Stable long-term outcomes after cochlear implantation in subjects with TMPRSS3 associated hearing loss: a retrospective multicentre study.

BACKGROUND: The spiral ganglion hypothesis suggests that pathogenic variants in genes preferentially expressed in the spiral ganglion nerves (SGN), may lead to poor cochlear implant (CI) performance. It was long thought that TMPRSS3 was particularly expressed in the SGNs. However, this is not in line with recent reviews evaluating CI performance in subjects with TMPRSS3-associated sensorineural hearing loss (SNHL) reporting overall beneficial outcomes. These outcomes are, however, based on variable follow-up times of, in general, 1 year or less. Therefore, we aimed to 1. evaluate long-term outcomes after CI implantation of speech recognition in quiet in subjects with TMPRSS3-associated SNHL, and 2. test the spiral ganglion hypothesis using the TMPRSS3-group. METHODS: This retrospective, multicentre study evaluated long-term CI performance in a Dutch population with TMPRSS3-associated SNHL. The phoneme scores at 70 dB with CI in the TMPRSS3-group were compared to a control group of fully genotyped cochlear implant users with post-lingual SNHL without genes affecting the SGN, or severe anatomical inner ear malformations. CI-recipients with a phoneme score ≤ 70% at least 1-year post-implantation were considered poor performers and were evaluated in more detail. RESULTS: The TMPRSS3 group consisted of 29 subjects (N = 33 ears), and the control group of 62 subjects (N = 67 ears). For the TMPRSS3-group, we found an average phoneme score of 89% after 5 years, which remained stable up to 10 years post-implantation. At both 5 and 10-year follow-up, no difference was found in speech recognition in quiet between both groups (p = 0.830 and p = 0.987, respectively). Despite these overall adequate CI outcomes, six CI recipients had a phoneme score of ≤ 70% and were considered poor performers. The latter was observed in subjects with residual hearing post-implantation or older age at implantation. CONCLUSION: Subjects with TMPRSS3-associated SNHL have adequate and stable long-term outcomes after cochlear implantation, equal to the performance of genotyped patient with affected genes not expressed in the SGN. These findings are not in line with the spiral ganglion hypothesis. However, more recent studies showed that TMPRSS3 is mainly expressed in the hair cells with only limited SGN expression. Therefore, we cannot confirm nor refute the spiral ganglion hypothesis.

The EORTC QLQ-CR29 quality of life questionnaire for colorectal cancer: validation of the Dutch version.

PURPOSE: To validate the Dutch version of the EORTC QLQ-CR29 quality of life questionnaire for colorectal cancer. METHODS: We translated and pilot-tested the original questionnaire in the Netherlands, following EORTC guidelines. We assessed factor structure, reliability and construct validity in different samples of patients from four hospitals. RESULTS: Of 296 patients, 236 (80 %) returned the questionnaire, and 27 out of 48 patients returned the retest questionnaire. In addition to the original three scales, we found a reliable bowel functioning scale (α = 0.80), reducing the number of individual items by five. Two of the other scales had sufficient to good reliability (urinary frequency, α = 0.71, original α = 0.75, body image α = 0.80, original α = 0.84), the third, blood and mucus in stool, only moderate (α = 0.56, original α = 0.69). Item functioning was sufficient to excellent for all but two items (urinary incontinence and dysuria). Construct validity was similar to that in earlier studies. CONCLUSION: We found a very satisfactory scale for bowel problems, in patients both with and without stoma. The body image and urinary incontinence scales were reliable, and construct validity was sufficient. We suggest the questionnaire to be adapted to decrease the number of individual items, improve the scales, and therefore increase reliability of the entire questionnaire.

Relevance of laboratory investigations in monitoring patients with psoriasis on etanercept or adalimumab.

