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Biomedical subjects

I O Ellis

Publications and source records attributed to I O Ellis.

At least 109 records · Page 6Linked to original sources

A comparison of 14 and 12 gauge needles for core biopsy of suspicious mammographic calcification.

This study was carried out to compare the efficacy of 14 vs 12 G needles in stereotactic core biopsy of mammographic calcification. A consecutive series of 100 impalpable mammographic calcifications, without an associated mass and requiring stereotactic core biopsy were randomly allocated to either 14 G or 12 G needle sampling. All biopsies were performed using an upright stereotactic digital unit (Senovision GE) and a Bard automated biopsy gun. Core biopsy results were categorized as either normal, benign, atypical ductal hyperplasia, suspicious of ductal carcinoma in situ (DCIS), DCIS or invasive cancer. The radiographic calcification retrieval rates, complete and absolute sensitivity for malignancy of DCIS and DCIS with an invasive focus were obtained by comparison of core results with surgical histology. Radiographic calcification retrieval was achieved in 86% when using 14 G and 12 G needles. The absolute sensitivity and complete sensitivity for diagnosing DCIS were the same with 12 G and 14 G needles (72% versus 71% and 93% versus 94%, respectively). The use of 12 G needles does not appear to confer benefit over the use of 14 G needles in the diagnosis of mammographic calcification.

Biopsy, Needle↗

A critical appraisal of existing classification systems of epithelial hyperplasia and in situ neoplasia of the breast with proposals for future methods of categorization: where are we going?

Current classification systems for borderline lesions of the breast including epithelial hyperplasia, atypical hyperplasia, and ductal carcinoma in situ fall short of the ideal. They present pathologists with problems of recognition or clear distinction and clinicians with difficult management choices. In addition, recent evidence indicates that different pathogenetic lesions are present in some categories. This article presents a brief critical appraisal of the existing classifications and offers suggestions for revision using a model of pathogenetic lineage.

Breast↗

c-erbB3 and c-erbB4 expression is a feature of the endocrine responsive phenotype in clinical breast cancer.

We examined c-erbB3 and c-erbB4 mRNA expression in 47 primary breast cancer samples by simultaneous RT-PCR and have investigated correlations between these parameters and the expression of both ER and EGFR mRNA and protein as measured by RT-PCR and ICA and with Ki67 immunostaining. A direct association was found between c-erbB3 and c-erbB4 mRNA and ER marker status measured by either RT-PCR (c-erbB3 P = 0.0003; c-erbB4 P = 0.02) or ICA (c-erbB-3 P = 0.002; c-erbB4 P = 0.01). Inverse associations were seen between c-erbB3 and c-erbB4 mRNA marker status and EGFR membrane protein (c-erbB3: P = 0.003; cerbB4: P = 0.003) and mRNA (c-erbB4: P = 0.009) status. These associations were reinforced by Spearman Rank Correlation Tests. A significant relationship was seen between Ki67 and c-erbB4 mRNA status and level. Measurements of c-erbB3 protein levels in tumour samples removed from a further 89 patients of known response to endocrine therapy: (i) confirmed the relationship between c-erbB3 and ER and (ii) identified that patients whose ER positive tumours expressed high levels of c-erbB3 were most likely to benefit from endocrine measures. A non-significant trend was recorded between c-erbB3 levels and Ki67 immunostaining. These results clearly demonstrate that increased c-erbB3 and c-erbB4 expression appears to be associated with the prognostically-favourable ER phenotype.

Antineoplastic Agents, Hormonal↗

The importance of the histologic grade of invasive breast carcinoma and response to chemotherapy.

