Biomedical subjects

S E Pinder

Publications and source records attributed to S E Pinder.

At least 55 records · Page 3Linked to original sources

PubMed2003

Spindle cell carcinoma of the breast: a case series of a rare histological subtype.

AIM: Spindle cell carcinoma (SpCC) represents <0.5% of breast cancers. We report the 15-year experience of SpCC at the Nottingham Breast Unit. METHODS: Histopathology and case notes of metaplastic carcinomas with predominant spindle cell differentiation were analysed for patient demographics, tumour pathology, c-erb B-2 oestrogen (ER) and progesterone (PR) receptor status and radiology. Treatment, recurrence and survival rates were also analysed. RESULTS: Nineteen patients with SpCC were identified. The median age was 68 years (range 27-92). Large ill-defined mass was the only consistent radiological features suggesting SpCC. Mean tumour size was 53 mm, (range 16-200 mm). Fifteen tumours were grade 3 and four were grade 2. Six out of 15 patients with axillary surgery had positive lymph nodes (40%). All tumours were oestrogen (ER) and progesterone (PR) negative. One tumour was focally c-erb B-2 positive in the non-spindle cell component. Median Nottingham Prognostic Index was 5.2 (range 3.6-6.6). Primary treatment was surgical in 89%. Adjuvant chemotherapy was given in four cases. The median disease free interval was 7 (range 2-109) months. Twelve cases recurred (63.2%). The main sites of metastasis were the lungs (9 cases), bone (6) and liver (1). Eleven cases have died of breast cancer (58%). Median survival was 18 months (range 4-109). CONCLUSION: SpCC is an aggressive histological type of carcinoma of the breast. Omitting node sampling may result in significant under-staging. Negative ER, PR and c-erb B-2 status limits treatment options.

Adult↗

PubMed2003

Size of invasive breast cancer and risk of local recurrence after breast-conservation therapy.

Risk of local recurrence is one important factor that determines a woman's suitability for breast-conservation therapy. With the evolution of oncoplastic surgery, tumours of a size that traditionally require mastectomy may be treated by breast conservation and partial breast reconstruction. This article reviews the evidence relating to tumour size as a risk factor for local recurrence to assess whether this change in practice is appropriate. A literature review through Medline and Pubmed was performed. All pathological studies analysing tumour size as a predictor of multifocality and all randomised trials and large case series of breast conservation including tumours larger than 2 cm were reviewed and critically interpreted. Pathological studies report consistent evidence that tumour size is not predictive of multifocality. Randomised trials and clinical series of breast conservation report conflicting evidence relating to tumour size as a risk factor for local recurrence, although most studies report no association. Evidence relating to cancers over 3 cm is limited. There is little evidence to justify the use of tumour size alone as an exclusion criterion for breast-conservation therapy. A registration study of patients with cancers larger than 3 cm treated by breast conservation with or without partial breast reconstruction is proposed.

Breast Neoplasms↗

PubMed2003

Excision biopsy findings of patients with breast needle core biopsies reported as suspicious of malignancy (B4) or lesion of uncertain malignant potential (B3).

AIMS: The UK National Health Service Breast Screening Programme has proposed five categories for reporting breast needle core biopsies. The majority of cores are reported as benign (B1), normal (B2) or malignant (B5). The predictive value of the two borderline categories suspicious of malignancy (B4) and lesion of uncertain malignant potential (B3) was studied. METHODS AND RESULTS: Over a 2-year period a total of 3822 breast needle core biopsies were performed, with 2997 from symptomatic patients and 825 from women undergoing mammographic screening, including 43 B4 reports (40 patients) and 120 B3 reports (116 lesions in 115 patients). The frequencies of B4 (2.5% versus 0.7%) and B3 cores (7.3% versus 2.0%) were both higher in screening than in symptomatic patients. B4 was most commonly used for small fragments of atypical cells separate from the main core or focal atypical intraductal proliferations. The criteria for calling a core B3 were: atypical intraductal epithelial proliferations (including foci that in excision specimens would be classified as atypical ductal hyperplasia), lobular neoplasia, radial scar, papillary lesion, fibroepithelial lesion with cellular stroma and spindle cell proliferations. Excision biopsies were performed in 39 patients with B4 core and 96 with B3 core. Invasive carcinoma or ductal carcinoma in situ was seen in 33 of the patients with B4 (85%) and in 29 of those with B3 cores (25%). Some categories of B3 core were associated with a higher rate of malignancy (40% for atypical intraductal epithelial proliferations and 46% for lobular neoplasia). CONCLUSIONS: The positive predictive value for carcinoma is high following a B4 core (86%). The lesion should be excised, but definitive cancer treatment is not appropriate. In some cases a definite diagnosis of malignancy can be made on repeat core. The B3 group is more heterogeneous and has a lower rate of malignancy on further biopsy (25%). The majority of B3 lesions require excision. All these patients should be discussed at multidisciplinary meetings.

