BACKGROUND In the National Polyp Study (NPS), colorectal cancer was prevented by colonoscopic removal of adenomatous polyps. We evaluated the long-term effect of colonoscopic polypectomy in a study on mortality from colorectal cancer. METHODS We included in this analysis all patients prospectively referred for initial colonoscopy (between 1980 and 1990) at NPS clinical centers who had polyps (adenomas and nonadenomas). The National Death Index was used to identify deaths and to determine the cause of death; follow-up time was as long as 23 years. Mortality from colorectal cancer among patients with adenomas removed was compared with the expected incidence-based mortality from colorectal cancer in the general population, as estimated from the Surveillance Epidemiology and End Results (SEER) Program, and with the observed mortality from colorectal cancer among patients with nonadenomatous polyps (internal control group). RESULTS Among 2602 patients who had adenomas removed during participation in the study, after a median of 15.8 years, 1246 patients had died from any cause and 12 had died from colorectal cancer. Given an estimated 25.4 expected deaths from colorectal cancer in the general population, the standardized incidence-based mortality ratio was 0.47 (95% confidence interval [CI], 0.26 to 0.80) with colonoscopic polypectomy, suggesting a 53% reduction in mortality. Mortality from colorectal cancer was similar among patients with adenomas and those with nonadenomatous polyps during the first 10 years after polypectomy (relative risk, 1.2; 95% CI, 0.1 to 10.6). CONCLUSIONS These findings support the hypothesis that colonoscopic removal of adenomatous polyps prevents death from colorectal cancer. (Funded by the National Cancer Institute and others.)

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Colonoscopic Polypectomy and Long-Term Prevention of Colorectal-Cancer Deaths

BACKGROUND We used modeling techniques to assess the relative and absolute contributions of screening mammography and adjuvant treatment to the reduction in breast-cancer mortality in the United States from 1975 to 2000. METHODS A consortium of investigators developed seven independent statistical models of breast-cancer incidence and mortality. All seven groups used the same sources to obtain data on the use of screening mammography, adjuvant treatment, and benefits of treatment with respect to the rate of death from breast cancer. RESULTS The proportion of the total reduction in the rate of death from breast cancer attributed to screening varied in the seven models from 28 to 65 percent (median, 46 percent), with adjuvant treatment contributing the rest. The variability across models in the absolute contribution of screening was larger than it was for treatment, reflecting the greater uncertainty associated with estimating the benefit of screening. CONCLUSIONS Seven statistical models showed that both screening mammography and treatment have helped reduce the rate of death from breast cancer in the United States.

https://www.nejm.org/doi/pdf/10.1056/NEJMoa050518

Effect of screening and adjuvant therapy on mortality from breast cancer

Each year the American Cancer Society publishes a summary of existing recommendations for early cancer detection, including updates, and/or emerging issues that are relevant to screening for cancer. In last year's article, the guidelines regarding screening for the early detection of prostate, colorectal, and endometrial cancers were updated, as was the narrative pertaining to testing for early lung cancer detection. Although none of the ACS's guidelines were updated in 2001, work is proceeding on an update of screening recommendations for breast and cervical cancer and an update of these guidelines will be announced in the January/February 2003 issue of CA. As in previous issues, we review recommendations for the "cancer-related check-up," in which clinical encounters provide case-finding and health counseling opportunities. Finally, we provide an update of the most recent data pertaining to participation rates in cancer screening by age, gender, and ethnicity from the Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance System (BRFSS) and National Health Interview Survey (NHIS).

https://onlinelibrary.wiley.com/doi/pdf/10.3322/canjclin.52.1.8

American Cancer Society guidelines for the early detection of cancer.

Screening with mammography uses X-ray imaging to find breast cancer before a lump can be felt. The goal is to treat cancer earlier, when a cure is more likely. The review includes seven trials that involved 600,000 women in the age range 39 to 74 years who were randomly assigned to receive screening mammograms or not. The studies which provided the most reliable information showed that screening did not reduce breast cancer mortality. Studies that were potentially more biased (less carefully done) found that screening reduced breast cancer mortality. However, screening will result in some women getting a cancer diagnosis even though their cancer would not have led to death or sickness. Currently, it is not possible to tell which women these are, and they are therefore likely to have breasts or lumps removed and to receive radiotherapy unnecessarily. If we assume that screening reduces breast cancer mortality by 15% after 13 years of follow-up and that overdiagnosis and overtreatment is at 30%, it means that for every 2000 women invited for screening throughout 10 years, one will avoid dying of breast cancer and 10 healthy women, who would not have been diagnosed if there had not been screening, will be treated unnecessarily. Furthermore, more than 200 women will experience important psychological distress including anxiety and uncertainty for years because of false positive findings.
Women invited to screening should be fully informed of both the benefits and harms. To help ensure that the requirements for informed choice for women contemplating whether or not to attend a screening programme can be met, we have written an evidence-based leaflet for lay people that is available in several languages on www.cochrane.dk. Because of substantial advances in treatment and greater breast cancer awareness since the trials were carried out, it is likely that the absolute effect of screening today is smaller than in the trials. Recent observational studies show more overdiagnosis than in the trials and very little or no reduction in the incidence of advanced cancers with screening.