BACKGROUND: Histologic grade is well recognized for its prognostic significance in cases of primary operable invasive breast carcinoma; however, the majority of studies in which grade has been assessed have been based on single-center trials. In addition, the role of grade in predicting response to chemotherapy has not been examined in many previous studies. METHODS: The authors assessed the value of Nottingham histologic grade (NHG) in a group of 465 patients enrolled in a multicenter, randomized International Breast Cancer Study Group clinical trial of adjuvant chemotherapy for patients with lymph node (LN) positive and LN negative primary breast carcinoma (formerly named Ludwig Trial V). RESULTS: NHG was a predictor of overall survival for both LN negative and LN positive patients (P=0.045 and P < 0.001, respectively). NHG was associated with a poorer prognosis for both LN positive and LN negative patients, with hazard ratios of 1.651 (P < 0.001) and 1.437 (P=0.045), respectively, for an increase of one grade. Among LN negative patients, this survival disadvantage was observed only for those who received perioperative chemotherapy. For LN positive patients, an increase of one grade resulted in a significant overall survival disadvantage regardless of whether prolonged or perioperative chemotherapy was given. For LN negative patients grouped by grade, there was no observed difference in overall or disease free survival according to whether perioperative chemotherapy or no adjuvant therapy was given. However, LN positive patients with Grade 3 tumors had a significantly greater overall and disease free survival benefit from prolonged chemotherapy than from perioperative chemotherapy (P=0.016 and P=0.013, respectively); LN positive patients with Grade 1 or 2 disease in both treatment arms had comparable overall and disease free survival. A strong correlation between the previously utilized Bloom-Richardson grading system (BRG) and NHG was observed (P < 0.001 and kappa=82%) and no apparent differences in overall and disease free survival were observed between the two systems. NHG did, however, identify a greater proportion of tumors as Grade 1, and BRG identified a greater proportion of breast carcinomas as Grade 3. CONCLUSIONS: This multicenter clinical study confirms the value of histologic grade, and the authors propose that this technique be used to identify Grade 3, LN positive patients who will benefit from prolonged rather than perioperative chemotherapy.

Antimetabolites, Antineoplastic↗

The accuracy of breast ultrasound in the evaluation of clinically benign discrete, symptomatic breast lumps.

INTRODUCTION: Recent reports have suggested that breast ultrasound (US) is of value in distinguishing malignant from benign processes. The aim of this study was to establish the accuracy of US in detecting invasive malignancy in clinically benign, discrete, symptomatic breast lumps. METHODS: The US appearances of 205 clinically benign breast masses were documented prospectively and prior to mammography by one radiologist (AJE). The US appearances were then correlated with the fine needle aspiration (FNA), core biopsy and surgical findings and compared with the mammographic findings. RESULTS: The US findings were normal 72 (35%), simple cyst 63 (31%), solid benign 51 (25%), solid indeterminate 15 (7%) and solid malignant four (2%). Ultrasound characterized 13 (93%) of the 14 patients found to have invasive carcinoma as indeterminate or malignant. No patients with normal or simple cyst US findings had invasive malignancy. Ultrasound had significantly better accuracy (97% vs 87%, P < 0.02) sensitivity (93% vs 57%, P < 0.05) and negative predictive value (99% vs 92%, P < 0.002) than mammography in the detection of invasive carcinoma when indeterminate and malignant imaging findings were taken as positive. CONCLUSION: US is a useful adjunct to FNA/core biopsy in confirming the nature of symptomatic, clinically benign breast masses and is superior to mammography in this clinical setting.

Adult↗

Prediction of local recurrence of ductal carcinoma in situ of the breast using five histological classifications: a comparative study with long follow-up.

The increased detection of ductal carcinoma in situ (DCIS) by mammographic screening and the more widespread use of breast-conserving surgery have led to a search for histological features associated with the risk of recurrence. In a case control study of 141 patients with long follow-up, we compared the ability of five morphological classifications to predict recurrence after local excision. A significant correlation was not found between recurrence and growth pattern when a traditional classification based on architecture was used nor with necrosis when a scheme based principally on this feature was employed. A correlation was, however, found between recurrence and "differentiation" as defined by nuclear features and cell polarization in a classification recently formulated by the European Pathologists Working Group (EPWG), but this failed to reach statistical significance at the 5% level. A stronger and statistically significant correlation was found between nuclear grade as defined by the EPWG and recurrence when cell polarization was disregarded, using the classification currently employed by the UK National Health Service and European Commission-funded Breast Screening Programmes. This was attributable to a small number of recurring cases being downgraded as a consequence of exhibiting polarized cells. A significant correlation between histology and recurrence was also observed using the Van Nuys classification, which is based on nuclear grade and necrosis. Whether the tumor recurred as in situ or invasive carcinoma was unrelated to histological classification, as was the time course over which it occurred. These findings strongly support the use of nuclear grade to identify cases of DCIS at high risk of recurrence after local excision, but further work is necessary to determine whether nuclear grade or necrosis is more appropriate to subdivide the non-high-grade cases.

