Population-based estimates of overtreatment with adjuvant systemic therapy in early breast cancer patients with data from the Netherlands and the USA.

PURPOSE: Although adjuvant systemic therapy (AST) helps increase breast cancer-specific survival (BCSS), there is a growing concern for overtreatment. By estimating the expected BCSS of AST using PREDICT, this study aims to quantify the number of patients treated with AST without benefit to provide estimates of overtreatment. METHODS: Data of all non-metastatic unilateral breast cancer patients diagnosed in 2015 were retrieved from cancer registries from The Netherlands and the USA. The PREDICT tool was used to estimate AST survival benefit. Overtreatment was defined as the proportion of patients that would have survived regardless of or died despite AST within 10 years. Three scenarios were evaluated: actual treatment, and recommendations by the Dutch or USA guidelines. RESULTS: 59.5% of Dutch patients were treated with AST. 6.4% (interquartile interval [IQI] = 2.5, 8.2%) was expected to survive at least 10 years due to AST, leaving 93.6% (IQI = 91.8, 97.5%) without AST benefit (overtreatment). The lowest expected amount of overtreatment was in the targeted and chemotherapy subgroup, with 86.5% (IQI = 83.4, 89.6%) overtreatment, and highest in the only endocrine treatment subgroup, with 96.7% (IQI = 96.0, 98.1%) overtreatment. Similar results were obtained using data from the USA, and guideline recommendations. CONCLUSION: Based on PREDICT, AST prevents 10-year breast cancer death in 6.4% of the patients treated with AST. Consequently, AST yields no survival benefit to many treated patients. Especially improved personalization of endocrine therapy is relevant, as this therapy is widely used and is associated with the highest amount of overtreatment.

Trends in delayed breast cancer diagnosis after recall at screening mammography.

OBJECTIVES: To determine the extent and characteristics of delay in breast cancer diagnosis in women recalled at screening mammography. METHODS: We included a consecutive series of 817,656 screens of women who received biennial screening mammography in a Dutch breast cancer screening region between 1997 and 2016. During at least 3.5 years follow-up, radiological reports and biopsy reports were collected of all recalled women. The inclusion period was divided into four cohorts of four years each. We determined the number of screen-detected cancers and their characteristics, and assessed the proportion of recalled women who experienced a diagnostic delay of at least 4 months in breast cancer confirmation. RESULTS: The proportion of recalled women who experienced diagnostic delay decreased from 7.5 % in 1997-2001 (47/623) to 3.0 % in 2012-2016 (67/2223, P < 0.001). The proportion of women with a delay of at least two years increased from 27.7 % (13/47) in 1997-2001 to 75.7 % (53/70) in 2012-2016 (P < 0.001). Cancers with a diagnostic delay > 2 years were more frequently invasive (P = 0.009) than cancers with a diagnostic delay of 4-24 months. The most frequent cause of diagnostic delays was incorrect radiological classifications by clinical radiologists (55.2 % overall) after recall. CONCLUSIONS: The proportion of recalled women with a delayed breast cancer diagnosis has more than halved during two decades of screening mammography. Delays in breast cancer diagnosis are characterized by longer delay intervals, although the proportion of these delays among all screen-detected cancers has not increased. Preventing longer delays in breast cancer confirmation may help improve breast cancer survival.

Diffusion weighted imaging of the breast: Performance of standardized breast tumor tissue selection methods in clinical decision making.

