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Biomedical subjects

R S Rampaul

Publications and source records attributed to R S Rampaul.

At least 19 recordsLinked to original sources
PubMed2005

Clinical value of epidermal growth factor receptor expression in primary breast cancer.

EGFR expression in primary breast cancer has been extensively investigated for its prognostic and predictive value. However overall there is no consensus on its potential to guide such prognostication. This is largely because of the great heterogeneity in study designs and methods used to assay the EGFR protein. The impetus to standardize such studies is much needed as there are now several tyrosine kinase inhibitors directed against the EGF receptor and phase II trials are showing significant promise.

Adenocarcinoma↗
PubMed2004

Expression and co-expression of the members of the epidermal growth factor receptor (EGFR) family in invasive breast carcinoma.

The epidermal growth factor receptor (EGFR) family plays an important role in breast carcinogenesis. Much interest has been focused recently on its members because of their potential role as prognostic indicators in breast cancer and their involvement in cancer therapy. We have evaluated more than 1500 cases of invasive breast carcinoma immunohistochemically using tissue microarray technology to examine the expression of EGFR family receptor proteins. We have found that 20.1 and 31.8% of cases were positive for EGFR and c-erbB-2, respectively, and 45 and 45.1% of tumours overexpressed for c-erbB-3 and c-erbB-4, respectively. The expression of either EGFR or c-erbB-2 was associated with other bad prognostic features and with poor outcome. Neither c-erbB-3 nor c-erbB-4 had any association with survival. c-erbB-2 had an independent prognostic effect on overall and disease-free survival (DFS) in all cases, as well as in the subset of breast carcinoma patients with nodal metastases. Several hetero- and homodimeric combinations have been reported between the EGFR members. Those dimers can evoke diverse signal transduction pathways with variable cellular responses. We stratified cases according to their co-expression of receptors into distinct groups with different receptor-positive combinations. Patients whose tumours co-expressed c-erbB-2 and c-erbB-3, as well as those whose tumours co-expressed EGFR, c-erbB-2 and c-erbB-4 showed an unfavourable outcome compared with other groups, while combined c-erbB-3 and c-erbB-4 expression was associated with a better outcome. In cases showing expression of one family member only (homodimers), we found a significant association between c-erbB-4 homodimer-expressing tumours and better DFS. In contrast, patients with c-erbB-2 homodimer-expressing tumours had a significant poorer DFS compared with other cases. These data imply that the combined profile expression patterns of the four receptor family members together provide more accurate information on the tumour behaviour than studying the expression of each receptor individually.

Adenocarcinoma↗
PubMed2004

Randomized clinical trial comparing radioisotope occult lesion localization and wire-guided excision for biopsy of occult breast lesions.

BACKGROUND: Accurate localization of impalpable breast lesions that require biopsy is important. This randomized trial compared radioisotope occult lesion localization (ROLL) with the standard hooked-wire technique. METHODS: Ninety-five patients were randomized to receive either ROLL or wire localization of an occult breast lesion. Correct placement of isotope was confirmed by mammography and a hand-held gamma probe was used to guide the surgical excision. Radiological, surgical and pathological data were compared for accuracy, duration and ease of technique, and histopathological diagnosis. Procedure-related pain was also assessed. RESULTS: Of the 95 patients entered, 48 were randomized to ROLL and 47 to wire localization. Two ROLL procedures failed. Marking was accurate in 46 of 48 ROLL procedures and 44 of 47 of wire localizations (P = 0.242). Difficulty in localization (Likert score 2.6 for ROLL versus 4.4 for wire localization; P < 0.001) and the degree of surgical difficulty (2.6 versus 4.0; P < 0.001) were significantly less for ROLL. ROLL was associated with less pain (score 2.7 versus 3.6; P = 0.012). There were no significant differences in mean duration of operation, specimen weight, need for intraoperative re-excision or second therapeutic operation. CONCLUSION: ROLL and wire-guided localization were similarly effective for breast biopsy, but ROLL was easier for both radiologist and surgeon, and less painful for the patient.

Biopsy↗
PubMed2004

Woman feels breast lump--surgeon cannot: the role of ultrasound in arbitration.

The role of ultrasound scanning (USS) in patients complaining of a breast lump where the clinical examination (CE) is normal is not clearly defined. To determine this in greater detail, all patients complaining of a breast lump underwent CE. Where no lump could be found, but was still reported by the patient, an USS was performed. All lesions underwent biopsy and/or aspiration, as well as mammography in suspicious cases or those over 40 years of age. This cohort represented 5% of all referrals in the study period. Four hundred and twenty women were prospectively studied in this way. Median follow up is 3.4 years (range 2.5-4.2 years). Twenty two had solid lumps (of which 3 were cancers) and 48 had cysts. Nineteen patients re-presented with symptoms in the same breast (median time = 12 months (range 4.5-20 months), all of which were imaged on USS: 15 cysts and 4 further cancers (3 in the same quadrant as the original lump, one contralateral) were identified. Women with symptomatic breast lumps and a normal CE can be considered a reliable indication that cancer is very unlikely to be present (negative predictive value = 0.98). Ultrasound may be a suitable complimentary investigation, which will relieve symptoms in those with cysts and can detect small clinically--and sometimes mammographically--occult breast cancers.