Adult↗

Prognostic factors affecting disease-free survival in patients with Hodgkin's disease stages IA and IIA treated initially with radiotherapy alone in a single centre during 1973 to 1992.

One hundred forty-nine patients with either stage IA (90 patients) or stage IIA (59 patients) Hodgkin's disease (HD) received radiotherapy alone as their first line treatment. Only stage of the nine factors selected for Cox multivariate analysis was of prognostic significance. Patients with grade 1 nodular sclerosing HD did not have a significantly better disease-free survival than those with grade 2 disease.

Adolescent↗

Screening women aged less than 50 years with a family history of breast cancer.

Family history is an important breast cancer risk factor and is a common reason for referral to specialist breast clinics for consideration of breast screening. The aims of this study were to determine cancer detection rates and prognostic features of breast cancers identified in women aged less than 50 years at increased risk of breast cancer who attend a Family History Breast Screening Clinic (FHC). Between January 1988 and December 1995, 1371 asymptomatic women aged less than 50 years underwent annual clinical breast examination and biennial mammography due to a family history of breast cancer. A total of 29 cancers (23 invasive and 6 in situ) were detected or presented as interval cancer during a mean follow-up of 22 months (range 0-96 months). This gave a relative risk for invasive breast cancer in this high-risk group of 5 when compared with an age-matched female population in the U.K. The cancer screening detection rates were similar to those of women aged 50 years or over undergoing population screening in the NHS Breast Screening Programme (NHSBSP)--FHC prevalent screen 8 per 1000 screening visits versus NHSBSP 6.5 per 1000, FHC incident screen 3.3 per 1000 screening visits versus NHSBSP 3.8 per 1000. A higher proportion of in situ cancers were detected in the FHC screened group compared with cancers identified in symptomatic patients from an age-matched risk group (21% versus 4%). No differences were demonstrated for invasive tumour size, grade or lymph node stage between symptomatic and screened women. The early results of this study suggests that young women at risk of breast cancer due to a family history may benefit from regular breast screening due to the early detection of in situ lesions.

Adolescent↗

Oestrogen-regulated genes in breast cancer: association of pLIV1 with response to endocrine therapy.

Northern hybridization analyses of the oestrogen-inducible mRNAs pLIV1 and pS2 were compared with oestrogen receptor (ER) immunocytochemistry assessments in 40 untreated primary or early recurrent breast tumours. Significant associations were observed between pLIV1/ER (P < 0.03), pS2/ER (P < 0.001) and pLIV1/pS2 (P < 0.04) status. After disease recurrence, patients were treated with assessable courses of endocrine therapies. Positive pLIV1, pS2 and ER statuses in primary disease were consequently found to be predictive of endocrine responsiveness in the secondary lesions (P < 0.03, P < 0.02, P < 0.005 respectively). However, despite these associations, a number of pLIV1- and/or pS2-positive tumours failed to respond to therapy.

Adult↗

Fibroadenomatoid hyperplasia: a cause of suspicious microcalcification on mammographic screening.

