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R Boer

Publications and source records attributed to R Boer.

At least 37 records · Page 2Linked to original sources
PubMed1998

Rhodamine 123 efflux modulation in the presence of low or high serum from CD56+ hematopoietic cells or CD34+ leukemic blasts by B9309-068, a newly designed pyridine derivative.

The newly designed pyridine derivative B9309-068 and a series of structurally different compounds were tested for their ability to modulate rhodamine 123 (RHO) efflux from CD56+ hematopoietic cells in the presence of either 10% fetal calf serum or undiluted human AB serum. Furthermore, efflux modulation was investigated on CD34+ blast populations obtained from four patients with relapsed state AML. Target cells were specified throughout by labeling with peridinine chlorophyll protein (PerCP)-conjugated monoclonal antibodies, allowing clear differentiation from RHO emission spectrum by flow cytometry. In the presence of low serum each compound efficiently modulated RHO efflux without significant differences in the range of final concentrations (1.0-3.0 microM). At 0.1 microM, however, RHO efflux was differentially modulated following the series GF120918 approximately B9309-068 > PSC 833 > DNIG approximately DVER. With CD56+ cells in the presence of undiluted human AB serum at a final modulator concentration of 0.1 microM, all chemosensitizers tested were found to be inefficient. At final concentrations of 0.3 microM or higher, distinct RHO efflux modulation was found with the following efficacies: B9309-068 approximately GF120918 > PSC 833 >> DVER approximately DNIG. The efficacies seen in undiluted human AB serum at 3.0 microM were comparable to those seen on CD56+ cells at final modulator concentrations of 0.1 microM in low serum. Our results identify the pyridine derivative B9309-068 as a promising compound for modulating P-glycoprotein-mediated drug resistance under conditions resembling the clinical setting. Nonetheless, modulation potencies of a series of structurally very different chemosensitizers was revealed to be substantially diminished at high serum concentrations in vitro.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Nation-wide breast cancer screening in The Netherlands: results of initial and subsequent screening 1990-1995. National Evaluation Team for Breast Cancer Screening.

Based on an extensive cost-effectiveness analysis, the Dutch nation-wide breast cancer screening programme started in 1990, providing a biennial screen examination to women aged 50 to 69 years. The programme is monitored by the National Evaluation Team, which annually collects tabulated regional evaluation data to determine performance indicators. This study presents (trends in) the outcomes of initial and subsequent screening rounds, 1990-1995, and compares them to the predictions of the cost-effectiveness-analysis. Up to 1996, 88% of the target population was covered by the programme and more than 2.4 x 10(6) women were invited. The overall attendance rate was 77.5% with little differences between screening rounds and age groups; the highest rate was found in non-urbanised areas (82.4%). Of 1,000 initially (and 2 years thereafter) screened women, 13.4 (6.6) were referred for further investigation, 9.7 (4.4) were biopsied and 6.4 (3.4) had breast cancer. The positive predictive values of screen test and biopsy were 47% (51%) and 66% (78%), respectively. DCIS was diagnosed in 0.9 (0.5) and invasive cancers < or = 10 mm in 1.5 (1.0) per 1,000 screens. Lymph node metastases were found in 28% (24%) of the invasive cancers. Except the increasing attendance, which was much higher than expected, the results were fairly constant over the years. Contrary to initial screens, the results of subsequent screens did not fulfil expectations with regard to breast cancer detection and tumour size distribution. We conclude that the nation-wide screening programme is being implemented successfully. Given the results, the programme should contribute to a substantial breast cancer mortality reduction in the future. The discrepancy between observed and expected results in subsequent screens has to be watched carefully.

Age Factors↗
PubMed1998

Radiation risk of mammography related to benefit in screening programmes: a favourable balance?