BACKGROUND: Guidelines concerning biological treatment of patients with psoriasis recommend different pretreatment and monitoring laboratory panels in variable frequencies to monitor treatment. OBJECTIVES: To investigate the relevance of laboratory investigations in monitoring patients with psoriasis on etanercept or adalimumab. METHODS: A prospective cohort study over 5 years was conducted in all consecutive patients with psoriasis on etanercept or adalimumab. All laboratory investigations performed for monitoring treatment were analysed. Laboratory abnormalities were graded according to the Common Terminology Criteria for Adverse Events v4.03. The primary endpoint was the percentage of patients with a grade 3 or grade 4 laboratory abnormality. The secondary endpoints were defined as: (i) significant changes in laboratory parameters during etanercept or adalimumab treatment and (ii) the percentage of patients having a laboratory abnormality requiring discontinuation of etanercept or adalimumab treatment. RESULTS: Laboratory parameters were available for 162 patients treated with etanercept and/or adalimumab. The number of treatment episodes was 155 for etanercept and 58 for adalimumab. Follow-up was 316 patient-years for etanercept and 54 patient-years for adalimumab. Thirty-eight of 146 patients treated with etanercept (26%) had one or more grade 3 and/or grade 4 laboratory abnormalities. For adalimumab, this was eight of 58 (14%). These were predominantly considered unrelated to biologic therapy. For both biologics, significant changes were observed in mean laboratory parameters during treatment compared with pretreatment as well as significant trends. However, mean values during treatment remained within normal ranges. Laboratory abnormalities did not lead to permanent discontinuation of biologic treatment in any patient. CONCLUSIONS: In this cohort, the incidence of biologic therapy-related serious laboratory abnormalities was low. Our findings do not support a need for routine laboratory testing in patients with psoriasis on etanercept or adalimumab beyond the laboratory testing required for concomitant therapies or comorbidities.

Clinician and cancer patient views on patient participation in treatment decision-making: a quantitative and qualitative exploration.

Patient participation in treatment decision-making is being increasingly advocated, although cancer treatments are often guideline-driven. Trade-offs between benefits and side effects underlying guidelines are made by clinicians. Evidence suggests that clinicians are inaccurate at predicting patient values. The aim was to assess what role oncologists and cancer patients prefer in deciding about treatment, and how they view patient participation in treatment decision-making. Seventy disease-free cancer patients and 60 oncologists (surgical, radiation, and medical) were interviewed about their role preferences using the Control Preferences Scale (CPS) and about their views on patient participation using closed- and open-ended questions. Almost all participants preferred treatment decisions to be the outcome of a shared process. Clinicians viewed participation more often as reaching an agreement, whereas 23% of patients defined participation exclusively as being informed. Of the participants, > or = 81% thought not all patients are able to participate and > or = 74% thought clinicians are not always able to weigh the pros and cons of treatment for patients, especially not quality as compared with length of life. Clinicians seemed reluctant to share probability information on the likely impact of adjuvant treatment. Clinicians should acknowledge the legitimacy of patients' values in treatment decisions. Guidelines should recommend elicitation of patient values at specific decision points.

Stability of preferences with regard to adjuvant chemotherapy: impact of treatment decision, experience and the passing of time.

Research has shown that patients' preferences for adjuvant chemotherapy do not change as a result of experience. However, the preferences of experienced patients are usually more favourable than those of inexperienced patients. These results indicate a shift in preferences after the decision to proceed with adjuvant chemotherapy has been made, but before actual experience. We tested this assumption in early-stage breast and colorectal cancer patients. We asked patients to provide their preferences for chemotherapy before surgery and thus before they knew whether chemotherapy would be advised (T(1)), after surgery but before the start of chemotherapy (T(2)) and about 1 month after chemotherapy (T(3)). Patients who did not undergo chemotherapy co-operated at similar points in time. Preferences were measured on a nine-point scale, ranging from (1) 'very strong preference for no chemotherapy' to (9) 'very strong preference for chemotherapy'. As hypothesized, the preferences of patients who would be treated with chemotherapy became more favourable after the treatment decision had been made (n = 7, P = 0.06). The preferences of patients for whom chemotherapy was not part of the treatment plan showed the opposite effect (n = 38, P = 0.03). We did not find any effect of experiencing treatment (n = 22, P = 0.62) or the passing of time (n = 81, P = 0.25) on the stability of preferences. We conclude that the frequently observed discrepancy in treatment preferences between experienced and inexperienced patients seems to be an effect of the treatment decision and not of experience of the treatment.

Patients' preferences for low rectal cancer surgery.