Adolescent↗
PubMed2003

Incidence of clinically significant lymphoedema as a complication following surgery for primary operable breast cancer.

There has recently been considerable interest for the need for specialist lymphoedema nurses to be appointed in the NHS. However, we had noticed in our cancer follow-up clinics that the incidence of lymphoedema appeared to be very low. Treatment for primary breast cancer (>5 cm) has been surgery and low axillary sampling (ANS). Radiotherapy (RT) or axillary clearance is subsequently performed in patients found to be node positive. The patients are followed-up in the primary breast cancer (PBC) clinic weekly. Follow-up is initially at 3-month intervals up to 2 years and then 1 yearly indefinitely. We conducted a two phased study in patients being followed up in our post cancer clinic in order to identify the incidence of LE in these patients. Phase 1 involved symptomatic patients identified at routine follow up in a 15-week period and the number of patients reporting arm swelling was recorded. The aim of this was to provide an estimate to power a phase 2 study (prospective questionnaire based). Phase 2 was conducted over a 13-week period. All patients attending the clinic were administered modified FACT B4, EQ-50 and Speilberger questionnaires. A total of 1242 patients were examined and lymphoedema found in 5 (0.04%). Of these 5, 3 had undergone axillary clearance, 1 ANS plus radiotherapy and only 1 had ANS alone. A policy of ANS, with prophylactic treatment for lymph node positivity either by surgery or RT alone, gives a very low rate of lymphoedema.

Arm↗
PubMed2003

Radioisotope for occult lesion localisation (ROLL) of the breast does not require extra radiation protection procedures.

AIM OF STUDY: Dosimetry data from patients and hospital personnel involved in the use of radioisotope for occult lesion localisation (ROLL) of the breast were collected to determine the need for extra radiation protection procedures. METHODS: Sixty-three patients have been enrolled to date into a randomised trial evaluating ROLL. Two megabecquerels of (99m)Tc- MAA in a syringe was mixed with X-ray contrast medium; this was injected directly into the lesion under image guidance. A gamma-detecting probe (Neo-Probe) was used to locate the area of radioactivity. Radiation doses to all staff groups were estimated using time and motion studies and dose rate measurements at a range of distances during each stage of ROLL. RESULTS: The finger dose [FD](+/-95% CI) was considered to be the critical variable for surgeons and radiologists. Surgeon FD=9.3+/-3.3 microSv, Radiologist FD=0.5+/-0.13 microSv. Whole body doses [WBD](+/-95% CI) were estimated for other staff groups. Nurse WBD=0.4+/-0.4 microSv, porter WBD: nil, contamination and waste: nil. CONCLUSIONS: In the case of a surgeon performing 100 procedures per annum, a FD dose of approximately 1 mSv is received, well within the annual dose limit of 150 mSv. Annual WBD to assisting staff may reach 0.04 mSv, compared to an annual limit of 6 mSv. These low doses and the lack of contamination of radioactive waste indicate that no additional radiation protection measures are required.

Breast Neoplasms↗
PubMed2003

Intraductal injection of the breast: a potential pitfall of radioisotope occult lesion localization.

The use of radioisotope for the localization of occult breast lesions (ROLL) has been advocated in preference to wire guided excision as it allows reduced excision volume and better lesion centering. However, as this technique is new, potential complications are unknown. In 2 out of 38 ROLL procedures performed at our institution, intraductal injection of isotope has occurred. This was diagnosed on check mammography as non-ionic iodinated contrast was mixed with the isotope. In one of these cases conversion to wire localization was required.

Breast Diseases↗
PubMed2002

HER-2 in breast cancer--methods of detection, clinical significance and future prospects for treatment.

The Human Epidermal Growth Factor (HER-2) oncogene encodes a transmembrane tyrosine kinase receptor with extensive homology to the Epidermal Growth Factor Receptor (EGFR) which is the prototypal member of this family of receptor tyrosine kinases. HER-2 gene amplification is found in 20-30% of breast cancers. Various methods such as immunohistochemistry, southern and slot blotting, enzyme immunoassays and fluorescence in situ hybridization have all been employed to evaluate HER-2 gene and protein abnormalities. Of these immunohistochemistry is the most frequently employed but there are valid indications for the other avaliable methods. However, it is prudent that whichever methods employed are standardized, especially those that possess may have a degree of subjectivity in their assesment.

Animals↗
PubMed2001

E-cadherin as a prognostic indicator in primary breast cancer.

