[Granulomatous lobular mastitis: a benign abnormality that mimics malignancy]. / Granulomateuze lobulaire mastitis: een benigne afwijking die imponeert als maligniteit.

A palpable abnormality of the breast was found in three women, one aged 57 and two aged 41. The first two patients predominantly showed the characteristics of a purulent inflammation, and on mammogram the third patient appeared to have mastitis carcinomatosa. Histopathological investigation revealed a lobular, non-caseating granulomatous inflammation. They were treated with prednisone and the first and third patients also received azathioprine. After some time, the condition recurred in the contralateral breast in the second and third patients. Once again, medicinal treatment was given. When a palpable tumour of the breast is found the primary goal is to exclude malignancy. Granulomatous lobular mastitis is a rare and benign tumour of the breast that clinically mimics carcinoma. Often, conventional imaging does not lead to the diagnosis. A histological needle biopsy is the best way to reach a diagnosis. Immunosuppressive therapy is effective and is preferred over surgery.

Baseline human papillomavirus status of women with abnormal smears in cervical screening: a 5-year follow-up study in The Netherlands.

OBJECTIVE: To determine in a screening population the human papillomavirus (HPV) status in those with cytological abnormalities and to evaluate the presence of high-risk (HR) HPV with a minimum of 5-year follow up. DESIGN: Retrospective examination of HPV status on prospectively collected and cytologically screened cervical smears. SETTING: Canisius-Wilhelmina Hospital in Nijmegen, The Netherlands. POPULATION: Three hundred and fifty-seven women aged 30-60 years, from the population screened. METHODS: Three hundred and fifty-seven women with borderline or higher cytological abnormalities were retrospectively examined for HPV with DNA microarray typing. Follow up was through the nationwide Dutch Pathology database (PALGA). MAIN OUTCOME MEASURES: For the cytological abnormalities, the CISOE-A classification was used. HPV was scored as negative or positive. In case of positive HPV polymerase chain reaction, the HPV genotype was determined. The occurrence of cervical intraepithelial neoplasia lesions of grade 3 or higher was considered as endpoint for follow up. RESULTS: The majority of the women with borderline cytology in this study were HPV negative (87%). Among the HPV-positive women in borderline cytology group, 74% had HR-HPV or probable high-risk types. The overall percentage of HR-HPV types increased with progressive cytological abnormalities. The cytological classifications of borderline dyskaryosis and moderate dyskaryosis contain all types of HPVs, e.g. low risk, HR and unknown risk. The samples with severe dyskaryosis or higher contain only HR types. The negative predictive value for HR-HPV typing in the group with borderline cytological abnormalities is more than 99%. CONCLUSIONS: In cervical screening with an interval of 5 years, HPV can be reliably used as triage point in cases of borderline cytological abnormalities.

[Intracystic carcinoma of the breast: diagnosis and treatment in retrospective investigation and published literature]. / Intracystisch mammacarcinoom: diagnostiek en behandeling in retrospectief onderzoek en literatuurgegevens.

OBJECTIVE: To describe policy and prognosis of patients with a cystic mammary lesion caused by an intracystic mammary carcinoma (ICMC). DESIGN: Retrospective, descriptive. METHOD: The study concerned retrospective analysis of 17 patients presenting with intracystic carcinoma of the breast in an educational clinic in the period 1988-2000, who were selected by searching the national pathology database (PALGA). None of the patients was on hormone replacement therapy. In addition a literature search was carried out in the Medline system. RESULTS: The patients with an intracystic carcinoma of the breast were 10 years older compared to the other breast cancer patients and presented themselves with a palpable mass. Mammography showed a single, well-defined and lobulated mass. Microcalcifications were uncommon. Ultrasound investigation showed a well-defined, inhomogenous and hypoechoic mass. 6 patients had encysted lesions and in 3 a solid, hypoechoic component within the cystic mass was found. Cytology of the cystic fluid is false negative in 36% (5/14). All patients were treated surgically, varying from excisional biopsy to modified radical mastectomy. In 15 patients an intracystic papillary carcinoma (ICPC) was found. 5 patients show a 'pure' ICPC. In the other 10 patients, 5 had an ICPC with a component of DCIS and 5 patients an ICPC with an invasive component. The median follow-up was 84 months (range: 28-165). In 15 patients no evidence of disease was found at follow-up; 2 patients developed local recurrence. The survival was 100%. CONCLUSION: Based on the investigation and on the available literature it is concluded that cysts in breasts of postmenopausal women, who do not use hormone replacement therapy, are malignant until proved otherwise. Ultrasound is invaluable in the diagnostic pathway of intracystic carcinoma of the breast. When ICPC is suspected excisional biopsy with sentinel node biopsy is the treatment of choice. The prognosis is good.

