Jean Ching Yuan Fann

Swedish Two-County Trial: Impact of Mammographic Screening on Breast Cancer Mortality during 3 Decades

PURPOSE To estimate the long-term (29-year) effect of mammographic screening on breast cancer mortality in terms of both relative and absolute effects. MATERIALS AND METHODS This study was carried out under the auspices of the Swedish National Board of Health and Welfare. The board determined that, because randomization was at a community level and was to invitation to screening, informed verbal consent could be given by the participants when they attended the screening examination. A total of 133 065 women aged 40-74 years residing in two Swedish counties were randomized into a group invited to mammographic screening and a control group receiving usual care. Case status and cause of death were determined by the local trial end point committees and, independently, by an external committee. Mortality analysis was performed by using negative binomial regression. RESULTS There was a highly significant reduction in breast cancer mortality in women invited to screening according to both local end point committee data (relative risk [RR] = 0.69; 95% confidence interval: 0.56, 0.84; P < .0001) and consensus data (RR = 0.73; 95% confidence interval: 0.59, 0.89; P = .002). At 29 years of follow-up, the number of women needed to undergo screening for 7 years to prevent one breast cancer death was 414 according to local data and 519 according to consensus data. Most prevented breast cancer deaths would have occurred (in the absence of screening) after the first 10 years of follow-up. CONCLUSION Invitation to mammographic screening results in a highly significant decrease in breast cancer-specific mortality. Evaluation of the full impact of screening, in particular estimates of absolute benefit and number needed to screen, requires follow-up times exceeding 20 years because the observed number of breast cancer deaths prevented increases with increasing time of follow-up.

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.

Insights from the Breast Cancer Screening Trials: How Screening Affects the Natural History of Breast Cancer and Implications for Evaluating Service Screening Programs

It is desirable to have a strategy for evaluation of breast cancer service screening programs years before the long‐term breast cancer mortality data are available. Since successful mammography screening has a significant impact on two components of the TNM (tumor size, node status, presence or absence of distant metastases) classification system, tumor size and node status, we investigated the effect of the randomized breast screening trials on incidence of advanced stage disease and on the subsequent breast cancer death rate. In the trials that achieved a 20% or greater reduction in advanced stage disease, there was an average breast cancer mortality reduction of 28% among women invited to screening (attenders and nonattenders combined). In the trials that achieved a reduction in advanced stage disease of less than 10%, there was no reduction in breast cancer mortality among women invited to screening. This study provides evidence that the average mortality reduction in all the trials underestimates the true mortality reduction, and that substantially greater breast cancer mortality reductions can be expected in screening programs that are effective in reducing advanced stage breast cancer. In addition, monitoring the incidence of advanced stage breast cancer in an ongoing screening program can provide a sensitive and early indicator of the subsequent mortality from the disease.

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)

Long‐term incidence of breast cancer by trial arm in one county of the Swedish Two‐County Trial of mammographic screening

This study estimated the excess incidence (overdiagnosis) of breast cancer associated with starting mammographic screening at an earlier age, by using data from the Dalarna County component of the Swedish Two‐County Trial of breast cancer screening.

Impact of faecal haemoglobin concentration on colorectal cancer mortality and all-cause death

Objective To assess the effect of an incremental increase in faecal haemoglobin (f-Hb) concentration on colorectal cancer (CRC) mortality and all-cause death. Design We conducted an observational study of cohorts over time based on two population-based CRC screening programmes. Setting Two cities of Taiwan. Participants 1233 individuals with CRC (217 prevalent cases and 1016 incident cases) and 2640 with colorectal adenoma (1246 prevalent cases and 1394 incident cases) found in the two cohorts of 59 767 and 125 976 apparently healthy individuals, aged 40 years and above, who had been invited to participate in screening since 2001 and 2003, respectively. Main outcome measures Death from CRC and all-cause death ascertained by following up from the entire two cohorts over time until 2009. Results The effect of an incremental increase in f-Hb on the risk for CRC mortality was noted, increasing from a slightly increased risk for the category of f-Hb of 20–49 ng Hb/mL (adjusted HR (aHR)=1.09; 95% CI 0.68 to 1.75) to 11.67 (95% CI 7.71 to 17.66) for the group with f-Hb≥450 ng Hb/mL as compared with the group considered baseline with f-Hb of 1–19 ng Hb/mL (p<0.001). A similar but less marked increasing trend was found for all-cause mortality, aHR increasing from 1.15 (95% CI 1.07 to 1.24) for the group with f-Hb of 20–49 ng Hb/mL to 1.67 (95% CI 1.54 to 2.07) for the group with f-Hb≥450 ng Hb/mL. Conclusions We substantiated the impacts of an incremental increase in f-Hb on the risk for death from CRC and all-cause death, consistently showing a significant gradient relationship. Both discoveries suggest that f-Hb may not only make contribution to facilitating individually tailored screening for CRC but also can be used as a significant predictor for life expectancy.

