Biomedical subjects

J H Hendriks

Publications and source records attributed to J H Hendriks.

At least 19 recordsLinked to original sources

PubMed2003

[The treatment of ductal carcinoma in situ (DCIS) of the breast].

Ductal carcinoma in situ (DCIS) of the breast is diagnosed more and more often in the Netherlands as a result of mammographic population screening and improved mammography techniques. Mastectomy and local excision, with or without radiotherapy, are used for the treatment of DCIS, but breast-conserving therapy seems a logical option in view of the favourable prognosis. Radiotherapy following total excision of DCIS reduces the local recurrence rate by half. Incomplete excision of DCIS is associated with a higher rate of local recurrence, which is invasive in about 50% of the cases and can therefore affect the prognosis adversely. There are conflicting opinions in the literature as to which patients with DCIS can be treated with breast-conserving therapy and whether local excision should be followed by radiotherapy, as is the case for breast-conserving treatment of invasive mammary carcinoma. The diagnosis and treatment of DCIS are therefore complex and require a multidisciplinary approach. Patients may be selected for breast-conserving therapy on the basis of diagnostic characteristics and risk factors.

Breast Neoplasms↗

PubMed2001

Reaction of carbon monoxide with the reduced active site of bacterial nitric oxide reductase.

Bacterial nitric oxide reductase (NOR), a member of the superfamily of heme-copper oxidases, catalyzes the two-electron reduction of nitric oxide to nitrous oxide. The key feature that distinguishes NOR from the typical heme-copper oxidases is the elemental composition of the dinuclear center, which contains non-heme iron (FeB) rather than copper (CuB). UV-vis electronic absorption and room-temperature magnetic circular dichroism (RT-MCD) spectroscopies showed that CO binds to Fe(II) heme b3 to yield a low-spin six-coordinate species. Photolysis of the Fe(II)-CO bond is followed by CO recombination (k(on) = 1.7 x 10(8) M(-1) x s(-1)) that is approximately 3 orders of magnitude faster than CO recombination to the active site of typical heme-copper oxidases (k(on) = 7 x 10(4) M(-1)x s(-1)). This rapid rate of CO recombination suggests an unimpeded pathway to the active site that may account for the enzyme's high affinity for substrate, essential for maintaining denitrification at low concentrations of NO. In contrast, the initial binding of CO to reduced heme b3 measured by stopped-flow spectroscopy is much slower (k(on) = 1.2 x 10(5) M(-1) x s(-1)). This suggests that an existing heme distal ligand (water/OH-) may be displaced to elicit the spin-state change observed in the RT-MCD spectrum.

Binding Sites↗

PubMed2001

Magnetic resonance imaging and mammography in women with a hereditary risk of breast cancer.

BACKGROUND: Although breast cancer screening is recommended to start at a younger age for women with a hereditary risk of breast cancer, the sensitivity of mammography for these women is reduced. We compared magnetic resonance imaging (MRI) with mammography to determine which is more sensitive and whether MRI could play a role in the early detection of breast cancer for these women. METHODS: We constructed a retrospective cohort of all breast MRI and mammography surveillance reports made in our department from November 1994 to February 2001. All of the 179 women in the cohort had received biannual palpation in addition to annual imaging by MRI, mammography, or both. The 258 MRI images and the 262 mammograms were classified with the use of the BI-RADS (i.e., Breast Imaging Reporting and Data System) scoring system, which has five categories to indicate the level of suspicion of a lesion. Receiver operator characteristic curves were generated for MRI and mammography, and the area under each curve (AUC) was assessed for the entire cohort of 179 women and for a subset of 75 women who had received both an MRI and a mammographic examination within a 4-month period. All statistical tests were two-sided. RESULTS: In the cohort of 179 women, we detected 13 breast cancers. Seven cancers were not revealed by mammography, but all were detected by MRI. For the entire cohort, the AUC for mammography was 0.74 (95% confidence interval [CI] = 0.68 to 0.79), and the AUC for MRI was 0.99 (95% CI = 0.98 to 1.0). For the subset of women who had both examinations, the AUC for mammography was 0.70 (95% CI = 0.60 to 0.80), and the AUC for MRI was 0.98 (95% CI = 0.95 to 1.0). CONCLUSION: MRI was more accurate than mammography in annual breast cancer surveillance of women with a hereditary risk of breast cancer. Larger prospective studies to examine the role of MRI in screening programs are justified.