OBJECTIVES: In breast diffusion weighted imaging (DWI) protocol standardization, it is recently shown that no breast tumor tissue selection (BTTS) method outperformed the others. The purpose of this study is to analyze the feasibility of three fixed-size breast tumor tissue selection (BTTS) methods based on the reproducibility, accuracy and time-measurement in comparison to the largest oval and manual delineation in breast diffusion weighted imaging data. METHODS: This study is performed with a consecutive dataset of 116 breast lesions (98 malignant) of at least 1.0 cm, scanned in accordance with the EUSOBI breast DWI working group recommendations. Reproducibility of the maximum size manual (BTTS1) and of the maximal size round/oval (BTTS2) methods were compared with three smaller fixed-size circular BTTS methods in the middle of each lesion (BTTS3, 0.12 cm3 volume) and at lowest apparent diffusion coefficient (ADC) (BTTS4, 0.12 cm3; BTTS5, 0.24 cm3). Mean ADC values, intraclass-correlation-coefficients (ICCs), area under the curve (AUC) and measurement times (sec) of the 5 BTTS methods were assessed by two observers. RESULTS: Excellent inter- and intra-observer agreement was found for any BTTS (with ICC 0.88-0.92 and 0.92-0.94, respectively). Significant difference in ADCmean between any pair of BTTS methods was shown (p = <0.001-0.009), except for BTTS2 vs. BTTS3 for observer 1 (p = 0.10). AUCs were comparable between BTTS methods, with highest AUC for BTTS2 (0.89-0.91) and lowest for BTTS4 (0.76-0.85). However, as an indicator of clinical feasibility, BTTS2-3 showed shortest measurement times (10-15 sec) compared to BTTS1, 4-5 (19-39 sec). CONCLUSION: The performance of fixed-size BTTS methods, as a potential tool for clinical decision making, shows equal AUC but shorter ADC measurement time compared to manual or oval whole lesion measurements. The advantage of a fixed size BTTS method is the excellent reproducibility. A central fixed breast tumor tissue volume of 0.12 cm3 is the most feasible method for use in clinical practice.

Diagnostic performance of breast tumor tissue selection in diffusion weighted imaging: A systematic review and meta-analysis.

BACKGROUND: Several methods for tumor delineation are used in literature on breast diffusion weighted imaging (DWI) to measure the apparent diffusion coefficient (ADC). However, in the process of reaching consensus on breast DWI scanning protocol, image analysis and interpretation, still no standardized optimal breast tumor tissue selection (BTTS) method exists. Therefore, the purpose of this study is to assess the impact of BTTS methods on ADC in the discrimination of benign from malignant breast lesions in DWI in terms of sensitivity, specificity and area under the curve (AUC). METHODS AND FINDINGS: In this systematic review and meta-analysis, adhering to the PRISMA statement, 61 studies, with 65 study subsets, in females with benign or malignant primary breast lesions (6291 lesions) were assessed. Studies on DWI, quantified by ADC, scanned on 1.5 and 3.0 Tesla and using b-values 0/50 and ≥ 800 s/mm2 were included. PubMed and EMBASE were searched for studies up to 23-10-2019 (n = 2897). Data were pooled based on four BTTS methods (by definition of measured region of interest, ROI): BTTS1: whole breast tumor tissue selection, BTTS2: subtracted whole breast tumor tissue selection, BTTS3: circular breast tumor tissue selection and BTTS4: lowest diffusion breast tumor tissue selection. BTTS methods 2 and 3 excluded necrotic, cystic and hemorrhagic areas. Pooled sensitivity, specificity and AUC of the BTTS methods were calculated. Heterogeneity was explored using the inconsistency index (I2) and considering covariables: field strength, lowest b-value, image of BTTS selection, pre-or post-contrast DWI, slice thickness and ADC threshold. Pooled sensitivity, specificity and AUC were: 0.82 (0.72-0.89), 0.79 (0.65-0.89), 0.88 (0.85-0.90) for BTTS1; 0.91 (0.89-0.93), 0.84 (0.80-0.87), 0.94 (0.91-0.96) for BTTS2; 0.89 (0.86-0.92), 0.90 (0.85-0.93), 0.95 (0.93-0.96) for BTTS3 and 0.90 (0.86-0.93), 0.84 (0.81-0.87), 0.86 (0.82-0.88) for BTTS4, respectively. Significant heterogeneity was found between studies (I2 = 95). CONCLUSIONS: None of the breast tissue selection (BTTS) methodologies outperformed in differentiating benign from malignant breast lesions. The high heterogeneity of ADC data acquisition demands further standardization, such as DWI acquisition parameters and tumor tissue selection to substantially increase the reliability of DWI of the breast.

Rapid Access to Contrast-Enhanced spectral mammogRaphy in women recalled from breast cancer screening: the RACER trial study design.