Coexisting high-grade glandular and squamous cervical lesions and human papillomavirus infections.

The frequency of high-risk human papillomavirus (hr-HPV) genotypes in patients with adenocarcinoma in situ (ACIS) with coexisting cervical intraepithelial neoplasia (CIN), ACIS without coexisting CIN, and high-grade CIN (CIN II/III) was studied, in order to gain more insight into the relation between hr-HPV infections and the development of coexisting squamous and glandular lesions. The SPF(10) LiPA PCR was used to detect simultaneously 25 different HPV genotypes in biopsies obtained from 90 patients with CIN II/III, 47 patients with ACIS without coexisting CIN, and 49 patients with ACIS and coexisting CIN. hr-HPV was detected in 84 patients (93%) with CIN II/III, 38 patients (81%) with ACIS without CIN, and in 47 patients (96%) with ACIS and coexisting CIN. A total of 13 different hr-HPV genotypes were detected in patients with CIN II/III, and only five in patients with ACIS with/without coexisting CIN. HPV 31, multiple hr-HPV genotypes, and HPV genotypes other than 16, 18, and 45 were significantly more often detected in patients with CIN II/III, while HPV 18 was significantly more often detected in patients with ACIS with/without CIN. There were no significant differences in the frequency of specific hr-HPV genotypes between patients with ACIS with or without coexisting CIN. In conclusion, the frequency of specific hr-HPV genotypes is similar for patients with ACIS without CIN and patients with ACIS and coexisting CIN, but is significantly different for patients with CIN II/III without ACIS. These findings suggest that squamous lesions, coexisting with high-grade glandular lesions, are aetiologically different from squamous lesions without coexisting glandular lesions.

Granulomatous angiopanniculitis of the breast. A case report.

BACKGROUND: Granulomatous angiopanniculitis (GAP) is a rare benign condition of the breast of unknown etiology. Clinically and by fine needle examination, GAP may simulate breast carcinoma. The cytologic characteristics have not been described before. CASE: A 63-year-old female exhibited a palpable mass in her left breast. The fine needle aspirate contained both epithelioid and stromal elements. The epithelioid component consisted of dissociated individual cells and small groups and clusters of atypical cells. The stromal component showed a uniform, not-atypical pattern. The lumpectomy specimen showed nonnecrotizing granulomatous panniculitis and lymphoid angiitis without involvement of ducts or lobules. CONCLUSION: Granulomatous lesions should be borne in mind in the differential diagnosis of breast cancer in fine needle aspiration cytology. GAP must be histopathologically distinguished from granulomatous inflammation in the breast of autoimmune or infectious origin as specific medical therapy may be available for these latter diseases.

Regression of invasive thymoma following corticosteroid therapy.

A case of invasive thymoma is presented showing tumour regression after palliative treatment with prednisone. Moderate doses of prednisone resulted in a longtime palliation via remarkable anti-tumour effect. The literature of corticosteroid responses of thymomas is reviewed.

Interpreting microbiopsies in cervical smears. A cytohistologic approach.

OBJECTIVE: To assess interobserver variation in the diagnosis of thick tissue specimens (microbiopsies) in cytology smears and histologic sections taken from them, to evaluate the applicability of MIB-1 in histologic sections from microbiopsies and to evaluate whether processing microbiopsies in inconclusive smears has additional diagnostic value. STUDY DESIGN: Cytologic smears were selected in which there were diagnostic disagreements between pathologists and cytologists and microbiopsies were present. Interobserver variation among three pathologists and three cytologists in the diagnosis of these microbiopsies was investigated. The smears were processed for histologic sections, and interobserver variation between pathologist diagnoses were analyzed. An additional histologic slide stained for MIB-1 was used for consensus diagnosis. The consensus diagnosis was compared with available follow-up and its sensitivity and specificity determined. The value of applying the microbiopsy technique in slides diagnosed as inadequate or atypical squamous cells of undetermined significance (ASCUS) was analysed. RESULTS: From a series of 62,334 cervical smears, 49 with microbiopsies were selected. It was possible to derive histologic slides from 38 cases. Interobserver variability in the diagnosis of microbiopsies and histologic sections from them was moderate--kappa = .44 (SE = .06) and kappa = .44 (SE = .09), respectively. In the consensus meeting for all cases, a conclusive diagnosis was reached. The Pearson correlation coefficient between the consensus diagnosis and MIB-1 staining was r = .62. The sensitivity of the consensus diagnosis for the follow-up diagnosis was 71% and the specificity 60%. Diagnosis on approximately 50% of slides diagnosed as inadequate or ASCUS could be made. CONCLUSION: The histotechnical workup of microbiopsies is not difficult; however, their diagnosis can be a problem. Adequate diagnostic criteria are not available. Aided by MIB-1 staining, histologic sections from microbiopsies can be diagnosed, and the diagnoses correlated with follow-up in most cases. Processing of microbiopsies in smears with an inconclusive cytologic diagnosis or a diagnosis of ASCUS allowed correct diagnosis in 50% of cases in this study.