OBJECTIVES: To estimate the number of breast cancer deaths induced by low dose radiation in breast cancer screening programmes compared with numbers prevented. METHODS: A computer simulation model on the natural history of breast cancer was combined with a model from BEIR-V on induced breast cancer mortality from low levels of radiation. The improvement in prognosis resulting from screening was based on the results of the Swedish overview of the randomised screening trials for breast cancer and the performance of screening in the Netherlands. Different scenarios (ages and intervals) were used to explore the objectives. Sensitivity analyses were carried out for latency period, dose of mammography, sensitivity of the screening test, early detection by screening of induced breast tumours, and new 1996 risk estimates by Howe and McLaughlin. RESULTS: For a screening programme, age group 50-69, two year interval, 2 mGy per view, the balance between the number of deaths induced versus those prevented was favourable: 1:242. When screening is expanded to the age group 40-49 with a one or two year interval the results may be less favourable, that is, 1:66 and 1:97. According to these scenarios and with the Dutch scenario as reference, one breast cancer death from radiation may be expected to occur to save eight extra deaths from breast cancer. If screening was equally effective in young women as in women aged 50-69, the marginal value was 1:+/- 30. Assuming detection of induced cancers by screening could influence the ratios by about 30%, but did not substantially change the conclusions. The new risk estimates by Howe and McLaughlin resulted in five times to eight times favourable ratios breast cancer deaths induced to prevented. Besides age group of screening, dose of mammography is the other determinant of risk. CONCLUSIONS: For screening under the age of 50, the balance between the number of breast cancer deaths prevented by screening compared with the number induced by radiation seem less favourable. Credibility intervals were however wide, because of many uncertainties of radiation risk at very low doses.

Aged↗
PubMed1997

Breast cancer screening in Navarra: interpretation of a high detection rate at the first screening round and a low rate at the second round.

Our objective was to evaluate the on-going European pilot project for breast cancer screening in Navarra, Spain, and to predict the effects and costs of the programme in the long run. Observed results in Navarra, consisting of more than 100,000 screens, were compared with expected results. A microsimulation screening analysis model was used that included demographical, epidemiological and screening characteristics of Navarra. Alternative assumptions on epidemiological and screening characteristics were also addressed. The observed detection rate (5.9 per 1,000 screened women) in the first round was 18% higher than expected; the observed rate in the subsequent round (2.9) was 17% lower than expected. Longer pre-clinical durations, lower sensitivity or the existence of a high-risk group in Navarra could not satisfactorily explain the first and second round results together. Nevertheless, the programme will have an important health benefit for the women involved, due to an important trend in incidence in recent years and the relatively unfavourable clinical stage distribution in Navarra. The proportion T2+ cancers that will be prevented after 10 years of screening amounts to 36%. The annual mortality reduction in steady state is expected to range between 17% (if the observed rates in the second round indicate real screening performance) to 23% (if the first round indicates real performance). Our results demonstrate that a high detection rate in the first round is insufficient to evaluate the quality of a programme. Interval cancer rates, results of the subsequent round and size distributions are also crucial indicators of the quality of the screening programme and should be analysed in their specific context.

Age Distribution↗
PubMed1997

Quantitative estimates of the impact of sensitivity and specificity in mammographic screening in Germany.

STUDY OBJECTIVE: To estimate quantitatively the impact of the quality of mammographic screening (in terms of sensitivity and specificity) on the effects and costs of nationwide breast cancer screening. DESIGN: Three plausible "quality" scenarios for a biennial breast cancer screening programme for women aged 50-69 in Germany were analysed in terms of costs and effects using the Microsimulation Screening Analysis model on breast cancer screening and the natural history of breast cancer. Firstly, sensitivity and specificity in the expected situation (or "baseline" scenario) were estimated from a model based analysis of empirical data from 35,000 screening examinations in two German pilot projects. In the second "high quality" scenario, these properties were based on the more favourable diagnostic results from breast cancer screening projects and the nationwide programme in The Netherlands. Thirdly, a worst case, "low quality" hypothetical scenario with a 25% lower sensitivity than that experienced in The Netherlands was analysed. SETTING: The epidemiological and social situation in Germany in relation to mass screening for breast cancer. RESULTS: In the "baseline" scenario, an 11% reduction in breast cancer mortality was expected in the total German female population, ie 2100 breast cancer deaths would be prevented per year. It was estimated that the "high quality" scenario, based on Dutch experience, would lead to the prevention of an additional 200 deaths per year and would also cut the number of false positive biopsy results by half. The cost per life year gained varied from Deutsche mark (DM) 15,000 on the "high quality" scenario to DM 21,000 in the "low quality" setting. CONCLUSIONS: Up to 20% of the total costs of a screening programme can be spent on quality improvement in order to achieve a substantially higher reduction in mortality and reduce undesirable side effects while retaining the same cost effectiveness ratio as that estimated from the German data.

Adult↗
PubMed1997

A comparison of disease specific survival of patients who died of and who had newly diagnosed prostate cancer.