BACKGROUND: In the Dutch breast cancer screening program, women recalled with a BI-RADS 0 score are referred for additional imaging, while those with BI-RADS 4/5 scores are also directed to an outpatient breast clinic. Approximately six out of ten women are recalled without being diagnosed with a malignancy. However, these recalls require additional imaging and doctor visits, which result in patient anxiety and increased health care costs. Conventional types of imaging used for additional imaging are full-field digital mammography and tomosynthesis. Contrast-enhanced spectral mammography has proved to have higher sensitivity and specificity than conventional imaging in women recalled from screening. Therefore, the aim is to study if CESM instead of conventional imaging is a more accurate, patient-friendly, and cost-effective strategy in the work-up of women recalled from breast cancer screening. METHODS: This prospective, multicenter, randomized controlled trial will be conducted at four centers and will include 528 patients recalled for suspicious breast lesions from the Dutch breast cancer screening program. Participants are randomized in two groups: (1) standard care using conventional breast imaging techniques as initial imaging after recall versus (2) work-up primarily based on CESM. Written informed consent will be collected prior to study inclusion. The primary outcome is the diagnostic accuracy for detection of breast cancer. Secondary outcomes are numbers of additional diagnostic exams, days until final diagnosis, health care costs, and experienced patient anxiety. DISCUSSION: Based on previously published retrospective studies, we expect to demonstrate in this prospective multicenter randomized controlled trial, that using CESM as a primary work-up tool in women recalled from breast cancer screening is a more accurate, cost-effective, and patient-friendly strategy. TRIAL REGISTRATION: Netherlands Trial Register, NL6413/NTR6589. Registered on 6 July, 2017.

Breast cancer-related deaths according to grade in ductal carcinoma in situ: A Dutch population-based study on patients diagnosed between 1999 and 2012.

BACKGROUND: The incidence of ductal carcinoma in situ (DCIS) has drastically increased over the past decades. Because DCIS is resected after diagnosis similar to invasive breast cancer, the natural cause and behaviour of DCIS is not well known. We aimed to determine breast cancer-specific survival (BCSS) and overall survival (OS) according to grade in DCIS patients after surgical treatment in the Netherlands. PATIENTS AND METHODS: All DCIS patients diagnosed between 1999 and 2012 were selected from the Netherlands Cancer Registry. The cause of death was obtained from 'Statistics Netherlands'. BCSS and OS were estimated using multivariable Cox regression in the entire cohort and stratified for grades. RESULTS: In total, 12,256 patients were included, of whom 1509 (12.3%) presented with grade I, 3675 (30.0%) with grade II, 6064 (49.5%) with grade III and 1008 (8.2%) with an unknown grade. During a median follow-up of 7.8 years, 1138 (9.3%) deaths were observed, and 179 (1.5%) were breast cancer-related. Of these, 10 patients had grade I; 46 grade II; 95 grade III and 28 an unknown grade. After adjustment for confounding, grade II and III were related to worse BCSS than grade I with hazard ratios of 1.92 (95% confidence interval [CI]: 0.97-3.81) and 2.14 (95% CI: 1.11-4.12), respectively. No association between grades and OS was observed. CONCLUSION: BCSS and OS in DCIS patients were excellent. Because superior rates were observed for low-grade DCIS, it seems justified to investigate whether active surveillance may be a balanced alternative for conventional surgical treatment.

Reasons for (non)participation in supplemental population-based MRI breast screening for women with extremely dense breasts.

AIM: To determine the willingness of women with extremely dense breasts to undergo breast cancer screening with magnetic resonance imaging (MRI) in a research setting, and to examine reasons for women to participate or not. MATERIALS AND METHODS: Between 2011 and 2015, 8,061 women (50-75 years) were invited for supplemental MRI as part of the Dense Tissue and Early Breast Neoplasm Screening (DENSE) trial (ClinicalTrials.gov Identifier: NCT01315015), after a negative screening mammography in the national population-based mammography screening programme. Demographics of participants and non-participants were compared. All invitees were asked to report reasons for (non)participation. Ethical approval was obtained. Participants provided written informed consent. RESULTS: Of the 8,061 invitees, 66% answered that they were interested, and 59% eventually participated. Participants were on average 54-years old (interquartile range: 51-59 years), comparable to women with extremely dense breasts in the population-based screening programme (55 years). Women with higher socio-economic status (SES) were more often interested in participation than women with lower SES (68% versus 59%, p<0.001). The most frequently stated reasons for non-participation were "MRI-related inconveniences and/or self-reported contraindications to MRI" (27%) and "anxiety regarding the result of supplemental screening" (21%). "Expected personal health benefit" (68%) and "contribution to science" (43%) were the most frequent reasons for participation. CONCLUSION: Of women invited for MRI because of extremely dense breasts, 59% participated. Common reasons for non-participation were "MRI-related inconveniences" and "anxiety regarding the result of supplemental screening". In case of future implementation, availability of precise evidence on benefits and harms might reduce this anxiety.