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Screening for breast cancer with mammography.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(02)08020-0.pdf

Long-term effects of mammography screening: updated overview of the Swedish randomised trials

BACKGROUND

The availability of breast carcinoma data from trials of mammographic screening provides an opportunity to study the natural history of breast carcinoma.



METHODS

The Swedish Two-County study is a randomized, controlled trial of mammographic screening for breast carcinoma in which 77,080 women were randomized to receive an invitation to mammographic screening and 55,985 were randomized to receive no invitation. During the trial, a total of 2468 breast carcinoma cases were diagnosed. The authors examined the effect of screening on the pathologic attributes of the tumors diagnosed, mortality and survival from breast carcinoma, and the consequences of arresting tumor development by screening.



RESULTS

Screening reduces mortality from breast carcinoma largely through its effect in detecting tumors at a smaller size, decreasing the probability of lymph node metastases, and reducing the opportunity for worsening of the grade of malignancy of the tumor.



CONCLUSIONS

Breast carcinoma is not a systemic disease at its inception, but is a progressive disease and its development can be arrested by screening. The point at which the tumor's progression is arrested is crucial. Detection of small (<15 mm) and lymph node negative invasive tumors will save lives and confer an opportunity for less radical treatment. Tumor progression in the preclinical phase occurs more rapidly in women age <50 years, suggesting the need for a shorter screening interval for this group. Cancer 1999;86:449–62. © 1999 American Cancer Society.

The natural history of breast carcinoma: what have we learned from screening?

Multiparameter analysis of core regulatory proteins involved in G1–S and G2–M cell-cycle transitions provides a powerful biomarker readout for assessment of the cell-cycle state. We have applied this algorithm to breast cancer to investigate how the cell cycle impacts on disease progression. Protein expression profiles of key constituents of the DNA replication licensing pathway (Mcm2, geminin) and mitotic machinery (Plk1, Aurora A and the Aurora substrate histone H3S10ph) were generated for a cohort of 182 patients and linked to clinicopathological parameters. Arrested differentiation and genomic instability were associated with an increased engagement of cells into the cell division cycle (P<0.0001). Three unique cell-cycle phenotypes were identified: (1) well-differentiated tumours composed predominantly of Mcm2-negative cells, indicative of an out-of-cycle state (18% of cases); (2) high Mcm2-expressing tumours but with low geminin, Aurora A, Plk1 and H3S10ph levels (S–G2–M progression markers), indicative of a G1-delayed/arrested state (24% cases); and (3) high Mcm2-expressing tumours and also expressing high levels of the S–G2–M progression markers, indicative of accelerated cell-cycle progression (58% of cases). The active cell-cycle progression phenotype had a higher risk of relapse when compared with out-of-cycle and G1-delayed/arrested phenotypes (HR=3.90 (1.81–8.40, P<0.001)), and was associated with Her-2 and triple negative subtypes (P<0.001). It is of note that high-grade tumours with the G1-delayed/arrested phenotype showed an identical low risk of relapse compared with well-differentiated out-of-cycle tumours (HR=1.00 (0.22–4.46), P=0.99). Our biomarker algorithm provides novel insights into the cell-cycle state of dynamic tumour cell populations in vivo. This information is of major prognostic significance and may impact on individualised therapeutic decisions. Patients with an accelerated phenotype are more likely to derive benefit from S- and M-phase-directed chemotherapeutic agents.

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Cell-cycle-phase progression analysis identifies unique phenotypes of major prognostic and predictive significance in breast cancer

The effectiveness of cancer screening depends crucially on two elements: the sojourn time (that is, the duration of the preclinical screen-detectable period) and the sensitivity of the screening test. Previous literature on methods of estimating mean sojourn time and sensitivity has largely concentrated on breast cancer screening. Screening for colorectal cancer has been shown to be effective in randomized trials, but there is little literature on the estimation of sojourn time and sensitivity. It would be interesting to demonstrate whether methods commonly used in breast cancer screening could be used in colorectal cancer screening. In this paper, the authors consider various analytic strategies for fitting exponential models to data from a screening program for colorectal cancer conducted in Calvados, France, between 1991 and 1994. The models yielded estimates of mean sojourn time of approximately 2 years for 45- to 54-year-olds, 3 years for 55- to 64-year-olds, and 6 years for 65- to 74-year-olds. Estimates of sensitivity were approximately 75%, 50%, and 40% for persons aged 45-54, 55-64, and 65-74 years, respectively. There is room for improvement in all models in terms of goodness of fit, particularly for the first year after screening, but results from randomized trials indicate that the sensitivity estimates are roughly correct. Am J Epidemiol 1998;148:609-19.