Applications of the microbiopsy technique in non-cervical cytology: where cytology and histology meet.

AIM: To evaluate a recently developed technique allowing the removal and processing for histology of thick tissue fragments, called microbiopsies, from noncervical cytology specimens. METHODS AND RESULTS: Forty-five non-cervical smears from malignant tumours which contained microbiopsies were selected and processed. Sufficient sections could be cut in most cases for haematoxylin and eosin and an extensive panel of immunostaining. Seventy-one per cent of histological slides from the microbiopsies were representative of the tumour and confirmed the diagnosis. In 29% of the cases they were too small, contained non-representative tissue or showed extensive necrosis. Surprisingly, immunostaining results were at least the same and often better than those observed in routine formalin-fixed, paraffin-embedded tissue. Immunostaining profiles allowed distinction of tumour subtypes. Antigen retrieval techniques could be avoided in all cases. CONCLUSIONS: Application of the microbiopsy technique in routine cytology smears containing microbiopsies is helpful, particularly in those cases in which the diagnosis is not clear on the basis of the cytology smear and in cases in which there are not enough cytology slides for immunohistochemical examination.

Histologic processing of microbiopsies from cervical smears is diagnostically useful in selected cases.

We analyzed the value in cervical cytology of a recently developed technique by which it is possible to remove thick tissue specimens, called microbiopsies, from cervical smears and to process them for histologic examination. In 12 (48%) of 25 cervical smears in which microbiopsies were found, the histologic sections from them confirmed the cytologic diagnosis. Most cases involved classification of lesions diagnosed as cervical intraepithelial neoplasia. In 13 (52%) of 25 smears, processing the microbiopsy allowed considerable modification of the cytologic diagnosis. In six of these cases, microbiopsies consisted of groups of columnar cells that were incorrectly classified as atypical on the basis of cytologic criteria. After histologic processing, the microbiopsies revealed nonatypical columnar cells in four cases and only mildly atypical columnar cells in two cases. In 3 of 13 smears, there were insufficient dispersed atypical cells for a conclusive diagnosis. Processing the microbiopsies in these cases allowed classification into one of the cervical intraepithelial neoplasia categories.

Morphometric study of the right gastroepiploic and inferior epigastric arteries.

BACKGROUND: Based on earlier observations that the thickness of the intima and structure of the media may have an impact on the long-term patency of arterial conduits and the lack of detailed histologic studies of the right gastroepiploic and inferior epigastric arteries, we subjected both vessels to morphometric analysis with emphasis on their suitability as conduits in myocardial revascularization. METHODS: The right gastroepiploic and inferior epigastric arteries were harvested from 28 unselected individuals (mean age, 73.2 years) at autopsy, and the luminal diameter and the width of the intima and media were measured. RESULTS: At all levels of measurement (origin, 10 cm, and 15 cm), the luminal diameter of the inferior epigastric artery was significantly smaller than that of the right gastroepiploic artery (p < 0.05). The right gastroepiploic artery demonstrated only mild intimal hyperplasia. In contrast, the inferior epigastric artery showed substantial intimal hyperplasia within the first 1-cm segment (mean, 134 +/- 131 microns versus 50 +/- 49 microns for the corresponding segment of the right gastroepiploic artery; p = 0.01). Intimal hyperplasia was only mild in the remainder of the inferior epigastric artery. In both vessels, the media was muscular with rare dispersed elastic fibers. The mean thickness of the media ranged from 380 +/- 116 microns proximally to 155 +/- 70 microns distally for the right gastroepiploic artery, and from 316 +/- 86 to 165 +/- 70 microns, respectively, for the inferior epigastric artery. CONCLUSIONS: In myocardial revascularization, use of the right gastroepiploic artery may generally be preferable to use of the inferior epigastric artery. This recommendation is based on the larger luminal diameter of the right gastroepiploic artery as compared with the inferior epigastric artery, the significantly greater intimal hyperplasia in the first segment of the inferior epigastric artery, and the limitation that the inferior epigastric artery can be used only as a free graft. The rate of development of intimal hyperplasia in the right gastroepiploic artery, if used as an in situ coronary artery bypass graft, may be slow, approximating that of the right gastroepiploic artery in its natural environment.

