A randomised trial of selective intracoronary hypothermia during primary PCI.

BACKGROUND: While experimental data suggest that selective intracoronary hypothermia decreases infarct size, studies in patients with ST-elevation myocardial infarction (STEMI) are lacking. AIMS: We investigated the efficacy of selective intracoronary hypothermia during primary percutaneous coronary intervention (PCI) to decrease infarct size in patients with STEMI. METHODS: In this multicentre randomised controlled trial, 200 patients with large anterior wall STEMI were randomised 1:1 to selective intracoronary hypothermia during primary PCI or primary PCI alone. Using an over-the-wire balloon catheter for infusion of cold saline and a pressure-temperature wire to monitor the intracoronary temperature, the anterior myocardium distal to the occlusion was selectively cooled to 30-33°C for 7-10 minutes before reperfusion (occlusion phase), immediately followed by 10 minutes of cooling after reperfusion (reperfusion phase). The primary endpoint was infarct size as a percentage of left ventricular mass on cardiovascular magnetic resonance imaging after 3 months. RESULTS: Selective intracoronary hypothermia was performed in 94/100 patients randomised to cooling. Distal coronary temperature decreased by 6°C within 43 seconds (interquartile range [IQR] 18-113). The median duration of the occlusion phase and reperfusion phase were 8.2 minutes (IQR 7.2-9.0) and 9.1 minutes (IQR 8.2-10.0), respectively. The infarct size at 3 months was 23.1±12.5% in the selective intracoronary hypothermia group and 21.6±12.2% in the primary PCI alone group (p=0.43). The left ventricular ejection fraction at 3 months in each group were 49.1±10.2% and 50.1±10.4%, respectively (p=0.53). CONCLUSIONS: Selective intracoronary hypothermia during primary PCI in patients with anterior wall STEMI was feasible and safe but did not decrease infarct size compared with standard primary PCI. (ClinicalTrials.gov: NCT03447834).

Diagnostic accuracy of supplemental three-dimensional breast ultrasound in the work-up of BI-RADS 0 screening recalls.

OBJECTIVE: To evaluate the diagnostic accuracy of supplemental 3D automated breast ultrasound (ABUS) in the diagnostic work-up of BI-RADS 0 recalls. We hypothesized that 3D ABUS may reduce the benign biopsy rate. MATERIALS AND METHODS: In this prospective multicenter diagnostic study, screening participants recalled after a BI-RADS 0 result underwent bilateral 3D ABUS supplemental to usual care: digital breast tomosynthesis (DBT) and targeted hand-held ultrasound (HHUS). Sensitivity, specificity, positive predictive value, and negative predictive value of 3D ABUS, and DBT plus HHUS, were calculated. New 3D ABUS findings and changes of management (biopsy or additional imaging) were recorded. RESULTS: A total of 501 women (median age 55 years, IQR [51-64]) with 525 BI-RADS 0 lesions were included between April 2018 and March 2020. Cancer was diagnosed in 45 patients. 3D ABUS sensitivity was 72.1% (95% CI [57.2-83.4%]), specificity 84.4% (95% CI [80.8-87.4%]), PPV 29.2% (95% CI [21.4-38.5%]), and NPV 97.1% 95.0-98.4%). Sensitivity of DBT plus HHUS was 100% (95% CI [90.2-100%]), specificity 71.4% (95% CI [67.2-75.2%]), PPV 23.8% (95% CI [18.1-30.5%]) and NPV 100% (95% CI [98.7-100%]). Twelve out of 43 (27.9%) malignancies in BI-RADS 0 lesions were missed on 3D ABUS, despite being detected on DBT and/or HHUS. Supplemental 3D ABUS resulted in the detection of 57 new lesions and six extra biopsy procedures, all were benign. CONCLUSION: 3D ABUS in the diagnostic work-up of BI-RADS 0 recalls may miss over a quarter of cancers detected with HHUS and/or DBT and should not be used to omit biopsy. Supplemental 3D ABUS increases the benign biopsy rate. TRIAL REGISTRATION: Dutch Trial Register, available via https://www.onderzoekmetmensen.nl/en/trial/29659 CRITICAL RELEVANCE STATEMENT: Supplemental 3D automated breast ultrasound in the work-up of BI-RADS 0 recalls may miss over a quarter of cancers detected with other methods and should not be used to omit biopsy; ABUS findings did increase benign biopsy rate. KEY POINTS: Automated breast ultrasound (ABUS) may miss over 25% of cancers detectable by alternative methods. Don't rely solely on 3D ABUS to assess indication for biopsy. New findings with supplemental 3D ABUS increase the benign biopsy rate.

