Hsiu Hsi Chen

THE SWEDISH TWO-COUNTY TRIAL TWENTY YEARS LATER: Updated Mortality Results and New Insights from Long-Term Follow-up

The benefit of invitation to mammographic screening observed in this trial is maintained as a highly significant 32% reduction in breast cancer mortality. Mammographic screening for breast cancer continues to save lives after up to 20 years. Screening derives this benefit by improving the distribution of tumors diagnosed with respect to prognostic categories based on node status, size, and histology of tumors. There is potential for modern screening programs with shorter interscreening intervals to achieve even greater improvements in prognostic category and greater reductions in breast cancer mortality. Mammography can discriminate a subpopulation of high-risk cases, those displaying casting-type calcifications on the mammogram, among very small tumors, with fundamental implications for diagnosis and treatment.

The Impact of Organized Mammography Service Screening on Breast Carcinoma Mortality in Seven Swedish Counties A Collaborative Evaluation

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.

A novel method for prediction of long-term outcome of women with T1a, T1b, and 10–14 mm invasive breast cancers: a prospective study

BACKGROUND Women with small mammographically detected breast cancers generally have good long-term outcomes, but a few with T1a (1-5 mm) and T1b (6-10 mm) tumours will eventually die from breast cancer. We investigated whether women at high risk of breast-cancer death could be identified with mammographic criteria and differentiated from women with small cancers of the breast and good outcomes. METHODS We prospectively applied mammographic classifications of tumour type to a consecutive series of 343 mammograms of invasive breast cancers of size 1-14 mm. Classifications were: stellate (spiculated) mass with no calcifications; circular or oval lesions with no calcifications; spiculated or circular lesions with non-casting-type calcifications; and casting-type calcifications. FINDINGS 20-year survival for women with 1-14 mm invasive tumours with casting-type calcifications was 55%. 14% of 138 women with 1-9 mm tumours had casting-type calcifications on mammography, which accounted for 73% of all breast-cancer deaths (p<0.001). T1a, T1b, and 10-14 mm tumours with casting-type calcifications behaved as if they were larger lesions, since the rate of death was similar to that for women with advanced high-grade tumours. Most women who died were node-negative. The long-term survival of women who had tumours of 1-9 mm with no casting-type calcifications was about 95%. INTERPRETATION Mammographic classification seemed to reliably predict good and bad long-term outcomes for survival in tumours of 14 mm or smaller, and especially for those smaller than 10 mm. The implications for therapy are substantial.

Effect of Baseline Breast Density on Breast Cancer Incidence, Stage, Mortality, and Screening Parameters: 25-Year Follow-up of a Swedish Mammographic Screening

Background: We aimed to quantitatively assess the effect of baseline breast density on the incidence, stage, and mortality, and also the natural course of the disease, considering the sensitivity of mammography to clarify its causal or masking effect. Methods: In total, 15,658 women ages 45 to 59 years from the Kopparberg randomized controlled trial in Sweden were prospectively followed from 1977 until 2004 to ascertain breast cancer incidence and death. Dense breast tissue collected at the beginning of the study was defined as pattern IV or V by the Tabár classification. Conventional risk factors were also collected at baseline. The three-state Markov model was used to estimate the preclinical incidence rate and the mean sojourn time given the fixed sensitivity. Results: Dense breast tissue was significantly associated with breast cancer incidence [relative risk (RR) = 1.57 (1.18-1.67)] and with breast cancer mortality [RR = 1.91 (1.26-2.91)] after adjusting for other risk factors. Cumulative incidence rates irrespective of nonadvanced and advanced breast cancer were higher in dense breast tissue compared with nondense tissue but no difference in survival was detected between dense and nondense breast tissue. Dense breast tissue had a higher preclinical incidence rate (causal effect) and shorter mean sojourn time (masking effect) compared with nondense breast tissue by controlling the sensitivity of mammography. Conclusion: We corroborated the effect of baseline breast density with a higher incidence and mortality and also showed its contribution to a masking effect with long-term follow-up data. Impact: Results suggest that the screening policy with a predominantly shorter screening interval and with alternative imaging techniques might be indicated in women with dense breast tissue. Cancer Epidemiol Biomarkers Prev; 19(5); 1219–28. ©2010 AACR.

