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Biomedical subjects

P G Peer

Publications and source records attributed to P G Peer.

At least 19 recordsLinked to original sources

Diverging breast cancer mortality rates in relation to screening? A comparison of Nijmegen to Arnhem and the Netherlands, 1969-1997.

Age-standardised breast cancer mortality rates have been stable for decades. However, rates have started to decline in several Western countries. In countries where population-based screening programmes for breast cancer were introduced in the late 1980s or early 1990s, the key question now is to what extent screening is responsible for the reported declines in mortality. This study compares breast cancer mortality rates in Nijmegen, where a screening programme for breast cancer was introduced in 1975, to a control city, Arnhem, and to the Netherlands as a whole over a 20-year period. Age-standardised breast cancer mortality rates as well as age-standardised mortality ratios were calculated for successive calendar years from 1969 to 1997. Further, a tailor-made period-cohort-group Poisson regression model was fitted. Figures displaying age-standardised mortality rates and ratios showed inconclusive patterns with regard to the expected impact of screening. Depending on when mortality rates were allowed to deviate between populations, the period-cohort-group analysis indicated a non-significant 6% to 16% reduction in breast cancer mortality after 2 decades in favour of the Nijmegen female population. Possible explanations are discussed as to why the mortality reductions reported by randomised trials might not be observed in a public health screening programme, such as the Nijmegen programme, evaluated by comparisons of geographical trends.

Aged↗

Assessment of myocardial velocities in healthy children using tissue Doppler imaging.

The objective was to determine the normal range of tissue velocities in paediatric hearts as measured by tissue Doppler imaging. A prospective study was carried out involving 160 healthy children (mean age 10.8 y, range 4.0-17.9 y). Using tissue Doppler imaging (TDI) from parasternal long axis and apical views, peak velocities and peak myocardial velocity differences across the right ventricular anterior wall, interventricular septum and left ventricular posterior wall were assessed during systole, early and late diastole. The existence of transmyocardial velocity differences between the left and right side of the interventricular septum, as well as between the endocardium and epicardium of the left ventricular posterior wall was observed throughout the heart cycle. With range-gated TDI from apical four-chamber view, peak velocities were measured within the basal, mid and apical parts of the interventricular septum, and the left and right free ventricular walls. The highest peak systolic, early and late diastolic velocities were measured within the basal parts of all myocardial walls. The ranges of the calculated velocity ratios (early-to-late diastolic velocity and early diastolic-to-systolic velocity) for the various wall parts appeared to be overlapping. The correlations of peak myocardial tissue velocities and their ratios with age and weight were weak and practically irrelevant. These normal values of peak myocardial velocities, transmyocardial velocity differences and the ratios of peak wall velocities can be used as reference values in future investigations of ventricular dysfunction in this age group.

Adolescent↗

Pain experienced by women attending breast cancer screening.

The purpose of this study was to evaluate the pain experience of women during mammography for breast cancer screening. Possible associations with personal and medical history, sociodemographics and/or situational factors were studied. It was also investigated whether this pain influenced the intention to return for future breast cancer screening. In the Netherlands, women between 50-75 years are invited for screening every two years. A total of 1200 participants were asked to fill up a questionnaire. The response rate was 79.5% (n = 954), and 945 questionnaires contained adequate information for analyses. A total of 689 women (72.9%) described mammography as mild to severely painful. In this group, compared to the group that reported no pain, the following factors occurred significantly more often: sensitive breasts (P = 0.001), family history of breast diseases (P = 0.017); expected pain based on former mammography (P = 0.001), high education (P = 0.008), anxiety (P = 0.001), breast sensitivity in last three days (P = 0.001), insufficient attention of technologist (P = 0.001). Other factors like age, hormonal status, breast size and hormone use were not associated with the pain experienced. Thirty-two women (3.3%) indicated that they would not attend further screening, 25 (2.6%) reported that the pain might deter them, six women (0.6%) had other reasons, one woman (0.1%) was sure not to come because of severe pain. In conclusion, a large majority of women attending breast cancer screening describes mammography as painful (72.9%). Factors associated with pain were described. Relatively few women (2.7%) indicated that the pain might deter them from future mammography. Recommendations are given to reduce the pain experienced during screening mammography.

