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Biomedical subjects

J Cuzick

Publications and source records attributed to J Cuzick.

At least 37 records · Page 2Linked to original sources
PubMed2002

Abnormal FHIT expression profiles in cervical intraepithelial neoplastic (CIN) lesions.

Abnormal fragile histidine triad transcripts were found in 20-30% of CIN2/3 lesions and 11% of normal cervical biopsies by RT-PCR. Bi-allelic loss of the fragile histidine triad gene and the loss of fragile histidine triad protein expression detectable by immunochemical staining with a polyclonal fragile histidine triad specific antibody was rare. The genomic changes showed no association with the presence of human papillomavirus types which carry high risk for cervical cancer (high risk human papillomavirus) as assessed by a type-specific multiplex PCR. The presence of abnormal fragile histidine triad transcripts in a subset of CIN2/3 lesions with no high risk human papillomavirus suggests that this could be an independent risk factor associated with an alternative carcinogenic pathway.

Acid Anhydride Hydrolases↗
PubMed2002

Avoidance of premature death: a new definition for the proportion cured.

For many cancers, five-year survival is used as a synonym for cure. For some sites, such as breast, this is inappropriate since there is still considerable excess mortality 5-15 years following diagnosis. We propose using the probability of not dying prematurely as a surrogate for the probability of being cured. This is estimated without the need for information on the cause of death by comparing all-cause-mortality rates in patients with cancer to those in the general population. We also consider the probability of 'cure' in those who have survived a certain number of years since diagnosis. These quantities are estimated for various cancer sites using SEER data. The proportion not dying prematurely varies considerably for common cancers from 12% for lung cancer to 84% for prostate cancer. In women, the percentage 'cured' for colon and breast cancer are very similar at 56% and 58% respectively, but in those who survive 5 years, they are quite different--91% and 78% respectively. The proposed statistic is useful. For diseases in which excess mortality is primarily within five years of diagnosis, it agrees well with 5-year relative survival. Interpretation of differences between countries or over time is complicated and requires consideration of incidence and mortality data.

Adult↗
PubMed2001

Pharmacokinetics of anastrozole and tamoxifen alone, and in combination, during adjuvant endocrine therapy for early breast cancer in postmenopausal women: a sub-protocol of the 'Arimidex and tamoxifen alone or in combination' (ATAC) trial.

The ATAC trial evaluates in a randomized, double-blind design, Arimidextrade mark (anastrozole) alone or in combination with tamoxifen, relative to tamoxifen alone as 5-year adjuvant treatment in postmenopausal women with early breast cancer. Patients included in the pharmacokinetic (PK) sub-protocol had been in ATAC for > or =3 months, taking their medication in the morning and were 100% compliant for the preceding 14 days. Blood samples were collected 24 +/- 4 h after last dose. Trough (C(min)) plasma concentrations of anastrozole, tamoxifen and desmethyltamoxifen (DMT) were measured by validated methods. The PK results were based on a total of 347 patients (131 anastrozole (1 mg o.d.), 111 tamoxifen (20 mg o.d.), 105 anastrozole and tamoxifen (1 and 20 mg o.d. respectively)). The geometric mean steady-state trough plasma concentrations of tamoxifen and DMT were statistically equivalent in patients receiving tamoxifen alone or in combination with anastrozole: geometric mean tamoxifen = 94.8 ng ml(-1)and 95.3 ng ml(-1)in tamoxifen alone and combination groups, respectively; geometric mean DMT = 265.1 and 277.6 ng ml(-1)in the tamoxifen and anastrozole and tamoxifen groups, respectively. The geometric mean anastrozole levels were 27% lower (90% Cl 20-33%;P< 0.001) in the presence of tamoxifen than with anastrozole alone. Baseline plasma oestradiol levels were not obtained in the PK sub-protocol, however, such information was available from a similar ATAC sub-protocol, which evaluated bone mineral density. Mean oestradiol levels were 21.3, 19.3, and 21.6 pmol l(-1)prior to treatment and 3.7, 20.9 and 3.6 pmol l(-1)after 3 months in the anastrozole, tamoxifen, and combination groups, respectively (n = 167). On-treatment values were below the detection limit (3 pmol l(-1)) in 43.6 and 38.5% of the anastrozole alone and anastrozole in combination with tamoxifen groups, respectively. As a result of (a) the lack of effect of anastrozole on tamoxifen and DMT levels and (b) the observed fall in blood anastrozole levels having no significant effect on oestradiol suppression by anastrozole, we conclude that the observed reduction in anastrozole levels by tamoxifen is unlikely to be of clinical significance when anastrozole and tamoxifen are administered together.