Redefining radiotherapy for early-stage breast cancer with single dose ablative treatment: a study protocol.

BACKGROUND: A shift towards less burdening and more patient friendly treatments for breast cancer is currently ongoing. In low-risk patients with early-stage disease, accelerated partial breast irradiation (APBI) is an alternative for whole breast irradiation following breast-conserving surgery. MRI-guided single dose ablative APBI has the potential to offer a minimally burdening, non-invasive treatment that could replace current breast-conserving therapy. METHODS: The ABLATIVE study is a prospective, single arm, multicenter study evaluating preoperative, single dose, ablative radiation treatment in patients with early-stage breast cancer. Patients with core biopsy proven non-lobular invasive breast cancer, (estrogen receptor positive, Her2 negative, maximum tumor size 3.0 cm on diagnostic MRI) and a negative sentinel node biopsy are eligible. Radiotherapy (RT) planning will be performed using a contrast enhanced (CE) planning CT-scan, co-registered with a CE-MRI, both in supine RT position. A total of twenty-five consecutive patients will be treated with a single ablative RT dose of 20 Gy to the tumor and 15 Gy to the tumorbed. Follow-up MRIs are scheduled within 1 week, 2, 4 and 6 months after single-dose RT. Breast-conserving surgery is scheduled at six months following RT. Primary study endpoint is pathological complete response. Secondary study endpoints are the radiological response and toxicity. Furthermore, patients will fill out questionnaires on quality of life and functional status. Cosmetic outcome will be evaluated by the treating radiation oncologist, patient and 'Breast Cancer Conservation Treatment cosmetic results' software. Recurrence and survival rates will be assessed. The patients will be followed up to 10 years after diagnosis. If patients give additional informed consent, a biopsy and a part of the irradiated specimen will be stored at the local Biobank and used for future research on radiotherapy response associated genotyping. DISCUSSION: The ABLATIVE study evaluates MRI-guided single dose ablative RT in patients with early-stage breast cancer, aiming at a less burdening and non-invasive alternative for current breast-conserving treatment. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT02316561 . The trial was registrated prospectively on October 10th 2014.

Sentinel lymph node localization with contrast-enhanced ultrasound and an I-125 seed: an ideal prospective development study.

INTRODUCTION: Our aim was to evaluate the development of microbubble-enhanced sentinel lymph node (SLN) localization with placement of an I-125 seed in breast cancer patients as a potential alternative for SLN localization with nanocolloid. The study is conducted and reported following the IDEAL recommendations for evaluation of a new technique at Stage 2a (Prospective Development Study). METHODS: Fourteen consecutive patients with 15 lesions underwent microbubble-enhanced SLN localization with placement of an I-125 seed after the standard SLN localization (nanocolloid). We placed an I-125 seed within or near the SLN following its identification using intradermally injected microbubbles. The SLN was excised guided by nanocolloid and the SLN containing the I-125 seed was searched for. All technical modifications are described and standardized outcomes measured. RESULTS: Twelve (80%) microbubble procedures with I-125 seed placements were technically successful. In three cases no microbubble-enhancing lymph node could be detected. Intraoperatively, we found nine I-125 seeds within 0.5 cm of the nanocolloid confirmed SLN. One I-125 seed was found next to a non-SLN and two I-125 seeds were not near any lymph node. Overall, the procedure was successful in 60% (9 out of 15) of the cases. CONCLUSION: Given the low success rate, we conclude that microbubble-enhanced SLN is not a viable alternative to the standard SLN procedure. Modifications to this technique did not improve its performance. Planned study (NTR3690 http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3690) was stopped early due to this conclusion and results reported in order to provide a full and transparent record of the evolution of technique.

Prediction of positive resection margins in patients with non-palpable breast cancer.

