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Biomedical subjects

U Chetty

Publications and source records attributed to U Chetty.

At least 19 recordsLinked to original sources

Excision biopsy of malignant melanoma by general practitioners in south east Scotland 1982-91.

OBJECTIVE: To examine the management of patients who had a malignant melanoma excised initially by general practitioners in south east Scotland over the past 10 years and to assess the impact of the April 1990 contract on this. DESIGN: A retrospective case-control study. SETTING: South east Scotland. SUBJECTS: All patients in south east Scotland who had malignant melanomas excised by general practitioners in 1982-91. OUTCOME MEASURES: Demographic details of patients; Breslow thickness, clearance of excision. RESULTS: 42 patients had malignant melanomas excised by general practitioners in 1982-91: 15 in 1982-9 and 27 in 1990-1. These patients were significantly younger than those who had their tumours excised initially in hospital. Although the longest diameter of melanomas excised by general practitioners was significantly less than of those excised in hospital, the Breslow thicknesses were similar. Completeness of initial excision was doubtful or incomplete in nine (23%) general practitioner excisions compared with 4% of hospital excisions, but the time interval between excision biopsy and wide excision was similar. Pathology requests accompanying excision biopsies mentioned melanoma as a possible diagnosis in 15% (6/40) of general practitioner cases compared with 79% of hospital cases. Thirty nine general practitioners responded to a questionnaire and only 12 had considered melanoma in the differential diagnosis. CONCLUSIONS: General practitioners need to think more often of malignant melanoma when they excise pigmented lesions and when they consider this tumour a possibility should perform an excision biopsy with a lateral clearance of at least 2 mm.

Adult

p53 mutations in breast cancer.

We have identified and analyzed 41 mutations in p53 in sporadic breast tumors from 136 unselected breast cancer patients and estimate that approximately 40% of such tumors contain p53 mutations. The frequency of G-T transversions and the incidence of guanosine mutations in the nontranscribed strand of the p53 gene were found to be higher than expected, and we suggest, therefore, that exogenous carcinogens have an etiological role in sporadic breast cancers. Mutations were recorded in 44 codons of the p53 gene, with no obvious mutational hot-spots, although mutations at codons 175, 194, 273, and 280 accounted for 25% of the changes. One germ-line mutation was found in 136 patients and so we conclude that constitutional mutation of p53 may be an uncommon etiological factor in breast cancer.

Base Composition

p53 allele losses, mutations and expression in breast cancer and their relationship to clinico-pathological parameters.

The p53 locus on the short arm of chromosome 17 at 17p 13.1 was examined for loss of heterozygosity, mutation, mRNA and protein expression in 60 primary breast cancers. Allele loss around the p53 locus was detected in 19/45 informative tumours (42%). p53 mutations in the evolutionarily conserved exons 5 to 9 were detected in 17/60 (28%) by amplification mismatch and confirmed by direct DNA sequencing. p53 mRNA expression was detected by Northern blot in 36/59 (61%) of tumours, and p53 protein expression using antibody 1801 on frozen-tissue sections in 13/44 of the tumours examined. p53 mutation was significantly associated with oestrogen-receptor-poor tumours (p less than 0.01) and hence with poor prognosis, but not with other clinical or pathological parameters. There was no statistical correlation between loss of heterozygosity around the p53 locus at 17p13.1 and p53 mutation. Furthermore, p53 mutation was not associated with p53 expression detected by immunohistochemical staining with antibody 1801 or as p53 mRNA. In addition, events on 17p (allele losses, p53 mutation, p53 expression) were independent of c-erbB-2 expression. In breast cancer, by contrast with colorectal, lung and ovarian cancer, there appears to be no clear association between p53 DNA abnormalities and p53 expression.

Alleles

Colour Doppler ultrasonography studies of benign and malignant breast lesions.

Colour Doppler scanning was carried out on 53 patients with solid, discrete breast masses. Twenty-five of 32 breast cancers and none of 21 benign lesions gave a positive scan, giving a sensitivity of 78 per cent for association with malignancy, a specificity of 100 per cent and a positive predictive value of 100 per cent. Tumours less than 1 cm in diameter and invasive lobular cancers were least likely to give a positive scan. Axillary node scans were performed in 31 of 32 patients with breast cancer with 29 undergoing an axillary staging procedure. Nine patients had a positive axillary scan and all nine had involved axillary nodes. Three patients had involved axillary nodes, but a negative axillary scan. The sensitivity of colour Doppler scanning for axillary node involvement was 75 per cent, with a specificity of 100 per cent and a positive predictive value of 100 per cent.