Adult↗

PubMed2001

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↗

PubMed2001

Breast carcinomas of limited extent: frequency, radiologic-pathologic characteristics, and surgical margin requirements.

BACKGROUND: Clinical trials established the value of breast-conserving treatment (BCT) including the macroscopic removal of the tumor followed by local radiation therapy (RT) for Stage I and II invasive carcinomas. The occurrence of local tumor recurrence is related to the extent and multifocality of the tumor. Various studies aim to identify those tumors that could be proper candidates for conventional BCT. Furthermore, recent studies have focused on the identification of tumors that may be treated by breast-conserving surgery alone without RT. Small, localized tumors theoretically should be the potential candidates for this type of treatment. The mammographic and pathologic criteria for the identification of tumors with limited extent are not yet established; furthermore, the optimal extent of the surgical excision and the method for margin examination are controversial. METHODS: Surgical breast-conserving procedures were simulated in a review of 135 mastectomy specimens of patients treated for an invasive carcinoma (> or = 4 cm in size, all pathologic types except invasive lobular carcinoma) who were theoretically eligible for conservative treatment. Tumor spread including possible multifocality and multicentricity was studied by the technique of correlated specimen radiography and pathology. Breast carcinoma of limited extent (BCLE), the proper tumor profile for BCT, was defined as having no invasive carcinoma, ductal carcinoma in situ, and lymphatic emboli foci beyond 1 cm from the edge of the dominant mass. RESULTS: Fifty-three percent of the patients in this series had a BCLE. No statistically significant relation was found between BCLE and patient age, pathologic size, type and grade of the tumor, lymph node status, mode of detection, and mammographic aspect of the index tumor. Based on mammography, the absence of calcification or tumor density beyond the edge of index tumor appears to be the best predictor for BCLE (P < 0.0001). A 1-cm microscopically tumor free margin as the outer rim of a macroscopic surgical margin of 2 cm gives the best positive predictive value based on pathology (P < 0.0001). By applying the above conditions, 72 of the 135 cancers were identified as being potential BCLE cases in this series. However, whereas 64 of these 72 tumors (89%) were correctly identified as being true BCLE, 8 (11%) were erroneously identified as such (non-BCLE cases), having "residual" tumor foci beyond 2 cm from the edge of the dominant tumor. CONCLUSIONS: We conclude, that approximately 50% of invasive ductal carcinomas may have limited extent. The accuracy of identifying this group of cancers, the proper candidates for BCT, by applying state-of-the-art mammography and pathology may be as high as 90%. A subset of these tumors might represent the potential candidates for treatment with surgery alone without RT. As a result, the routine application of BCT complemented by RT would have led to the overtreatment of 89% of the patients with a BCLE in this series; conversely, 11% of the tumors may have recurred without the use of RT. Considering that these conclusions are based on a theoretic morphologic model, further clinical studies with facilities for high quality team approach in diagnosis and therapy are needed to evaluate the impact of BCLE on BCT strategies. The results of this study should not justify the withholding of RT outside the context of clinical trials.

Breast Neoplasms↗

PubMed2001

Nationwide breast cancer screening programme fully implemented in The Netherlands.

The period 1990-1997 saw the implementation of a nationwide breast cancer screening programme in the Netherlands, which provided biennial mammography for all women aged 50-69 years (50-75 years at present). The National Evaluation Team monitors the programme annually collecting regional data on screening outcomes; regional cancer registries provide data on interval cancers and on breast cancers in unscreened women by linkage of cancer registry data to data on screened women. Of 4 million women invited, 78.5% attended for screening. Screening resulted in 13.1 referrals, 9.2 biopsies and 6.1 breast cancers detected per 1000 women screened initially (6.9, 4.5 and 3.5 per 1000 in subsequently screened women, respectively). Within the first 2 years following screening 0.95 interval cancers per 1000 women-years were diagnosed. The stage distribution of screen-detected cancers was more favourable than that of interval cancers and of those diagnosed in unscreened women. The results are largely consistent with expectations. Results may nonetheless be further improved, particularly the detection rate in subsequent screens.