AIM: To elicit surgery preferences of patients who have experience with either low anterior resection (LAR) or abdominoperineal resection (APR) and its outcomes, to support decision-making in future patients with resectable rectal cancer. METHODS: One hundred and twenty-two patients were interviewed. Surgery preference was assessed in two ways. In the treatment trade-off method, the certainty of a stoma was hypothetically weighed against the risk of incontinence. In the time trade-off method, remaining life expectancy was traded off to avoid a permanent stoma or faecal incontinence. RESULTS: To avoid APR, LAR patients accepted a much higher risk of incontinence than APR patients. In fact, 71% of the LAR patients chose LAR if they would certainly suffer monthly incontinence, and still 32% if they would certainly suffer daily incontinence. Nevertheless, APR patients would give up less remaining life years to be without a permanent stoma than LAR patients to be without monthly incontinence. CONCLUSIONS: Most patients preferred LAR above APR, even if LAR involved a risk of faecal incontinence. This seems to justify that LAR, if surgically possible, is performed in the first instance. However, since APR patients could live well with a permanent stoma, we recommend clearly informing patients before surgery about the surgical options and their potential outcomes.

Benefit from preoperative radiotherapy in rectal cancer treatment: disease-free patients' and oncologists' preferences.

Preoperative radiotherapy (PRT) in resectable rectal cancer improves local control but increases probability of faecal incontinence and sexual dysfunction. Consensus was reached in 2001 in the Netherlands on a guideline advising PRT to new patients. Purpose was to assess at what benefit oncologists and rectal cancer patients prefer PRT followed by surgery to surgery alone, and how oncologists and patients value various treatment outcomes. Sixty-six disease-free patients and 60 oncologists (surgical, radiation, medical) were interviewed. Minimally desired benefit from PRT (local control) was assessed using the Treatment Tradeoff Method. Importance of survival, local control, faecal incontinence, and sexual dysfunction in determining treatment outcome preferences was assessed using Adaptive Conjoint Analysis. The range of required benefit from PRT varied widely within participant groups. Seventeen percent of patients would choose PRT at a 0% benefit; 11% would not choose PRT for the maximum benefit of 11%. Mean minimally desired benefit excluding these two groups was 4%. For oncologists, the required benefit was 5%. Also, how strongly participants valued treatment outcomes varied widely within groups. Of the four outcomes, participants considered incontinence most often as most important. Relative treatment outcome importance differed between specialties. Patients considered sexual functioning more important than oncologists. Large differences in treatment preferences exist between individual patients and oncologists. Oncologists should adequately inform their patients about the risks and benefits of PRT, and elicit patient preferences regarding treatment outcomes.

How important is the opinion of significant others to cancer patients' adjuvant chemotherapy decision-making?

GOALS: Decisions regarding adjuvant chemotherapy are difficult, since value tradeoffs are involved. Little is known about the importance of the significant others in patients' decision-making regarding adjuvant treatment. We surveyed patients with breast and colorectal cancer about the importance they assigned to the opinions of their significant others and assessed correlates of these importance scores. MATERIALS AND METHODS: One hundred and twenty-three patients rated on a five-point scale how much they cared about the opinion of six significant others. MAIN RESULTS: Most important was the opinion of their treating specialist, followed by that of their partner, children, other family, friends, and colleagues. Women assigned higher scores to the opinion of their children, younger patients to that of their specialist, and patients who were about to undergo chemotherapy to that of their family. Patients with breast cancer and patients without paid employment assigned slightly more importance to the opinion of their partner. CONCLUSIONS: Information on the influence of significant others may help clinicians when involving patients in treatment decision-making and discussing patients' treatment preferences.

New global communication process in thermodynamics: impact on quality of published experimental data.

Thermodynamic data are a key resource in the search for new relationships between properties of chemical systems that constitutes the basis of the scientific discovery process. In addition, thermodynamic information is critical for development and improvement of all chemical process technologies. Historically, peer-reviewed journals are the major source of this information obtained by experimental measurement or prediction. Technological advances in measurement science have propelled enormous growth in the scale of published thermodynamic data (almost doubling every 10 years). This expansion has created new challenges in data validation at all stages of the data delivery process. Despite the peer-review process, problems in data validation have led, in many instances, to publication of data that are grossly erroneous and, at times, inconsistent with the fundamental laws of nature. This article describes a new global data communication process in thermodynamics and its impact in addressing these challenges as well as in streamlining the delivery of the thermodynamic data from "data producers" to "data users". We believe that the prolific growth of scientific data in numerous and diverse fields outside thermodynamics, together with the demonstrated effectiveness and versatility of the process described in this article, will foster development of such processes in other scientific fields.

Glandularity and mean glandular dose determined for individual women at four regional breast cancer screening units in the Netherlands.