Adolescent

Assessment of non-palpable mammographic abnormalities: comparison between screening and symptomatic clinics.

A retrospective study found that a breast screening clinic generated fewer localization biopsies for non-palpable mammographic abnormalities than a symptomatic clinic (3.36 versus 9.89 per 1000 mammograms, respectively) and that a greater proportion of such biopsies were malignant. This study determined the reason for this difference. There were 108 of 304 (35.5 per cent) and 17 of 130 (13.1 per cent) carcinomas in women attending the screening and breast clinics respectively (relative risk 2.72 (95 per cent confidence interval 1.70-4.34)). This difference was regardless of age. The characteristics of the mammographic abnormality, the Wolfe pattern, a family history of breast carcinoma, parity and age at first pregnancy were similar in both groups. Women attending the screening clinic were referred for localization biopsy after assessment by clinicians and radiologists at a joint clinic; there was no joint assessment for patients attending the breast clinic. The same staff attended both clinics, although the proportion of time spent at each varied. This study suggests that all women with a non-palpable mammographic abnormality should be reviewed at a joint assessment clinic before localization biopsy is recommended.

Biopsy

Indications for primary tamoxifen therapy in elderly women with breast cancer.

A group of 66 elderly women with primary breast cancer were treated with tamoxifen and followed for a minimum of 2 years. Of these, 32 whose disease remained controlled for the 2-year period were considered to have had a 'worthwhile' response, 27 in whom disease progressed were considered to have had an unsatisfactory result and seven opted for alternative treatment. By Union Internacional Contra la Cancrum (UICC) criteria, 14 women had a complete response, 20 a partial response, in five disease remained static and in 20 it progressed without response. Prediction of outcome after assessment according to UICC criteria at 3 and 6 months was unsatisfactory (19 and 34 of 59 correctly predicted respectively). Analysis of multiple tumour measurements over 12 weeks was no better (33 of 59 correctly predicted). Immunocytochemical assay of fine-needle aspirates for oestrogen receptor (ER) provided a better predictor (38 of 47 correct) and the difference in survival between patients with and without ER activity was significant (P < 0.001). Conventional assessments of response at 3 and 6 months are unsatisfactory for judging the long-term benefit to the patient. ER status is the best predictor of response and outcome.

Aged

Pathological features predictive of local recurrence after management by conservation of invasive breast cancer: importance of non-invasive carcinoma.

The pathological features of 236 clinical stage I and II invasive breast carcinomas treated by conservation were reviewed. On follow-up (minimum 2 years) 13 patients (6%) have developed breast relapse, 10 (4%) regional lymph node relapse and 26 (11%) distant metastases. Nineteen patients have died from breast carcinoma. On univariate analyses lymph node metastases, increasing amounts of non-invasive carcinoma and multiple foci of invasion were significant risk factors for breast relapse. A Cox's multivariate analysis showed the first two of these to be independently significant. The results are in agreement with other published series and confirm that assessment of non-invasive carcinoma is important. The study compares simple quantitation with the original method reported to define cases with an "extensive intraduct component".

Breast Neoplasms

Locally advanced breast cancer: report of phase II study and subsequent phase III trial.

Twenty-four evaluable patients with stage T4 breast cancer were entered into a phase II study and received chemotherapy comprising cyclophosphamide 1,000 mg m-2 i.v., doxorubicin 50 mg m-2 i.v., vincristine 1.4 mg m-2 i.v. and prednisolone 40 mg orally for 5 days, given 3 weekly for four cycles prior to undergoing loco-regional radiotherapy. All patients completed treatment as planned with no major acute toxicity from either chemotherapy or radiotherapy. Subsequently 52 patients with stage T4 breast cancer were randomised in a phase III trial to receive either radiotherapy alone (RT) or this chemotherapy and radiotherapy (CHOP + RT). A significantly higher complete response rate was achieved in the CHOP + RT treatment arm (P = 0.03). However a larger proportion of the RT arm achieved loco-regional control after salvage treatment for relapse such that 50% of the RT arm and 57% of the CHOP + RT arm had no evidence of loco-regional disease at the time of last follow-up or death. There was no statistical difference in time to distant relapse or overall survival. Analysis of the pilot study showed results comparable to the trial CHOP + RT arm. This trial suggests that this cytotoxic therapy used in conjunction with radiotherapy has only marginal value in improving prognosis in locally advanced breast cancer.

