Side effects expected and experienced by women receiving chemotherapy for breast cancer.
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Adult↗
Biomedical subjects
U Chetty
Publications and source records attributed to U Chetty.
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↗
Primary systemic therapy for operable breast cancer.
Eighty-eight patients presenting with operable breast cancer of 4 cm or greater in diameter (T2, T3, N0, N1, M0) have received primary systemic therapy. Response was assessed following 12 weeks of systemic therapy by linear regression analysis of changes in tumour volume. Definitive locoregional surgery (mastectomy n = 82, wide local excision n = 6) was performed on completion of systemic therapy (3-6 months). Response was observed in 24 (39%) of the 61 patients who received endocrine therapy; all 24 had tumours with an oestrogen receptor (ER) concentration of greater than or equal to 20 fmol mb-1 cytosol protein. Cytotoxic therapy was reserved for patients with tumours of ER concentration less than 20 fmol mg-1 cytosol protein (n = 27) or when endocrine therapy had failed (n = 20). Response was observed in 34 patients (72%). The overall survival rate at 3 years was 86%, with 81% remaining free from local relapse. We propose that the treatment policy outlined in this paper should now be tested against orthodox management by controlled randomised trial.
Adult↗
Comparative pathology of breast cancer in a randomised trial of screening.
In the Edinburgh Randomised Breast Screening Project (EBSP) to December 1988 there were 500 cancers in the study population invited to screening and 340 cancers identified in the control population. The size and negative lymph node status characteristics of invasive cancers from the two populations were significantly different (P less than 0.05). The cancers detected by screening were predominantly 'early stage', with 16% noninvasive (PTIS) and 42% invasive stage I (pT1 node negative), whereas cancers were frequently 'late stage' (more than pT2) and inoperable in nonattenders (44%) and controls (36%). Grouped according to customary size ranges of invasive cancers, the proportion of cases lymph node positive differed in those screen detected compared with controls, but the benefit in favour of screen detection was not constant. In comparisons of cancers detected at prevalence and incidence screens, as a test of conformity with screening theory, no significant differences were apparent according to size and lymph node status, yet the characteristics of histological type of cancer discriminated significantly (P less than 0.05). When these same histological characteristics were used to compare survival, the capacity to separate invasive cancers into two groups having good and poor survival probabilities was evident, with a significant improvement for the screen detected poor survival group compared with controls (P less than 0.05).
Breast Neoplasms↗
Diagnosis of the impalpable lesion.
The use of mammography, to aid the diagnosis of patients with symptoms or as a screening test, presents the problem of diagnosing mammographic abnormalities not associated with a palpable lesion. To deal adequately with this, close co-operation is required amongst the radiologist, clinician/surgeon and pathologist/cytologist. A significant number of unnecessary biopsies have been carried out when each of the opinions or procedures are performed in isolation and when communication between the different specialties involved is via formal reports as compared to assessment carried out jointly.
Adult↗
The activity of locally applied cytotoxics to breast cancer cells in vitro.
The ability of commonly used operative lavage solutions to destroy breast cancer cells was investigated. The cytotoxicity of solutions of Savlon, noxythiolin, povidone iodine, hydrogen peroxide, bleomycin and water on two human breast cancer cell lines was measured in vitro. Viable cells were determined by ability to exclude trypan blue. Results have been analysed with standard non-parametric tests and demonstrate that all solutions tested significantly (P less than 0.01) reduced the number of viable cells recovered when compared with a control solution of phosphate buffered saline. Solutions of Savlon, 2.5% noxythiolin and povidone iodine were more effective than the other agents in reducing the number of recovered viable cells.
Anti-Infective Agents, Local↗
Non-palpable mammographic abnormalities.
The radiological characteristics of non-palpable mammographic abnormalities are reviewed and their diagnostic limitations discussed. Alternative methods of detection and diagnosis are reviewed. The development of needle localization for non-palpable mammographic abnormalities is traced from the initial crude excisions through to stereotactic needle localization. Non-palpable carcinomas have a greater proportion of favourable histopathologies. However, the preferred management of these early lesions has yet to be determined.
Biopsy, Needle↗
Reasons for non-entry of patients with DCIS of the breast into a randomised trial (EORTC 10853).
