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Biomedical subjects

S E Pinder

Publications and source records attributed to S E Pinder.

At least 37 records · Page 2Linked to original sources
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

The role of PTEN and its signalling pathways, including AKT, in breast cancer; an assessment of relationships with other prognostic factors and with outcome.

PTEN is a novel tumour suppressor gene located on chromosome 10. PTEN mutations are believed to exert their effects through the putative PI3K-AKT-mTOR signalling pathway. Specifically, loss of PTEN leads to activation of AKT, which in turn promotes anti-apoptotic and pro-cell cycle entry pathways believed to be essential in tumourigenesis. Whilst PTEN mutations are frequent in a variety of sporadic cancers and inherited cancer syndromes, it is not clear how frequently PTEN mutations and immunohistochemical loss of PTEN expression occur in sporadic breast cancer. This study used tissue microarrays (TMAs) to assess wild-type PTEN and pAKT immunohistochemical staining in 670 and 691 cases, respectively, of primary operable breast cancer. Scores of 0, 1, and 2 were given for negative, weakly positive, and strongly positive degrees of immunoreactivity, respectively. In addition, immunohistochemical assessment of epidermal growth factor receptor (EGFR), Her2, and proliferation by MIB1 expression was performed on the same TMAs and the scores were compared with those of PTEN and pAKT. Eight per cent of cases did not express wild-type PTEN. No correlation was observed between patient, tumour and outcome variables and PTEN. pAKT expression correlated inversely with adverse tumour variables such as tumour grade (p< 0.001) and correlated positively with ER status (p< 0.001). No correlation was seen between either PTEN or AKT and EGFR, Her2 or MIB1. No association of PTEN or pAKT was seen in Kaplan-Meier or multivariate analysis for overall survival. The results indicate that loss of PTEN expression is infrequent in breast cancer. PTEN and AKT do not appear to be prognostic markers. The study argues against the current model of a simple linear tumourigenic PTEN-PI3K-AKT-mTOR pathway in breast cancer. It also suggests that, in this group of breast cancers, the most common upstream regulator of AKT may be ER rather than PTEN, EGFR or Her2.

Adult↗
PubMed2004

Metastatic carcinoma of the breast with tubular features: differences compared with metastatic ductal carcinoma of no specific type.

AIMS: To compare the metastatic pattern at presentation and the prognosis with metastases of 48 patients with carcinomas with tubular features (45 tubular mixed and three pure tubular) and 302 patients with tumours of ductal of no special type (DNST). MATERIALS AND METHODS: We carried out a retrospective study from a prospectively maintained database of all patients who developed metastatic disease from carcinoma of the breast in Nottingham, U.K., since 1997. We recorded site of first presentation with metastatic disease, radiological features, histological features and characteristics of the primary tumour. RESULTS: The group of patients with tubular features were older at metastatic presentation (63.9 years vs 59.6 years; P=0.012), had a longer disease-free interval (87 months vs 34 months: P<0.001) and a longer survival with metastases (P<0.002). This group were less likely to have liver metastases (23% vs 41%; P=0.028), in particular multiple liver metastases (50% vs 71%; P=0.015) than the patients with DNST. Other factors known to be associated with prolonged survival, such as low histological grade of the primary invasive tumour and positive oestrogen receptor (ER) status, were more common in the group of patients with tumours with tubular features (Grade 1: 33% vs 3%; Grade 2: 42% vs 25%; Grade 3: 25% vs 72%; P<0.001), (ER positivity 76% vs 52%; P=0.009). When patients with grade 2 tumours were compared, the age at metastatic presentation, disease-free interval and the presence of multiple liver metastases were still significantly different between the two groups. CONCLUSION: Patients with metastatic breast carcinoma with tubular features have a longer survival with metastases than patients with metastatic DNST carcinoma. This improved survival can be explained by better well-recognised prognostic features, such as metastatic site pattern, histological grade, ER status and disease-free interval.

Adenocarcinoma↗
PubMed2004

Brain metastases from breast cancer: identification of a high-risk group.

