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P J Carleton

Publications and source records attributed to P J Carleton.

14 recordsLinked to original sources
PubMed1999

Coexpression of estrogen receptor alpha and beta: poor prognostic factors in human breast cancer?

The cloning of a second estrogen receptor (ER), ER beta, has prompted a reevaluation of the role of ERs in breast cancer. The aim of this study was to determine the expression of both ER isoforms in normal (n = 23) and malignant (n = 60) human breast tissue by reverse transcription-PCR and correlate this information with known prognostic factors including tumor grade and node status. In normal breast tissue, expression of ER beta predominated, with 22% of samples exclusively expressing ER beta; this was not observed in any of the breast tumor samples investigated. Most breast tumors expressed ER alpha, either alone or in combination with ER beta. Interestingly, those tumors that coexpressed ER alpha and ER beta were node positive (P = 0.02; Fisher's exact test) and tended to be of higher grade. Because antiestrogens are agonists when signaling through the AP1 element, overexpression of ER beta in tumors expressing both ER subtypes may explain the failure of antiestrogen therapy in some breast cancer patients. Thus, ER beta may be a useful prognostic factor in patients with breast cancer.

Adult↗
PubMed1999

Dynamic contrast enhanced magnetic resonance imaging of the breast is superior to triple assessment for the pre-operative detection of multifocal breast cancer.

BACKGROUND: Inadequately treated multifocal and multicentric disease results in increased local recurrence following breast-conserving surgery. The accurate preoperative diagnosis of multifocal/ centric breast cancer would facilitate the planning of appropriate surgery and prevent reoperation for residual disease. While triple assessment remains the established diagnostic technique, its sensitivity for the diagnosis of multifocal disease remains poor. Dynamic contrast enhanced Magnetic Resonance Imaging (DCE-MRI) of the breast represents an alternative emerging diagnostic modality that has been shown to be highly sensitive for the delineation of primary breast cancer. The aim of this study was to prospectively compare the diagnostic accuracy of DCE-MRI of the breast with conventional triple assessment for the preoperative diagnosis of multifocal/centric breast cancer. METHODS: Patients were recruited from the symptomatic breast clinics. All patients underwent standard triple assessment and DCE-MRI. The MRI scans were reported by a single radiologist blinded to the results of the triple assessment. Surgery was then planned accordingly to all available scan results and the specimens examined by a single pathologist. All patients who did not undergo surgery have been followed up for a minimum of 18 months. RESULTS: A total of 334 women were recruited. There were 178 (52%) cancers that were histologically confirmed and multifocal/centric breast cancer was diagnosed provisionally by the preoperative investigations in 68 (38%); multifocal n = 33, multicentric n = 35, of these patients. In this group, subsequent histology confirmed multifocal/centric disease in 50 (73.5%): multifocal n = 15, multicentric n = 35. Unifocal cancer was found in 15 (22%) and benign disease in 3 (4.4%). The resultant sensitivity, specificity, positive, and negative predictive values were 18%, 100%, 100%, and 76% for triple assessment and 100%, 86%, 73%, and 100% for DCE-MRI. CONCLUSION: DCE-MRI identified a subgroup of breast cancer patients with multifocal/centric disease not evident on standard triple assessment. MRI of the breast should be considered for the preoperative planning of surgery for primary breast cancer.

Aged↗
PubMed1999

Prospective comparison of standard triple assessment and dynamic magnetic resonance imaging of the breast for the evaluation of symptomatic breast lesions.

