGS: Ipsilateral invasive disease was not reduced by tamoxifen but recurrence of overall ductal carcinoma in situ was decreased (hazard ratio 0.68 [0.49-0.96]; p=0.03). Radiotherapy reduced the incidence of ipsilateral invasive disease (0.45 [0.24-0.85]; p=0.01) and ipsilateral ductal carcinoma in situ (0.36 [0.19-0.66]; p=0.0004), but there was no effect on the occurrence of contralateral disease. There was no evidence of interaction between radiotherapy and tamoxifen. INTERPRETATION: Radiotherapy can be recommended for patients with ductal carcinoma in situ treated by complete local excision; however, there is little evidence for the use of tamoxifen in these women.

Antineoplastic Agents, Hormonal↗

PubMed2003

Pooled analysis of prognostic impact of uPA and PAI-1 in breast cancer patients.

In this report we present an extension of the pooled analysis of the prognostic impact of urokinase-type plasminogen activator (uPA) and its inhibitor PAI-I in breast cancer patients. We analyzed a different endpoint, metastasis-free survival (MFS). We checked the consistency of the estimates for uPA and PAI-1 for relapse-free survival (RFS) and MFS exploring possible sources of heterogeneity. Nodal status, the most important prognostic factor for breast cancer, introduced heterogeneity in the uPA/PAI-1 survival analyses, reflecting the interaction between nodal status and uPA/PAI-1. The estimates for uPA and PAI-1 were found to be consistent, even when a different transformation of their values was used. The heterogeneity of the separate data sets decreased if the levels of uPA and PAI-1 were ranked, data sets were pooled, and the analyses corrected for the base model that included all traditional prognostic factors, and stratified by data set. We conclude that uPA and PAI-1 are ready to be used in the clinic to help classify breast cancer patients into high and low risk groups.

Breast Neoplasms↗

PubMed2002

Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in 8377 breast cancer patients.

BACKGROUND: Urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) play essential roles in tumor invasion and metastasis. High levels of both uPA and PAI-1 are associated with poor prognosis in breast cancer patients. To confirm the prognostic value of uPA and PAI-1 in primary breast cancer, we reanalyzed individual patient data provided by members of the European Organization for Research and Treatment of Cancer-Receptor and Biomarker Group (EORTC-RBG). METHODS: The study included 18 datasets involving 8377 breast cancer patients. During follow-up (median 79 months), 35% of the patients relapsed and 27% died. Levels of uPA and PAI-1 in tumor tissue extracts were determined by different immunoassays; values were ranked within each dataset and divided by the number of patients in that dataset to produce fractional ranks that could be compared directly across datasets. Associations of ranks of uPA and PAI-1 levels with relapse-free survival (RFS) and overall survival (OS) were analyzed by Cox multivariable regression analysis stratified by dataset, including the following traditional prognostic variables: age, menopausal status, lymph node status, tumor size, histologic grade, and steroid hormone-receptor status. All P values were two-sided. RESULTS: Apart from lymph node status, high levels of uPA and PAI-1 were the strongest predictors of both poor RFS and poor OS in the analyses of all patients. Moreover, in both lymph node-positive and lymph node-negative patients, higher uPA and PAI-1 values were independently associated with poor RFS and poor OS. For (untreated) lymph node-negative patients in particular, uPA and PAI-1 included together showed strong prognostic ability (all P<.001). CONCLUSIONS: This pooled analysis of the EORTC-RBG datasets confirmed the strong and independent prognostic value of uPA and PAI-1 in primary breast cancer. For patients with lymph node-negative breast cancer, uPA and PAI-1 measurements in primary tumors may be especially useful for designing individualized treatment strategies.

Adult↗

PubMed2002

Evaluation of a complex intervention for changing professional behaviour: the Evidence Based Out Reach (EBOR) Trial.

OBJECTIVES: To identify the effect of a complex intervention (educational outreach visits by pharmacists) designed to change general practitioners' (GPs') prescribing on each step of a hypothesised pathway of change leading to the final primary trial outcome of change in prescribing. METHOD: The study was undertaken in six health authorities in the North of England and six in London. We described three steps leading to this outcome: the general practices agreeing to participate; GPs in each practice attending the outreach visit conducted by the pharmacists; and the GPs' prescribing practice being influenced by these visits. The outcomes of each step were assessed using a combination of quantitative and qualitative methods. RESULTS: Of the 102 practices randomly selected, 75 (73.5%) agreed to participate. The odds of all the doctors attending the outreach meeting in small practices (i.e. 1-2 partners) was 6.7 (95% CI: 4.4-23.5) compared with other practices (i.e. > 3 partners). Although the pharmacists reported that they had established a good rapport at 100 (72%) first visits and had agreed management plans for 110 (79%) of these visits, they were confident that the practice was likely to alter its prescribing in only 41% of these visits. Pharmacists' and GPs' satisfaction with the outreach visits did not necessarily lead to prescribing changes after the practice visit, and the GPs' knowledge of the guidelines promoted by the pharmacists did not necessarily translate into changes in clinical practice. The main barriers to the implementation of guidelines identified by the pharmacists at the follow-up visits were organisational difficulties, the GPs' scepticism of the evidence presented to them and the doctors' lack of interest in changing their prescribing behaviour. CONCLUSIONS: Although our study is limited by a post hoc rather than a pre hoc design, it provides a pragmatic approach to understanding the factors influencing the pathway of change in prescribing behaviour in response to academic outreach visits.

Cardiovascular Diseases↗