OBJECTIVE: Fibroadenomatoid hyperplasia is a well-described but rare benign breast lesion with composite features of fibroadenoma and fibrocystic change. Because fibroadenomatoid hyperplasia has not to our knowledge been reported as a cause of suspicious microcalcifications and because several pathology reports of biopsies of mammographically detected microcalcification at our institution included fibroadenomatoid hyperplasia, we undertook this study to describe the features of mammographically detected microcalcification seen in patients with fibroadenomatoid hyperplasia. MATERIALS AND METHODS: Two breast pathologists reviewed the records of 54 mammographically detected lesions that were compatible with a diagnosis of fibroadenomatoid hyperplasia and that provoked subsequent core biopsy or surgical excision of microcalcifications. Eleven cases (20%) fulfilled the diagnostic criteria for fibroadenomatoid hyperplasia. The sites of all calcifications found at histology were documented, and the mammographic features were described. RESULTS: Eleven cases of fibroadenomatoid hyperplasia were identified in nine core biopsy samples and two surgical specimens. Calcification was present in all 11 pathologic specimens. Calcification was stromal in nine, subepithelial in two, and epithelial in none. The mammographic features of fibroadenomatoid hyperplasia in all 11 cases were granular microcalcifications that varied in shape, size, and density and had no associated mass; of these calcifications, 91% were in a localized, irregularly shaped cluster. Rod-shaped calcifications were also seen in 64% of cases. CONCLUSION: Fibroadenomatoid hyperplasia is a cause of suspicious, granular, clustered microcalcifications on screening mammography. Fibroadenomatoid hyperplasia can be confirmed using 14-gauge core biopsy in most cases.

Aged↗

Quality assurance in DNA image analysis on diploid cells.

DNA image analysis is presently performed in many laboratories. Before general extrapolation of results between different laboratories, validation has to be performed for interlaboratory studies on DNA image analysis. The aim of this study was to establish the performance of different DNA image analysis instruments when measuring different diploid cells. On three separate parts of the same object slide, human liver cells, white blood cells, and imprints of a breast fibroadenoma were sampled. In this quality assurance interlaboratory study, 13 laboratories participated voluntarily. Two slides were sent to each participating laboratory: one Feulgen and one unstained to be stained according the participating laboratory in-house procedure. The features integrated optical density (IOD) and object AREA were recorded for each nucleus. For calculation of the results, the average IOD value of liver diploid cells was set at 2c. A striking difference was observed between the different presumed diploid cell types, from almost 1c to 3c. This variation was not dependent on central or in-house staining. Although in-house calibration was performed for each image analysis system, a surprisingly large variation existed in the reported object AREA, irrespective of the cell type. These results clearly demonstrate that measurements performed in one laboratory cannot be extrapolated to the outcome of others and support the need for standardization. The use of external control cells works well for comparison of instruments. In conclusion, in DNA image analysis quality control is necessary, standardization is obligatory, and the use of an internal control for determination of the diploid peak in a histogram of patient samples is recommended.

Breast Neoplasms↗

A comparison outcome of male breast cancer with female breast cancer.

BACKGROUND: It is unclear whether breast cancer has a similar prognosis in males and females. METHODS: A 20-year retrospective study of all male breast cancer patients in our region was undertaken. We compared this series with a group of females matched for the major prognostic factors and an unmatched series of female patients treated over the same period. RESULTS: Forty-one patients with invasive cancer and 2 with ductal carcinoma in situ were identified. One invasive cancer was treated with radiotherapy, 40 had surgery. Local recurrence occurred in 23% and axillary recurrence in 40% of cases. Male and female patients (n = 123) matched for the major prognostic factors showed a similar outcome for disease-free interval (P = 0.90) and survival (P = 0.27). However, both the above groups had a significantly worse outcome than the unmatched series of female patients with breast cancer. CONCLUSIONS: When prognostic factors are allowed for, male and female breast cancer patients have a similar outcome. This suggests that such features should be taken into account when determining management for males with breast cancer just as they are in females.

Adult↗

Radiological features of papillary carcinoma of the breast.