OBJECTIVE: To compare the sensitivity and specificity of the traditional triple assessment of symptomatic breast lesions with contrast-enhanced dynamic magnetic resonance imaging. BACKGROUND: Although triple assessment is currently the gold standard for the assessment of symptomatic breast disease, its specificity is such that open biopsies are still required in many cases to be confident of the diagnosis. Contrast-enhanced dynamic magnetic resonance imaging of the breast represents an alternative diagnostic modality. METHODS: Patients were recruited from the symptomatic breast clinics. If any of the diagnostic modalities suggested malignancy, the lesion was excised. The remaining patients were followed clinically and radiologically. RESULTS: Two hundred eighty-five patients with a mean age of 43 years (range 21 to 77) were recruited. Malignant lesions were excised in 131 patients and benign lesions in 55 patients. The 99 patients who did not undergo surgery were followed clinically and radiologically for a median of 20 months. The sensitivity of each modality was as follows: clinical examination 84%, mammography 87.6%, fine-needle aspiration cytology 79.1%, triple assessment 99.2%, and magnetic resonance imaging 99.2%. In addition, histologically confirmed multifocal disease was detected in 40 patients on magnetic resonance imaging but in only 9 (22.5%) on mammography. The specificity for the diagnosis of benign disease was as follows: clinical examination 83.1%, ultrasound 88.9%, mammography 86.4%, fine-needle aspiration cytology 97%, triple assessment 59.1%, and magnetic resonance imaging 90.9%. CONCLUSION: Contrast-enhanced dynamic magnetic resonance imaging of the breast is as sensitive and more specific than the combined traditional triple assessment for the diagnosis of malignant breast lesions.

Adult↗
PubMed1998

Interactive multimedia information program for use by breast-care nurses--a patient acceptability study.

AIMS: To design an interactive multimedia program for use by breast-care nurses and evaluate the acceptability of this technology to patients in the clinical setting. METHODS: In order to ensure that the clarity of the information was maintained the multimedia program was developed by a multidisciplinary team, including non-medical personnel and patients. A prospective analysis of the subjective impressions of patients with symptomatic breast disorders and breast-care nurses to a multimedia patient information system was then performed using a standard questionnaire and semi-structured interviews. RESULTS: Fifty women were recruited for the study. Thirty-six (72%) considered the multimedia counselling to be superior to the traditional modalities. Forty-nine (98%) graded the system as good or better. No patient regarded the technology as anxiety-provoking or inferior to the traditional leaflet-based approach. Women over 55 years old found the system as acceptable and easy to use as the younger women. CONCLUSIONS: The multimedia breast counselling programme was acceptable to patients and was considered superior to the traditional leaflet-based approach by the majority. The inherent advantages of this technology will lead to its increasing utilization in the clinical setting.

Adult↗
PubMed1998

Vascular endothelial growth factor in premenopausal women--indicator of the best time for breast cancer surgery?

Timing of surgery in premenopausal patients with breast cancer remains controversial. Angiogenesis is essential for tumour growth and vascular endothelial growth factor (VEGF) is one of the most potent angiogenic cytokines. We aimed to determine whether the study of VEGF in relation to the menstrual cycle could help further the understanding of this issue of surgical intervention. Fourteen premenopausal women were recruited, along with three post-menopausal women, a woman on an oral contraceptive pill and a single male subject. Between eight and 11 samples were taken per person, over one menstrual cycle (over 1 month in the five controls) and analysed for sex hormones and VEGF165. Serum VEGF was significantly lower in the luteal phase and showed a significant negative correlation with progesterone in all 14 premenopausal women. No inter-sample variations of VEGF were noted in the controls. Serum from both phases of the cycle from one subject was added to MCF-7 breast cancer cells; VEGF expression in the supernatant was lower in the cells to which the luteal phase serum was added. The lowering of a potent angiogenic cytokine in the luteal phase suggests a possible decreased potential for micrometastasis establishment in that phase. This fall in VEGF may be an effect of progesterone and should be the focus of future studies.

Analysis of Variance↗
PubMed1998

Short-term primary culture of epithelial cells derived from human breast tumours.