Trends in the pre-operative diagnosis and surgical management of axillary lymph node metastases in women with screen-detected breast cancer.

AIM: The aim of the current study was to investigate time-trends in pre-operative diagnosis and surgical treatment of axillary lymph node metastases in breast cancers detected at screening mammography. METHODS: We included all women who underwent screening mammography in the South of the Netherlands between 2005 and 2020. During a follow-up period of at least two years, data on clinical radiological examinations, biopsy procedures and surgical interventions were obtained. The 15 years of inclusion were divided into five cohorts of three years each. RESULTS: Of the 4049 women with invasive breast cancer, 22.1 % (896/4049) had axillary lymph node metastasis at pathology (ALN+). Percutaneous axillary biopsy was performed in 39.6 % (355/896) of these women, with the proportions of fine needle aspiration biopsy (FNAB) decreasing from 97.6 % (40/41) in 2005-2007 to 41.6 % (37/89) in 2017-2019 and core needle biopsy (CNB) rising from 2.4 % (1/41) in 2005-2007 to 58.4 % (52/89) in 2017-2019 (P < 0.001). Sensitivity of FNAB and CNB was comparable (77.4 % (188/243, 95%CI = 71%-82 %) versus 82.4 % (103/125), 95%CI = 74%-88 %) (P = 0.26). Pre-operative confirmation of ALN + by percutaneous biopsy ranged from 27.3 % (56/205) in 2011-2013 to 39.0 % (80/205) in 2017-2019, with no significant trend changes over time (P = 0.103). The proportion of ALN + women who underwent axillary lymph node dissection (ALND) decreased from 96.0 % (97/101) in 2005-2007 to 16.6 % (34/205) in 2017-2019 (P < 0.001). CONCLUSION: Pre-operative confirmation of axillary lymph node metastasis by ultrasound-guided biopsy did not rise despite the increased use of CNB at the expense of less invasive FNAB. A significant reduction in ALND was observed through the years.

Effects of nonparticipation at previous screening rounds on the characteristics of screen-detected breast cancers.

PURPOSE: We determined the incidence and effects of different screening intervals prior to a true positive recall on the tumour characteristics of screen-detected cancers (SDC) and interval cancers (ICs) at biennial screening mammography. METHODS: A consecutive series of 553020 subsequent screens was included, obtained in a Dutch screening region between January 2009 and July 2019. During 2-year follow-up, we obtained data on radiological procedures, pathology and surgical interventions of all recalled women. RESULTS: A total of 13,221 women were recalled (2.4% recall rate), yielding 3662 women with a SDC (6.6 SDCs per 1000 screen). Of these, 3477 (94.9%) had attended their two most recent screens as scheduled (i.e., 2-year screening interval), whereas the interval between the two most recent screens was four years or at least six years in respectively 132 (3.6%) and 53 (1.4%) women. There was a trend of higher cancer detection rates in case of longer screening intervals. The proportions of DCIS versus invasive cancer, as well as tumour histology, tumour size, axillary lymph node status, B&R grading, hormone receptor status and type of surgical treatment (breast conserving surgery or mastectomy) were comparable for women with a 2-year or 4-year interval between their two latest screens. SDCs in women with at least six years between their two latest screens were more frequently estrogen receptor negative or triple negative and were more frequently treated by mastectomy. All tumour characteristics mentioned above were less favourable for ICs than SDCs. CONCLUSIONS: A vast majority of women with a SDC had a 2-year screening interval between their two latest screens. A screening interval of at least six years had a slight negative influence on the tumour characteristics and treatment of SDCs.

Failure of stereotactic core needle biopsy in women recalled for suspicious calcifications at screening mammography: frequency, causes, and final outcome in a multi-institutional, observational follow-up study.