Epithelial cadherin (E-CD) is a member of the cadherin family of cell adhesion molecules and has been implicated as an invasion suppressor molecule in vitro and in vivo. We analysed 174 breast tumours from the Nottingham/Tenovus Breast Cancer Series immunohistochemically for E-CD expression using the mouse monoclonal antibody HECD-1 (Zymed Laboratories Inc.). In normal epithelial cells E-CD was strongly expressed at cell-cell boundaries. 66% of the breast cancers examined had reduced intensity of E-CD expression with 74% having significant reductions in the proportion of E-CD-positive tumour cells. Using a combined intensity/proportion score, significant associations were found between E-CD expression and tumour type (P </= 0.001). ER status (P = 0.026) and histological grade (P = 0.031). Expression of E-CD was not found to be related to recurrence, distant metastases, lymph node stage, vascular invasion, primary tumour size, prognostic group or survival. Thus E-CD expression in human breast cancer appears to have minimal prognostic value, but may have a role as a phenotypic marker.

Adult↗
PubMed2001

Pathological validation and significance of micrometastasis in sentinel nodes in primary breast cancer.

In embracing a multidisciplinary approach to the management of patients with sentinel node biopsy in breast cancer, the pathologist task is to screen sentinel nodes for possible metastasis. The consequences of missing sentinel node micrometastasis can directly influence treatment strategies, and this screening therefore has to be performed with more attention than usual. There is presently great diversity in the histopathological work-up of sentinel nodes, with many centres employing additional techniques such as immunohistochemistry, reverse transcription polymerase chain reaction or flow cytometry in addition to routine haematoxylin and eosin staining. In this review, we address the pathological validation and significance of micrometastasis in sentinel node biopsy in primary breast cancer.

Breast Neoplasms↗
PubMed2001

Sentinel node biopsy for breast cancer may have little to offer four-node-samplers. results of a prospective comparison study.

The aims of the study were to determine how often four node axillary sampling (4NAS) encompasses the sentinel node (SN) and to compare the relative sensitivity of 4NAS with sentinel node biopsy (SNB) for axillary node staging. 200 patients with breast cancer were preoperatively injected with 27 MBq 99m-Tc-labelled colloid adjacent to the tumour. At operation, standard 4NAS was performed. Each node was counted ex vivo using a probe. A search was then made to find a node with higher counts in vivo directed by the probe. If found, it was excised. Each node was submitted separately to pathology. A SN was identified in 191 patients (96%). The SN was contained in the 4NAS in 153 patients (80%) and identified separately in 38 patients (20%). Of 60 node-positive patients, 49 were positive by 4NAS and SNB, the SN was not identified in 2 and in 8 the SN was falsely negative compared with 4NAS. For 1 patient, the SN was positive and the 4NAS negative. SNB performed using radiolabelled colloid has no advantage over 4NAS when nodes are assessed by standard histological technique.

Axilla↗
PubMed2001

Extent of ductal carcinoma in situ within and surrounding invasive primary breast carcinoma.

BACKGROUND: The aim of this study was to evaluate the pathological and morphological features of ductal carcinoma in situ (DCIS) within and surrounding invasive ductal carcinoma, and to investigate its relationship with clinical outcome and established prognostic variables. METHODS: One hundred and seven patients with primary operable invasive breast carcinoma and associated DCIS treated by simple or subcutaneous mastectomy or wide local excision with radiotherapy were assessed. Those with pure DCIS and insufficient tumour available for examination were excluded. The most representative haematoxylin and eosin-stained sections from the remaining 91 samples were selected and examined at x 100 magnification using a 45-point, 2-mm grid graticule. The entire section was assessed and the cell under each point of the graticule was classed as either normal (a), DCIS surrounded by normal tissue (b), invasive tumour (c) or DCIS surrounded by invasive malignancy (d). The volume ratio of DCIS in the normal (b/(a + b)) and invasive (d/(c + d)) tissue was then calculated. RESULTS: The DCIS volume within invasive tumour was not associated with outcome. The DCIS volume within adjacent normal tissue, however, was associated with local recurrence (P = 0.025), disease-free interval (P = 0.048), the occurrence of distant metastases (P = 0.019), death (P = 0.049) and disease-free survival (P = 0.048). Volume ratios of DCIS in normal and invasive tissue were not related to known prognostic factors including lymph node stage, grade, tumour size, vascular invasion or patient age. CONCLUSION: There is a significant prognostic effect relating to the extent of DCIS associated with an invasive cancer, particularly with respect to local recurrence of tumour. This effect is restricted to the volume of DCIS in the tissue surrounding the invasive lesion rather than the intratumoral component.

Adult↗
PubMed2001

Prognostic and predictive factors in primary breast cancer and their role in patient management: The Nottingham Breast Team.

Breast cancer is the most common carcinoma amongst women in the Western world, yet there are now encouraging signs that improvements in mortality may be a realistic target. Increasing breast awareness amongst women due to better health education can lead to earlier clinical detection. In addition, population screening with mammography can achieve a significant improvement in survival. With significant changes in the range and type of therapeutic options available for patients with breast cancer, there is now a trend towards patients exercising their right in management and therapeutic decisions. All these developments highlight the increasing importance of prognostic and predictive factors in the management of patients with breast cancer. In this review we will discuss current prognostic and predictive factors with particular emphasis on those of relevance in routine histopathology, especially with respect to their clinical applications.

Adult↗