PURPOSE: We investigated the validity of calculating prostate specific survival from a population of deaths occurring during a given period. MATERIALS AND METHODS: Stochastic simulation was used to generate a large number of life histories of men with prostate cancer. RESULTS: The investigated method of calculating survival can lead to different outcomes compared to the standard method. In an example with a Dutch population structure the investigated method leads to strong underestimation of 25 years of survival. CONCLUSIONS: The method of calculating survival studied is theoretically not valid. Several probable changes in the population can produce results that are different from the standard method of calculating survival.

Humans↗
PubMed1996

Reversible labeling of a chemosensitizer binding domain of p-glycoprotein with a novel 1,4-dihydropyridine drug transport inhibitor.

A photoreactive dihydropyridine (DHP), BZDC-DHP (2,6-dimethyl-4-(2-(trifluoromethyl)-phenyl)-1,4-dihydropyridine-3,5- dicarboxylic acid (2-[3-(4-benzoylphenyl)propionylamino]ethyl) ester ethyl ester), and its tritiated derivative were synthesized as novel probes for human p-glycoprotein (p-gp). (-)-[3H]BZDC-DHP specifically photolabeled p-gp in membranes of multidrug-resistant CCRF-ADR5000 cells. In reversible labeling experiments a saturable, vinblastine-sensitive and high-affinity (Kd = 16.3 nM, Bmax = 58 pmol/mg of protein, k(+1) = 0.031 nM-1 min-1, k(-1) = 0.172 min-1) binding component was present in CCRF-ADR5000 membranes but absent in the sensitive parent cell line. Binding was inhibited by cytotoxics and known chemosensitizers with a p-gp characteristic pharmacological profile. For eight chemosensitizers tested, the potency for binding inhibition correlated (r > 0.94) with the potency for drug transport inhibition (measured using rhodamine 123 accumulation). The DHP niguldipine and a structurally related pyrimidine stereoselectively stimulated reversible (-)-[3H]BZDC-DHP binding, suggesting that more than one DHP molecule can bind to p-gp at the same time. Our data demonstrate that DHPs label multiple chemosensitizer domains on p-gp, distinct from the vinblastine interaction site. (-)-[3H]BZDC-DHP represents a valuable tool to characterize the molecular organization of chemosensitizer binding domains on p-gp by both reversible binding and photoinduced covalent modification. It provides a novel simple screening assay for p-gp active drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Interaction of cytostatics and chemosensitizers with the dexniguldipine binding site on P-glycoprotein.

The interaction of cytostatics and chemosensitizers with the dexniguldipine binding site of P-glycoprotein was investigated in photoaffinity labeling experiments. A tritiated azidoderivative of the chemosensitizer dexniguldipine with dihydropyridine structure, [3H]B9209-005, was used to irreversibly label P-glycoprotein. The apparent affinity of cytostatics and chemosensitizers to this binding site was estimated from labeling experiments in the presence of increasing concentrations of compounds. From the cytostatics tested, the vinca alkaloids and taxol showed the highest affinity, anthracyclins possessed moderate affinity while methotrexate, ara C and camptothecin, cytostatics not involved in P-glycoprotein-mediated multidrug resistance, were almost inactive. The chemosensitizers GF 120918, cyclosporin A and SDZ PSC-833 inhibited photoincorporation with the highest potency. Steep dose-inhibition curves were obtained with the cyclic peptides and S9788, indicating that these compounds may bind allosterically to a separate binding site. Compounds with dihydropyridine structure with or without chemosensitizing potency were also tested and some structure-activity relationships could be derived from the data. Our data show that inhibition of photoaffinity labeling by [3H]B9209-005 is a valuable and reliable system for measuring the interaction with and potency of chemosensitizing compounds at P-glycoprotein. Furthermore, data obtained in this test system are well suited to investigate structure-activity relationships for chemosensitizers at P-glycoprotein. In addition cytostatics underlying P-glycoprotein-mediated multidrug resistance can be identified.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Modulation of P-glycoprotein mediated drug accumulation in multidrug resistant CCRF VCR-1000 cells by chemosensitisers.