BACKGROUND: In patients undergoing breast conserving surgery for non-palpable breast cancer, obtaining tumour free resection margins is important to prevent reexcision and local recurrence. We developed a model to predict positive resection margins in patients undergoing breast conserving surgery for non-palpable invasive breast cancer. METHODS: A total of 576 patients with non-palpable invasive breast cancer underwent breast conserving surgery in five hospitals in the Netherlands. A prediction model for positive resection margins was developed using multivariate logistic regression. Calibration and discrimination of the model were assessed and the model was internally validated by bootstrapping. RESULTS: Positive resection margins were present in 69/576 (12%) patients. Factors independently associated with positive resection margins included mammographic microcalcifications (OR 2.14, 1.22-3.77), tumour size (OR 1.75, 1.20-2.56), presence of DCIS (OR 2.61, 1.41-4.82), Bloom and Richardson grade 2/3 (OR 1.82, 1.05-3.14), and caudal location of the lesion (OR 2.4, 1.35-4.27). The model was well calibrated and moderately able to discriminate between patients with positive versus negative resection margins (AUC 0.70, 95% CI, 0.63-0.77, and 0.69 after internal validation). CONCLUSION: The presented prediction model is moderately able to differentiate between women with high versus low risk of positive margins, and may be useful for surgical planning and preoperative patient counselling.

Assessment of a fully automated, high-throughput mammographic density measurement tool for use with processed digital mammograms.

PURPOSE: The ImageJ model is a recently developed automated breast density measurement tool based on analysis of Cumulus outcomes. It has been validated on digitized film-screen mammograms. In this study, the ImageJ model was assessed on processed full-field digital mammograms and correlated with the Breast Imaging Reporting and Data System (BI-RADS) density classification. Also, the association with breast cancer risk factors is observed. METHODS: Women with mammographies between 2001 and 2011 at the University Medical Center Utrecht, The Netherlands were included. We composed a training set, read with Cumulus, for building the ImageJ model [n = 100 women, 331 images; craniocaudal (CC) and mediolateral oblique (MLO) views, left and right] and a validation set for model assessment and correlation with the BI-RADS classification [n = 530 women, 1,977 images; average of available CC and MLO views, left and right]. Pearson product-moment correlation coefficient was used to compare Cumulus with ImageJ, Spearman correlation coefficient for ImageJ with BI-RADS density, and generalized linear models for association with breast cancer risk factors. RESULTS: The correlation between ImageJ and Cumulus in the training set was 0.90 [95 % confidence interval (CI) 0.86-0.93]. After application to the validation set, we observed a high correlation between ImageJ and the BI-RADS readings (Spearman r = 0.86, 95 % CI 0.84-0.88). Women with higher density were significantly younger, more often premenopausal, had lower parity, more often a benign breast lesion or family history of breast cancer. CONCLUSIONS: The ImageJ model can be used on processed digital mammograms. The measurements strongly correlate with Cumulus, the BI-RADS density classification, and breast cancer risk factors.

Mammographic screening detects low-risk tumor biology breast cancers.

Overdiagnosis of breast cancer, i.e. the detection of slow-growing tumors that would never have caused symptoms or death, became more prevalent with the implementation of population-based screening. Only rough estimates have been made of the proportion of patients that are overdiagnosed and identification of those patients is difficult. Therefore, the aim of this study is to evaluate whether tumor biology can help identify patients with screen-detected tumors at such a low risk of recurrence that they are likely to be overdiagnosed. Furthermore, we wish to evaluate the impact of the transition from film-screen mammography (FSM) to the more sensitive full-field digital mammography (FFDM) on the biology of the tumors detected by each screening-modality. All Dutch breast cancer patients enrolled in the MINDACT trial (EORTC-10041) accrued 2007-2011, who participated in the national screening program (biennial screening ages 50-75) were included (n = 1,165). We calculated the proportions of high-, low- and among those the ultralow-risk tumors according to the 70-gene signature for patients with screen-detected (n = 775) and interval (n = 390) cancers for FSM and FFDM. Screen-detected cancers had significantly more often a low-risk tumor biology (68 %) of which 54 % even an ultralow-risk compared to interval cancers (53 % low-, of which 45 % ultralow-risk (p = 0.001) with an OR of 2.33 (p < 0.0001; 95 % CI 1.73-3.15). FFDM detected significantly more high-risk tumors (35 %) compared to FSM (27 %) (p = 0.011). Aside from favorable clinico-pathological factors, screen-detected cancers were also more likely to have a biologically low-risk or even ultralow-risk tumor. Especially for patients with screen-detected cancers the use of tools, such as the 70-gene signature, to differentiate breast cancers by risk of recurrence may minimize overtreatment. The recent transition in screening-modalities led to an increase in the detection of biologically high-risk cancers using FFDM.