Biopsy, Needle↗

PubMed2003

Expert opinion: Reporting needle core biopsies of breast carcinomas.

Many breast carcinomas are now diagnosed in needle core biopsies, after either mammographic detection or symptomatic presentation. There is dispute, however, about the range of information that should be included in the diagnostic report of these small and possibly unrepresentative samples. Is it sufficient to simply report the presence of carcinoma, in situ or invasive? Or should the histopathologist give a more detailed report including features of prognostic and predictive significance? If so, what is the evidence that the further information is, first, of clinical benefit and, second, not unreliable because of sampling variability? To address the question "What should be included in reports of needle core biopsies of breast carcinomas?" contributions were invited from authors in the USA and the UK.

Adenocarcinoma↗

PubMed2003

Is the presence of mammographic comedo calcification really a prognostic factor for small screen-detected invasive breast cancers?

AIM: It has been suggested that the use of traditional prognostic factors such as histological grade and lymph node stage are not reliable predictors of outcome for small (<15 mm diameter) screen-detected breast cancers. It has also been suggested that the presence of mammographic comedo (casting) microcalcifications may be an important prognostic factor. We have determined prognostic factors for small screen-detected cancers in a univariate and multivariate fashion. MATERIALS AND METHODS: Histological grade, lymph node stage, invasive tumour size and vascular invasion status was obtained on 161 consecutive patients with primary invasive breast cancer <15 mm diameter, detected by screening. The Nottingham Prognostic Index was calculated for each patient. The mammograms were assessed for the presence of microcalcifications, these being classified as either comedo or non-comedo. Survival data was also obtained. RESULTS: Overall survival in this group of patients was excellent with only 12 patients (7.5%) dying from their breast cancer (mean follow-up 7.5 years). Univariate analysis showed a significant association between lymph stage and outcome (chi(2)=9.68, P=0.008). No significant association was demonstrated between the presence of comedo calcification and survival. Multivariate analysis confirmed lymph node stage as the only independent prognostic factor for these small screen-detected breast cancers (chi(2)=7.18, P=0.007). There were significant associations between the presence of comedo calcification on the screening mammogram and high histological grade and small tumour size. CONCLUSION: Although the overall outcome for small screen-detected breast cancers (<15 mm diameter) is excellent, the presence of lymph node metastases is associated with a significant reduction in long-term survival. The presence of mammographic comedo calcification is not an independent prognostic factor, but is closely related to histological grade.

Breast Neoplasms↗

PubMed2003

X-ray refraction effects: application to the imaging of biological tissues.

The purpose of this study was to explore the potential of refraction contrast X-ray imaging of biological tissues. Images of dissected mouse lungs, heart, liver and legs were produced using the medical beamline at the Elettra Synchrotron at Trieste, Italy. The technique used was diffraction enhanced imaging. This utilizes a silicon crystal positioned between the tissue sample and the detector to separate refracted X-rays from transmitted and scattered radiation by Bragg diffraction. The contrast in the images produced is related to changes in the X-ray refractive index of the tissues, resulting in remarkable clarity compared with conventional X-ray images based on absorption effects. These changes were greatest at the boundaries between different tissues, giving a marked edge enhancement effect and three-dimensional appearance to the images. The technique provides a way of imaging a property of biological tissues not yet exploited, and further studies are planned to identify specific applications in medical imaging.

Animals↗

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↗

PubMed2002

Neuroendocrine differentiation and prognosis in breast adenocarcinoma.

AIMS: Neuroendocrine differentiation has been detected, and its prognostic value studied, in a number of common human carcinomas. To date there are few detailed studies examining its relevance in breast carcinoma. In this study we evaluate the frequency and prognostic importance of neuroendocrine differentiation in breast adenocarcinoma. METHODS AND RESULTS: The presence of neuroendocrine differentiation, defined as positive reactivity for three markers, neuron-specific enolase (NSE), chromogranin A and/or synaptophysin, has been evaluated in 99 patients with primary operable breast cancer using standard immunocytochemical techniques. A consecutive cohort of patients were selected from the Nottingham/Tenovus series. Comprehensive patient and tumour records have been maintained, and patients were followed up according to a defined protocol. Eighteen cases were positive for NSE, 10 for chromogranin A and 13 for synaptophysin. Eleven percent were positive with more than one neuroendocrine marker. No significant association was found between neuroendocrine differentiation and tumour size, grade, stage or the prevalence of vascular invasion. There was no significant difference in either overall or disease-free survival between patients with or without neuroendocrine differentiation. CONCLUSIONS: In this study we confirm that neuroendocrine differentiation can be identified in a subset (10-18%) of human breast carcinomas. This phenomenon appears to have no relationship to established prognostic factors or patient outcome.