Journal Article↗

PubMed2000

[Alterations of stage distribution for breast cancer since the implementation of national screening program in the Netherlands during 1989-1995].

OBJECTIVE: To determine the results of the nation-wide breast cancer screening on the basis of the stage distribution of diagnosed breast cancer 1989-1995. DESIGN: Descriptive, inventory. METHOD: At the University of Nijmegen data concerning the numbers of diagnosed breast cancer cases and age and stage at diagnosis were obtained from the Netherlands Cancer Registry for the years 1989-1995. Population data were provided by Statistics Netherlands. With these data incidence figures were calculated. RESULTS: The number of invasive breast cancers rose from almost 8,000 in 1989 to almost 10,500 in 1994. In 1995, a small decrease was visible. The increase was largest in women aged 50-69 years, the target population of the screening programme (introduced in 1988), and less in older women. In women aged 50-69 years, the incidence of stage I tumours doubled, stage II tumours increased but had returned to original levels in 1995, whereas stage III and IV had decreased by more than 24%. The number of carcinomas in situ rose from 336 in 1989 to 829 in 1995 in all age categories, but most in women aged 50-69 years. CONCLUSION: When the implementation scheme of the national screening programme is taken into account, the results are indicative of a reduction in breast cancer mortality. Whether such a mortality reduction actually will follow, has to be awaited.

Adult↗

PubMed2000

An automatic method to discriminate malignant masses from normal tissue in digital mammograms.

Specificity levels of automatic mass detection methods in mammography are generally rather low, because suspicious looking normal tissue is often hard to discriminate from real malignant masses. In this work a number of features were defined that are related to image characteristics that radiologists use to discriminate real lesions from normal tissue. An artificial neural network was used to map the computed features to a measure of suspiciousness for each region that was found suspicious by a mass detection method. Two data sets were used to test the method. The first set of 72 malignant cases (132 films) was a consecutive series taken from the Nijmegen screening programme, 208 normal films were added to improve the estimation of the specificity of the method. The second set was part of the new DDSM data set from the University of South Florida. A total of 193 cases (772 films) with 372 annotated malignancies was used. The measure of suspiciousness that was computed using the image characteristics was successful in discriminating tumours from false positive detections. Approximately 75% of all cancers were detected in at least one view at a specificity level of 0.1 false positive per image.

Breast Neoplasms↗

PubMed2000

Parity and mammographic breast density in relation to breast cancer risk: indication of interaction.

We examined whether the harmful influence of nulliparity on breast cancer risk could be mediated by high mammographic density. Another possibility is that mammographic density and nulliparity act independently or perhaps synergistically on breast cancer risk. Our study population consisted of 129 cases and 517 controls who had been participants in the Nijmegen breast cancer screening programme for 10 years. Breast density was classified with a fully automated technique on digitized mammograms from the screening examination 10 years before diagnosis. Classification was based on the proportion of the breast that was composed of high density: < 5%, 5-25% or > 25%. Data on parity and potential confounders were obtained using a questionnaire, administered at the same examination. We found that nulliparae with low breast density (< 5%) were not at increased risk compared to parous women with low density: OR 1.1 (95% CI 0.2-5.8). Parous women with < 5% density formed the reference category throughout all analyses. The risks for parous women with 5-25% or > 25% density were 2.7 (95% CI 1.3-5.6) and 3.6 (95% CI 1.7-7.7) fold increased, respectively. However, when both factors were present (nulliparity and > or = 5% density), breast cancer risk was 7.1 times higher (95% CI 3.2-15.9). This could indicate that nulliparity and high breast density might work synergistically and that breast density is not just an explanatory factor in the influence of nulliparity on breast cancer risk. It is hypothesized that high breast density (reflecting fibro-glandular tissue with increased epithelial cell proliferation) is more susceptible to carcinogenic effects in the undifferentiated epithelial breast tissue of nulliparae than in the differentiated tissue of parous women. Since there were few data, no firm conclusions can be drawn. If these findings can be confirmed in a larger study population, however, they may have important implications for the prevention and early detection of breast cancer.