Experiences with a self-test for Dutch breast screening radiologists: lessons learnt.

PURPOSE: To evaluate a self-test for Dutch breast screening radiologists introduced as part of the national quality assurance programme. METHODS AND MATERIALS: A total of 144 radiologists were invited to complete a test-set of 60 screening mammograms (20 malignancies). Participants assigned findings such as location, lesion type and BI-RADS. We determined areas under the receiver operating characteristics (ROC) curves (AUC), case and lesion sensitivity and specificity, agreement (kappa) and correlation between reader characteristics and case sensitivity (Spearman correlation coefficients). RESULTS: A total of 110 radiologists completed the test (76%). Participants read a median number of 10,000 screening mammograms/year. Median AUC value was 0.93, case and lesion sensitivity was 91% and case specificity 94%. We found substantial agreement for recall (κ = 0.77) and laterality (κ = 0.80), moderate agreement for lesion type (κ = 0.57) and BI-RADS (κ = 0.45) and no correlation between case sensitivity and reader characteristics. CONCLUSION: Areas under the ROC curve, case sensitivity and lesion sensitivity were satisfactory and recall agreement was substantial. However, agreement in lesion type and BI-RADS could be improved; further education might be aimed at reducing interobserver variation in interpretation and description of abnormalities. We offered individual feedback on interpretive performance and overall feedback at group level. Future research will determine whether performance has improved. KEY POINTS: • We introduced and evaluated a self-test for Dutch breast screening radiologists. • ROC curves, case and lesion sensitivity and recall agreement were all satisfactory. • Agreement in BI-RADS interpretation and description of abnormalities could be improved. • These are areas that should be targeted with further education and training. • We offered individual feedback on interpretative performance and overall group feedback.

Axillary ultrasound for preoperative nodal staging in breast cancer patients: is it of added value?

BACKGROUND: New insights show that an axillary lymph node dissection (ALND) may not always be indicated for metastases detected by ultrasound (pathologically proven). This study investigated whether axillary ultrasound accurately predicts pN0, pN1 and pN2-pN3 status. METHODS: Data were retrospectively collected from all consecutive patients with invasive breast cancer who underwent (primary) surgery between 2008 and 2012. False negative percentages and negative predictive values (NPVs) for sonographic nodal staging were calculated for all patients and again for cT1-2 patients treated by breast conserving therapy (BCT). RESULTS: A total of 577 axillary ultrasounds were included. After negative ultrasound findings (cN0), pathology showed pN2-pN3 disease in 4.4% of these cases, with an NPV of 95.5% (93.4-97.1%). When cN1 (1-3 suspicious nodes) was predicted, pathology showed pN2-pN3 disease in 41.2%, with an NPV of 58.5% (44.2-71.5%). In the subgroup of patients with cT1-2 breast cancer that were treated by BCT, pathology showed pN2-pN3 disease in 2.3% after negative ultrasound findings (cN0), with an NPV of 97.7% (94.9-99.0%). When cN1 was predicted (n = 12), pathology showed pN2-pN3 disease in 50.0%, with an NPV of 50.0% (22.3-77.9%). A direct ALND was performed in these 12 cN1 cases; pathology showed six patients with pN1 (three patients with one and three with two macrometastases) and six with pN2-pN3 disease (4, 5, 11, 13, 16 or 22 macrometastases, respectively). CONCLUSION: In conclusion, a negative axillary ultrasound generally excludes the presence of pN2-pN3 disease. An axillary ultrasound cannot accurately differentiate between pN1 and pN2-pN3. It could be argued that the standard performance of an axillary ultrasound in breast cancer patients is questionable; multidisciplinary discussion could guide decisions on the use of axillary ultrasound for the individual patient.

Breast cancer risk prediction model: a nomogram based on common mammographic screening findings.