All-cause mortality among breast cancer patients in a screening trial: support for breast cancer mortality as an end point

BACKGROUND: It has recently been suggested that all-cause mortality is a more appropriate end point than disease specific mortality in cancer screening trials, and that disease specific mortality is biased in favour of screening. This suggestion is based partly on supposed inconsistencies between all-cause mortality results and disease specific results in cancer screening trials, and alleged increases in deaths from causes other than breast cancer among breast cancer cases diagnosed among women invited to screening. METHODS: We used data from the Swedish Two-County Trial of mammographic screening for breast cancer, in which 77 080 women were randomised to an invitation to screening and 55 985 to no invitation. We estimated relative risks (RRs) (invited v control) of death from breast cancer, death from other causes within the breast cancer cases, and death from all causes within the breast cancer cases. RRs were adjusted for age and took account of the longer follow up of breast cancer cases in the invited group due to lead time. RESULTS: There was a significant 31% reduction in breast cancer mortality in the invited group (RR 0.69, 95% confidence interval (CI) 0.58–0.80; p<0.001). There was no significant increase in deaths from other causes among breast cancer cases in the invited group (RR 1.12, 95% CI 0.96–1.31; p=0.14). A significant 19% reduction in deaths from all causes was observed among breast cancer cases in the group invited to screening (RR 0.81, 95% CI 0.72–0.90; p<0.001). A more conservative estimation gave a significant 13% reduction (RR 0.87, 95% CI 0.78–0.97; p=0.01). These findings are consistent with the magnitude of the reduction in breast cancer mortality. CONCLUSIONS: Invitation to screening was associated with a reduction in deaths from all causes among breast cancer cases, consistent with high participation rates in screening. There is no significant evidence of bias in cause of death classification in the Two-County Trial, and as breast cancer mortality is the targeted clinical outcome in breast cancer screening, it is the appropriate end point in a breast cancer screening trial. All-cause mortality is a poor and inefficient surrogate for breast cancer mortality.

Difference in Performance of Fecal Immunochemical Tests With the Same Hemoglobin Cutoff Concentration in a Nationwide Colorectal Cancer Screening Program

BACKGROUND & AIMS We investigated whether 2 quantitative fecal immunochemical tests (FITs) with the same cutoff concentration of fecal hemoglobin perform equivalently in identifying patients with colorectal cancer (CRC). METHODS A total of 956,005 Taiwanese subjects, 50 to 69 years old, participated in a nationwide CRC screening program to compare results from 2 FITs; 78% were tested using the OC-Sensor (n = 747,076; Eiken Chemical Co, Tokyo, Japan) and 22% were tested using the HM-Jack (n = 208,929; Kyowa Medex Co Ltd, Tokyo, Japan), from 2004 through 2009. The cutoff concentration for a positive finding was 20 μg hemoglobin/g feces, based on a standardized reporting unit system. The tests were compared using short-term and long-term indicators of performance. RESULTS The OC-Sensor test detected CRC in 0.21% of patients, with a positive predictive value of 6.8%. The HM-Jack test detected CRC in 0.17% of patients, with a positive predictive value of 5.2%. The rate of interval cancer rate was 30.7/100,000 person-years among subjects receiving the OC-Sensor test and 40.6/100,000 person-years among those receiving the HM-Jack test; there was significant difference in test sensitivity (80% vs 68%, P = .005) that was related to the detectability of proximal CRC. After adjusting for differences in city/county, age, sex, ambient temperature, and colonoscopy quality, significant differences were observed between the tests in the positive predictive value for cancer detection (adjusted relative risk = 1.29; 95% confidence interval, 1.14-1.46) and the rates of interval cancer (0.75; 95% confidence interval, 0.62-0.92). Although each test was estimated to reduce CRC mortality by approximately 10%, no significant difference in mortality was observed when the 2 groups were compared. CONCLUSIONS Different brands of quantitative FITs, even with the same cutoff hemoglobin concentration, perform differently in mass screening. Population-level data should be gathered to verify the credibility of quantitative laboratory findings.

Effectiveness of fecal immunochemical testing in reducing colorectal cancer mortality from the One Million Taiwanese Screening Program

The effectiveness of fecal immunochemical testing (FIT) in reducing colorectal cancer (CRC) mortality has not yet been fully assessed in a large, population‐based service screening program.