Adult↗

PubMed2000

Automated classification of clustered microcalcifications into malignant and benign types.

The objectives in this study were to design and test a fully automated method for classification of microcalcification clusters into malignant and benign types, and to compare the method's performance with that of radiologists. A novel aspect of the approach is that the relative location and orientation of clusters inside the breast was taken into account for feature calculation. Furthermore, correspondence of location of clusters in mediolateral oblique (MLO) and cranio-caudal (CC) views, was used in feature calculation and in final classification. Initially, microcalcifications were automatically detected by using a statistical method based on Bayesian techniques and a Markov random field model. To determine malignancy or benignancy of a cluster, a method based on two classification steps was developed. In the first step, classification of clusters was performed and in the second step a patient based classification was done. A total of 16 features was used in the study. To identify meaningful features, a feature selection was applied, using the area under the receiver operating characteristic (ROC) curve (Az value) as a criterion. For classification the k-nearest-neighbor method was used in a leave-one-patient-out procedure. A database of 192 mammograms with 280 true positive detected microcalcification clusters was used for evaluation of the method. The set consisted of cases that were selected for diagnostic work up during a 4 year period of screening in the Nijmegen region (The Netherlands). Because of the high positive predictive value in the screening program (50%), this set did not contain obvious benign cases. The method's best patient-based performance on this set corresponded with Az = 0.83, using nine features. A subset of the data set, containing mammograms from 90 patients, was used for comparing the computer results to radiologists' performance. Ten radiologists read these cases on a light-box and assessed the probability of malignancy for each patient. All participants had experience in clinical mammography and participated in our observer study during the last 2 days of a 2-week training session leading to screening mammography certification. Results on the subset showed that the method's performance (Az = 0.83) was considerably higher than that of the radiologists (Az = 0.63).

Breast Neoplasms↗

PubMed1999

[Reading screening mammograms with the help of neural networks].

With digital mammography it is possible to assist radiologists in breast cancer screening with computers to improve their reading performance. The need for this has been demonstrated by studies showing a large variability in skill of radiologists reading mammograms. Moreover, retrospective studies show that a significant number of cancers are clearly visible on earlier screening mammograms, even for 'trained' computers. Methods for automated detection of breast cancer in mammograms often use artificial neural networks. These are 'trained' to recognize abnormal mammographic areas using a large database of known cases. For detection of microcalcification clusters very reliable algorithms exist, with such high sensitivity that radiologists can limit their search to areas that have been marked 'suspect' by the computer. The development of methods to recognize malignant masses is much more difficult, but ample progress has been achieved in recent years.

Adult↗

PubMed1999

Interval cancers in the Dutch breast cancer screening programme.

The nationwide breast cancer screening programme in The Netherlands for women aged 50-69 started in 1989. In our study we assessed the occurrence and stage distribution of interval cancers in women screened during 1990-1993. Records of 0.84 million screened women were linked to the regional cancer registries yielding a follow-up of at least 2.5 years. Age-adjusted incidence rates and relative (proportionate) incidences per tumour size including ductal carcinoma in-situ were calculated for screen-detected and interval cancers, and cancers in not (yet) screened women, comparing them with published data from the UK regions North West and East Anglia. In total 1527 interval cancers were identified: 0.95 and 0.99 per 1000 woman-years of follow-up in the 2-year interval after initial and subsequent screens respectively. In the first year after initial screening interval cancers amounted to 27% (26% after subsequent screens) of underlying incidence, and in the second year to 52% (55%). Generally, interval cancers had a more favourable tumour size distribution than breast cancer in not (yet) screened women. The Dutch programme detected relatively less (favourable) invasive cancers in initial screens than the UK programme, whereas the number of interval cancers confirms UK findings. Measures should be considered to improve the detection of small invasive cancers and to reduce false-negative rates, even if this will lead to increasing referral rates.