OBJECTIVES: We determined the failure rate of stereotactic core needle biopsy (SCNB) and its causes and final outcome in women recalled for calcifications at screening mammography. METHODS: We included a consecutive series of 624,039 screens obtained in a Dutch screening region between January 2009 and July 2019. Radiology reports and pathology results were obtained of all recalled women during 2-year follow-up. RESULTS: A total of 3495 women (19.6% of 17,809 recalls) were recalled for suspicious calcifications. SCNB was indicated in 2818 women, of whom 12 had incomplete follow-up and another 12 women refused biopsy. DCIS or invasive cancer was diagnosed in 880 of the remaining 2794 women (31.5%). SCNB failed in 62 women (2.2%, 36/2794). These failures were mainly due to a too posterior (n = 30) or too superficial location (n = 17) of the calcifications or calcifications too faint for biopsy (n = 13). Of these 62 women, 10 underwent surgical biopsy, yielding one DCIS (intermediate grade) and two invasive cancers (one intermediate grade and one high grade) and another two women were diagnosed with DCIS (both high grade) at follow-up. Thus, the malignancy rate after SCNB failure was 8.1% (5/62). Calcifications were depicted neither at SCNB specimen radiography nor at pathology in 16 women after (repeated) SCNB (0.6%, 31/2732). None of them proved to have breast cancer at 2-year follow-up. CONCLUSIONS: The failure rate of SCNB for suspicious calcifications is low but close surveillance is warranted, as breast cancer may be present in up to 8% of these women. KEY POINTS: • The failure rate of stereotactic core needle biopsy (SCNB) for calcifications recalled at screening mammography was 2.2%. • Failures were mainly due to calcifications that could not be reached by SCNB or calcifications too faint for biopsy. • The management after failed SCNB was various. At least, close surveillance with a low threshold for surgical biopsy is recommended as breast cancer may be present in up to 8% of women with SCNB failure.

Added Value of Prereading Screening Mammograms for Breast Cancer by Radiologic Technologists on Early Screening Outcomes.

Background In the Dutch breast cancer screening program, mammograms are preread by technologists to identify possible abnormalities, leading to "warning signals" (an audible and visual alert if the technologist observed an abnormality suspicious for cancer) for radiologists. The best moment to present these warning signals is unknown. Purpose To determine the effect that blinding of technologists' warning signals has on radiologists' early screening outcome measures during interpretation of mammograms. Materials and Methods In this prospective study from September 2017 to May 2019, on alternating months, radiologists were either blinded or nonblinded to the warning signals of the technologist when interpreting screening mammograms for breast cancer. All discrepancies between radiologists and technologists were reviewed during quality assurance sessions every 6 weeks, which could result in secondary recalls. The outcome measures of this study were recall rate, cancer detection rate, and positive predictive value of recall. A χ2 test was used to test for differences between the two groups. Results During the study period, 109 596 women (mean age, 62 years ± 7 [standard deviation]), including 53 291 in the blinded and 56 305 in the nonblinded groups, participated. The overall recall rate (including secondary recalls) was lower for women in the blinded group than in the nonblinded group (blinded: 1140 of 53 291 women [2.1%], nonblinded: 1372 of 56 305 women [2.4%]; P = .001). There was no evidence of cancer detection rate differences between the groups (blinded: 349 of 53 291 women [6.5 per 1000 screening examinations], nonblinded: 360 of 56 305 women [6.4 per 1000 screening examinations]; P = .75). The blinded group thus had a higher positive predictive value of recall (blinded: 349 of 1140 women [30.6%], nonblinded: 360 of 1372 women [26.2%]; P = .02). Conclusion While interpreting screening mammograms for breast cancer, radiologists blinded to technologists' warning signals had lower recall rates with higher positive predictive values than nonblinded radiologists, yet cancer detection rates seemed to remain unchanged. See also the editorial by Hofvind and Lee in this issue. © RSNA, 2021.

Delayed breast cancer diagnosis after repeated recall at biennial screening mammography: an observational follow-up study from the Netherlands.

BACKGROUND: Delay in detection of breast cancer may worsen tumour characteristics, with progression of tumour size and a higher risk of metastatic lymph nodes. The purpose of this study was to investigate delayed breast cancer diagnosis after repeated recall for the same mammographic abnormality at screening. METHODS: This was a retrospective study performed in two cohorts of women enrolled in a mammography screening programme in the Netherlands. All women aged 50-75 who underwent biennial screening mammography either between January 1, 1997 and December 31, 2006 (cohort 1) or between January 1, 2007 and December 31, 2016 (cohort 2) were included. RESULTS: The cohorts showed no difference in proportions of women with delayed breast cancer diagnosis of at least 2 years (2.2% versus 2.8%, P = 0.29). Most delays were caused by incorrect BI-RADS classifications after recall (74.2%). An increase in mean tumour size was seen when comparing sizes at initial false-negative recall and at diagnosis of breast cancer (P < 0.001). CONCLUSIONS: The proportion of women with a long delay in breast cancer confirmation following repeated recall at screening mammography has not decreased during 20 years of screening. These delays lead to larger tumour size at detection and may negatively influence prognosis.