Breast-cancer mortality in a non-randomized trial on mammographic screening in women over age 65.

Recent case-referent studies in the Nijmegen breast-screening programme have shown a reduction in breast-cancer mortality of approximately 50% due to screening of women aged 65 years and older. In this type of study, however, the results may be biased because of self-selection. The purpose of our present study was to compare the breast-cancer mortality rate in a population invited for screening with that of a reference population from an area without a screening programme. In 1977-1978, 6773 women aged 68-83 years were enrolled in the mammographic screening programme in Nijmegen, The Netherlands. The women were followed up until 31 December, 1990. The reference population consisted of women from the same birth cohort from Arnhem, a neighbouring city without mass screening, for whom the entry date was 1 January, 1978. The ratios of the Nijmegen and Arnhem breast-cancer mortality rates with 95% confidence intervals (CI) were calculated. In the study period, 173 patients were diagnosed with primary breast cancer in Nijmegen vs. 183 in Arnhem; 40 Nijmegen patients had died of breast cancer vs. 51 Arnhem patients. The cumulative mortality-rate ratio was 0.80 (95% CI = 0.53-1.22). In the periods 1978-1981, 1982-1985 and 1986-1990, the mortality rate ratios were 1.44 (95% CI = 0.67-3.10), 081 (95% CI = 0.37-1.79) and 0.53 (95% CI = 0.27-1.04), respectively. After adjustment for the difference in incidence rate that existed between the Nijmegen and Arnhem populations, mammographic screening of women older than 65 can be expected to yield a 40% reduction in breast-cancer mortality after 10 years.

Mammographic screening after the age of 65 years: early outcomes in the Nijmegen programme.

We studied outcomes of mammographic screening in women older than 65 years. In 1975, breast cancer screening was started in Nijmegen, The Netherlands, for women aged 35-65 years. Since 1977, approximately 7700 older women have also been invited for biennial one-view mammography. This report is based on ten screening rounds from 1975 to 1994. The results of the subsequent screening rounds in the age groups 65-69 years, 70-74 years and 75 years and older were: participation rates 55%, 39% and 15%; screen-detected cancer rates 5.6%, 6.9% and 7.8%; interval cancer rates 2.0%, 1.8%, and 3.5%; and predictive values of referral 62%, 64% and 62% respectively. In all age groups, screen-detected patients had smaller tumours and a lower prevalence of axillary lymph node involvement than unscreened patients. Our conclusion is that, in women aged 65 years, and older, breast cancer can be detected at an earlier stage by mammographic screening.

Histologic processing of thick tissue specimens from cytology slides. A novel technique.

OBJECTIVE: To describe a novel method by which small tissue fragments found in routine cytology specimens can be processed for histologic slides without destroying or damaging the cytologic specimen. STUDY DESIGN: To develop a method by which small tissue fragments (microbiopsies) are removed from cytologic slides and processed through paraffin or plastic, after which histologic slides can be prepared. RESULTS: In all cases described, the histologic sections from the microbiopsies were of excellent quality. Microscopic examination gave additional important information. Furthermore, immunochemistry could be performed on paraffin-processed microbiopsies. CONCLUSION: This method can be of great value in cytologic specimens in which microbiopsies are present, not only in those cases in which cytologic information is insufficient for diagnosis, but also in cases with conclusive diagnostic information. Routinely applied, this method could make biopsies unnecessary in some cases.

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.

Mammographic screening after the age of 65 years: evidence for a reduction in breast cancer mortality.