Aged↗

Screen-detected breast cancers have a lower mitotic activity index.

We know that screening for breast cancer leads to detection of smaller tumours with less lymph node metastases. Could it be possible that the decrease in mortality after screening is not only caused by this earlier stage, but also by a different mitotic activity index (MAI) of the tumours that are detected by screening? Is MAI a prognostic factor for recurrence-free survival? A retrospective study was carried out of 387 patients with breast cancer, treated at the University Hospital Nijmegen between January 1992 and September 1997. Ninety patients had screen-detected breast cancer, 297 patients had breast cancers detected outside the screening programme. The MAI, other prognostic factors and recurrence-free survival were determined. In non-screen-detected tumours the MAI is twice as high as in screen-detected tumours, even after correction for age took place. The MAI correlated well with other tumour characteristics. The MAI in itself is a prognostic factor for recurrence-free survival. Favourable outcome in screen detected breast cancer is not entirely caused by detecting cancer in early stages: quantitative features such as the MAI indicate a less malignant character of screen detected breast cancer. The MAI is an independent prognostic factor for recurrence-free survival.

Age Factors↗

A study on effectiveness of screening mammograms.

BACKGROUND: So far, no randomized controlled trials with a mean mammographic screening interval of > or = 2 years has demonstrated statistically significant mortality reduction for women younger than age 50. The issue of screening frequency is vital in detection of primary breast cancer. METHODS: The study group consisted of cancers diagnosed in women who participated in a serial screening programme with a mean screening interval of 2 years. To study the effectiveness of the screening, a comparison is made between the distribution of age at which the tumour could be detected when biennial mammographic screening is the only detection method, and the distribution of age at which the tumour would be detected by either biennial mammographic screening or the development of symptoms. Some recently developed statistic methods, such as bootstrap, the maximum likelihood distribution estimator for doubly censored data and the EM algorithm, are used in estimation of these distributions. RESULTS: The hypothesis tests and confidence intervals show that the difference between the two distributions was statistically significant for women younger than 50 and 50-70 years old, but not for women over 70 years. CONCLUSIONS: The statistical analysis indicates that for women younger than 50, and 50-70 years of age, a screening mammogram every other year is not frequent enough to detect primary breast cancer, but for women over 70 years, it might be sufficient.

Age Distribution↗

Estimating lead time and sensitivity in a screening program without estimating the incidence in the screened group.

Early indicators of the effectiveness of a screening test for chronic diseases such as breast cancer are the length of time the diagnosis is advanced by screening, the lead time, and the sensitivity of the screening test. This paper describes a model for simultaneously estimating the mean lead time and the sensitivity when only the number of cancers detected at the successive screenings and the number of cancers occurring in the time interval between the screening examinations are known. This model is particularly useful in assessing the effect of screening when the underlying cancer incidence in the screened group is unknown. The model is fitted to the data of 235 screen-detected breast cancer cases and 146 interval cancers diagnosed across 6 screening rounds of the program in Nijmegen. The maximum likelihood estimate for the mean lead time ranges from 1.3 years in the under age 50 group to 2.2 years in the age 50-65 group, both estimates having large confidence intervals. The corresponding sensitivity estimates are 0.92 and 1.00.

Adult↗

Age-specific sensitivities of mammographic screening for breast cancer.