P-glycoprotein (PGP) mediated transport of cytostatic drugs out of resistant cancer cells is a major cause of experimental and probably also of clinical multidrug resistance, which often leads to treatment failure during chemotherapy. The broad substrate specificity of PGP strongly restricts effective chemotherapy and diminishes the patients' prognosis. Inhibition of PGP's pumping function by chemosensitisers is one way to restore cellular responsiveness to otherwise ineffective cytostatics. Clinical trials with several chemosensitisers are under way. To date, it is not clear whether a certain chemosensitiser potentiates the action of different cytostatic drugs, transported by PGP equally well, or whether the chemosensitising potency is dependent on the cytostatic drugs used. Therefore, we compared the effects of five potent chemosensitisers on cellular accumulation using [3H]daunomycin, [3H]vincristine and rhodamine-123 as substrates for PGP. The acridonecarboxamide derivative GF 120918 was the most potent compound and a half-maximal effect was seen at concentrations ranging from 5 nM for rhodamine-123 accumulation to 14 and 19 nM for [3H]vincristine or [3H]daunomycin accumulation, respectively. The new chemosensitiser B9203-016 was slightly less effective than GF 120918 in all three test systems. Dexniguldipine was of intermediate potency with half-maximal effects at concentrations between 62 and 194 nM. The cyclic undecapeptide SDZ PSC 833 showed somewhat lower potency ranging from 151 to 331 nM. Cyclosporin A was less potent than SDZ PSC 833. Furthermore, enhancement of drug accumulation produced by each chemosensitiser was similar, regardless of which PGP substrate was measured, that is, the rank order of potency to increase accumulation was the same in each of the assays used. Our data point to similar, if not identical, mechanisms of drug transport by PGP and inhibition of drug transport by chemosensitisers at least for the substrates rhodamine-123, vincristine and daunomycin.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Effects of the selective bisindolylmaleimide protein kinase C inhibitor GF 109203X on P-glycoprotein-mediated multidrug resistance.

Inhibition of protein kinase C (PKC) is discussed as a new approach for overcoming multidrug resistance (MDR) in cancer chemotherapy. For evaluation of this concept we applied the bisindolylmaleimide GF 109203X, which shows a highly selective inhibition of PKC isozymes alpha, beta 1, beta 2, gamma, delta and epsilon in vitro. The efficacy of this compound in modulation of MDR was examined using several P-glycoprotein (P-gp)-overexpressing cell lines including a MDR1-transfected HeLa clone, and was compared with the activities of dexniguldipine-HCI (DNIG) and dexverapamil-HC1 (DVER), both of which essentially act via binding to P-gp. As PKC alpha has been suggested to play a major role in P-gp-mediated MDR, cell lines exhibiting different expression levels of this PKC isozyme were chosen. On crude PKC preparations or in a cellular assay using a cfos(-711)CAT-transfected NIH 3T3 clone, the inhibitory qualities of the bisindolylmaleimide at submicromolar concentrations were demonstrated. At up 1 microM final concentrations of the PKC inhibitor GF 109203X, a concentration at which many PKC isozymes should be blocked substantially, no cytotoxic or MDR-reversing effects whatsoever were seen, as monitored by 72 h tetrazolium-based colorimetric MTT assays or a 90 min rhodamine 123 accumulation assay. Moreover, depletion of PKC alpha by phorbol ester in HeLa-MDR1 transfectants had no influence on rhodamine 123 accumulation after 24 or 48 h. MDR reversal activity of GF 109203X was seen at higher final drug concentrations, however. Remarkably, [3H]vinblastine-sulphate binding competition experiments using P-gp-containing crude membrane preparations demonstrated similar dose dependencies as found for MDR reversion by the three modulators, i.e. decreasing efficacy in the series dexniguldipine-HCl > dexverapamil-HCl > GF 109203X. Similar interaction with the P-gp in the micromolar concentration range was revealed by competition of GF 109203X with photoincorporation of [3H]azidopine into P-gp-containing crude membrane preparations. No significant effect of the PKC inhibitor on MDR1 expression was seen, which was examined by cDNA-PCR. Thus, the bisindolylmaleimide GF 109203X probably influences MDR mostly via direct binding to P-gp. Our work identifies the bisindolylmaleimide GF 109203X as a new type of drug interacting with P-gp directly, but does not support the concept of a major contribution of PKC to a P-gp-associated MDR, at least using the particular cellular model systems and the selective, albeit general, PKC inhibitor GF 109203X.

3T3 Cells↗
PubMed1995

Quantitative interpretation of age-specific mortality reductions from the Swedish breast cancer-screening trials.