The nationwide breast cancer screening programme using mammography has been in full operation in The Netherlands since 1997. There is concern that the mean glandular doses due to mammography might be differing between different regions of the country due to differences in glandularity and compressed breast thickness. To investigate regional differences, glandularity, compressed breast thickness and mean glandular dose were determined for individual breasts during screening at mammography units at four locations in The Netherlands. Differences in glandularity were observed, which could be related qualitatively to differences in age of the participants at the different locations. Mean glandular dose depends on compressed breast thickness, glandularity and technical conditions of screening. The lowest average value of the mean glandular dose was found for the unit in Amsterdam. This is most likely due to the use of the Mo/Rh anode/filter combination at this unit, in addition to the Mo/Mo combination. At the other three units, almost exclusively the Mo/Mo anode/filter combination was used. Differences in mean glandular dose averaged per unit could be related mainly to differences in tube-current exposure-time product values. Consequently, it is concluded that differences in mean glandular dose at different units are marginal.

Method for determination of the mean fraction of glandular tissue in individual female breasts using mammography.

The nationwide breast cancer screening programme using mammography has been in full operation in the Netherlands since 1997. Quality control of the screening programme has been assigned to the National Expert and Training Centre for Breast Cancer Screening. Limits are set to the mean glandular dose and the centre monitors these for all facilities engaged in the screening programme. This procedure is restricted to the determination of the entrance dose on a 5 cm thick polymethylmethacrylate (PMMA) phantom. The mean glandular dose for a compressed breast is estimated from these data. Individual breasts may deviate largely from this 5 cm PMMA breast model. Not only may the compressed breast size vary from 2 to 10 cm, but breast composition varies also. The mean glandular dose is dependent on the fraction of glandular tissue (glandularity) of the breast. To estimate the risk related to individual mammograms requires the development of a method for determination of the glandularity of individual breasts. A method has been developed to derive the glandularity using the attenuation of mammography x-rays in the breast. The method was applied to a series of mammograms at a screening unit. The results, i.e., a glandularity of 93% within the range of 0 to 1, were comparable with data in the literature. The glandularity as a function of compressed breast thickness is similar to results from other investigators using differing methods.

Explaining differences in attitude toward adjuvant chemotherapy between experienced and inexperienced breast cancer patients.

PURPOSE: Previous studies have shown that patients who have experienced adjuvant chemotherapy (experienced patients) have a more favorable attitude towards chemotherapy than those who have not (inexperienced patients). However, not much is known about the reasons underlying this difference. According to the Theory of Planned Behavior, the attitude towards a particular behavior (eg, accepting chemotherapy) is based on beliefs about the likelihood of outcomes of the behavior and the evaluations of these outcomes. We used this theory to explore in what way the beliefs of experienced patients differed from those of inexperienced patients. PATIENTS AND METHODS: A cross-sectional survey was undertaken among 719 patients who had been treated for early-stage breast cancer between 1998 and 2003. Patients were asked, first, to indicate the likelihood of six positive and six negative outcomes of undergoing chemotherapy and, second, to give their evaluation of these outcomes. RESULTS: Four hundred forty-six women filled in the questionnaire (response rate, 62%). As hypothesized, experienced patients (ie, patients who had been treated with adjuvant chemotherapy as part of their primary treatment plan) had a more positive attitude towards chemotherapy. Experienced patients provided higher likelihood estimates of treatment advantages, such as life prolongation. In addition, they evaluated the positive outcomes of chemotherapy more favorably. With regard to the negative outcomes of chemotherapy, few differences were observed between treatment groups. CONCLUSION: Experienced patients have more confidence in the positive outcomes of chemotherapy than inexperienced patients. This might be the result of a cognitive mechanism to justify the way in which patients were treated.

Fatty acids and atherosclerotic risk.