The sensitivity of the mammographic screening test in the biennial screening program of Nijmegen is assessed by analyzing the occurrence of interval cancers, i.e. cancers surfacing clinically in the interval between a negative screening examination and the subsequent scheduled examination. The difference between the observed number of interval cancers and the expected number of clinically manifest cancers in the absence of screening for the interval period reflects the number of cancers detected by screening. The expected number should be limited by the number of those cancers that were not detectable at the time of the screening examination because their size was under the threshold of mammographic detectability (5 mm). In contrast to other sensitivity studies we took these 'fast growing' cancers into consideration, the numbers of which are estimated in each of the six-month periods of the two-year interval using age-specific tumor volume growth rates for three age groups: < 50, 50-69, and > or = 70 years. In patients under age 50, the sensitivity was 64% for cancers which would become clinically manifest within one year after screening. This sensitivity was lower than those obtained from the 50-69 and > or = 70 age groups, being 85% and 80%, respectively. For cancers that would become clinically manifest 12-18 months after screening, sensitivity decreases to 22% in the under age 50 group, and to 56% and 65% in the two above age 50 groups, respectively. We conclude that even when adjusted for growth rate, the mammographic screening test has a poor performance in the under age 50 group.

Adult↗

Prognosis of younger and older patients with early breast cancer.

The use of mammography in recent years has resulted in an increase in the detection of small breast cancers. The beneficial effects of early detection on breast cancer mortality seem to differ with age. To obtain more insight into this matter we studied the long-term prognosis of patients with early invasive breast cancers (T1) in three age groups: 144 patients of age 40-49, 402 patients of age 50-69 and 192 patients 70 years or older at diagnosis. In all age groups, patients with a tumour of 1 cm or less have a longer breast cancer specific survival than patients with a tumour larger than 2 cm. The survival advantage in the case of tumours of a size rounded to 1.5 cm compared with tumours larger than 2 cm in the under age 50 group was marginal (and not significant). However, older patients with tumours of this size do have a significantly improved survival. It is more difficult to improve survival in younger patients through early detection, partly because of an apparent early metastatic potential of their tumours. A reduction in breast cancer mortality might be expected in women younger than 50 years of age only if a substantial proportion of the invasive cancers are detected before their size exceeds 1 cm.

Adult↗

Long term breast cancer screening in Nijmegen, The Netherlands: the nine rounds from 1975-92.

STUDY OBJECTIVE: To assess the performance of breast cancer screening in different age categories over two decades. DESIGN: Important determinants of reduced breast cancer mortality such as attendance, mammography performance, cancer detection, and disease stage were recorded. SETTING: Nijmegen, The Netherlands, 1975-92. SUBJECTS: Since 1975 more than 40,000 women aged 35 years and older have been invited biennially for breast screening in a population based project in Nijmegen. MAIN RESULTS: Rates of attendance, referral, detection, and disease stage were calculated, as well as the specificity of screening mammography and the predictive value of referral and biopsy. From round 3 onwards, the attendance rate of women younger than 50 years stabilised at 70%, in women of 50-69 years it was 62%, and in women aged 70 and over it was 22%. In these three age categories, the referral rates of a positive screening mammography per 1000 screened women were 4.9, 6.2, and 11.8, respectively. Specificity rates were between 99% and 100%. Current predictive values of referral were high: in the specific age categories 39%, 59%, and 68% of the referred women had cancer. Detection rates remained fairly stable over the rounds 4-9, at 1.9, 3.6, and 8.0 cancers per 1000 screened women. In the two year period between screening the numbers of interval cancers per 1000 screened women were 2.2, 2.2, and 2.9, for the three age categories respectively. With regard to invasive cancers detected during screening, the percentage of small tumours (< or = 20 mm on the mammogram) was 84% in each age category. For women younger than 50 years, the proportion of intraductal carcinoma in all the cancers detected at screening was 40%, while it was 15% in the other age categories. CONCLUSION: Throughout the nine rounds, the screening outcomes were found to be adequate, particularly considering the high specificity rate and the predictive value of referral without the interference of a low detection rate. Although the occurrence of interval cancers seemed high, it was similar to other screening programmes. Despite a relatively low referral rate, the ratios of screen detected versus interval cancer cases were favourable. Well organised screening programmes can achieve good mammography results without too many false positives. It is important that women continue to participate in a screening programme because cancer can still be detected even after several successive negative screening examinations.