OBJECTIVES: To develop a prediction model for breast cancer based on common mammographic findings on screening mammograms aiming to reduce reader variability in assigning BI-RADS. METHODS: We retrospectively reviewed 352 positive screening mammograms of women participating in the Dutch screening programme (Nijmegen region, 2006-2008). The following mammographic findings were assessed by consensus reading of three expert radiologists: masses and mass density, calcifications, architectural distortion, focal asymmetry and mammographic density, and BI-RADS. Data on age, diagnostic workup and final diagnosis were collected from patient records. Multivariate logistic regression analyses were used to build a breast cancer prediction model, presented as a nomogram. RESULTS: Breast cancer was diagnosed in 108 cases (31 %). The highest positive predictive value (PPV) was found for spiculated masses (96 %) and the lowest for well-defined masses (10 %). Characteristics included in the nomogram are age, mass, calcifications, architectural distortion and focal asymmetry. CONCLUSION: With our nomogram we developed a tool assisting screening radiologists in determining the chance of malignancy based on mammographic findings. We propose cutoff values for assigning BI-RADS in the Dutch programme based on our nomogram, which will need to be validated in future research. These values can easily be adapted for use in other screening programmes. KEY POINTS: • There is substantial reader variability in assigning BI-RADS in mammographic screening. • There are no strict guidelines linking mammographic findings to BI-RADS categories. • We developed a model (nomogram) predicting the presence of breast cancer. • Our nomogram is based on common findings on positive screening mammograms. • The nomogram aims to assist screening radiologists in assigning BI-RADS categories.

Radioactive seed localization for non-palpable breast cancer.

BACKGROUND: Radioactive seed localization (RSL) is an alternative to wire localization for guiding surgical excision of non-palpable breast cancer. This review provides an overview of the available evidence on the accuracy of RSL in patients undergoing breast-conserving surgery. METHODS: PubMed, Embase and the Cochrane Library were searched systematically in January 2012 for studies that addressed localization of non-palpable breast cancer using an iodine-125-labelled seed. Studies were deemed eligible if they reported on the proportion of patients with tumour-positive margins after RSL, the proportion of patients needing re-excision after RSL, and procedural complications. RESULTS: Six studies reported data on RSL in 1611 patients with non-palpable breast lesions. Overall complete resection rates ranged from 73 to 96.7 per cent. Three studies included over 300 patients, and complete resection rates in these studies varied between 89.5 and 96.7 per cent. The risk of seed migration and failure of seed placement ranged from 0 to 0.6 per cent and 0 to 7.2 per cent respectively. CONCLUSION: Available scientific evidence suggests that RSL is a safe and accurate technique for localization of non-palpable breast lesions.

Intraoperative ultrasound guidance for excision of non-palpable invasive breast cancer: a hospital-based series and an overview of the literature.

Intraoperative ultrasound (IOUS) can be used in the operation theatre for localization of non-palpable breast cancers. In this prospective cohort study, we compared the yield of IOUS to guidewire localization (GWL). A total of 258 consecutive patients with non-palpable invasive breast cancer underwent breast conserving surgery between 1999 and 2010. GWL was performed in 138 (54 %) and IOUS in 120 (46 %) patients. Tumor dimensions, resection volume, margin status and re-excision rates were compared by means of multivariate regression analysis. The groups were similar in terms of age, histological subtype and presence of DCIS. Lesions in the IOUS group were larger (1.24 vs. 0.98 cm, P < 0.001), while microcalcifications were more common in the GWL group (19 vs. 3 %, P < 0.001). Even after stratification for tumor diameter, presence of DCIS and findings on mammography, resection volumes were similar in both groups. Tumor-free resection margins were obtained in >93 % of patients (93.5 % with GWL vs. 93.3 % with IOUS, P = 0.958) and re-excision was performed in 11 % of patients undergoing GWL and 12.5 % of patients undergoing IOUS (P = 0.684). For localization of non-palpable breast cancer, IOUS is a reliable alternative to GWL, as it achieves similar results in terms of complete tumor removal, re-excision rate and excised volume.

The added value of quantitative multi-voxel MR spectroscopy in breast magnetic resonance imaging.