Seventeen patients with papillary carcinoma of the breast were analysed with respect to the radiological findings by three experienced breast radiologists. The most frequent mammographic appearance of papillary tumours was of an ill-defined (70%) and lobulated (60%) mass and at ultrasound as a well-defined (76%), inhomogeneous (62%) and hypoechoic (92%) lesion. Histopathological subtypes of encysted papillary carcinoma, encysted papillary carcinoma with an invasive focus and invasive papillary carcinomas could not be predicted from the radiological features, although invasive tumours tended to be larger at presentation than the other subtypes.

Breast Neoplasms↗

Subcutaneous mastectomy for primary breast cancer and ductal carcinoma in situ.

Subcutaneous mastectomy (SCM) has been performed in 323 patients with invasive breast cancer or ductal carcinoma in situ (DCIS) over the last 20 years. This paper assesses the oncological safety of this operation with particular reference to local recurrences (LR) in the skin flaps. LR was assessed in the 134 patients who did not receive post-operative irradiation to the flaps and were followed up for a minimum of 30 months. The rates of LR were similar for SCM (16%) and for women who underwent simple mastectomy without post-operative irradiation (SM) for invasive cancer (14%) over the same time period, both overall and after prognostic stratification. In DCIS LR was only found in women treated with SCM. Four of the five recurrences (from 33 women) were in the nipple and later in the series patients with microscopic tumour involvement in the nipple received prophylactic irradiation to the nipple only; five patients treated in this way have not suffered LR. Subcutaneous mastectomy followed by insertion of a prosthesis is a safe alternative to mastectomy, since it carries no higher risk of LR. It is the simplest form of reconstruction in those proceeding to silicone implant and has the potential of achieving an excellent cosmetic result. Failure does not compromise the chance of more complex reconstruction procedures.

Adult↗

The effect of onapristone, a progesterone antagonist, on the growth of human gastrointestinal cancer xenografts.

Onapristone is a progesterone antagonist which inhibits the growth of mammary tumours in mice. The effect of Onapristone and concomitant oestrogen (E2) supplements on the growth of five human gastrointestinal cancer xenografts was examined. E2 stimulated RD19 (gastric tumour) tumour growth in female mice and tumours grew less well when also treated with Onapristone (P < 0.05). Onapristone had no effect on male mice bearing RD19 tumours or mice of either sex bearing MKN45G (gastric) tumours. PAN-1 (pancreatic) tumours were significantly stimulated by E2 (by 64% of control, P = 0.02) and Onapristone treatment inhibited E2 stimulated growth (52% reduction of E2 control, P > 0.05). C146 (colorectal) tumour growth was not stimulated by E2 nor inhibited by Onapristone. E2 stimulated formation of AP5LV (colorectal) tumour nodules (in lungs) (mean 38-52, P = 0.001). Onapristone significantly reduced the number of nodules (mean 32, P < 0.05) only in female mice not given E2. Xenografts of some GI tumour cell lines grow at different rates in male and female mice. E2 may cause additional growth stimulation and E2 stimulated growth can be reversed by Onapristone to basal levels.

Analysis of Variance↗

Predictors of response to second-line endocrine therapy for breast cancer.

This study reports on factors predicting response to second-line endocrine therapy in 250 patients with breast cancer for which they were assessable for response by the International Union Against Cancer (UICC) criteria. Clinical details relating to first-line endocrine therapy were available for all patients. We have not included in this study patients who received first-line endocrine therapy but did not or have not yet proceeded to second-line hormone therapy--e.g. died from rapidly progressive disease, started chemotherapy for rapidly progressive disease, or remained in long-term remission on first-line endocrine therapy. One hundred and fifty nine patients (72%) achieved remission (objective response and static disease [OR + SD]) on first-line endocrine therapy with a median duration of 19 months. For second-line endocrine therapy the remission rate was 53% (132/225) with a median duration of 15 months. Tumour grade and oestrogen receptor status of the primary tumour were shown to be independent predictors of response to second-line endocrine therapy while response to first-line endocrine therapy was a predictor of the duration of response to second-line endocrine therapy. In the sub-group of patients who showed OR or SD to both first and second-line therapies, there was no correlation between the time to progression (TTP) on first and second-line therapies.

Adult↗