In EORTC trial 10853, patients with histologically confirmed surgical clearance of ductal carcinoma in situ (DCIS) are being randomised to observation alone or to receive external radiation to the breast (50 Gy). So far, 190 patients have been entered from 27 centres. An analysis has been conducted of patients with DCIS presenting to 6 of the participating hospitals. Within these centres there was a total of 216 patients with biopsy confirmed DCIS, without invasion, between 1985 and 1989. However only 77 (36%) were entered into the trial. The major reason for non-entry was that DCIS was too extensive (76/139, 55%), so that in situ disease extended to the margins of excision. Other reasons for exclusion included prior breast cancer (18%), delay in histological diagnosis (6%) and a lump measuring more than 3 cm in diameter (4%). Only 6 patients (4%) refused to take part in the trial. Thus the eventual results of the trial may be applicable only to a minority of patients with DCIS.
Adult↗
Evidence implicating at least two genes on chromosome 17p in breast carcinogenesis.
The DNA of paired tumour and blood leucocyte samples from a large series of breast cancer patients was analysed to map regions of loss of heterozygosity on chromosome 17. The high frequency of loss of heterozygosity on 17p was confirmed, and a third of informative tumours had also lost an allele at the long arm locus THH59. On the short arm two distinct regions of loss of heterozygosity were identified, in bands p13-3 and p13-1. The latter probably involves the structural gene p53, which has been implicated as an oncogene or as a tumour suppressor in various human cancers. 17p 13-3, however, showed a significantly higher frequency of loss of heterozygosity, and there was no correlation between allele losses at the two sites. Nevertheless, loss of heterozygosity at 17p 13-3 is associated with overexpression of p53 mRNA, suggesting the existence of a gene some 20 megabases telomeric of p53 that regulates its expression. Lesions of this regulatory gene seem to be involved in the majority of breast cancers.
Alleles↗
Recruitment to a prospective breast conservation trial: why are so few patients randomised?
OBJECTIVE: To investigate the rate of recruitment to early breast cancer trials and elucidate the reasons for ineligibility and refusal to participate among patients otherwise suitable for these trials. DESIGN: Prospective study of one year's cohort of patients referred to a breast unit with special reference to the subgroup suitable for conservation management and to the proportion eligible for and (after informed consent) ultimately randomised within the Scottish early breast cancer trials. SETTING: The breast unit, Longmore Hospital, Edinburgh, during 1988. PATIENTS: All 3054 patients referred to the breast unit during the year. 324 Found to have invasive breast cancer and 147 initially thought suitable for conservation management. RESULTS: 63 Patients were treated by mastectomy, 19 of whom requested mastectomy rather than conservation management. 84 Patients were excluded from trials, and of the 63 eligible patients, 40 gave informed consent. Most of the 23 patients who refused the trials requested a specific adjuvant treatment after discussion of their management and the trials. CONCLUSIONS: Recruitment to prospective trials in which informed consent is required before randomisation may be slower than predicted because of a high proportion of exclusions and also refusal by patients. Trials may therefore take longer to complete and give distorted results by virtue of the unpredictable nature of the selection of patients.
Axilla↗
Edinburgh trial of screening for breast cancer: mortality at seven years.
Between 1979 and 1981, 45,130 women in Edinburgh aged 45-64 were entered into a randomised trial of breast cancer screening by mammography and clinical examination. The initial attendance rate was 61% but this varied according to age and socioeconomic status and decreased over succeeding years. The cancer detection rate was 6.2 per 1000 women attending at the first visit; the rate fell to around 3 per 1000 in the years when mammography was routinely repeated and to around 1 per 1000 at the intervening visits with clinical examination alone as the screening method. After 7 years of follow-up the mortality reduction achieved was 17% (relative risk = 0.83, 95% CI 0.58-1.18), which was not statistically significant, even when corrected for socioeconomic status. In women aged 50 years and over a mortality reduction of 20% was achieved.
Age Factors↗
Assessment of surgical excision during breast conservation surgery by intraoperative two-dimensional specimen radiology.
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Breast Neoplasms↗
Outcome of surgery for non-palpable mammographic abnormalities.
