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Biomedical subjects

Stephen W Duffy

Publications and source records attributed to Stephen W Duffy.

14 recordsLinked to original sources

Misclassification in a matched case-control study with variable matching ratio: application to a study of c-erbB-2 overexpression and breast cancer.

We provide a simple analytic correction for risk factor misclassification in a matched case-control study with variable numbers of controls per case. The method is an extension of existing methodology, and involves estimating the corrected proportions of controls and cases in risk factor categories within each matched set. These estimates are then used to calculate the Mantel-Haenszel odds ratio estimate corrected for misclassification. A simulation-based interval estimate is developed. An example is given from a study of risk factors for progression of benign breast disease to breast cancer, in which the risk factor is a biological marker measured with poor sensitivity.

Breast Neoplasms↗

Bayesian evaluation of breast cancer screening using data from two studies.

The mean sojourn time (the duration of the period during which a cancer is symptom free but potentially detectable by screening) and the screening sensitivity (the probability that a screen applied to a cancer in the preclinical screen detectable period will result in a positive diagnosis) are two important features of a cancer screening programme. Little data from any single study are available on the potential effectiveness of mammographic screening for breast cancer in women with a family history of the disease, despite this being an important public health issue. We develop a method of estimation, from two separate studies, of the two parameters, assuming that transition from no disease to preclinical screen detectable disease, and from preclinical disease to clinical disease, are Poisson processes. Estimation is performed by a Markov chain Monte Carlo algorithm. The method is applied to the synthesis of two studies of mammographic screening in women with a family history of breast cancer, one in Manchester and one in Kopparberg, Sweden.

Adult↗

The Gothenburg Breast Screening Trial.

BACKGROUND: Although there is evidence for a reduction in breast carcinoma mortality with mammographic screening, some doubts have been expressed, and there is still uncertainty regarding the age specific effects. METHODS: The authors report on a randomized, controlled trial of mammographic screening for breast carcinoma that was conducted among 51,611 women (21,650 women who were invited to a screening [the study group] and 29,961 women in a control group) ages 39-59 years in Gothenburg, Sweden. Among women in the study group, the screening interval was 18 months. The screening phase of the trial took place in 1982-1991, and follow-up for breast carcinoma mortality continued until December 31, 1996. Mortality from breast carcinoma was analyzed using a Poisson regression model. Overall and age specific effects of invitation to mammography screening on breast carcinoma mortality were calculated. Three mortality effects were estimated: the effect on deaths from breast tumors diagnosed during the screening phase of the trial, as assessed by an independent Endpoint Committee (the EPC evaluation model); the effect on deaths from breast carcinoma diagnosed during the screening phase of the trial, as determined by data from the National Cancer Registry and the National Cause of Death Register (the SCB evaluation model); and the effect on deaths from all breast carcinomas diagnosed up to December 31, 1996, as determined by the National Cancer Registry and the National Cause of Death Register (the SCB follow-up model). RESULTS: A nonsignificant, 21% reduction in the rate of mortality from breast carcinoma with invitation to screening was observed using the EPC evaluation model (relative risk [RR], 0.79; 95% confidence interval [95% CI], 0.58-1.08; P = 0.14); and a borderline significant, 23% rate reduction was observed using the SCB follow-up model (RR, 0.77; 95% CI, 0.60-1.00; P = 0.05). Age specific analyses yielded greater mortality rate reductions for the groups of women ages 39-44 years, 45-49 years, and 55-59 years, but there was no mortality rate reduction in the group of women ages 50-54 years. The effects of invitation to mammographic screening on the incidence of lymph node-positive disease closely paralleled the effects of invitation on breast carcinoma mortality. The effect on breast carcinoma mortality was consistent with the effect on all-cause mortality, suggesting no bias in classification of cause of death. Breast carcinoma incidence in the study group was almost identical to the incidence in the control group after trial by screening had ended in the control group (RR, 0.98; 95% CI, 0.88-1.09; P = 0.7). CONCLUSIONS: The current results support the commonly observed 20-30% reduction in breast carcinoma mortality with invitation to screening. The impression that screening is less effective in women younger than 50 years may be an oversimplification. Age specific effects should be a target for further research.

Adult↗

Mammography service screening and mortality in breast cancer patients: 20-year follow-up before and after introduction of screening.