OBJECTIVE: To determine whether quantitative multivoxel MRS improves the accuracy of MRI in the assessment of breast lesions. METHODS: Twenty-five consecutive patients with 26 breast lesions ≥ 1 cm assessed as BI-RADS 3 or 4 with mammography underwent quantitative multivoxel MRS and contrast-enhanced MRI. The choline (Cho) concentration was calculated using the unsuppressed water signal as a concentration reference. ROC analysis established the diagnostic accuracy of MRI and MRS in the assessment of breast lesions. RESULTS: Respective Cho concentrations in 26 breast lesions re-classified by MRI as BI-RADS 2 (n = 5), 3 (n = 8), 4 (n = 5) and 5 (n = 8) were 1.16 ± 0.43 (mean ± SD), 1.43 ± 0.47, 2.98 ± 2.15 and 4.94 ± 3.10 mM. Two BI-RADS 3 lesions and all BI-RADS 4 and 5 lesions were malignant on histopathology and had Cho concentrations between 1.7 and 11.8 mM (4.03 ± 2.72 SD), which were significantly higher (P = 0.01) than that in the 11 benign lesions (0.4-1.5 mM; 1.19 ± 0.33 SD). Furthermore, Cho concentrations in the benign and malignant breast lesions in BI-RADS 3 category differed (P = 0.01). The accuracy of combined multivoxel MRS/breast MRI BI-RADS re-classification (AUC = 1.00) exceeded that of MRI alone (AUC = 0.96 ± 0.03). CONCLUSIONS: These preliminary data indicate that multivoxel MRS improves the accuracy of MRI when using a Cho concentration cut-off ≤ 1.5 mM for benign lesions. KEY POINTS: Quantitative multivoxel MR spectroscopy can improve the accuracy of contrast-enhanced breast MRI. Multivoxel-MRS can differentiate breast lesions by using the highest Cho-concentration. Multivoxel-MRS can exclude patients with benign breast lesions from further invasive diagnostic procedures.

The negative predictive value of breast Magnetic Resonance Imaging in noncalcified BIRADS 3 lesions.

PURPOSE: The purpose of this study is to determine whether breast MRI can provide a sufficient NPV to safely rule out malignancy in mammographic BIRADS 3 lesions. MATERIALS AND METHODS: In a 3-year consecutive mammographic examination study 176 out of 4391 patients had a lesion classified as BIRADS 3. 76 out of 176 patients underwent breast MRI as diagnostic work-up. Lesions which MRI classified as BIRADS 1 or 2 were considered negative for malignancy. Sensitivity, specificity, PPV and NPV were calculated. RESULTS: In 27 out of 76 (35.5%) patients MRI showed no enhancement and was classified as BIRADS 1. In 25 (32.9%) patients MRI showed focal or mass enhancement classified as BIRADS 2. In these 52 (68.4%) patients no malignancy was found during at least 2 years study follow-up. The other 24 (31.6%) patients had a lesion classified as BIRADS ≥ 3. Thirteen of these 24 lesions were malignant by pathology. MRI had a sensitivity of 100% (95% CI: 75-100%), specificity of 82.5% (95% CI: 71-91%), PPV of 54.2% (95% CI: 33-74%) and NPV of 100% (95% CI: 93-100%). CONCLUSION: Breast MRI should be used in a diagnostic strategy for the work-up of noncalcified BIRADS 3 lesions. Malignancy is ruled out with a very high level of confidence in the majority of patients (68%), herewith avoiding invasive diagnostic procedures.

Breast magnetic resonance imaging as a problem-solving modality in mammographic BI-RADS 3 lesions.

The probability of a mammographic Breast Imaging Reporting and Data System (BI-RADS) 3 lesion being cancer is considered to be less than 2%. Therefore, the work-up of a mammographic BI-RADS 3 lesion should be biopsy or follow-up mammography after 6 months. However, most patients referred for biopsy have benign disease. Although the negative predictive value (NPV) of magnetic resonance imaging (MRI) is highest of all imaging techniques, it is not yet common practice to use breast MRI as a problem-solving modality to exclude patients for further diagnostic work-up. Therefore, in this meta-analysis the usefulness of breast MRI as a problem-solving modality in mammographic BI-RADS 3 lesions is investigated. After a systematic search only 5 out of 61 studies met the inclusion criteria. The NPV in 2 of those studies was reported to be 100%. It was concluded that MRI can be used as an adjunctive tool to mammographic BI-RADS 3 findings to exclude patients for further diagnostic work-up. The other 3 studies assessed the accuracy of MRI in mammographic BI-RADS 3 microcalcifications. These studies reported an NPV of MRI between 76% and 97%. Therefore, MRI cannot be implemented as a diagnostic tool to evaluate mammographic microcalcifications at this time. The first solid data indicate that breast MRI might be useful as a problem-solving modality to exclude patients with non-calcified mammographic BI-RADS 3 lesions for further diagnostic work-up. However, further research is needed to verify these results.