AIMS: Brain metastases from breast cancer are an uncommon initial presentation of metastatic breast cancer, but brain metastases commonly occur later in women's metastatic illness. The aims of this study were to document the type, frequency, and temporal occurrence of brain metastases from breast cancer as well as the survival of women with such metastases, and to attempt to identify a subgroup of women at high risk of brain metastases who may benefit from pre-emptive medical intervention. MATERIALS AND METHODS: The radiological reports of all women presenting with metastases aged under 70 years who had subsequently died were examined. The type, frequency, temporal occurrence and survival with brain metastases were documented. Correlations were sought between the frequency of brain metastases and age at metastatic presentation, tumour grade, histological type and oestrogen receptor (ER) status. RESULTS: Of 219 patients who had died with metastatic disease and who were under 70 years of age at metastatic presentation, 49 (22%) developed brain metastases. The development of brain metastases was related to young age (P = 0.0002), with 43% of women under 40 years developing brain metastases. Brain metastases were more common in women whose tumours were ER negative (38%) compared with women with ER-positive disease (14%) (P = 0.0003). By combining age and ER status, it is possible to identify a group of women (age under 50 years and ER negative) with a 53% risk of developing brain metastases. This group included many women who had chemotherapy for visceral metastases, and 68% had either stable disease or disease response at other sites at the time of brain metastases presentation. CONCLUSION: It is possible to identify a subgroup of women with metastatic breast cancer at high risk of brain metastases who may benefit from pre-emptive medical intervention, such as screening or prophylactic treatment.

Adult↗
PubMed2004

Breast imaging findings in women with BRCA1- and BRCA2-associated breast carcinoma.

AIM: To document the breast imaging findings of women with BRCA1 and BRCA2-associated breast carcinoma. MATERIALS AND METHODS: Family history clinic records identified 18 BRCA1 and 10 BRCA2 cases who collectively were diagnosed with 27 invasive breast carcinomas and four ductal carcinoma in situ (DCIS) lesions. All underwent pre-operative imaging (29 mammogram and 22 ultrasound examinations). All invasive BRCA-associated breast carcinoma cases were compared with age-matched cases of sporadic breast carcinoma. RESULTS: Within the BRCA cases the age range was 26-62 years, mean 36 years. Two mammograms were normal and 27 (93%) abnormal. The most common mammographic features were defined mass (63%) and microcalcifications (37%). Thirty-four percent of women had a dense mammographic pattern, 59% mixed and 7% fatty. Ultrasound was performed in 22 patients and in 21 (95%) indicated a mass. This was classified as benign in 24%, indeterminate in 29% and malignant in 48%. Mammograms of BRCA1-associated carcinomas more frequently showed a defined mass compared with BRCA2-associated carcinomas, 72 versus 36% (73% control group) whilst mammograms of BRCA2-associated carcinomas more frequently showed microcalcification, 73 versus 12% (8% control group; p < 0.001). Thirty-six percent of the BRCA2-associated carcinomas were pure DCIS while none of the BRCA1 associated carcinomas were pure DCIS (p = 0.004). Of those patients undergoing regular mammographic screening, 100% of BRCA2-associated carcinomas were detected compared with 75% of BRCA1-associated carcinomas. CONCLUSION: These data suggest that the imaging findings of BRCA1 and BRCA2-associated carcinomas differ from each other and from age-matched cases of sporadic breast carcinoma.

Adult↗
PubMed2004

Patterns of metastatic breast carcinoma: influence of tumour histological grade.

AIM: To assess if the pattern of metastatic spread of carcinoma of the breast varies according to tumour histological grade. MATERIALS AND METHODS: The clinical details, histological features of the primary tumour, and imaging findings at presentation of patients with metastatic breast cancer have been recorded prospectively since 1997. The pattern of metastatic spread, age at metastasis, metastasis-free interval (MFI), and length of survival with metastases were analysed by tumour grade. RESULTS: There was a significant association between histological high-grade tumours and high frequency of intra-pulmonary metastases (p=0.013); liver metastases (p=0.039); para-aortic lymphadenopathy (p=0.022) and metastatic presentation under 50 years of age (p=0.003). A significant correlation was also demonstrated between histological low-grade tumours and increased frequency of pleural disease (p=0.020); increased frequency of bone metastases (p=0.004); prolonged MFI (MFI>5 years; p<0.0001); and increased length of survival (p<0.0001). CONCLUSION: There is a correlation between patterns of metastatic spread and tumour histological grade. This partly explains the negative prognostic value of high tumour grade, as metastases from grade 3 tumours more commonly occur at sites associated with a worse prognosis. This finding may also prove useful in interpreting imaging in patients who have a history of breast cancer and undergo subsequent imaging because of new symptoms.