Adult↗
PubMed2001

Tamoxifen for the prevention of breast cancer: psychosocial impact on women participating in two randomized controlled trials.

PURPOSE: The purpose of this study was to evaluate the psychosocial implications of tamoxifen versus placebo in women who are at increased risk of breast cancer. PATIENTS AND METHODS: The 488 women in the psychosocial study were recruited from participants in two placebo-controlled, double-blind, randomized, controlled trials that investigated the efficacy of tamoxifen in the prevention of breast cancer in women who are at high familial risk. During a 5-year period, repeated assessments were made of anxiety, psychological distress, and sexual functioning using standardized questionnaires before treatment at baseline and at 6-month intervals during the trial. RESULTS: Questionnaire completion over 5 years was good, with 71.1% of women returning at least 8 of 10 follow-up assessments. Although scores from individuals showed considerable fluctuation and variation over time, changes in anxiety, mood, and sexual functioning were not associated with treatment group. The number of symptoms reported at 48 months via a self-report checklist were not associated with treatment group, but vasomotor symptoms were more frequent among tamoxifen-treated women. Symptoms of low energy, breast sensitivity, and visual blurring were reported most frequently in the placebo group. CONCLUSION: In general, these results are comparable to those from the National Surgical Adjuvant Breast and Bowel Project psychosocial study despite differences in study populations, methodology, and instruments. The long-term use of tamoxifen and other selective estrogen response modulators as preventive agents in high-risk groups has been questioned, but we found no evidence of treatment-related side effects that affect women's psychosocial and sexual functioning.

Adult↗
PubMed2001

The effect of stopping smoking on cervical Langerhans' cells and lymphocytes.

OBJECTIVE: To investigate the effects of stopping smoking on cervical Langerhans' cells and lymphocytes. DESIGN: Prospective intervention study. SETTING: A large family planning clinic in central London. POPULATION: Women volunteers prepared to attempt to give up smoking for six months. Their most recent cervical smear showed no abnormality greater than mild dyskaryosis. METHODS: The women were seen at three-month intervals for six months. Reduction in smoking was assessed by self-reporting and validated by salivary cotinine concentrations. Colposcopy and a biopsy of a normal area were performed at the first and last visits. Any area of abnormality was also biopsied at the final visit. Langerhans' cells and lymphocytes were counted. MAIN OUTCOME MEASURES: Proportional changes in counts of Langerhans' cells and lymphocytes with reduction in smoking. RESULTS: Reduction in smoking by 20 to 40 cigarettes per day was significantly associated with a reduction of between 6% and 16% in counts of Langerhans cells, CD8 and total lymphocytes. Heavy smoking was significantly associated (P = 0.02) with an increased chance of persistent human papillomavirus infection. The presence of candida was associated with significantly higher counts of between 41% and 47% in total lymphocytes and CD8 lymphocytes. In contrast, the presence of anaerobic vaginosis was associated with significantly lower counts of between 16% and 30% in Langerhans cells, CD4 and CD8 lymphocytes. CONCLUSIONS: This large intervention study has demonstrated a clear relationship between reduction in smoking and changes in cervical immune cell counts. Future studies need to take into account cytokine interactions, which recent studies suggest may be significant in the immune response to both human papillomavirus and cervical intraepithelial neoplasia and the ever-increasing complexity of the cell-mediated immune system of the cervix.

Adult↗
PubMed2001

A brief review of the International Breast Cancer Intervention Study (IBIS), the other current breast cancer prevention trials, and proposals for future trials.

The available results from breast cancer chemoprevention trials are reviewed. Four trials using tamoxifen have been performed, of which three have reported efficacy results. A fifth trial using raloxifene has also been published. The largest tamoxifen trial shows approximately a 50% reduction in breast cancer incidence in the short term, but the two smaller trials have not found any incidence reduction. Greater agreement exists for side effects: thromboembolic disease and endometrial cancers are raised about 2- to 3-fold when tamoxifen is used for 5 years. The possible reasons for the discrepancy in breast cancer reduction are explored. A review of trial parameters does not clearly explain this difference, and a metanalysis indicates that all results are compatible with a 42% reduction in short-term incidence. Several important questions remain about the clinical implication of this result, including the effect on mortality, the appropriate risk groups for chemoprevention, and the long-term effects on incidence. Continued follow-up of these trials is crucial for resolving these issues.

Adult↗
PubMed2001

Design of a multicentre randomised trial to evaluate flexible sigmoidoscopy in colorectal cancer screening.