Adenocarcinoma↗

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

Growth pattern of ductal carcinoma in situ (DCIS): a retrospective analysis based on mammographic findings.

The aim of this study was to obtain information concerning the direction and rates of growth of ductal carcinoma in situ (DCIS). The previous mammograms of 124 women diagnosed with DCIS were examined. If in retrospect calcifications were present on the previous examination, the exact size and position were recorded on both diagnostic and previous imaging. The rates of change and direction of change in extent of calcifications were calculated. 39 women with a diagnosis of DCIS in retrospect had calcifications visible on both their current and prior examinations; these formed the study group. For individual clusters of calcification, change occurred along an axis to the nipple at a mean of 5.5 mm y(-1)and along an axis at 90 degrees to the nipple at 2.6 mm y(-1). Increase in calcifications along the axis to the nipple occurred at 2.6 mm y(-1)toward and 2.8 mm y(-1)away from the nipple. Increase in the axis to the nipple occurred at 1.8 mm y(-1)for low grade, 4.2 mm y(-1)for intermediate grade and 7.1 mm y(-1)for high grade. DCIS growth along an axis to the nipple occurs at over twice the rate of growth in the other direction(s) and growth toward and away from the nipple occurred equally. Growth rates increased with increasing nuclear grade of DCIS. These results validate nuclear grading of DCIS. Additionally, the results suggest that increased importance should be placed on identifying the 'nipple' and 'anti-nipple' margins of DCIS represented by calcifications for both surgical excision and pathological scrutiny.

Breast Neoplasms↗

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

Mammographic size of ductal carcinoma in situ does not predict the presence of an invasive focus.

A proportion of women thought to have ductal carcinoma in situ (DCIS) on mammography and a core biopsy showing DCIS only, in fact have an invasive focus on surgical excision. This study aims to identify the percentage of such patients who harbour an invasive focus and to ascertain features which can predict the presence of invasion. 140 patients had a core biopsy diagnosis of DCIS without invasion. All patients had their core biopsy graded and mammography was performed on 128 patients. Mammographic findings were classified by a radiologist blinded to the surgical findings into normal, mass/distortion or microcalcification. The extent of the microcalcifications was measured. The core biopsies were graded into high, intermediate or low grade DCIS groups. The core biopsy and radiological findings were compared to see if they could predict the presence of invasive disease at surgical excision. Of the 140 patients, 61 (44%) had an invasive focus. 8 (47%) of 17 patients with normal mammography had an invasive focus. 4 (36%) of 11 patients with a mammographic mass had evidence of invasion. Of the 100 patients with mammographic microcalcifications 48 (48%) had an invasive focus. In the 10 patients with low grade DCIS on core biopsy, 3 (30%) had an invasive focus. Comparative studies in patients with intermediate and high grade DCIS, were 7 of 18 (39%) and 51 of 112 (46%), respectively. Thus, 44% of women thought to have DCIS only on preoperative investigation had an invasive focus. In contrast to previous expressed opinions, neither mammography or grade were predictive. We have not identified any factor capable of predicting a higher likelihood of an invasive focus.

Adult↗

PubMed2001

Change in expression of ER, bcl-2 and MIB1 on primary tamoxifen and relation to response in ER positive breast cancer.

Pre-treatment oestrogen receptor (ER) expression in breast cancer predicts for rate of response to endocrine therapy but not for the quality or duration of response (DofR). ER is known to be down-regulated by anti-oestrogens. This study has tested the hypothesis that the degree of down-regulation of ER and the ER-regulated marker bcl-2 are associated with the quality and duration of tamoxifen response. 80 patients with ER+ve breast cancer (H-score > 10) receiving primary tamoxifen (n = 51 Stage I-II elderly; n = 29 Stage III) underwent sequential tumour biopsies for immunocytochemical assessment of ER, bcl-2 and the proliferation marker MIB1. Median follow-up is 45 months. By 6-months on therapy three patients had attained complete response (CR), 27 partial response (PR); 44 static disease (SD) and six progression (PD) by UICC criteria. Greater decrease in ER and bcl-2 H-score from pre-treatment to 6 weeks (p = 0.035, p = 0.037) and ER and bcl-2 H-score from pre-treatment to 6 months (p = 0.058, p = 0.036) were significantly associated with better quality of response (CR/PR vs SD/PD). Greater 6-week and 6-month reduction in bcl-2 H-score (p = 0.041, p = 0.036) and 6-week reduction in MIB1 (p = 0.013) were significantly correlated with longer DofR. This study demonstrates that greater down-regulation of ER and the ER-regulated protein bcl-2 on primary tamoxifen are significantly associated with a better quality of response and bcl-2 and the proliferation marker MIB1 a longer duration of response in ER+ve breast cancer.