BACKGROUND: Results from five Swedish randomized trials may provide the most conclusive evidence on the effect of mammographic screening and have been used to forecast the expected reduction in breast cancer mortality in other programs. However, those trials demonstrated different degrees of reduction. The interpretation of observed mortality reduction after long follow-up for women aged 40-49 years at trial entry is both important and controversial. PURPOSE: We estimated what percentage of the observed mortality reduction for women aged 40-49 years at entry into the five Swedish screening trials might be attributable to screening these women at 50 years of age or older. Moreover, we calculated the most likely percentage mortality reduction for specific screening programs if the Swedish results were generalized and analyzed whether characteristics of each trial might at least partly explain the observed differences in reductions among the trials. METHODS: Each Swedish trial was simulated with one underlying computer simulation model (MISCAN--MIcrosimulation SCreening ANalysis) of the natural history of the disease and the performance of screening, taking into account nine important trial characteristics. Improvement in prognosis for screen-detected case patients was estimated with age-specific reduction for all trials and each trial design as a reference. RESULTS: An expected 7% reduction in breast cancer mortality for women aged 40-49 years at trial entry (relative risk [RR] = 0.93) was determined by computer modeling, assuming no improvement in prognosis for cancers that are screen detected before 50 years of age. This result indicates that, of the overall 10% observed reduction (RR = 0.90) in the five Swedish trials analyzed, most (70%) of this reduction might be attributable to screening these women in later rounds after their 50th birthday. Using additional trial information, predictions of breast cancer mortality reduction in women 50 years or older might be 11% larger than previously expected, assuming that high-quality mammographic screening can be achieved in nationwide programs. For women aged 50-69 years at trial entry, the differences in expected versus observed mortality reduction among the trials are estimated to be relatively small. (Expected mortality reductions range from 24% to 32%). CONCLUSIONS: Results from the Swedish randomized breast cancer-screening trials should be seen as more favorable regarding the effect of mammographic screening in reducing breast cancer mortality for women aged 50-69 years than was estimated earlier. Our analyses also suggest that the improvement in prognosis due to screening for women aged 40-49 years is much smaller than that for women aged 50 years or older. Approximately, 70% of the 10% observed reduction in breast cancer mortality (i.e., 7%) for women aged 40-49 years at trial entry might be attributable to a reduction due to screening these women after they reach age 50. IMPLICATIONS: Detailed screening data for the 40- to 49-year age group of all Swedish trials should be analyzed to specifically estimate the natural history and performance of screening in this age group.

Adult↗
PubMed1995

Nation-wide breast cancer screening in The Netherlands: support for breast-cancer mortality reduction. National Evaluation Team for Breast Cancer Screening (NETB).

The nation-wide 2-yearly breast-cancer screening programme in The Netherlands, for women aged 50-69, started around 1988, and was predicted to result eventually in a 16% reduction in breast-cancer mortality in the total female population. We present the results of screening up to January 1, 1993, and compare these with the predicted results from the cost-effectiveness analysis, on which basis this mortality reduction has been calculated. At least 550,000 women aged 50-69 were invited to screening in 1990-1992, and 75% of these participated. Cancer was suspected from 5,162 examinations and further investigation was therefore required. Excision biopsy was done in 72% of referrals, and 2,515 breast cancers were detected. The results for 404,000 newly invited women compare favourably with expected values (in parentheses): 78% attendance rate (70%), 1.4% screen positive (1.6%), 6.8 cancers detected per 1,000 women screened (6.4) and 38% of these cancers were DCIS or invasive carcinomas smaller than 11 mm in diameter (36%). More data, e.g., on treatment and interval cancers, will follow in the years to come. These first results can be interpreted as strong early signs of a reduction in breast-cancer mortality of at least the predicted size. Screening has sufficiently advanced the diagnosis, as well as or better than expected. Breast cancers diagnosed in this age group without screening are diagnosed at a worse stage than expected. Unfavourable side-effects, especially false-positive referrals, might be kept lower than those reported in other countries.

Aged↗
PubMed1995

Mechanism of action of dexniguldipine-HCl (B8509-035), a new potent modulator of multidrug resistance.