Tumour characteristics of bilateral screen-detected cancers and bilateral interval cancers in women participating at biennial screening mammography.

BACKGROUND: Unilateral interval breast cancers show less favourable prognostic features than unilateral screen-detected cancers, but data on tumour characteristics of bilateral interval cancers in a systematically screened population are sparse. Therefore, we compared tumour characteristics of bilateral interval cancers with those of bilateral screen-detected cancers. METHODS: We included all 468,720 screening mammograms of women who underwent biennial screening mammography in the South of the Netherlands between January 2005 and January 2015. We collected breast imaging reports, biopsy results and surgical reports of all recalled women and of all women who presented with interval breast cancer. In women with synchronous bilateral breast cancer, the tumour with the highest tumour stage was defined as the index cancer. For comparison of data between both groups Fisher exact test and Chi-square test were used. RESULTS: Synchronous bilateral cancer was diagnosed in 2.2% of screen-detected cancers (64/2947) and in 3.2% of interval cancers (24/753) (P = 0.1). Index tumours of bilateral screen-detected cancers and interval cancers showed similar characteristics, except for a larger proportion of T-stage 2 or worse (T2+) cancers among interval cancers (16/24 (66.7%) versus 23/58 (39.7%) (P = 0.03). Index cancers, compared to contralateral cancers, were less frequently stage T1 in both bilateral screen-detected cancers and bilateral interval cancers (35/64 (60.3%) versus 40/64 (88.9%) (P = 0.001) and 8/24 (33.3%) versus 18/24 (85.7%) (P < 0.001), respectively). In bilateral screen-detected cancers, contralateral cancers were more often stage 1a-c (P < 0.001) compared to index cancers. In bilateral index cancers, index cancers were more often of the lobular subtype (P < 0.001). CONCLUSION: Index cancers of bilateral screen-detected cancers and bilateral interval cancers show significant differences in tumour size, whereas nodal status, receptor status and final surgical treatment are comparable. In bilateral screen-detected cancer, index cancers had a significantly higher tumour stage. In bilateral screen-detected cancer, index cancers were more often the ductal invasive subtype compared to contralateral cancers.

Incidence and tumour characteristics of bilateral and unilateral interval breast cancers at screening mammography.

BACKGROUND: Detected by screening mammography, bilateral breast cancer has a different pathological profile compared to unilateral breast cancer. We investigated the incidence of bilateral interval breast cancers and compared their characteristics with those of unilateral interval breast cancers. METHODS: We included all 468,720 screening mammograms of women who underwent biennial screening mammography in the South of the Netherlands between January 2005 and January 2015. We collected breast imaging reports, biopsy results and surgical reports of all referred women and of all women who presented with interval breast cancer. The tumour with the highest tumour stage (index cancer) was used for comparison with unilateral interval cancers. RESULTS: A total of 753 interval cancers were detected, of which 24 (3.2%) were bilateral. Among the invasive interval cancers, bilateral cancers more frequently showed a lobular histology than unilateral cancers (37.5% (9/24) vs. 16.1% (111/691), P = .01). There is a trend towards a larger proportion of bilateral than unilateral interval cancers graded 1 (45.8% (11/24) vs. 27.8% (192/691), P = .08). There were no other statistically significant differences in tumour characteristics. Also, the proportion of interval cancers showing significant mammographic abnormalities at the latest screen was comparable for unilateral and bilateral interval cancers (23.0% vs. 25.0%, P = .9). DISCUSSION: Bilateral interval cancers comprise a small proportion of all interval cancers. Except of a higher proportion of invasive lobular cancers and a more favourable histological grade of invasive cancers, tumour characteristics are comparable for bilateral and unilateral interval breast cancers.

Type and Extent of Surgery for Screen-Detected and Interval Cancers at Blinded Versus Nonblinded Double-Reading in a Population-Based Screening Mammography Program.

