Prognostic assessment in node-negative breast cancer patients.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to A L Verbeek.
Explore the source record for details and available documents.
Breast cancer screening with mammography is strongly advocated by some and rejected by others. Discussions in the medical literature focus on the beneficial and unfavourable effects of breast cancer screening. Among the latter are the suggested excess mortality rate of screen-detected breast cancer patients, the high number of unnecessary biopsies, the possibility of overdiagnosis and subsequent unnecessary treatment, and the occurrence of interval breast cancer cases. It is concluded that screening can to a certain extent prevent women from dying of breast cancer but some negative effects are unavoidable. However, adequate training of the screening team can minimize the number of unnecessary biopsies and the occurrence of interval cancers. Research is needed to evaluate the natural course of so-called 'minimal' lesions, and to optimize screening tests. The search for new (imaging) techniques is needed to detect lobular cancers in dense breasts.
Patients with achlorhydria are suspected to have an increased risk of developing gastric adenocarcinoma. However, in the literature the reported risk varies considerably. In The Netherlands no such data are available. The risk of developing gastric adenocarcinoma was investigated in 129 achlorhydric patients. During a mean observation period of 12.3 yrs gastric adenocarcinoma was diagnosed in six patients. The expected incidence was 1,275, calculated by making use of age, sex and calendar specific incidence and mortality rates of gastric cancer in the Dutch population. The relative risk to develop gastric cancer was 4.7 (95% confidence limits: 1.7-10.2; p less than 0.05). Despite a significantly increased risk, screening of achlorhydric patients for gastric cancer is not advised.
The costs and effects of different invitation schedules of breast cancer screening are compared. The effect estimates are based on trials from the USA, Sweden and the Netherlands. The cost estimates use registration data, file studies and organization charts. The calculations were performed with the MISCAN computer simulation package, which is developed especially for the evaluation of mass screening programmes. Screening women of 50-70 years at 2-yearly intervals is a relatively cost-effective schedule. In a real population, it will reduce breast cancer mortality by 12%. Screening of women under 50 is probably far less cost-effective. Screening induces a considerable shift towards breast-conserving therapy. Although a 12% mortality reduction may seem low, in absolute numbers this represents more than the total mortality from, e.g., cervical cancer. Moreover, cost per death prevented or per life-year saved is much lower than for most other medical interventions for which cost-effectiveness ratios are known, screening for cervical cancer included.
A population-based screening programme for breast cancer was initiated in Nijmegen in 1975 with mammography as the only screening procedure. Up to January 1987, 6 screening rounds were carried out with a 2-year screening interval. Rates of attendance, referral, biopsy and detection were calculated and numbers of interval cancers are presented in order to give a clear view of what repeated screening can accomplish in a population. At the first screening round the attendance rate was 87% for women under age 50 and 83% for women aged 50-64. For women aged 65 or over the initial attendance rate was 40%. Rates of attendance declined in subsequent years. Detection rates were highest for elderly women at their first examination: 9.5 per 1,000 screened women. Corresponding rates were 5.6 and 2.3 per 1,000 for women aged 50-64 and below 50 respectively. The positive predictive value for referral was, on average, 20% for women under age 50 and 50% for elderly women, although a sharp increase was seen in the last 2 screening examinations for all age-groups. Predictive values for biopsy were higher: 30% on average for women aged under 50 and 60%-70% for elderly women, again with a sharp increase in the last 2 screening rounds. Interval cancer rates, calculated as the number of cancers occurring within 2 years among negatively screened women at risk, showed no particular trend and varied between 0.9-1.3 per 1,000 woman-years after each screening round. Compared to screen-detected cancers, interval cancers occurred more frequently in younger women. In women under age 50, the ratio between screen-detected and interval cancer was about 1:1, while it was about 2:1 for elderly women.
Decision analysis was used to evaluate the results of treatment of T2N0M0 glottic carcinoma as presented in the literature. Based on mean values for recurrence, salvage eligibility after recurrence and salvage success, the 5-year survival after radiotherapy and surgery proved to be almost identical, 85 and 86%. If the recurrence rates and the salvage rates were varied, a marginal advantage for surgery in small tumours (T2a) and a major advantage in more extended (T2b) tumours was seen if only survival is considered. To take the quality of speech into account, a utility analysis was performed. A utility scale was defined ranging from 0.0 as the value for death, to 1.0 for a successfully irradiated patient with preservation of normal speech. A utility of 0.99 or less for the laryngectomized patient would favour radiotherapy over surgery for all T2 tumours. In patients with T2b tumours and in extreme circumstances, e.g. if failure rates of radiotherapy are extremely high or if recurrence rates after surgery are extremely low, an exact assessment of patient utilities may be pivotal. Under normal circumstances radiotherapy is preferred for T2N0M0 glottic carcinoma if both survival and the quality of speech are taken into account.
In a study of 213 patients with oral cancer, we investigated the incidence and prognosis of lung malignancies in patients offered a yearly chest radiography in the follow-up. Three conclusions can be drawn. (1) Metastatic or primary lung cancer was diagnosed in 22 (10.3%) patients. The 2-year actuarial incidence rate of lung cancer following cancer of the oral cavity is 13%. No new lung cancers were detected after 2 years follow-up. This suggests that after this period, yearly chest radiography may be superfluous for the early detection of lung cancer. (2) The survival rate of patients with a lung malignancy following cancer of the oral cavity is poor (1-year = 25%). The survival rate of patients detected by the yearly chest radiography without symptoms is higher than for patients detected after symptoms (p = 0.006). It is not clear to what extent this different survival rate is biased by lead-time and selection of patients with a favourable prognosis. A randomized study would be required to assess whether patients with oral cancer do benefit from the yearly chest radiography compared with no regular chest radiography. (3) Of 22 patients with lung cancer, 13 (59%) were detected by chest radiography without symptoms. In the first year following oral cancer, 11 patients were diagnosed with lung cancer. Only 4 of these 11 patients (36%) were detected by chest radiography in an asymptomatic stage. The detection of patients with lung cancer in an asymptomatic stage may be increased by more frequent chest radiography examinations in the 1st year following oral cancer.