Faecal haemoglobin concentration influences risk prediction of interval cancers resulting from inadequate colonoscopy quality: analysis of the Taiwanese Nationwide Colorectal Cancer Screening Program

Objectives Interval colorectal cancer (CRC) after colonoscopy may affect effectiveness and cost-effectiveness of screening programmes. We aimed to investigate whether and how faecal haemoglobin concentration (FHbC) of faecal immunochemical testing (FIT) affected the risk prediction of interval cancer (IC) caused by inadequate colonoscopy quality in a FIT-based population screening programme. Design From 2004 to 2009, 29 969 subjects underwent complete colonoscopy after positive FIT in the Taiwanese Nationwide CRC Screening Program. The IC rate was traced until the end of 2012. The incidence of IC was calculated in relation to patient characteristics, endoscopy-related factors (such adenoma detection rate (ADR)) and FHbC. Poisson regression analysis was performed to assess the potential risk factors for colonoscopy IC. Results One hundred and sixty-two ICs developed after an index colonoscopy and the estimated incidence was 1.14 per 1000 person-years of observation for the entire cohort. Increased risk of IC was most remarkable in the uptake of colonoscopy in settings with ADR lower than 15% (adjusted relative risk (aRR)=3.09, 95% CI 1.55 to 6.18) and then higher FHbC (μg Hb/g faeces) (100–149: aRR=2.55, 95% CI 1.52 to 4.29, ≥150: aRR=2.74, 95% CI 1.84 to 4.09) with adjustment for older age and colorectal neoplasm detected at baseline colonoscopy. Similar findings were observed for subjects with negative index colonoscopy. Conclusions Colonoscopy ICs arising from FIT-based population screening programmes were mainly influenced by inadequate colonoscopy quality and independently predicted by FHbC that is associated with a priori chance of advanced neoplasm. This finding is helpful for future modification of screening logistics based on FHbC.

A new insight into fecal hemoglobin concentration-dependent predictor for colorectal neoplasia

We sought to assess how much of the variation in incidence of colorectal neoplasia is explained by baseline fecal hemoglobin concentration (FHbC) and also to assess the additional predictive value of conventional risk factors. We enrolled subjects aged 40 years and over who attended screening for colorectal cancer with the fecal immunochemical test (FIT) in Keelung community‐based integrated screening program. The accelerated failure time model was used to train the clinical weights of covariates in the prediction model. Datasets from two external communities were used for external validation. The area under curve (AUC) for the model containing only FHbC was 83.0% (95% CI: 81.5–84.4%), which was considerably greater than the one containing only conventional risk factors (65.8%, 95% CI: 64.2–67.4%). Adding conventional risk factors did not make significant additional contribution (p = 0.62, AUC = 83.5%, 95% CI: 82.1–84.9%) to the predictive model with FHbC only. Males showed a stronger linear dose‐response relationship than females, yielding gender‐specific FHbC predictive models. External validation confirms these results. The high predictive ability supported by a dose‐dependent relationship between baseline FHbC and the risk of developing colorectal neoplasia suggests that FHbC may be useful for identifying cases requiring closer postdiagnosis clinical surveillance as well as being an early indicator of colorectal neoplasia risk in the general population. Our findings may also make contribution to the development of the FHbC‐guided screening policy but its pros and cons in connection with cost and effectiveness of screening should be evaluated before it can be applied to population‐based screening for colorectal cancer.

Accuracy of faecal occult blood test and Helicobacter pylori stool antigen test for detection of upper gastrointestinal lesions

Objective Highly sensitive guaiac-based faecal occult blood (Hemoccult SENSA) and Helicobacter pylori stool antigen testing might help detect upper gastrointestinal lesions when appended to a colorectal cancer screening programme with faecal immunochemical testing. We evaluated the diagnostic accuracies of two stool tests in detecting upper gastrointestinal lesions. Design Cross-sectional design. Setting Hospital-based and community-based screening settings. Participants A hospital-based deviation cohort of 3172 participants to evaluate test performance and a community-based validation cohort of 3621 to verify the findings. Interventions Three types of stool tests with bidirectional endoscopy as the reference standard. Outcomes Sensitivity, specificity and positive and negative likelihood ratios. Results For detecting upper gastrointestinal lesions in cases with negative immunochemical tests, the sensitivity, specificity, and positive and negative likelihood ratios of the guaiac-based and H pylori antigen tests were 16.3% (95% CI 13.3% to 19.8%), 90.1% (88.9% to 91.2%), 1.64 (1.31 to 2.07), and 0.93 (0.89 to 0.97), respectively, and 52.5% (48.1% to 56.9%), 80.6% (79.0% to 82.1%), 2.71 (2.41 to 3.04) and 0.59 (0.54 to 0.65), respectively. For detecting upper gastrointestinal lesions in cases with normal colonoscopy, the results of the guaiac-based and H pylori antigen tests were 17.9% (14.8% to 21.5%), 90.1% (88.9% to 91.2%), 1.81 (1.45 to 2.26) and 0.91 (0.87 to 0.95), respectively, and 53.1% (48.6% to 57.4%), 80.7% (79.1% to 82.2%), 2.75 (2.45 to 3.08) and 0.58 (0.53 to 0.64), respectively. Within the community, positive predictive values of the immunochemical and H pylori antigen tests were 36.0% (26.0% to 46.0%) and 31.9% (28.3% to 35.5%), respectively, for detecting lower and upper gastrointestinal lesions, which were similar to expected values. Conclusions The H pylori stool antigen test is more accurate than the guaiac-based test in the screening of upper gastrointestinal lesions in a population with high prevalence of H pylori infection and upper gastrointestinal lesions. It is applicable to add the H pylori antigen test to the immunochemical test for pan detection. Trial registration NCT01341197 (ClinicalTrial.gov).