BACKGROUND: This study aimed to compare the type and extent of surgery in patients with screen-detected and interval cancers after blinded or nonblinded double-reading of screening mammograms. METHODS: The study investigated a consecutive series of screens double-read in either a blinded (n = 44,491) or nonblinded (n = 42,996) fashion between 2009 and 2011. During a 2 year follow-up period, the radiology reports, surgical correspondence, and pathology reports of all the screen-detected and interval cancers were collected. RESULTS: Screen-detected breast cancer was diagnosed for 325 women at blinded and 284 women at nonblinded double-reading. The majority of the women were treated by breast-conserving surgery (BCS) at both reading strategies (78.2 vs. 81.7 %; p = 0.51). Larger total resection volumes were observed at BCS for ductal carcinoma in situ (DCIS) treatment for patients after blinded double-reading (p = 0.005). The proportions of positive resection margins after BCS were comparable for patients with DCIS (p = 0.81) or invasive screen-detected cancers (p = 0.38) for the two reading strategies. A total of 158 interval cancers were diagnosed. The proportions of patients treated with BCS were comparable for the two reading strategies (p = 0.42). The total resection volume (p = 0.13) and the proportion of positive resection margins after BCS (p = 0.32) for invasive interval cancer were comparable for the two cohorts. The BCS rate was higher for women after nonblinded double-reading (p = 0.04). CONCLUSIONS: Blinded and nonblinded double-reading yielded comparable surgical treatments for women with screen-detected or interval breast cancer except for larger total resection volumes at BCS for screen-detected DCIS and a higher BCS rate for interval cancers at nonblinded double-reading.

Prognostic value of cardiovascular MR imaging biomarkers on outcome in peripheral arterial disease: a 6-year follow-up pilot study.

The objective of this pilot study was to explore the prognostic value of outcome of cardiovascular magnetic resonance (MR) imaging biomarkers in patients with symptomatic peripheral arterial disease (PAD) in comparison with traditional risk factors. Forty-two consecutive patients (mean age 64 ± 11 years, 22 men) referred for contrast-enhanced MR angiography (CE-MRA) were included. At baseline a comprehensive cardiovascular MRI examination was performed: CE-MRA of the infra-renal aorta and run-off vessels, carotid vessel wall imaging, cardiac cine imaging and aortic pulse wave velocity (PWV) assessment. Patients were categorized for outcome at 72 ± 5 months follow-up. One patient was lost to follow-up. Over 6 years, six patients had died (mortality rate 14.6 %), six patients (14.6 %) had experienced a cardiac event and three patients (7.3 %) a cerebral event. The mean MRA stenosis class (i.e., average stenosis severity visually scored over 27 standardized segments) was a significant independent predictor for all-cause mortality (beta 3.0 ± standard error 1.3, p = 0.02). Descending aorta PWV, age and diabetes mellitus were interrelated with stenosis severity but none of these were significant independent predictors. For cardiac morbidity, left ventricular ejection fraction (LVEF) and mean MRA stenosis class were associated, but only LVEF was a significant independent predictor (beta -0.14 ± 0.05, p = 0.005). Diabetes mellitus was a significant independent predictor for cerebral morbidity (beta 2.8 ± 1.3, p = 0.03). Significant independent predictors for outcome in PAD are mean MRA stenosis class for all-cause mortality, LVEF for cardiac morbidity and diabetes mellitus for cerebral morbidity.

Site-specific association between distal aortic pulse wave velocity and peripheral arterial stenosis severity: a prospective cardiovascular magnetic resonance study.

BACKGROUND: Vascular disease expression in one location may not be representative for disease severity in other vascular territories, however, strong correlation between disease expression and severity within the same vascular segment may be expected. Therefore, we hypothesized that aortic stiffening is more strongly associated with disease expression in a vascular territory directly linked to that aortic segment rather than in a more remote segment. We prospectively compared the association between aortic wall stiffness, expressed by pulse wave velocity (PWV), sampled in the distal aorta, with the severity of peripheral arterial occlusive disease (PAOD) as compared to atherosclerotic markers sampled in remote vascular territories such as PWV in the proximal aorta and the normalized wall index (NWI), representing the vessel wall thickness, of the left common carotid artery. METHODS: Forty-two patients (23 men; mean age 64±10 years) underwent velocity-encoded cardiovascular magnetic resonance (CMR) in the proximal and distal aorta, whole-body contrast-enhanced MR angiography (CE-MRA) and carotid vessel wall imaging with black-blood CMR in the work-up for PAOD. Strength of associations between aortic stiffness, carotid NWI and peripheral vascular stenosis grade were assessed and evaluated with multiple linear regression. RESULTS: Stenosis severity correlated well with PWV in the distal aorta (Pearson rP=0.64, p<0.001, Spearman rS=0.65, p<0.001) but to a lesser extent with PWV in the proximal aorta (rP=0.48, p=0.002, rS=0.22, p=0.18). Carotid NWI was not associated with peripheral stenosis severity (rP=0.17, p=0.28, rS=0.14, p=0.37) nor with PWV in the proximal aorta (rP=0.22, p=0.17) nor in the distal aorta (rP=0.21, p=0.18). Correlation between stenosis severity and distal aortic PWV remained statistically significant after correction for age and gender. CONCLUSIONS: Distal aortic wall stiffness is more directly related to peripheral arterial stenosis severity than markers from more remote vascular territories such as proximal aortic wall stiffness or carotid arterial wall thickness. Site-specific evaluation of vascular disease may be required for full vascular risk estimation.