Adult↗

Effect on breast cancer mortality of biennial mammographic screening of women under age 50.

The effects on breast cancer mortality seen after 16 years of biennial screening of younger women are assessed in this prospective cohort study. Since 1975 some 13,500 women, aged 35-49 in 1975, were invited to participate in the Nijmegen screening programme comprising a mammographic examination every 2 years. By the end of 1990, 75 women had died of breast cancer out of the 332 cases diagnosed after the start of the screening project. Women from the same birth cohort, living in Arnhem, a neighbouring city with a comparable population and without a screening project, were used as controls. In this city, 74 breast cancer deaths out of 284 cases occurred during the same period. In Nijmegen, after 16 years of follow-up, breast cancer mortality showed a non-significant reduction of 6% (95% confidence interval: 32% reduction, 29% excess). In the relevant period, after a time lag of 10 years from the start of the programme, this reduction rose to 20% (95% confidence interval: 48% reduction, 23% excess). No reduction in breast cancer mortality was observed in the first decade of screening. For a later period, a shift towards a reduction emerges, but the data are as yet inconclusive.

Adult↗

Sample size determination for a trial of breast cancer screening under age 50: population versus case mortality approach.

OBJECTIVE: To determine the efficacy of screening for breast cancer in women aged 40 to 49. METHODS: A large number of women will have to be enrolled to ensure adequate statistical power. Attention will be restricted to the deaths from breast cancer that occur among comparable groups of patients with breast cancer rather than to an analysis in which all women entering into the trial are considered at risk of dying from breast cancer (population mortality analysis). As the new trial is likely to be conducted in regions where screening has been established for all women from age 50 onward, comparability may be reached by including the breast cancers detected at the routine screening examination at age 50. CONCLUSIONS: When comparability of cases can be reached, such a case mortality analysis requires 15-30% fewer women to be enrolled than a population approach.

Adult↗

Age-specific effectiveness of the Nijmegen population-based breast cancer-screening program: assessment of early indicators of screening effectiveness.

BACKGROUND: The benefits of mammographic screening for breast cancer are not clear for women less than 50 years old. PURPOSE: Our aim was to evaluate the effectiveness of breast cancer screening in different age groups. METHODS: A mammographic breast cancer-screening program with a 2-year screening interval has been under way in Nijmegen, The Netherlands, since 1975. After eight rounds, more than 40,000 women have been invited to participate. All breast cancer cases diagnosed in the invited population, whether detected by screening or clinically, have been considered in this study. The age groups are younger than 50 years, 50-69 years, and 70 years or older at last invitation before diagnosis. Our assessment of the effectiveness of screening is based on the proportion of screen-detected cancers among all cancers and on the disease stage at diagnosis. RESULTS: For women younger than 50, compliance was 75%, and 37% (85/230) of the cancers were detected by screening. The age group 50-69 years had a compliance of 65% with 48% (288/595) of cancers detected by screening, and the group 70 years or older had a 25% compliance with 35% (108/305) of cancers detected by screening. The sizes of the cancers detected by screening were smaller than those detected clinically for all age groups. The age group under 50 showed no substantial difference in the proportion of positive axillary lymph node status between screening-detected and clinically diagnosed cancers, while among older women, the proportion of lymph node involvement was substantially higher for clinically detected cases. A significantly lower frequency of advanced stages was observed in screen-detected compared with clinically diagnosed cancers for women 50 years of age or older (P < .001) but not in women under 50 (P = .35). CONCLUSIONS: No positive effect of the biennial screening program is apparent for women under age 50. For women aged 50 and above, the screen-detected cancers have a more favorable stage distribution than clinically diagnosed cancers, a prerequisite for a reduction in breast cancer mortality.