BACKGROUND: The long term effect of mammographic service screening is not well established. We aimed to assess the long-term effect of mammographic screening on death from breast cancer, taking into account potential biases from self-selection, changes in breast cancer incidence, and classification of cause of death. METHODS: We compared deaths from breast cancer diagnosed in the 20 years before screening was introduced (1958-77) with those from breast cancer diagnosed in the 20 years after the introduction of screening (1978-97) in two Swedish counties, in 210000 women aged 20-69 years. We also compared deaths from all cancers and from all causes in patients diagnosed with breast cancer in the 20 years before and after screening was introduced. In the analysis, data were stratified into age-groups invited for screening (40-69 years) and not invited (20-39 years), and by whether or not the women had actually received screening. We also analysed mortality for the 40-49-year age-group separately. FINDINGS: The unadjusted risk of death from breast cancer dropped significantly in the second screening period compared with the first in women aged 40-69 years (relative risk [RR] 0.77 [95% CI 0.7-0.85]; p<0.0001). No such decline was seen in 20-39 year olds. After adjustment for age, self-selection bias, and changes in breast-cancer incidence in the 40-69 years age-group, breast-cancer mortality was reduced in women who were screened (0.56; 0.49-0.64 p<0.0001), in those who were not screened (0.84 [0.71-0.99]; p=0.03), and in screened and unscreened women combined (0.59 [0.53-0.66]; p<0.0001). After adjustment for age, self-selection bias, and changes in incidence in the 40-49-year age-group, deaths from breast cancer fell significantly in those who were screened (0.52 [0.4-0.67]; p<0.0001); and in all women, screened and unscreened combined (0.55 [0.44-0.7] p<0.0001) but not in unscreened women (p=0.2). In both 40-69-year and 40-49-year age-groups, reductions in deaths from all cancers and from all-causes in women with breast cancer were consistent with these results. INTERPRETATION: Taking account of potential biases, changes in clinical practice and changes in the incidence of breast cancer, mammography screening is contributing to substantial reductions in breast cancer mortality in these two Swedish counties.

Adult↗

The impact of organized mammography service screening on breast carcinoma mortality in seven Swedish counties.

BACKGROUND: The evaluation of organized mammographic service screening programs is a major challenge in public health. In particular, there is a need to evaluate the effect of the screening program on the mortality of breast carcinoma, uncontaminated in the screening epoch by mortality from 1) cases diagnosed in the prescreening period and 2) cases diagnosed among unscreened women (i.e., nonattenders) after the initiation of organized screening. METHODS: In the current study, the authors ascertained breast carcinoma deaths in the prescreening and screening epochs in 7 Swedish counties from tumors diagnosed in these epochs and in the age group 40-69 years in 6 counties and 50-69 years in 1 county. Data regarding deaths were obtained from the Uppsala Regional Oncologic Center in conjunction with the National Cause of Death Register. The total number of women in the eligible age range living in each county was obtained from the annual population data of Statistics Sweden. Detailed screening data were provided by the screening centers in the seven counties, including the number of invited, the number attended, and whether each individual breast carcinoma case was exposed (screen-detected and interval cases combined) or unexposed (not-invited or nonattenders) to mammographic screening. There were 2044 breast carcinoma deaths from 14,092 incident tumors diagnosed in the prescreening and screening epochs, and the total number of person-years was 7.5 million. Data were analyzed using Poisson regression with corrections for self-selection bias and lead-time bias when appropriate. RESULTS: The mortality reduction for breast carcinoma in all 7 counties combined for women actually exposed to screening compared with the prescreening period was 44% (relative risk [RR] = 0.56; 95% confidence interval [95% CI], 0.50-0.62). When all incident tumors were considered, both those exposed and those unexposed to screening combined, counties with > 10 years of screening were found to demonstrate a significant 32% mortality reduction (RR = 0.68; 95% CI, 0.60-0.77) and counties with < or = 10 years of screening showed a significant 18% reduction in breast carcinoma mortality (RR = 0.82; 95% CI, 0.72-0.94) for the screening epoch compared with the prescreening epoch. Within the screening epoch, after adjustment for self-selection bias, a 39% mortality reduction (RR = 0.61; 95%CI, 0.55-0.68) was observed in association with invitation to screening. CONCLUSIONS: Organized service screening in 7 Swedish counties, covering approximately 33% of the population of Sweden, resulted in a 40-45% reduction in breast carcinoma mortality among women actually screened. The policy of offering screening is associated with a mortality reduction in breast carcinoma of 30% in the invited population, exposed and unexposed combined. The results of the current study indicate that the majority of the breast carcinoma mortality reduction is indeed due to the screening.

Adult↗

Ultrasound screening and risk factors for death from hepatocellular carcinoma in a high risk group in Taiwan.