Since January 1975 a population-based screening programme for the early detection of breast cancer has been carried out in the city of Nijmegen. During five interscreening periods of 2 years each a total of 158 so-called interval cancers were diagnosed. Careful revision of all screening and diagnostic mammograms was executed. Of all interval cancers 26% were 'missed' at the previous screening examination (due to technical or observer error), 16% were radiographically occult at the time of diagnosis and 58% were 'true' interval cancers. Interval cancers were regarded as 'true' when an obvious lesion was observed on the diagnostic mammogram while no suspect signs were seen on the previous screening mammogram. The prevalence of 'missed' cancers did not decline in the course of the screening programme. Radiographically occult tumours were localised, mostly in Wolfe's P2/DY breast parenchyma (83%), 33% were lobular invasive and 25% ductal non-invasive. 'True' interval cancer cases (58%) showed the same overall survival as control breast cancer patients, diagnosed in a non-screening situation. Shortening the screening interval would reduce interval cancer rates and probably further decrease breast cancer mortality in a screened population. However, from the present series of interval cancers 63% would not have been prevented by an annual screening examination. As regards women under age 50 annual screening would still leave 66% of all interval cancers in this age group undetected. Probably more benefit will be gained by searching for new imaging techniques to reduce numbers of 'missed' cancers and to detect lobular invasive and ductal non-invasive cancers in dense breast parenchyma.
After 12 years of screening for breast cancer in Nijmegen (1975-86), during which period six mammographic examination rounds were carried out, the extent of overdiagnosis was evaluated. Overdiagnosis is defined as a histologically established diagnosis of invasive or intraductal breast cancer that would never have developed into a clinically manifest tumour during the patient's normal life expectancy if no screening examination had been carried out. The whole 12-year period shows an excess of 11% of breast cancer cases in Nijmegen, compared with the neighbouring city of Arnhem, where no mass screening was performed. The incidence of breast cancers in Nijmegen in the period 1975-78 is higher, compared with the incidence rates in Arnhem; the rate ratio is 1.30. For the time-intervals 1979-82 and 1983-86 the rate ratios are 1.03 and 1.01 respectively with (0.89; 1.18) and (0.86; 1.16) as 95% confidence intervals. This leads to the conclusion that there is no evidence that screening programmes using modern mammography constitute a significant risk for overdiagnosis of breast cancers.
The study comprised 223 patients with airflow obstruction and/or bronchial hyperreactivity from 29 general practices in the catchment area of Nijmegen University. Fifty-six patients were treated by 19 chest physicians, the remaining 167 by their general practitioners (GPs), without specialist care. The specialists treated more allergic patients than the GP (p less than 0.05). No other relevant differences in sex, age, smoking behaviour, and severity of the disease (symptoms, lung function, and bronchial hyperreactivity) could be observed between these two groups of patients. Chest physicians prescribed almost three times as many drugs as GPs. No immediate response to the prescribed bronchodilators was found in 16% of the patients treated by the GPs, nor in 20% of the patients treated by the specialists. We could identify only a weak relationship between the severity of the disease (symptoms and pulmonary function combined) and the prescribed pharmacotherapy: with growing degrees of severity the GP seems to prescribe more bronchodilators, the specialist more inhaled corticosteroids. Prescribed pharmacotherapy should be based on the combination of symptoms, pulmonary function, bronchial hyperreactivity, and reversibility on the prescribed bronchodilators.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Using the immunoblotting technique, sera from 433 patients with rheumatic diseases were screened for the presence of antibodies against several nuclear and cytoplasmic antigens, such as RNP, Sm, Ro(SSA), La(SSB), CR-19 (centromeric antigen), Topo-1 (Scl-70), Jo-1, histone and 56 kD. At the same time clinical data from these patients were collected without prior knowledge of the immunoblotting results. Syndrome-specific autoantibodies were found for mixed connective tissue disease (antibodies against the RNP related 70 kD antigen), for CREST (anti-CR-19 antibodies), for diffuse scleroderma (anti-Topo-1 antibodies) and for polymyositis (anti-Jo-1 antibodies). Almost all specific autoantibodies were present exclusively in patients with a connective tissue disease. Controls were only in a few cases positive for antihistone and anti-56 kD antibodies. Associations of specific autoantibodies with clinical and laboratory features of the patients were mostly as expected. However, some unexpected associations were found, for example polymyositis and calcinosis with anti-Sm antibodies, sicca symptoms with anti-centromere antibodies and leucopenia with Ro(SSA) and La(SSB).
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
After 10 years of screening for breast cancer by mammography in Nijmegen, the predictive value of positive screening results (PV+) was evaluated. The percentage of women with breast cancer in the group of referred women (PV+) for women under age 50 was 16-26%, regardless of the number of screening examinations they had. The percentage of women with breast cancer in the group of women who were biopsied was 25-40%, regardless of the number of examinations. For women aged 50 and over the predictive value was 34-57% and 58-90% respectively. It was further evaluated whether characteristics such as age, Quetelet index, parity, and Wolfe-classification could be used to increase the PV+ in women who were identified as positive by mammography. A logistic regression model analysis showed that true-positive and false-positive cases differ significantly only in terms of age and breast complaints. Although the model had a good fit, it could not be used to distinguish false-positive from true-positive test results.