Most research concerning the effects of dietary fatty acids on atherosclerotic risk has focused on their effects on lipid and lipoprotein metabolism. However, it is known that fatty acids also influence a number of other relevant mechanisms involved in atherosclerosis such as lipid peroxidation, inflammation and haemostasis. The most favourable distribution of cholesterol over the various lipoproteins is achieved when saturated and trans fatty acids are replaced by a mixture of cis-unsaturated fatty acids. Furthermore, fatty acids from fish oil lower triacylglycerol concentrations. Effects on other atherosclerotic risk markers are less evident. Monounsaturated fatty acids maybe preferable above other fatty acids with respect to low-density lipoprotein oxidation as measured by indirect in vitro assays. The relevance of these assays for the in vivo situation is, however, limited. With respect to inflammation, mainly the effects of n-3 polyunsaturated fatty acids from fish oil have been studied, but results were inconsistent. Also results from studies evaluating the effects of fatty acids on haemostatic risk markers were inconsistent, which may be partly related to the use of different analytical methods. The most consistent finding however is the potential beneficial effect of moderate intakes of fish oil on platelet aggregation. Furthermore, reducing total fat intake rather than changing the fatty acid composition of the diet may beneficially affect the coagulation system. In conclusion, while beneficial effects on atherosclerotic risk are mainly ascribed to cis-unsaturated fatty acids, it remains debateable whether trans and saturated fatty acids in the diet have to be replaced by cis-unsaturated fatty acids or by carbohydrates. To answer this question adequately more validated methods are needed that reflect in vivo lipid peroxidation, inflammation and haemostasis.

Reliability and validity of the Canadian Occupational Performance Measure in stroke patients.

OBJECTIVE: To research test-retest reliability and discriminant validity of the Canadian Occupational Performance Measure (COPM), a client-centred outcome measure, in stroke patients. DESIGN: The COPM was administered twice with a mean interval of eight days (SD 2.5, range 5-16). On both occasions the patient identified a maximum of five problems in daily activities. The problems of both interviews were compared. The problems identified during the first COPM were rated by the patient on a performance and satisfaction rating scale on both occasions. The individually identified items with use of the client-centred COPM were compared with the fixed items of standardized measures (Barthel Index, Frenchay Activities Index, Stroke Adapted Sickness Impact Profile-30, Euroqol 5D and Rankin Scale). SETTING: Patients were interviewed at their place of residence. SUBJECTS: Twenty-six stroke patients participated, 11 men and 15 women, aged from 26 to 83 years (mean 68, SD 15). Twenty-four patients were six months, two patients were two months post stroke. RESULTS: Of the 115 problems identified during the first COPM, 64 (56%) were also identified the second time. Correlation coefficients for the scores were 0.89 (p < 0.001) for performance and 0.88 (p < 0.001) for satisfaction. Of the individual problems identified with the COPM, 25% or less were present in the standardized measures. Correlations between the scores on the COPM and the standardized measures were low and nonsignificant, while all standardized measures correlated significantly with each other. CONCLUSIONS: Test-retest reliability of the COPM was moderate for the item pool but was good for the performance and satisfaction scores. Discriminant validity was confirmed. Many patient-unique problems identified with the COPM were not evaluated by standardized measures.

Synthetic 6B di-, tri-, and tetrasaccharide-protein conjugates contain pneumococcal type 6A and 6B common and 6B-specific epitopes that elicit protective antibodies in mice.

The immunogenicity and protective capacity of Streptococcus pneumoniae 6B capsular polysaccharide (PS)-derived synthetic phosphate-containing disaccharide (Rha-ribitol-P-), trisaccharide (ribitol-P-Gal-Glc-), and tetrasaccharide (Rha-ribitol-P-Gal-Glc-)-protein conjugates in rabbits and mice were studied. In rabbits, all saccharides conjugated to keyhole limpet hemocyanin (KLH) evoked high levels of pneumococcal (Pn) type 6B antibodies that facilitated type-specific phagocytosis. Unlike the disaccharide rabbit antisera, tri- and tetrasaccharide rabbit antisera also reacted with 6A PS in an enzyme-linked immunosorbent assay (ELISA) and promoted phagocytosis of 6A pneumococci. All these rabbit antisera passively protected mice against a Pn 6B challenge. The disaccharide conjugate-induced antiserum, however, failed to protect mice against a 6A challenge. In mice, phagocytic and protective anti-Pn 6B antibodies were only induced by the tetrasaccharide conjugate and not by PS 6B or PS 6B-protein conjugates. These antibodies did not cross-react with 6A PS in ELISA and were unable to phagocytize 6A pneumococci. In conclusion, the disaccharide and tetrasaccharide conjugates already contain epitopes capable of inducing 6B-specific, fully protective antibodies in rabbits and mice, respectively.

Synthesis of spacer-containing di- and tri-saccharides that represent parts of the capsular polysaccharide of Streptococcus pneumoniae type 6B.