Age Factors↗
PubMed2004

Identification of carcinoma cells in peripheral blood samples of patients with advanced breast carcinoma using RT-PCR amplification of CK7 and MUC1.

We have undertaken a pilot study to attempt to identify circulating carcinoma cells in a series of patients with advanced breast carcinoma, using reverse transcription-polymerase chain reaction (RT-PCR) to amplify mRNA of epithelial specific antigens. Using this method to amplify mRNA of MUC1 and cytokeratin 7 (CK7) the sensitivity of the technique was demonstrated by means of diluted concentrations of "spiked MCF7" cells in whole blood, showing a detection limit of 1 in 10(6) (CK7) and 1 in 10(5) (MUC1). Positive results were obtained from the peripheral blood of all nine female patients with advanced breast cancer for CK7 and eight of the nine patients for MUC1. CK7 was however detected in five of 11 healthy controls (eight females, three males) and MUC1 in one of the 11 controls. None of the control group were positive for both CK7 and MUC1, in contrast to eight of the nine patients with advanced breast carcinoma who were positive for both markers. The RT-PCR method thus appears sufficiently sensitive to identify circulating tumour cells in peripheral blood samples from patients with advanced breast carcinoma. However a high proportion of false-positive results was seen in the control population. More extensive investigation is required before the technique is likely to be of benefit clinically.

Adult↗
PubMed2004

Phenotypic similarities in bilateral breast cancer.

Bilateral breast cancers that develop at similar times in an individual are likely to have been subjected to similar hormonal, environmental and genetic influences during tumourogenesis compared with metachronous tumours. As such, it is possible that tumour phenotype in synchronous bilateral breast cancer may display similar biological characteristics. The aim of this study was to identify phenotypic similarities between synchronous and metachronous bilateral breast cancers which may suggest a common origin. Thirty-three cases of synchronous and 46 cases of metachronous bilateral breast cancer that displayed similar tumour type were analysed for concordance in relation to various histological and immunohistochemical parameters. A higher level of concordance was demonstrated for synchronous cases with the highest level seen for oestrogen receptor. It is likely that this is related to similar tumourogenic pathways occurring at equivalent exposure times to various environmental and hormonal influences, although, in a proportion of cases, inherited genetic factors may play a role.

Adult↗
PubMed2004

Best Practice No 176: Updated recommendations for HER2 testing in the UK.

This paper serves to update previously published guidance on rationale and methodology for HER2 laboratory testing following the recommendation for the use of HER2 targeted treatment in the management of advanced breast cancer in the UK. Emphasis is placed on the standardisation of methodology and assessment and strategies to achieve high quality performance. A two phase testing algorithm based on first line immunocytochemistry evaluation and second line fluorescence in situ hybridisation assessment of borderline cases is recommended. To ensure maintenance of expertise, an annual caseload volume of at least 250 cases is recommended for laboratories providing a testing service.

Algorithms↗
PubMed2004

Best Practice No 179. Guidelines for breast needle core biopsy handling and reporting in breast screening assessment.

Non-operative diagnosis has become the norm in breast disease assessment and, until relatively recently, fine needle aspiration cytology has been the sampling method of choice. The introduction of automated core biopsy guns in the mid 1990s led to the additional introduction of core biopsy in assessment units. This paper presents a summary of the guidance on handling and routine reporting of breast needle core biopsy specimens in the context of breast disease multidisciplinary assessment. This guidance has been produced by the UK National Coordinating Committee for Breast Screening Pathology and is endorsed by the European Commission working group on breast screening pathology.

Biopsy, Needle↗
PubMed2003

Diagnosis of axillary nodal metastases by ultrasound-guided core biopsy in primary operable breast cancer.

The purpose of this study was to examine the use of ultrasound (US)-guided core biopsy of axillary nodes in patients with operable breast cancer. The ipsilateral axillae of 187 patients with suspected primary operable breast cancer were scanned. Nodes were classified based on their shape and cortical morphology. Abnormal nodes underwent US-guided core biopsy/fine needle aspiration (FNA), and the results correlated with subsequent axillary surgery. The nodes were identified on US in 103 of 166 axillae of patients with confirmed invasive carcinoma. In total, 54 (52%) met the criteria for biopsy: 48 core biopsies (26 malignant, 20 benign node, two normal) and six FNA were performed. On subsequent definitive histological examination, 64 of 166 (39%) had axillary metastases. Of the 64 patients with involved nodes at surgery, preoperative US identified nodes in 46 patients (72%), of which 35 (55%) met the criteria for biopsy and 27 (42%) of these were diagnosed preoperatively by US-guided biopsy. In conclusion, US can identify abnormal nodes in patients presenting with primary operable breast cancer. In all, 65% of these nodes are malignant and this can often be confirmed with US-guided core biopsy.