We evaluated whether regular mammographic screening of women aged 65 years or older affected breast cancer mortality. In Nijmegen, a population-based screening program for breast cancer was started in 1975, with biennial mammography for women aged 35-64 years. Since 1977, elderly women have also been participating. For the present case-control study, women were selected who were over 64 years of age at the most recent invitation. Eighty-two of them had died from breast cancer. For these cases, 410 age-matched population controls were selected. The ratio of breast cancer mortality rates of the women who had participated regularly (ie., in the 2 most recent screening rounds prior to diagnosis) vs. the women who had not participated in the screening was 0.56 (95% CI = 0.28-1.13). The rate ratio was 0.45 in the women aged 65-74 years at the most recent invitation (95% CI = 0.20-1.02), whereas it was 1.05 in the women aged 75 years and older (95% CI = 0.27- 4.14). While the breast cancer survival rate of the non-participant patients was fairly equal to that of patients from a control population, the underlying incidence rate of breast cancer was higher in the participants than in the non-participants. Therefore, we conclude that bias was present, but that it had decreased our effect estimate. The real reduction in breast cancer mortality due to regular screening will be even larger. Regular mammographic screening of women over age 65 (at least up to 75 years) can reduce breast cancer mortality by approximately 45%.

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.

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.

Improvement of gastric inflammation and resolution of epithelial damage one year after eradication of Helicobacter pylori.

AIMS: To investigate the effect of eradication of Helicobacter pylori infection on gastric epithelial damage and gastritis, scored according to the Sydney system. METHODS: Gastritis scores and epithelial damage were assessed in gastric biopsy specimens before, and five weeks and one year after anti-H pylori therapy in 66 patients with H pylori related gastritis. RESULTS: The mean initial levels of activity, inflammation, atrophy, intestinal metaplasia, and H pylori scores were higher in the antrum than in the corpus or fundus. Eradication of H pylori resulted in an improvement in the mean inflammatory score in antral biopsy specimens from 2.23 before treatment to 1.32 and 1.06, respectively, five weeks and one year after treatment. Corresponding values for fundic biopsy specimens were 1.30, 0.36 and 0.35. Activity scores improved from 1.41 before treatment to 0.13 and zero, respectively, five weeks and one year after treatment in antral biopsy specimens and from 0.60 before treatment to zero in fundic biopsy specimens. Before treatment, epithelial damage was present in 51% of biopsy specimens taken from the antrum and 23% of those from the corpus. Five weeks after eradication of H pylori none of the biopsy specimens revealed evidence of epithelial damage. CONCLUSION: Eradication of H pylori is followed by a rapid, significant improvement in the gastritis score and resolution of epithelial damage in antral and fundic mucosa.

Efficacy of mammographic screening of the elderly: a case-referent study in the Nijmegen program in The Netherlands.

BACKGROUND: Only a few small studies have been conducted to examine the usefulness of mammographic screening in elderly women. These studies suggest that the screening-related reduction in breast cancer mortality rates is less than the estimated 20%-40% reduction observed for women aged 50-70 years at the time of their first screening. PURPOSE: We have studied the efficacy of continued mammographic screening for breast cancer of elderly women within our screening program. METHODS: In 1975, a breast cancer screening program was started in the city of Nijmegen. The Netherlands. During each biennial screening round, approximately 30,000 women aged 40 years and older were personally invited to participate. Single-view mammography was administered. The present study was conducted using a case-referent design. In order to be eligible for inclusion in this study, women had to have been invited to participate in the mammography screening program at least twice, with the most recent invitation having occurred when each woman was 65 years or older. The cases studied comprised 33 women in this group who had died of breast cancer at some point during 1977 through 1988. Referents were matched for age at last invitation to screening prior to the diagnosis of breast cancer and for the number of previous invitations to screenings. Five referents were randomly selected for each case. Breast cancer mortality rate ratios (RR) were calculated for several categories of attendance to the screening. RESULTS: The RR of those who attended the last screening versus those who failed to do so was 0.58 (95% confidence interval [CI] = 0.24-1.41); for women aged 65-74, the RR was 0.34 (95% CI = 0.12-0.97) and for women aged 75 or over, 2.87 (95% CI = 0.62-13.2). The RR of those who attended the screening before and after the age of 65, relative to those who attended before 65 only, was 0.26 (95% CI = 0.05-1.32). CONCLUSION: Although self-selection bias was present in our data, it was not likely to be responsible for the beneficial effect in women aged 65-74 at the time of invitation to screenings. It probably was responsible for the reversed RR (RR > 1) in the group of women 75 years and older. IMPLICATION: Continuation of mammographic screening until at least the age of 75 years may lead to a reduction of breast cancer mortality among elderly women.

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.