Aged↗

PubMed1999

Changes in mammographic breast density and concomitant changes in breast cancer risk.

Among participants of the biennial Nijmegen breast cancer screening programme, we examined whether diminution of mammographic breast density lowered breast cancer risk. Post-menopausal breast cancer cases (n = 108), who had to have participated in all the five screening rounds prior to their diagnosis, were matched to 400 controls on year of birth and screening history. Controls had to be free of breast cancer at the time of the case's diagnosis. Changes in breast density were measured over a 10-year period, by a fully computerized method. Women in whom 5-25% or >25% of the breast was composed of fibro-glandular density showed a threefold increased 10-year risk compared to women with <5% density. In women with 5-25% density initially, we observed a trend of decreasing risk with diminishing density: when women with <5% density throughout the whole period formed the reference category, the odds ratio (OR) for those who decreased from 5-25% to <5% density was 1.9 [95% confidence interval (CI) = 0.6-6.1] in contrast to the OR of 5.7 (95% CI = 2.2-15.2) for those with persisting 5-25% density. In women who increased from 5-25% density to >25% density the OR was 6.9 (95% CI = 2.1-22.9). In women with >25% density initially, diminishing density was not clearly associated with lowering risk, which may be partly explained by the low number of women who decreased to <5% (n = 12). Due to the limited size of the study these results have to be interpreted with caution. Although the results are not conclusive, they could indicate a trend of decreasing risk with diminishing breast density. Should this effect be real, it may have great implications for the primary prevention of breast cancer or for the identification of high-risk groups who would benefit by more frequent screening. Therefore, large-scale, long-term follow-up studies on the effects of changes in breast density are needed.

Adult↗

PubMed1999

High mammographic breast density and its implications for the early detection of breast cancer.

OBJECTIVES: Women with high mammographic breast density are at increased risk of breast cancer. This study explores whether these women should receive intensified screening (more frequent screening or screening with alternative techniques that increase the length of the preclinical detectable phase) to reduce further breast cancer mortality. METHODS: Mathematical models were used to estimate the effects of intensified screening in women with high breast density. The effects were expressed as a reduction in the number of interval cancers. RESULTS: If women with > 25% breast density (comprising about one fifth of all women) are screened annually instead of biennially, an 18% reduction in the total number of interval cancers can be expected. Screening these women with alternative screening techniques biennially may produce the same reduction, provided that these techniques double the mean lead time. CONCLUSIONS: By screening women with dense breasts more intensively, many more breast cancers can theoretically be detected at an early stage. The results provide an early indication of what may be expected from screening strategies. Next, cost-benefit analyses are needed.

Breast Neoplasms↗

PubMed1998

Value of breast imaging in women with painful breasts: observational follow up study.

OBJECTIVES: To determine the value of breast imaging in patients with localised or diffuse pain in the breast in whom physical examination shows no abnormalities. DESIGN: Observational follow up study. SETTING: Radiology department of a teaching hospital in the Netherlands. SUBJECTS: Altogether 987 women referred for radiological breast imaging because of pain alone and a control group of 987 asymptomatic women referred for a screening mammogram. MAIN OUTCOME MEASURES: Correlation of the radiological findings with clinical and pathological findings over two years of follow up. RESULTS: Radiological examination of the painful breast(s) showed the following: normal findings in 854 (86.5%) women, benign abnormalities in 85 (8.6%; mainly small cysts or mastopathy), abnormalities that were probably benign in 36 (3.6%), suspicious findings in 8 (0.8%), and malignancy in 4 (0.4%). Biopsy of the painful area was performed in 10 of the 939 women with normal findings or benign abnormalities, in two of 36 women with radiological abnormalities that were probably benign, and in all women with suspicious or malignant findings. Only the four lesions that had been classified radiologically as malignant were found to be malignant at surgery. The prevalence of breast cancer was similar in symptomatic and control women. CONCLUSIONS: Breast imaging in women who present with pain alone is of value only in providing reassurance--no abnormalities are usually found in the painful area, radiological abnormalities classified as benign do not generally have any clinical consequences, and the prevalence of cancer is low in these women. Biopsy of the painful area should be performed only where radiological findings are suspicious.