Adult

The differing predictive values of oestrogen receptor assays for large breast cancers.

Thirty elderly patients with T3 or T4 breast cancer underwent a wedge biopsy for radioligand-binding assay (RLA) of oestrogen receptor (ER) activity. A second, separate group of 21 elderly patients with T3 and T4 breast cancers underwent fine needle aspiration biopsy (FNA) for immunocytochemical assay of ER (ER-ICA). All the women received tamoxifen as primary treatment and response was assessed by UICC criteria. Tumour ER concentration by RLA was correlated with both response (Spearman's R = + 0.52) and time to progression (R = + 0.76). Nine patients with receptor-rich tumours (> 100 fmol/mg protein) failed to show a response. However, the percentage of cells staining for ER by ER-ICA assay was much more strongly related to the likelihood of response (R = + 0.89); no patient with < 20% cells staining responded. Wedge biopsy and the biochemical determination of ER activity is of limited value in predicting the likely response to tamoxifen; ER-ICA assays on such tumours may be more informative.

Aged

Cyclical breast pain--some observations and the difficulties in treatment.

This paper describes a retrospective study of the clinical aspects and treatment of 566 women with cyclical breast pain over a seven-year period. Figures for the effectiveness of simple treatments including some homeopathic drugs are reported. The article concludes that reassurance is the fundamental treatment. Good responses are obtained from simple and safe drugs (oil of evening primrose, vitamin B6) with minimal side-effects. The use of stronger hormone drugs such as tamoxifen and danazol was only necessary in a small proportion of patients and resulted in a higher incidence of side-effects.

Adolescent

Mammography in the management of patients with small breast cancers.

Findings on mammography resulted in a change of treatment policy in 17 of 200 patients with small breast cancers (T1/T2 less than 4 cm, N0/N1, M0). Twelve patients were considered unsuitable for conservation therapy because of mammographic evidence of either extensive in situ carcinoma or more than one focus of invasive carcinoma. These patients were treated by mastectomy and histology confirmed widespread in situ carcinoma or multifocal/multicentric invasive carcinoma. Seven patients were found to have unsuspected contralateral lesions on mammography, of which five were subsequently shown to be malignant. Routine preoperative mammography is essential in the management of patients with small breast cancers.

Adult

Mitozantrone and prednimustine in the treatment of advanced breast cancer--a toxic regimen with low activity.

The combination of mitozantrone and prednimustine has been reported to elicit response rates of around 50% in patients with advanced breast cancer. In the present trial, either three or nine courses of this combination were given to previously untreated patients with advanced breast cancer. Mitozantrone was given at 12 mg/m2 on day 1 and prednimustine was given orally at 130 mg/m2 on days 1-5; treatment was repeated every 4 weeks. A total of 34 patients were treated; the performance status was 0-1 in 29 subjects and 2 in 5 cases. Locoregional disease only was present in 13 patients; 9 showed lung involvement; 8, liver; 3, bone; and 1, stomach involvement. A total of 10 subjects had received no prior hormone therapy. The median disease-free interval from the time of initial diagnosis was 24 months (range, 0-144 months). In all 14/23 patients exhibited an oestrogen receptor level of greater than 20 fmol. Grade 1 nausea and vomiting occurred in 16 patients and that of grade 2-3, in 11 subjects; nausea was prolonged for greater than 10 days in 7 cases. Grade 4 neutropenia occurred in 2 patients. The response rate was 21% (95% confidence interval, 8%-38%). The combination of mitozantrone and oral prednimustine is toxic and displays low activity.

Adult

Epidermal growth factor receptors in intracranial and breast tumours: their clinical significance.

A method to determine the binding of epidermal growth factor (EGF) to the particulate fraction of the cell has been established and evaluated using rat liver, human placenta, and tumours of human breast and brain. Little EGF receptor (EGFR) activity was detected in normal or benign tumour tissues except for meningioma (positive in 95% samples), but EGFR were present in 43% of 131 breast tumours and 75% of 55 primary cerebral tumours. Despite the strong inverse correlation between EGFR activity and oestrogen receptors in breast tumours and a tendency for high levels of EGFR activity to be associated with glioblastoma multiforme, analysis showed that EGFR was of little prognostic significance in patients with tumours of either breast or brain.

Adolescent