Adult↗
PubMed2003

Bone metastases from breast carcinoma: histopathological - radiological correlations and prognostic features.

The aim of this study was to identify factors that may be associated with the development of bone metastases in patients with metastatic breast carcinoma and to see if any of these factors had a bearing on subsequent survival. In total, 492 patients presented to the Nottingham City Hospital with metastatic breast carcinoma between July 1997 and December 2001. Of these, 267 patients had bone metastases at presentation with metastatic disease, 91 patients in this group had bone as their only site of metastatic disease. Sites of first presentation of metastatic disease were prospectively recorded, as were histological features of the primary tumour (tumour type, histological grade, lymph node stage, tumour size and oestrogen receptor (ER) status). The radiological features of the bone metastases, the metastasis-free interval and serological tumour marker levels at presentation with metastases were all recorded. There was a significant association between the development of bone metastases and lower grade tumours (P=0.019), ER-positive tumours (P<0.0001) and the lymph node stage of the primary tumour (P=0.047). A multivariate analysis found that metastasis-free interval, additional sites of metastatic disease other than bone, ER status and serological tumour marker levels all independently contributed to survival from time of presentation with bone metastases.

Adult↗
PubMed2003

Prognostic factors for patients with hepatic metastases from breast cancer.

Median survival from liver metastases secondary to breast cancer is only a few months, with very rare 5-year survival. This study reviewed 145 patients with liver metastases from breast cancer to determine factors that may influence survival. Data were analysed using Kaplan-Meier survival curves, univariate and multivariate analysis. Median survival was 4.23 months (range 0.16-51), with a 27.6% 1-year survival. Factors that significantly predicted a poor prognosis on univariate analysis included symptomatic liver disease, deranged liver function tests, the presence of ascites, histological grade 3 disease at primary presentation, advanced age, oestrogen receptor (ER) negative tumours, carcinoembryonic antigen of over 1000 ng ml(-1) and multiple vs single liver metastases. Response to treatment was also a significant predictor of survival with patients responding to chemo- or endocrine therapy surviving for a median of 13 and 13.9 months, respectively. Multivariate analysis of pretreatment variables identified a low albumin, advanced age and ER negativity as independent predictors of poor survival. The time interval between primary and metastatic disease, metastases at extrahepatic sites, histological subtype and nodal stage at primary presentation did not predict prognosis. Awareness of the prognostic implications of the above factors may assist in selecting the most appropriate treatment for these patients.British Journal of Cancer (2003) 89, 284-290. doi:10.1038/sj.bjc.6601038 www.bjcancer.com

Adult↗
PubMed2003

Correlation between immunohistochemistry (HercepTest) and fluorescence in situ hybridization (FISH) for HER-2 in 426 breast carcinomas from 37 centres.

Accurate diagnostic assessment of HER-2 is essential for the appropriate application of the humanized anti-HER-2 monoclonal antibody trastuzumab (Herceptin) to the treatment of patients with metastatic breast cancer. The diagnostic test needs to be applicable to archival, fixed tissue removed at excision, in many cases several years earlier. We compared the assessment of HER-2 by immunohistochemistry (IHC; HercepTest) and fluorescence in situ hybridization (FISH) in 426 breast carcinomas from patients being considered for trastuzumab therapy. The tumours were tested in three reference centres having been sent in from 37 hospitals. Only 2/270 (0.7%) IHC 0/1+ tumours were FISH positive. Six of 102 (5.9%) IHC 3+ tumours were FISH negative. Five of the six had between 1.75 and 2.0 HER-2 gene copies per chromosome 17 and the sixth had multiple copies of chromosome 17. Thirteen per cent of tumours were IHC 2+ and overall 48% of these were FISH positive but this proportion varied markedly between the centres. Sixty IHC-stained slides selected to be enriched with 2+ cases were circulated between the three laboratories and scored. There were 20 cases in which there was some discordance in scoring. Consideration of the FISH score in these cases led to concordance in the designation of positivity/negativity in 19 of these 20 cases. These data support an algorithm in which FISH testing is restricted to IHC 2+ tumours in reference centres. The results may not extrapolate to laboratories with less experience or using different methodologies.