Adolescent↗

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

Mammographic breast density and risk of breast cancer: masking bias or causality?

Masking bias is hypothesized to explain associations between breast density and breast cancer risk. Tumours in dense breasts may be concealed at the initial examination, but manifest themselves in later years, suggesting an increase in breast cancer incidence. We studied the association between breast density and breast cancer risk in 0, 1-2, 3-4 and 5-6 year periods between initial examination and diagnosis. We studied 359 cases and 922 referents, identified in a breast cancer screening programme in Nijmegen, The Netherlands. Breast density was assessed at the initial examination and classified as 'dense' (if > 25% of the breast was composed of density) or 'lucent' (< or = 25% density). In women examined with mid-1970s film screen mammography, we found that at time 0 the odds ratio (OR) for women with dense breasts compared to those with lucent breasts was 1.4 (95% confidence interval (CI): 0.7-6.2). After a 3-4 year period the risk was increased to 3.3 (95% CI: 1.5-7.1). Then, the risk decreased again (OR: 1.2, 95% CI: 0.6-2.7). This rise and decline in risk are in accordance with the masking hypothesis. The observation, however, that the risk at time 0 does not appear to be lower for women with dense breasts than for those with lucent breasts, seems to be inconsistent with the masking hypothesis and may be indicative of causality. The same analysis were performed in women whose initial screening examination was done with current high-quality mammography. Due to the small size of this study group no firm conclusions could be drawn, but it seems as if masking bias could still play a role with high-quality mammography.

Adult↗

PubMed1998

Effect of mammographic breast density on breast cancer screening performance: a study in Nijmegen, The Netherlands.

STUDY OBJECTIVE: To study the implications of breast density on mammographic screening performance. DESIGN: Screening outcomes of women with dense breast patterns were compared with those of women with lucent breast patterns (dense > 25% densities, lucent < or = 25% densities); the women were screened in different periods (before/after improvement of the mammographic technique in 1982). SETTING: Nijmegen, the Netherlands, 1977-1994. PARTICIPANTS: Between 1977 and 1994, 73,525 repeat screenings were performed in 19,152 participants (aged 50-69 years) in the Nijmegen breast cancer screening programme (repeat screenings were defined as mammographic examinations that were preceded by an examination in the previous screening round). Participants were screened biennially with mammography. There were 258 screen detected and 145 interval cancers. MAIN RESULTS: Before 1982 (rounds 2-4) the predictive value of a positive screening test (PV+) was lower in women with dense breasts than in those with lucent breasts (dense 29% v lucent 52%, p = 0.003). Also, the ratio of screen detected cancers to the total number of screen detected plus interval cancers (as a proxy for sensitivity) was lower in this group (based on a one year interval: dense 63% v lucent 92%, p = 0.001 and based on a two year interval: dense 41% v lucent 68%, p = 0.002). Moreover, the survival rate was less favourable for those with dense breasts (p = 0.07). In rounds 5-10, there were no important differences with respect to PV+ (dense 66% v lucent 62%, p = 0.57) or survival (p = 0.48). Moreover, sensitivity based on a one year interval was nearly as high in women with dense breasts as in those with lucent breasts (85% v 86%, p = 0.75). However, based on a two year interval sensitivity was lower (dense 59% v lucent 72%, p = 0.04). CONCLUSIONS: In the early screening years (rounds 2-4) high breast density had an unfavourable effect on screening performance. Nowadays, the situation has improved with respect to PV+, survival and detecting tumours in dense breasts with a lead time of up to one year, but little improvement has occurred in the detection of tumours with a lead time greater than one year.

Aged↗