/pdf/estimating-sensitivity-and-sojourn-time-in-screening-for-9azeqvxgki.pdf

Estimating Sensitivity and Sojourn Time in Screening for Colorectal Cancer A Comparison of Statistical Approaches

Background and purpose Venous thromboembolism (VTE) remains a substantial cause of morbidity and mortality following hip fracture. Previous work has not identified any risk factors associated with the type of hip fracture. We report the incidence of and risk factors for development of symptomatic VTE in patients following a hip fracture.

Patients and methods In this prospective study, we collected information on 5,300 consecutive patients who were admitted to a single unit with a hip fracture—in terms of their pre-admission status, details of any operation performed, and details of complications in the form of symptomatic venous thromboembolism. All patients received thromboprophylaxis with heparin.

Results The incidence of symptomatic VTE was 2.2% (95% CI: 1.8–2.6). 85% of these events occurred within 5 weeks of the fracture. The statistically significant risk factors for symptomatic VTE were better preoperative mobility, living in one's own home, high mental test score, high preoperative hemoglobin, inter-trochanteric fractures, and fixation with a dynamic hip screw. In multivariate analysis adjusting for sex and age, type of residence on admission, type of fracture, and hemoglobin values on admission remained independently significant.

Interpretation We found that the rate of symptomatic VTE using thromboprophylaxis with heparin was low but that there were a number of groups that were at a significantly higher risk of developing VTE. The patients who are particularly at risk appear to be those with a subtrochanteric or intertrochanteric hip fracture; here, the incidence of symptomatic VTE was twice that of intracapsular hip fractures.

https://www.tandfonline.com/doi/pdf/10.3109/17453670903448273

Symptomatic venous thromboembolism following a hip fracture.

BACKGROUND

Although the efficacy of mass screening for colorectal carcinoma (CRC) with a fecal occult blood test has been demonstrated in several randomized trials, a mass screening approach used in countries with intermediate or low incidence of CRC might be costly. Screening high risk people may be an alternative approach, to aid in the prevention of death from CRC. However, the efficacy of CRC screening for high risk people in such countries is uncertain.



METHODS

For this study, a multicenter design was devised to identify high risk groups without clinical symptoms related to CRC; these subjects were identified through the study of index cases of CRC in Taiwan. Colonoscopy, in combination with a fecal occult blood test or double-contrast barium enema, was used to screen high risk groups. A total of 8909 subjects were invited to attend screening. Of 8909, 81 with asymptomatic CRC were detected in one-shot screening. Markov models, in conjunction with a simulated approach, were proposed to estimate relevant parameters in relation to disease progression and to assess the effect of the interval between screenings on the efficacy of CRC screening for these high risk groups.



RESULTS

The estimated preclinical incidence rate was 0.00396 (95% confidence interval [CI], 0.002944–0.004985), which was 21 times that reported from a cancer registry in 1994. The simultaneous estimations of mean sojourn time (the average duration between the preclinical screen-detectable phase and the clinical phase) and sensitivity were 2.8 years (95% CI, 2.15–4.30) and 95.0% (95% CI, 24.4–99.9%), respectively. Predictions of mortality reduction for people who received annual, biennial, and triennial screening regimes compared with controls were 26% (95% CI, 0–50%), 23% (95% CI, 0–48%), and 21% (95% CI, 0–47%), respectively.



CONCLUSIONS

The efficacy of selective colorectal carcinoma screening has been demonstrated in this study. A high preclinical CRC incidence rate also suggests that such a screening strategy might be cost-effective for countries with intermediate or low incidence of CRC. Methods proposed in this study can be used to evaluate the efficacy of CRC screening in similar screening trials. Cancer 1999;86:1116–28. © 1999 American Cancer Society.

T. C. Prevost

Papers

The natural history of breast carcinoma: what have we learned from screening?

Cell-cycle-phase progression analysis identifies unique phenotypes of major prognostic and predictive significance in breast cancer

Estimating Sensitivity and Sojourn Time in Screening for Colorectal Cancer A Comparison of Statistical Approaches

Symptomatic venous thromboembolism following a hip fracture.

Evaluation of a selective screening for colorectal carcinoma: the Taiwan Multicenter Cancer Screening (TAMCAS) project.