Although previous studies have demonstrated the ability of ultrasonography (US) screening to detect small asymptomatic hepatocellular carcinoma (HCC), the efficacy of US screening in reducing deaths from HCC still remained unresolved. A 2-stage screening program was designed to identify a high risk group in 7 townships in Taiwan by 6 markers (of risk for HCC) and repeated US screening was further applied to those with at least 1 positive result for the 6 markers, with a range of 3- to 6-month inter-screening intervals to those with liver cirrhosis or other chronic liver diseases and an annual screening regime for the remaining subjects with normal findings according to US. The 4,843 subjects in this cohort were followed up for an average of 7 years. We compared 4,385 attenders with 458 non-attenders, in conjunction with baseline assessment for self-selection bias. In addition, we assessed baseline variables with respect to their effects on risk of incidence of and mortality from HCC and on risk of incidence of liver cirrhosis. The difference in mortality between attenders and non-attenders was then re-estimated adjusting for significant predictors of cirrhosis, HCC incidence and HCC death as a further guard against baseline differences between attenders and non-attenders in risk profiles. Results of US screening for this high risk group found the mortality was lower by 24% (95% CI: -52 to 62%) in the attenders compared to the non-attenders. After adjustment for sensitivity, the mean sojourn time (MST) were 1.57 (95% CI: 0.94-4.68) for subjects with liver cirrhosis and 2.66 (95% CI: 1.68-6.37) years for non-cirrhotic patient. Significant increases in risk of HCC incidence were associated with increasing age, male gender, hepatitis B surface antigen positive (HbsAg), hepatitis C antibody positive (Anti-HCV), high levels of alanine transaminase (ALT) and alpha-fetoprotein (AFP) and a family history of HCC. Significantly increased risks of liver cirrhosis were associated with predictors of cirrhosis were increasing age, HbsAg, high levels of ALT and of AFP. Significant or borderline significant increases in risk of HCC death were associated with increasing age, male gender, HbsAg, high levels of AST and AFP. Adjusted for the significant variables, the mortality was lower by 41% (95% CI: -20 to 71%, p = 0.1446) in the attenders compared to the non-attenders. The present study provides suggestive evidence on the efficacy of US screening in a selective high risk group in an endemic area of hepatitis B. A randomized controlled trial would yield definitive evidence. Within the protocol of such a trial, a shorter interscreening interval for patients with liver cirrhosis is suggested.

Carcinoma, Hepatocellular↗

Prognosis of small hepatocellular carcinoma treated by percutaneous ethanol injection and transcatheter arterial chemoembolization.

This study was conducted to assess the progression and prognosis of a total of 108 patients with hepatocellular carcinoma (HCCs) smaller than 5 cm in diameter treated by percutaneous ethanol injection (PEI) with or without transcatheter arterial chemoembolization. All patients were classified as Child-Pugh A (n = 84) or B (n = 24). Logarithm of hazard rate (per month) with time since therapy was assessed. The Weibull model was used to elucidate the effect of pretreatment clinico-pathologic variables on prognosis. The rate of death increased by 4.7% (95% CI: 3.7-5.7%) per month since treatment. Child-Pugh B status was associated with a 2.8-fold risk (95% CI: 1.52-5.16) of death. Those with a high level of AST or alcoholic cirrhotics had a two-fold risk (95% CI:1.14-3.42) for death from HCC. Our results suggest the optimal frequency of clinical surveillance of small HCC cases after treatment should take account of increased hazard rate with time and the roles of pretreatment clinico-pathologic variables.

Aged↗

Mammographic parenchymal patterns and self-reported soy intake in Singapore Chinese women.

The study aimed to investigate whether self-reported dietary variables were associated with mammographic parenchymal patterns, which have been shown to predict risk of breast cancer. Among the 3,421 women, ages 45-74 years, common to two independent population-based cohorts, mammographic parenchymal patterns and current dietary habits were assessed for 406 randomly chosen participants. Logistic regression methods were used to compare dietary and other lifestyle profiles between subjects classified as displaying high (cases) and low risk (controls) parenchymal patterns. After adjustment for energy intake and other potential confounders, dietary soy protein intake was inversely related to risk of high-risk parenchymal pattern (odds ratio, 0.41; 95% confidence interval, 0.18-0.94, highest versus lowest quartile of intake). Similarly, the highest versus lowest quartile of dietary soy isoflavone intake was significantly related to low-risk parenchymal patterns (odds ratio, 0.44; 95% confidence interval, 0.20-0.98). The association between high soy intake and a reduced risk of mammographic parenchymal patterns that are associated with high breast cancer risk may have important implications in breast cancer prevention.

Age Distribution↗

Role of Dietary Intake and Biomarkers in Risk of Breast Cancer: A Case Control Study.

Reproductive factors are not considered to play a significant role in the aetiology of breast cancer in low incidence regions like Gujarat, although it is well established that they exert a major influence on such tumours in the western developed world. Women in the western Indian region have a very low prevalence of smoking, alcohol consumption but a high prevalence of vegetarianism. Noting the changes in the life style practices with increasing affluence is likely to yield several interesting findings in such a population. Physical activity and dietary factors have emerged as important parameters and their lack may contribute significantly to the risk of breast cancers. The breast cancer risk significantly increased with higher consumption of total fat (>25% of total calories), frequent intake of fried foods and sweets. A significant protection was offered by frequent consumption of green yellow leafy vegetables, foods rich in b-carotene and isoflavonoids. The present study demonstrated a good protective effect of dietary intake of antioxidant vitamins. The breast cancer risk increases with elevation of circulating lipid components except HDL-cholesterol.

Journal Article↗