As experimental models for breast cancer, most studies rely on established human breast cancer cell lines. However, many of these lines were established over 20 years ago, many from pleural effusions rather than the primary tumour, so the validity of using them as representative models is questionable. This paper describes our experiences, over a 3-year period, in establishing short-term epithelial-cell-enriched preparations from primary breast tumours based on differential centrifugation followed by culture in selective media. Epithelial cells were successfully cultured from 55% of samples, but culture success did not appear to be correlated with tumour histology, stage, grade or node status. Epithelial cell-enriched cultures were immunopositive for broad-spectrum cytokeratin and epithelial membrane antigen (EMA). Positivity for keratin 19 confirmed that the cultures contained tumour-derived cells, which additionally showed significantly higher activity of the reductive pathway of the steroid-converting enzyme 17beta-hydroxysteroid dehydrogenase type I. That the cultures contained tumour and not normal epithelial cells was further substantiated by the complete absence of the calmodulin-like gene NB-1 in tumour-derived cultures; this is only associated with normal breast epithelia. Eighty-five per cent of cultures established from oestrogen receptor (ER)-positive tumours expressed ER in vitro; this was functional in 66% of cultures, although ER-positive phenotype was gradually lost over time. In conclusion, epithelial cells can be isolated and maintained as short-term cultures from primary breast tumours irrespective of histopathological or clinical details, providing a model system with a greater biological and clinical relevance than breast cancer cell lines.

17-Hydroxysteroid Dehydrogenases↗
PubMed1997

Dynamic MR imaging of the breast combined with analysis of contrast agent kinetics in the differentiation of primary breast tumours.

OBJECTIVE: To assess dynamic Gd-DTPA-enhanced magnetic resonance (MR) imaging in the diagnosis of primary breast pathology, and to test the hypothesis that analysis of contrast agent kinetics increases specificity. METHODS: Forty-seven women underwent breast MR imaging using three-dimensional and dynamic spoiled gradient-recalled sequences. Image interpretation was based on the evaluation of lesion conspicuity, signal intensity, contour and enhancement pattern from the static acquisitions. Assessment of contrast kinetics was based on pixel-by-pixel analysis of the dynamic data. A two-compartment model described by three parameters (amplitude of uptake, exchange rate and washout rate), and a three-compartment model described by two parameters (permeability and exchange rate) were used. Regions of interest were drawn for all lesions found in the dynamic sections. Mean regional pixel values were calculated for each parameter and tested for diagnostic efficacy. RESULTS: Twenty-two malignant and 36 benign lesions were examined. Fibroadenomas accounted for 86% of the benign tumours. Image interpretation had a sensitivity of 0.95 and specificity of 0.86. The fat-suppressed post-contrast images permitted good visualization of the contour and matrix characteristics of fibroadenomas, but all non-fibroadenomatous benign lesions were classified as indeterminate or suspicious. Significant differences were found between benign and malignant lesions in the amplitude of uptake (P = 0.0008) and exchange rate (P < 0.00005) of the two-compartment model, and permeability (P=0.0001) and exchange rate (P < 0.00005) of the three-compartment model. However, image interpretation was superior to the isolated use of quantitative indices (P=0.02). The most discriminating parameters were the exchange rates of both models, with no significant difference between them. CONCLUSION: Assessment of lesion morphology is essential and probably sufficient for the differentiation of fibroadenomas from malignant tumours. However, specificity of conventional MR imaging may be much lower for other types of primary benign breast pathology. Analysis of Gd-DTPA kinetics improves the specificity obtained using simple enhancement measurements and can be used to produce parametric images that provide information about lesion heterogeneity, permeability and vascularity.

Adult↗
PubMed1997

MR imaging of primary non-Hodgkin's breast lymphoma. A case report.

In this report we describe the MR imaging findings, including dynamic data, in a patient with primary non-Hodgkin's lymphoma of the breast. The precontrast T1-weighted sequence showed several hypointense, ill-defined, non-spiculated masses. In the T2-weighted images the masses showed a hyperintense halo. In the dynamic and postcontrast sequences all lesions enhanced markedly, and a further large mass was discovered. In comparison to mammography and sonography, only MR imaging identified the multicentric extent of the tumour. Differentiation from invasive cancer, based on either MR or conventional imaging features, was not possible.

