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Biomedical subjects

U Chetty

Publications and source records attributed to U Chetty.

At least 37 records · Page 2Linked to original sources

Noninvasive ductal carcinoma of the breast: the relevance of histologic categorization.

A consecutive series of 130 review-confirmed cases of noninvasive ductal carcinoma of breast (DCIS) in women without previous breast carcinoma was analyzed. Histologic variables assessed included histologic pattern, nuclear grade, necrosis, and involved duct counts. These were correlated with presentation, extent of DCIS in the breast, completeness of excision, and outcome. Comedo DCIS had an occult presentation significantly more often than noncomedo DCIS. Micropapillary DCIS was significantly more likely than other patterns to involve multiple quadrants of breast, irrespective of nuclear grade or necrosis. Solid DCIS was significantly more often completely excised when compared with all other patterns, while high-grade DCIS was significantly more often incompletely excised compared with low-grade DCIS. Follow-up showed invasive recurrence in 16% of cases treated by primary local excision only and 3% cases treated by mastectomy or with re-excision. Of local excision cases with follow-up longer than 3 years, 22% had invasive recurrence. Invasive recurrence only followed high-grade DCIS and most often followed comedo DCIS. The need for strict definition of categories of DCIS is stressed.

Adult

The importance of interpectoral nodes in breast cancer.

In a consecutive series of 73 patients undergoing a level III axillary clearance, interpectoral nodes were sought and, if palpable, excised. 18 interpectoral nodes were identified in 15 patients, 10 (14%) of whom had involved and 5 of whom had uninvolved interpectoral nodes. 7 of the 10 patients with involved interpectoral nodes also had axillary node involvement, but 3 patients had positive interpectoral nodes in the absence of involved axillary nodes. A comparison of patient and tumour characteristics in the groups of patients with and without interpectoral node involvement showed that patients who had involved interpectoral nodes were significantly younger and had significantly larger tumours. Interpectoral node involvement by breast cancer is not uncommon and these nodes can be involved in the absence of axillary nodal involvement. They should be looked for, and if identified, excised during axillary clearance.

Adult

Cervical intraepithelial neoplasia in patients with breast cancer: a cytological and colposcopic study.

Twenty-six patients with treated breast cancer who had been randomised previously to receive combination chemotherapy including alkylating agents (n = 14) or to undergo oophorectomy (n = 12) following surgery underwent cytological and colposcopic screening of the uterine cervix. Colposcopically directed cervical punch biopsies were taken from all patients in whom a colposcopic abnormality was detected. Breast cancer patients were compared with 79 controls with normal cervical cytology and no known breast malignancy. Colposcopically directed punch biopsies were taken from the cervical transformation zone of all controls. Significantly more breast cancer patients who had received chemotherapy (43%) than controls (10%) had CIN (P < 0.01) and significantly more patients who had received chemotherapy (14%) than controls (3%) had CIN 2 or 3 (P < 0.05). The proportion of breast cancer patients in the oophorectomy group with CIN (17%) did not differ significantly from the control group. No case of CIN was detected by cervical cytology. This study suggests that breast cancer patients receiving combination chemotherapy including alkylating agents are at increased risk of CIN, and that cervical cytology alone may be an inadequate form of screening for these patients.

Adult

pS2 is an independent factor of good prognosis in primary breast cancer.

In breast cancer, oestrogen regulated genes, such as pS2, may be expressed in well differentiated tumours with a good prognosis. We have examined pS2 mRNA expression in 78 primary, untreated breast cancers and related pS2 expression to disease behaviour and known prognostic factors. pS2 mRNA expression was detected in 25/78 (32%) of cancers and was significantly associated with a moderate/high oestrogen receptor content (P = 0.045, Chi Square test). pS2 mRNA expression was associated with freedom from disease at median 31 months clinical and radiological follow-up (P = 0.015, Fisher's exact test, odds ratio 8.6). Using multiple logistic regression analysis of six potential prognostic factors only pathological axillary node status (P < 0.01) and pS2 mRNA expression (P < 0.05) provided independent prognostic information. Furthermore, pS2 was associated with a good prognosis in the axillary node positive patients where only 1/13 (8%) with pS2 mRNA expression compared with 13/29 (45%) without detectable expression had recurrence of their disease. These data provides strong support for pS2 as a useful independent prognostic factor in primary breast cancer.

Adult

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