Adult↗

The phase of the menstrual cycle has no influence on the disease-free survival of patients with mammary carcinoma.

We evaluated the outcome of treatment for mammary carcinoma in 89 premenopausal women in relation to the phase of the menstrual cycle. The phase of the cycle was determined on the basis of serum concentrations of 17 beta-oestradiol and progesterone. The serum samples were collected 1 day prior to or on the day of operation. After a median follow-up of 4.1 years no significant differences in disease-free survival were found between the preovulatory (proliferative), periovulatory and post-ovulatory (luteal) groups. No differences in survival were found in these subgroups between the N0 and N1 subgroup. On the basis of this study we cannot confirm that the phase of the menstrual cycle during surgery has any effect on the eventual outcome in mammary carcinoma patients. However larger studies of this type are required before definitive conclusions can be reached.

Antineoplastic Combined Chemotherapy Protocols↗

Age-dependent growth rate of primary breast cancer.

BACKGROUND: Currently, there have been no reports of clear-cut beneficial effects of regular screening with mammography at a mean screening interval of 2 years in women younger than 50 years of age. It may be that, because of a higher growth rate of breast cancer, more frequent screening is necessary if any effect is to be observed in this age group. However, good quantitative estimates for the growth rate in different age groups are lacking. METHODS: The study group consisted of cancers diagnosed in women who participated in a screening program with serial mammography available. The growth rate, expressed as the tumor volume doubling time, was calculated on the assumption of exponential growth. The analysis was based, not only on the increase in tumor volume for cancers with at least two mammograms showing a measurable tumor nucleus shadow (n = 85), but also on censored values, calculated for cancers showing no growth (n = 6) and for cancers showing only a measurable tumor nucleus shadow on the mammogram at diagnosis (n = 109). In calculating these latter growth rates, the density of the breast parenchyma was taken into account. RESULTS: The median volume doubling time of the primary breast cancers diagnosed in women aged 50-70 years was 157 days (95% confidence limits, 121-204 days). This was significantly longer than in women younger than 50 years of age at diagnosis (80 days; 95% confidence limits, 44-147 days). Primary breast cancer in women older than 70 years of age at diagnosis grew even more slowly (median, 188 days; 95% confidence limits, 120-295). CONCLUSIONS: To observe a beneficial effect of screening, if any, for women younger than age 50 years, more frequent screening than in the older age group is necessary.

Age Factors↗

Continuation and maintenance therapy with antidepressive agents. Meta-analysis of research.

The purpose of this study was to ascertain the clinical benefits of long-term antidepressant drug treatment in patients with recurrent major depression. Bibliographic reviews of four textbooks and five review articles, literature searches using MEDLINE (1977-1987) and EXCERPTA MEDICA (1974-1987), hand-searching of the bibliographies of identified papers, and a private set were used for data identification. The most informative, definitive research report was selected using explicit criteria for evaluating study design and quality, of each described, randomized, controlled, double-blind trial of long-term antidepressant agent treatment. The trials were started at a specified period after recovery from an affective episode, in patients with major depression. Of the fifty-five originally identified articles, nine were selected that specifically addressed this purpose. The basic data were extracted in the form of 2 x 2 tables comparing the number of patients with an affective relapse to those remaining well and meta-analysed. Six of the selected trials addressed continuation and three addressed maintenance therapy. In two trials of continuation and in one trial of maintenance treatment, antidepressants were significantly more active than a placebo. In none of the trials were antidepressants inferior to a placebo. Continuation therapy with antidepressants (amitriptyline and imipramine) is effective. There are insufficient data to allow any conclusions about the efficacy of maintenance therapy with antidepressants, long-term treatment with antidepressants relative to that with lithium carbonate, or long-term antidepressant treatment in patients with chronic depression.

Antidepressive Agents↗