Biopsy, Needle↗
PubMed1996

Case report: MR imaging of juvenile papillomatosis of the breast.

Juvenile papillomatosis of the breast is a benign, localized proliferative condition encountered mainly in young women. We describe the contrast-enhanced MR imaging findings, including dynamic data, of a patient with histologically proven juvenile papillomatosis of the breast. The pre-contrast T1 weighted sequence showed a hypointense lobulated mass which enhanced markedly in the post-contrast images. In the dynamic sequence the lesion showed a benign enhancement profile. The most specific feature was the presence of multiple small internal cysts, best shown on the T2 weighted images. This constellation of findings should suggest juvenile papillomatosis.

Adult↗
PubMed1995

Dynamic gradient-echo and fat-suppressed spin-echo contrast-enhanced MRI of the breast.

PURPOSE: To evaluate heavily T2-weighted, dynamic contrast-enhanced and fat-suppressed magnetic resonance imaging (MRI) of the breast in comparison with conventional imaging and fine needle aspiration cytology (FNAC). PATIENTS AND METHODS: Fifty patients with surgically/pathologically proven breast disease were examined pre-operatively by MRI. The majority, 45 patients, had invasive carcinoma. T1-weighted spin-echo, T2-weighted fast spin-echo (with chemical-shift-selective fat-suppression in 20 cases), rapid dynamic contrast-enhanced gradient-echo and post-contrast fat-suppressed T1-weighted images were obtained. Signal intensity changes during dynamic scanning were assessed qualitatively and quantitatively. Comparison was made with the results of X-ray mammography, ultrasound and fine needle aspiration cytology. RESULTS: Unenhanced MRI was inadequate for determining the location, extent or nature of most lesions even when fat-suppressed T2-weighted images were obtained. Following contrast injection, there was significantly greater enhancement of invasive carcinomas than normal parenchyma. Invasive carcinomas of ductal and lobular subtypes did not differ significantly in their enhancement profiles. Prominent enhancement of the lesion periphery, which was a feature in 33 out of 50 cases (the majority of which were invasive carcinomas) was not due to central tumour necrosis. In four cases, invasive carcinomas which were clearly visible on early dynamic scans could not be identified on post-contrast fat-suppressed images. Lesions that were more numerous or extensive than had been recognised clinically or mammographically were revealed by MRI in 14 patients, though MRI was no more specific than conventional assessment. Invasion of the chest wall was accurately predicted by MRI in three cases. There was excellent correlation between tumour size shown by MRI and histopathology. FNAC was accurate in predicting the final histological diagnosis except in those cases where samples were unsatisfactory. CONCLUSIONS: Contrast-enhanced MRI appears useful in the assessment of suspected malignant breast masses, especially in younger women with predominantly glandular breast tissue. Specificity is no better than FNAC but tumour extent and multifocality are more accurately disclosed than by conventional imaging techniques. Contrast-enhanced chemical-shift-selective fat-suppressed images are sub-optimal in a small proportion of cases (particularly where lesions are located posteriorly) and some benign breast disease may appear misleadingly conspicuous on such images. Morphological features and quantification of lesion enhancement during dynamic scanning presently offer only limited prospects for discrimination between various pathologies. Heavily T2-weighted sequences appear of marginal value.

Adolescent↗
PubMed1995

Dynamic contrast-enhanced magnetic resonance imaging of the breast combined with pharmacokinetic analysis of gadolinium-DTPA uptake in the diagnosis of local recurrence of early stage breast carcinoma.