In the framework of studies towards oligosaccharide-conjugate-based vaccines against Streptococcus pneumoniae, the synthesis is reported of several spacer-containing oligosaccharides that represent parts of the capsular polysaccharide of S. pneumoniae serotype 6B, namely alpha-L-rhamnopyranosyl-(1-->4)-5-O-(3-aminopropyl hydrogen phosphate)-D-ribitol, 3-aminopropyl D-ribitol-(5-->hydrogen phosphate-->2)-alpha-D-galactopyranoside, 3-aminopropyl alpha-L-rhamnopyranosyl-(1-->4)-D-ribityl-(5-->hydrogen phosphate-->2) -alpha-D-galactopyranoside, and 3-aminopropyl D-ribityl-(5-->hydrogen phosphate-->2) -alpha-D-galactopyranosyl-(1-->3)-alpha-D-glucopyranoside. Phosphorylations were carried out using the H-phosphonate method.

Synthesis of four spacer-containing 'tetrasaccharides' that represent four possible repeating units of the capsular polysaccharide of Streptococcus pneumoniae type 6B.

In the framework of studies towards oligosaccharide-conjugate based vaccines against Streptococcus pneumoniae, the synthesis is reported of four spacer-containing tetrasaccharides that each can be conceived as representing a repeating unit of the capsular polysaccharide of S. pneumoniae serotype 6B, namely, 3-aminopropyl D-ribityl-(5-->hydrogen phosphate-->2)-alpha-D-galactopyranosyl-(1-->3) -alpha-D-glucopyranosyl-(1-->3)-alpha-L-rhamnopyranoside, 3-aminopropyl alpha-L-rhamnopyranosyl-(1-->4)-D-ribityl-5(-->hydrogen phosphate-->2)-alpha-D-galactopyranosyl-(1-->3)-alpha-D-glucopyranoside, 3-aminopropyl alpha-D-glucopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->4) -D-ribityl-(5-->hydrogen phosphate-->2) -alpha-D-galactopyranoside, and alpha-D-galactopyranosyl-(1-->3)-alpha-D-glucopyranosyl-(1-->3)-alpha-L -rhamnopyranosyl-(1-->4)-5-O-(3-aminopropyl hydrogen phosphate)-D-ribitol. Phosphorylations were carried out using the H-phosphonate method.

[Sleeping disorders rarely come singly]. / Een slaapstoornis komt vaak niet alleen.

Four patients, a woman aged 60 and three men aged 61, 53 and 56 years, presented with hypersomnia during the day. The cause was determined by polygraphic registration and was a variable combination of sleep apnoea syndrome, narcolepsy and periodic movements of the limbs in sleep syndrome (PMLS). Such a combination may lead to a therapeutic paradox as the treatment of one disturbance may lead to aggravation of another one. Therapy is possible but only when it is completely clear which component of the disorder prevails. Whole night polygraphy is indispensable for this approach.

Do non-specific minimal signs in a biennial mammographic breast cancer screening programme need further diagnostic assessment?

Mammographic features such as small vague densities, indefinable microcalcifications, subtle architectural distortions, alone or in combination, are non-specific appearances for breast cancer. These features sometimes precede malignancy and a decisive strategy on how to deal with non-specific minimal signs in a breast cancer screening programme is therefore desirable. After studying the prevalence of these signs in a Dutch Breast Cancer Screening Centre and estimating the risk of participants with these signs acquiring breast cancer within 2 years, we have developed such a strategy. Non-specific minimal signs were seen on the mammograms of 53 of 500 (10.6%) participants, aged 50-70 years, in this programme. After retrospective analysis of the mammograms of 254 patients with screen-detected or interval carcinoma, non-specific minimal signs were detected in 77 cases. Combining the incidence of breast cancer with the difference between the expected number of non-specific minimal signs in the screening programme and its actual occurrence in previous mammograms of patients with breast cancer, the risk of cancer in women with these signs, additional to that of screened women in general (additional risk), is calculated as being 0.5%. Invasive breast cancer in women with previously detected non-specific minimal signs demonstrated a favourable stage at diagnosis (axillary metastasis in 23% vs 37% in cancers without these previous signs, p < or = 0.05). Our strategy for follow-up in case of non-specific minimal signs remains unchanged because of the low additional risk and favourable staging, and is restricted to an invitation for the next screening round in 2 years time.