A randomised, controlled trial in progress in 14 United Kingdom and six Italian centres is evaluating screening for colorectal cancer using a single flexible sigmoidoscopy (FS) at around the age of 60 with removal during FS of all small adenomas, and colonoscopy for "high risk" polyps. The regimen aims to ensure that 95% of people (with either no polyps or only low risk polyps) complete the entire screening process in a single visit. This paper describes the rationale and design of the trial. Participants were patients aged between 55 and 64 on the lists of designated general practitioners (GPs) who were not excluded by their GP. A two stage recruitment procedure was employed to raise compliance rates in the intervention group. Potentially eligible persons were sent an "interest in screening" questionnaire; those who responded positively were randomised to the intervention or control groups. The trial is sufficiently large to estimate within narrow confidence intervals the magnitude of benefit and the duration of effect and optimum age for a single screen. It also examines the feasibility and acceptability of the screening regimen, and will identify training and quality assurance issues. Recruitment and screening are now complete and all baseline data have been collected. The first analysis of the effect on colorectal cancer incidence and mortality rates and suitability for a national screening programme can be expected in 2004.

Age Factors↗
PubMed2001

Detection of high-risk HPV types by the hybrid capture 2 test.

A hybrid capture test that can be used to detect at least 13 high-risk HPV types (referred to collectively as HPV-HR) in cervical scrapes (Hybrid Capture 2 probe set B, HC2-B) was evaluated. The HC2-B test is accurate and highly reproducible and the results obtained show excellent agreement with those obtained by a multiplexed type-specific polymerase chain reaction (mts-PCR). An additional assay to identify a subset of HPV-HR types may improve specificity without compromising sensitivity in HC2-B positive specimens with a test result close to the cut-off value given by 1 pg/ml HPV DNA.

Cervix Uteri↗
PubMed2001

Development of a protocol for evaluation of mammographic surveillance services in women under 50 with a family history of breast cancer.

BACKGROUND: Preliminary retrospective data suggest it is possible to identify impalpable breast cancer in women presenting with a family history of breast cancer under the age of 50, by using regular mammography. In consequence, this service is offered in a number of centres in the UK. The effectiveness of such a service, however, has not been fully evaluated. METHODS: We propose to perform such an evaluation in a cohort of 20000 women under the age of 50 with a significant family history of breast cancer, given regular mammographic surveillance over 5 years. Comparison of surgical and pathological data with completed and ongoing population screening trials using analysis techniques of varying complexity will be performed to obtain an accurate prediction of future breast-cancer mortality reduction. The formal aims are: i) to estimate the difference in breast-cancer mortality in women under the age of 50 with a significant family history of breast cancer having regular mammography, compared with those not being screened; ii) to estimate the cost-effectiveness of regular mammography in this group of women, compared with no screening. The increase in health service resource use attributable to such a policy will be compared with no screening, and costed. Incremental cost-effectiveness ratios of implementing the standardised mammography strategy compared with no screening will be presented in terms of the additional cost per cancer detected, per life saved and per life-year saved.

Adult↗
PubMed2000

Single blind, randomised trial of efficacy and acceptability of oral picolax versus self administered phosphate enema in bowel preparation for flexible sigmoidoscopy screening.

OBJECTIVE: To compare the acceptability and efficacy of two methods of self administered bowel preparation for flexible sigmoidoscopy screening: a single phosphate enema and a single sachet of Picolax. DESIGN: Single blind, randomised trial. SETTING: Endoscopy units of two general hospitals. PARTICIPANTS: 1442 men and women aged 55-64 years who had agreed to be screened by flexible sigmoidoscopy. MAIN OUTCOME MESURESs: Attendance rates, compliance with allocated preparations, adverse effects, quality of bowel preparation, procedure time, and yield of neoplasia. RESULTS: Compliance with the enema was higher than with the Picolax (608 (84%) v 566 (79%); difference 6%, 95% confidence interval 2% to 10%). Almost half of those who refused Picolax used an enema at home. Wind, incontinence, and sleep disturbance were more frequent in the Picolax group than the enema group; bottom soreness was more frequent in the enema group. Around 30% (187) found the diet restriction required by Picolax difficult; 78% (471) found the enema easy to administer. The quality of preparation was better with the enema; the proportion of procedures complete to the descending colon was greater and the mean duration of the procedure was shorter. There was no significant difference in polyp detection rates. CONCLUSION: A single phosphate enema self administered around one hour before leaving home is a more acceptable and effective method of preparing the distal bowel for flexible sigmoidoscopy than Picolax.

Administration, Oral↗