RATIONALE AND OBJECTIVES: This study was designed to assess the efficacy of dynamic contrast-enhanced magnetic resonance imaging (MRI) of the breast combined with pharmacokinetic analysis of gadolinium (Gd)-DTPA uptake in the diagnosis of local recurrence of early stage breast carcinoma. METHODS: Fifty women treated with breast-conserving surgery and radiotherapy underwent breast MRI. Dynamic magnetic resonance data obtained at four preselected slice locations were analyzed to examine Gd-DTPA uptake based on a pharmacokinetic model using three parameters: wash-in rate, wash-out rate, and amplitude of uptake. Synthetic images were produced from the above parameters and their derivatives--maximum uptake and reciprocal of half the time to maximum. For each region of interest (ROI), median parameter values were calculated. The mean pixel signal intensity of each ROI was plotted against time, and an enhancement index was determined. RESULTS: Sixty ROIs were selected: 49 lesions were benign, and 11, malignant. Significant differences between benign and malignant lesions were found for the enhancement index (P < 0.0001), maximum uptake (P < 0.0001), amplitude of uptake (P < 0.0001), wash-in rate (P = 0.03), wash-out rate (P = 0.01), and the reciprocal of half the time to maximum (P = 0.0005). The respective sensitivities and specificities were as follows: for the enhancement index, 1.00 and 0.96; for maximum uptake, 1.00 and 0.96; for amplitude of uptake, 0.91 and 0.94; for wash-in rate 0.82 and 0.47; for wash-out rate 0.91 and 0.59; and for the reciprocal of half the time to maximum, 1.00 and 0.51. CONCLUSIONS: Dynamic scanning proved essential for the detection and differential diagnosis of local tumor recurrence. Pharmacokinetic analysis of Gd-DTPA uptake can be used to produce parametric images that retain the spatial resolution of the original images while providing additional information about lesion permeability and vascularity, and helping to avoid the observer variability associated with ROI analysis.

Adult↗
PubMed1994

Dynamic contrast-enhanced and fat suppressed magnetic resonance imaging in suspected recurrent carcinoma of the breast: preliminary experience.

20 women with suspected recurrent breast cancer who had undergone previous breast-conserving operations were investigated using dynamic contrast-enhanced gradient echo (GRE) and fat suppressed spin echo (SE) magnetic resonance (MR) imaging. Histologically confirmed recurrent tumour was readily recognized on dynamic GRE scans by virtue of rapid, early and avid enhancement. Benign scars enhanced more slowly and reached lower magnitudes of enhancement. Fat suppressed SE images, which were typically acquired 10 min after contrast administration, were sensitive for the detection of tumour recurrence but lacked specificity. Early scanning after contrast administration offers the best prospects for distinguishing tumour recurrence from benign scarring. The criteria used to distinguish these two entities are highly dependent on the scan technique and the time at which images are obtained post-contrast.

Aged↗
PubMedDate not supplied

Routine screening for local recurrence following breast-conserving therapy for cancer with dynamic contrast-enhanced magnetic resonance imaging of the breast.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (MRI) of the breast is highly sensitive for the diagnosis of primary breast malignancy. We investigated the clinical application of dedicated dynamic breast MR for routine screening for local recurrence following breast-conserving therapy. METHODS: Patients underwent a single dynamic MR of the breast routinely in the period 1 to 2 years following treatment, or earlier if recurrence was suspected. A biopsy was performed if there was suspicion of recurrence on MR. RESULTS: One hundred and five patients with a median age of 58 years (range 50 to 65 years) were recruited for the study. Sixteen biopsies were performed and nine recurrences were confirmed histologically. Patients not undergoing biopsy have been followed up for a median of 341 days (range 168 to 451 days) following the MR. The sensitivity for clinical examination, mammography, examination combined with mammography, and MRI alone for the detection of recurrent cancer were 89%, 67%, 100%, and 100%, respectively, and the specificity was 76%, 85%, 67%, and 93%. CONCLUSION: Combined clinical examination and mammography are as sensitive as dedicated dynamic MR of the breast for the detection of locoregional recurrence, but breast MRI is associated with a far greater specificity. Therefore, dedicated dynamic breast MRI should be used when there is clinical or mammographic suspicion of recurrence to confirm or refute its presence.

Aftercare↗