Baseline faecal occult blood concentration as a predictor of incident colorectal neoplasia: longitudinal follow-up of a Taiwanese population-based colorectal cancer screening cohort

BACKGROUND Despite widespread use of the immunochemical faecal occult blood test (iFOBT), little is known about the subsequent risk of developing colorectal neoplasia for participants with negative iFOBT results. We investigated whether the concentration of faecal haemoglobin at the first screen is predictive of the subsequent incidence of colorectal neoplasia in those with a negative screening result. METHODS Between 2001 and 2007, we did a prospective cohort study within the Keelung community-based iFOBT screening programme for residents aged 40-69 years, using a cutoff faecal haemoglobin concentration of 100 ng/mL to classify attendees as negative and positive groups for further clinical investigations. 44,324 participants with negative findings and 1668 with a positive result at the first screen (854 non-referrals who refused colonoscopy and 814 with a false-positive result as assessed by colonoscopy) were followed up to ascertain cases of colorectal neoplasia. We investigated the association between baseline faecal haemoglobin concentration and risk of incident colorectal neoplasia, after adjusting for possible confounders. FINDINGS Median follow-up was 4·39 years (IQR 2·53-6·12) for all 45 992 participants, during which the incidence of colorectal neoplasia increased from 1·74 per 1000 person-years for those with baseline faecal haemoglobin concentration 1-19 ng/mL, to 7·08 per 1000 person-years for those with a baseline concentration of 80-99 ng/mL. The adjusted hazard ratios (HRs) increased from 1·43 (95% CI 1·08-1·88) for baseline faecal haemoglobin concentration of 20-39 ng/mL, to 3·41 (2·02-5·75) for a baseline concentration of 80-99 ng/mL (trend test p<0·0001), relative to 1-19 ng/mL. These results did not change when we included repeated iFOBT measurements. Non-referrals had the highest risk of incident colorectal neoplasia (adjusted HR 8·46 [6·08-11·76]). INTERPRETATION Quantitative faecal haemoglobin concentration at first screening predicts subsequent risk of incident colorectal neoplasia. During follow-up, risk stratification based on faecal haemoglobin could help clinicians, with particular attention being paid to those with higher initial faecal haemoglobin concentrations, especially those just under the threshold taken to indicate presence of colorectal neoplasia. FUNDING None.

A population-based study on the immediate and prolonged effects of the 1999 Taiwan earthquake on mortality

PURPOSE To investigate the patterns of immediate seismic deaths and post-earthquake mortality changes in the disaster area after the September 21, 1999 Taiwan earthquake. METHODS We used the data of 1826 seismic deaths to elucidate the immediate seismic effects on mortality patterns, and to determine the association between seismic death rates and house damage among 23 townships in the disaster area. We used standardized mortality ratios (SMRs) to estimate the changes in mortality of all natural causes (ICD-9: 1-799) in the 12 months after the earthquake. RESULTS For the 1826 seismic deaths, two leading causes of death were asphyxiation and intracranial injury and the death rates were higher among the female and elderly population. Township-specific seismic death rates were proportional to the proportion of completely collapsed houses. SMRs decreased six months after the earthquake for all residents and female adults aged 45 years and over. CONCLUSIONS The immediate effects of the Taiwan earthquake included a higher proportion of female and elderly seismic deaths and an association between seismic death rates and earthquake damages in the disaster area. The prolonged effect of the earthquake on mortality in the post-earthquake year was a decrease in mortality for all residents except male adults.

Evaluation of abdominal ultrasonography mass screening for hepatocellular carcinoma in Taiwan

Mass screening with abdominal ultrasonography (AUS) has been suggested as a tool to control adult hepatocellular carcinoma (HCC) in individuals, but its efficacy in reducing HCC mortality has never been demonstrated. This study aimed to assess the effectiveness of reducing HCC mortality by mass AUS screening for HCC based on a program designed and implemented in the Changhua Community‐based Integrated Screening (CHCIS) program with an efficient invitation scheme guided by the risk score. We invited 11,114 (27.0%) of 41,219 eligible Taiwanese subjects between 45 and 69 years of age who resided in an HCC high‐incidence area to attend a risk score‐guided mass AUS screening between 2008 and 2010. The efficacy of reducing HCC mortality was estimated. Of the 8,962 AUS screening attendees (with an 80.6% attendance rate), a total of 16 confirmed HCC cases were identified through community‐based ultrasonography screening. Among the 16 screen‐detected HCC cases, only two died from HCC, indicating a favorable survival. The cumulative mortality due to HCC (per 100,000) was considerably lower in the invited AUS group (17.26) compared with the uninvited AUS group (42.87) and the historical control group (47.51), yielding age‐ and gender‐adjusted relative mortality rates of 0.69 (95% confidence interval [CI]: 0.56‐0.84) and 0.63 (95% CI: 0.52‐0.77), respectively. Conclusion: The residents invited to community‐based AUS screening for HCC, compared with those who were not invited, showed a reduction in HCC mortality by ∼31% among subjects aged 45‐69 years who had not been included in the nationwide vaccination program against hepatitis B virus infection. (Hepatology 2014;59:1840–1849)