Algorithms↗
PubMed2003

Prognostic significance of BRCA1 expression in sporadic breast carcinomas.

BRCA1 is a tumour suppresser gene frequently mutated in familial breast cancer and thought to influence the progression of sporadic breast cancer. Decreased BRCA1 mRNA and protein expression has been identified in breast cancer cell lines and sporadic breast tumours. Here the prognostic significance of reduced BRCA1 protein expression is investigated in primary operable breast cancer. Immunohistochemical analysis was used to determine the level of BRCA1 protein expression in 100 breast cancers. BRCA1 expression was compared with known prognostic factors and survival to investigate its prognostic significance. BRCA1 nuclear expression was reduced by varying amounts in breast carcinomas. A progressive loss of BRCA1 expression correlated well with higher histological grade (p = 0.002) and an excess of medullary/atypical medullary/grade 3 ductal carcinomas (p = 0.0001). When adjusted for grade, patients with loss of BRCA1 expression had a significantly longer disease-free survival time. Loss of BRCA1 expression associated with high-grade breast tumours suggests that BRCA1 may play an important role in the pathogenesis of sporadic breast cancer.

Adult↗
PubMed2003

Loss of CD59 expression in breast tumours correlates with poor survival.

CD59 (protectin), a phosphatidylinositol-anchored glycoprotein, is a member of the cell membrane-bound complement regulatory proteins that inhibits the formation of the terminal membrane attack complex (MAC) of complement. In this study, the expression of CD59 was evaluated in 520 breast carcinomas from patients with a mean follow-up of 87 months. This expression was correlated with clinicopathological features and patient survival. Marked variation in the intensity of CD59 expression, which correlated with histological grade and Nottingham prognostic index (NPI), was found, with higher expression of CD59 found more often in well and moderately differentiated tumours and those of good prognosis (NPI < or = 3.4). In contrast, high grade and poor prognosis (NPI > 5.4) carcinomas significantly demonstrated lack of CD59 expression (p < 0.001). Moreover, it was found that the percentage of CD59-positive cells correlated significantly with patient survival, ie patients with a high percentage of positive cells (>50%) had a better overall survival (p = 0.006). A correlation was also found between the percentage of CD59-positive cells and tumour type and also the development of distant metastases. No association was found between either the intensity or the percentage of cells expressing CD59 and vascular invasion, lymph node stage, tumour size, patient age or menopausal status. In multivariate analysis, CD59 percentage positivity was of independent prognostic significance with grade and lymph node stage. These findings indicate that loss of CD59 may offer a selective advantage for breast cancers, resulting in more aggressive tumours and conferring a poor prognosis for patients.

Adult↗
PubMed2003

Expression of p27kip1 in breast cancer and its prognostic significance.

p27kip1 is a member of the KIP/CIP family of cyclin-dependent kinase inhibitors and is a negative cell-cycle regulator that is thought to play a role in tumour suppression. Reduced levels of this protein have been observed in a number of human cancers. However, evidence is conflicting as to whether p27kip1 has a role to play in breast cancer, including predicting behaviour and prognosis. The present investigation aimed to provide a definitive study of 830 breast cancer cases with median patient follow-up of 104 months to determine the true prognostic significance, if any. Immunohistochemical analysis of tissue microarrays and three scoring methods were used to assess p27kip1 expression. Univariate analysis showed a significant relationship between reduced p27kip1 expression and increasing tumour grade, nuclear pleomorphism, mitosis, and decreasing tubule formation (all p<0.001). Significant associations between reduced p27, negative oestrogen receptor status, and ductal/no special type tumours were also observed. Survival analysis demonstrated that patients with tumours with high p27kip1 levels had an improved survival compared with those with cancers with low expression. On multivariate analysis, when compared with existing factors, p27kip1 was not, however, an independent prognostic factor. It is concluded that the inverse relationship between p27kip1 levels and histological grade and individual grade components suggests a role for p27kip1 in both cell proliferation and differentiation, but is not clinically useful.

Adult↗