It has previously been shown that dexniguldipine-HCl (B8509-035) is a potent chemosensitizer in multidrug resistant cells [Hofmann et al., J Cancer Res Clin Oncol 118: 361-366, 1992]. It is shown here that dexniguldipine-HCl causes a dose-dependent reduction of the labeling of the P-glycoprotein by azidopine, indicating a competition of dexniguldipine-HCl with the photoaffinity label for the multidrug resistance gene 1 (MDR-1) product. Exposure to dexniguldipine-HCl results in a dose-dependent accumulation of rhodamine 123 in MDR-1 overexpressing cells. In the presence of 1 microM dexniguldipine-HCl, rhodamine 123 accumulated in multidrug resistant cells to similar levels as in the sensitive parental cell lines. At this concentration, dexniguldipine-HCl enhances the cytotoxicities of Adriamycin and vincristine. The resistance modulating factors (RMF), i.e. IC50 drug/IC50 drug + modulator, were found to be proportional to the expression of MDR-1, ranging from 8 to 42 for Adriamycin and from 16 to 63 for vincristine. Transfection with the MDR-1 gene was found to be sufficient to sensitize cells to the modulation by dexniguldipine-HCl. The compound does not affect the expression of the MDR-1 gene. Dexniguldipine-HCl has no effect on a multidrug resistant phenotype caused by a mutation of topoisomerase II. It is concluded that dexniguldipine-HCl modulates multidrug resistance by direct interaction with the P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

The specific bisindolylmaleimide PKC-inhibitor GF 109203X efficiently modulates MRP-associated multiple drug resistance.

The newly identified drug transporter MRP is functionally linked to a multiple drug resistance independent from P-glycoprotein. Resistance modifiers for this type of MDR are rare at present. We analyzed the modulating effect of the highly selective bisindolylmaleimide PKC inhibitor GF 109203X on the MRP overexpressing human MDR sublines HL60/AR and GLC4/ADR. Applying a 72 hour MTT-assay we demonstrate a complete reversal of the vincristine resistance of HL60/AR cells. Adriamycin resistance of HL60/AR, or vincristine resistance of GLC4/ADR were partially reversed. Furthermore, rhodamine 123 efflux from HL60/AR was strongly modulated by GF 109203X. Since the PKC inhibitor did not significantly influence MRP gene expression at the mRNA level which was examined by cDNA-PCR, our results suggest either a direct interaction of the compound with MRP or/and an indirect influence on MRP activity via altering the phosphorylation status of the transporter.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

In search of the best upper age limit for breast cancer screening.

The aim of this study was to determine the best upper age limit for a breast cancer screening programme. We used a model-based study using optimistic and pessimistic assumptions, concerning improvement of prognosis due to screen-detection and duration of the period of mammographic detectability, resulting in upper and lower limits for favourable and unfavourable effects. Under pessimistic assumptions, the balance between positive and negative effects of screening remains favourable up to an age of around 80 years. Under optimistic assumptions, this balance never becomes clearly negative with increase of the upper age limit of a screening programme. When including the costs in the analysis, the balance between effects and costs of increasing the upper age limit from 69 to 75 years is likely to be at least as favourable as intensifying a screening programme within the age group 50-69 years. A further increase leads to a markedly less favourable balance. Competing causes of death do not lead to missing net benefit for women up to at least age 80 years, but the disproportional rise of negative effects of screening with age in older women leads to a lower cost-effectiveness ratio than intensifying screening at ages 50-69 years.

Adult↗
PubMed1995

A model-based prediction of the impact on reduction in mortality by a breast cancer screening programme in the city of Florence, Italy.

The efficacy of breast cancer screening for women older than 50 years has been shown in several studies. Service screening is now ongoing or planned in several countries in Europe. MISCAN, a computer simulation programme, has been used to analyse data from the Florence District Programme (FDP) breast cancer experience. First, the model was fitted to the screening results for the period 1975-1986. A good correspondence between the model outcomes and the FDP results was achieved. It was then used to predict the impact on mortality of the new starting programme of the city of Florence (63,000 women, 50-69 years old). Assuming a 70% attendance rate, then for the city of Florence, 2563 screen-detected breast cancers are predicted for the period 1991-2020 out of the total number of 9095 breast cancers for all ages (28%). A total of 3720 deaths for breast cancer are expected without screening. An absolute reduction of 472 deaths (13%) is predicted for the whole population. The estimated number of years of life gained by screening until 2020 is 4354. Simulation by MISCAN has previously been a useful support tool for decision-making about screening. The present paper is the first based on a southern European experience. The possibility of applying MISCAN to predict the impact of a national programme in Italy is discussed.

Adult↗