Four hundred and ninety-three women underwent 515 localization biopsies for non-palpable mammographic abnormalities. The mammographic abnormality was located with a hooked wire in 509 cases. Specimen radiology was performed on all excised tissue. The mammographic abnormality was visualized in the first piece of tissue excised in 402 (78.1 per cent) cases and complete excision was achieved in 476 (92.4 per cent). A palpable nodule was removed in 38 (7.4 per cent) cases and in 17 (44.7 per cent) was shown to contain a carcinoma. The mammographic abnormality was missed in 14 (2.7 per cent) cases or only partly excised in 13 (2.5 per cent). Overall 144 (28.0 per cent) localization biopsies were malignant. The mammographic abnormality was not visualized on the specimen radiograph more frequently in women aged under 55 years, in women with dense breast (Wolfe grade DM or DY) or in those whose mammographic abnormality contained only microcalcification. The 27 women in whom the mammographic abnormality was not visible on the specimen radiograph underwent repeat mammography 2 months later. Only two women required a further localization biopsy and the mammographic abnormality was recovered in the first piece of tissue excised. Women with a carcinoma underwent mastectomy or wide local excision, and residual carcinoma at the localization biopsy site was found in 64 (44.4 per cent) cases. Oestrogen receptor analysis by ligand binding assay was possible in only 71 (49.3 per cent) carcinomas. If the specimen radiograph does not show the mammographic abnormality within pieces of tissue excised and there is no palpable nodule it may be best to conclude the biopsy. In this series these missed lesions were usually benign. Only rarely is a second localization biopsy required and this is performed without difficulty.
Adult↗
p53 gene mRNA expression and chromosome 17p allele loss in breast cancer.
p53 messenger RNA expression was examined using a cDNA probe in 76 fresh primary breast tumour specimens, 15 of which came from patients treated with toxoxifen prior to surgery. A 2.8 kb mRNA for p53 was expressed in 43 of the 76 specimens. In 19 tumours the levels were similar to those seen in non-malignant (reduction mammoplasty) breast tissue, but in 24 tumours over-expression of mRNA for p53, approaching that seen in three breast cancer cell lines, was found. The cell lines MCF-7, T-47D and MDA-MB-231 expressed three p53 mRNA species of about 2.8 kb and a forth of 1.6 kb. Increased mRNA expression for p53 correlated (P less than 0.05) with loss of genetic material from the short arm of chromosome 17 as demonstrated by allele loss with the VNTR probe YNZ 22.1. There was also statistically significant correlation between increased p53 mRNA expression and low oestrogen receptor protein content in the tumours (P less than 0.05), but not with other clinical parameters. The findings support the view that p53 is involved in breast tumour biology, and suggest that its role may be complex.
Alleles↗
Does the oestrogen receptor concentration of a breast cancer change during systemic therapy?
The effect of systemic therapy on tumour oestrogen receptor (ER) concentration has been studied in 88 patients with large, operable, primary tumours (total 89) of the breast. In 26 patients, tumour was not available for study on one occasion (usually post-treatment). Forty-five patients were treated initially by endocrine therapy but, of these, 13 who had failed to respond went on to receive chemotherapy also. Seventeen patients with low concentrations of ER (less than 20 fmol mg-1 protein) were treated directly by chemotherapy. Patients underwent an incisional biopsy for confirmation of diagnosis and determination of pre-treatment ER by radioligand binding assay, followed by systemic therapy for 3 months (or 6 months for both endocrine and cytotoxic therapies). Response was assessed clinically and mammographically before mastectomy. ER concentration was then determined in the post-treatment tumour specimen. No significant change in ER concentration was seen in any treatment group except when the patients had received tamoxifen; there, receptor concentration fell to very low levels, presumably due to interference with the assay. There was no relationship between tumour response to systemic treatment and change in ER concentration. It is concluded that changes in ER concentration are unlikely to play a major role in the early response of breast tumours to systemic therapy.
Adult↗
Cyclic AMP binding proteins and prognosis in breast cancer.
Cyclic AMP binding proteins were measured in the primary tumour from 100 patients with non-disseminated breast cancer selected on the basis that sufficient tumour material was available for analysis. These measurements have been related to factors of established prognostic value and to the patients' disease-free interval and survival. There was a wide variation in amounts of binding proteins in different tumours. Values were significantly higher (P less than 0.05) in oestrogen receptor-negative tumours but no statistically significant correlations were apparent between levels and tumour grade or whether the patients had lymph node metastasis or adjuvant treatment. However, levels were significantly higher in patients whose disease recurred within 3 years of primary treatment as compared with those who remained disease-free. Using a retrospectively determined cut off point of 8 pmol mg-1 cytosol protein, it was shown that patients with tumour cyclic AMP binding in excess of this value had a significantly greater chance of developing recurrent disease and poorer survival rates (P less than 0.001 by Cox analysis) than those with lower levels. This remained true when other prognostic factors were taken into account in a multivariate analysis. It is suggested that the level of tumour cyclic AMP binding may be an independent prognostic factor for patients with early breast cancer.
Breast Neoplasms↗