Aged↗

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

An audit of "equivocal" (C3) and "suspicious" (C4) categories in fine needle aspiration cytology of the breast.

We have audited the frequency of use and outcome of the "equivocal/atypia probably benign" (C3) and "suspicious of malignancy" (C4) category for breast cytology in our Unit. A total of 14 935 cytological specimens were reported by at least one of the three pathologists with a special interest in breast pathology, according to five categories of the NHSBSP guidelines for cytology reporting, 1992; 3.7% (555 cases) and 3.9% (587 cases) of cases were classified as equivocal (C3) and suspicious (C4), respectively, giving a total rate (C3 + C4) of 7.6%. Of the C3 cases, 68% were subsequently benign and 32% were malignant. Of the C4 cases, 19% were subsequently benign and 81% malignant. The commonest benign lesions in both categories were fibroadenomas (7.6% of C3 and 19.8% of C4), fibrocystic change (14.3% of C3 and 12.5% of C4), radial scars (6.2% of C3 and 10.4% of C4) and papillomas (6.2% of C3 and 6.3% of C4). Of the malignant lesions (particularly those classified as C3), a high proportion were low grade or special type cancers. The categories of atypia probably benign (C3) and suspicious of malignancy (C4) in breast cytology provide a strategy for classification of problematic or uncertain cases; this maintains the predictive value of the benign (C2) and malignant (C5) categories, and allows separation of these difficult cases into clinically useful groups with differing probabilities of malignancy.

Biopsy, Needle↗

PubMed2001

False-negative breast screening assessment: what lessons can we learn?

AIM: To review women who have had breast cancer diagnosed following previous assessment of a screen-detected mammographic abnormality in order to ascertain the frequency and characteristics of false-negative assessment. MATERIALS AND METHODS: The assessment process was reviewed in the study population of 28 women. This included the nature of the lesion recalled for assessment, additional mammography, clinical and ultrasound findings, and the results of fine needle aspiration cytology and needle histology. RESULTS: The frequency of false-negative assessment was approximately 0.56%. The median time between false-negative assessment and diagnosis of breast cancer was 33 months. The most common mammographic lesion resulting in false-negative assessment was micro-calcification seen in 12 cases (43%). Only five of these 12 cases had image-guided biopsy, the remainder were thought to be benign on magnification views. Other mammographic abnormalities were nine masses (32%), five architectural distortions (18%) and two asymmetric densities (7%). Of the 16 women with mammographic lesions other than micro-calcifications 10 had a normal ultrasound. CONCLUSION: Radiological interpretation of indeterminate micro-calcifications as benign or malignant is unreliable. An isolated cluster of micro-calcification requires image-guided core biopsy with representative micro-calcification obtained on specimen radiography. Further mammography done at assessment, particularly paddle compression views, should be carefully analysed to ensure areas of architectural distortion have truly resolved. If one imaging modality shows a significant abnormality and another does not the cases must be managed on the basis of the abnormal finding. Burrell, H.C.et al. (2001). Clinical Radiology56, 385-388.

Adult↗

PubMed2001

Predicting invasion in mammographically detected microcalcification.

AIM: To identify pre-operative factors which predict presence of invasive disease within mammographically detected malignant microcalcification. MATERIALS AND METHODS: A retrospective analysis was undertaken of 116 serial stereotactic core needle biopsies (SCNBs) performed on malignant mammographic calcification. Final surgical pathology was correlated with pre-operative features (clinical, radiological and core histology) in an attempt to predict the presence of an invasive component. RESULTS: Thirty-eight clusters contained invasive carcinoma. The sensitivity of SCNB for invasion was 55%. Clinical features, calcium morphology and cluster size were not shown to be predictive of invasive disease. Ductal carcinoma in situ (DCIS) of high grade on core histology and increasing number of calcifications were predictive of increased risk of invasion (high grade core biopsy DCIS and > 40 calcifications 48% invasive at surgical histology; high grade core biopsy DCIS and < 40 calcifications 15% invasive; non-high grade core biopsy DCIS 0% invasive). CONCLUSIONS: Identification of those clusters diagnosed as DCIS by percutaneous biopsy which are likely to harbour an invasive component is possible. It would seem reasonable to consider staging the axilla at therapeutic surgery in these patients.

Adult↗