Characteristics and screening outcome of women referred twice at screening mammography.

OBJECTIVES: To determine the characteristics and screening outcome of women referred twice at screening mammography. METHODS: We included 424,703 consecutive screening mammograms and collected imaging, biopsy and surgery reports of women with screen-detected breast cancer. Review of screening mammograms was performed to determine whether or not an initial and second referral comprised the same lesion. RESULTS: The overall positive predictive value of referral for cancer was 38.6% (95% CI 37.3-39.8%). Of 147 (2.6%) women referred twice, 86 had been referred for a different lesion at second referral and 32 of these proved malignant (37.2%, 95% CI 27.0-47.4%). Sixty-one women had been referred twice for the same lesion, of which 22 proved malignant (36.1%, 95% CI 24.1-48.0%). Characteristics of these women were comparable to women with cancer diagnosed after first referral. Compared with women without cancer at second referral for the same lesion, women with cancer more frequently showed suspicious densities at screening mammography (86.4% vs 53.8%, P = 0.02) and work-up at first referral had less frequently included biopsy (22.7% vs 61.5%, P = 0.004). CONCLUSIONS: Cancer risk in women referred twice for the same lesion is similar to that observed in women referred once, or referred for a second time but for a different lesion. KEY POINTS: Cancer risk was 36% for lesions referred twice at screening mammography. The cancer risk was similar for lesions referred only once at screening. Densities at first referral were associated with increased cancer risk at second referral. No biopsy at first referral was associated with increased cancer risk at second referral. Patient and tumour characteristics were similar for women with and without diagnostic delay.

Malpractice claims following screening mammography in The Netherlands.

Although malpractice lawsuits are frequently related to a delayed breast cancer diagnosis in symptomatic patients, information on claims at European screening mammography programs is lacking. We determined the type and frequency of malpractice claims at a Dutch breast cancer screening region. We included all 85,274 women (351,009 screens) who underwent biennial screening mammography at a southern breast screening region in The Netherlands between 1997 and 2009. Two screening radiologists reviewed the screening mammograms of all screen detected cancers and interval cancers and determined whether the cancer had been missed at the previous screen or at the latest screen, respectively. We analyzed all correspondence between the screening organization, clinicians and screened women, and collected complaints and claims until September 2011. At review, 20.9% (308/1,475) of screen detected cancers and 24.3% (163/670) of interval cancers were considered to be missed at a previous screen. A total of 19 women (of which 2, 6 and 11 women had been screened between 1997 and 2001 (102,439 screens), 2001 and 2005 (114,740 screens) and 2005 and 2009 (133,830 screens), respectively) had contacted the screening organization for additional information about their screen detected cancer or interval cancer, but filed no claim. Three other women directly initiated an insurance claim for financial compensation of their interval cancer without previously having contacted the screening organization. We conclude that screening-related claims were rarely encountered, although many screen detected cancers and interval cancers had been missed at a previous screen. A small but increasing proportion of women sought additional information about their breast cancer from the screening organization.

Patient and tumor characteristics of bilateral breast cancer at screening mammography in the Netherlands, a population-based study.

Few data are available on bilateral breast cancer in the screening population. The aim of this study was to determine patient and tumor characteristics of women with bilateral breast cancer at screening mammography. We included all 350,637 screening mammography examinations of women participating in a biennial screening program in a southern screening region of the Netherlands between May 1998 and January 2010. For referred women, all breast imaging reports, biopsy results, and surgery reports during one year after referral were collected. We compared patient and tumor characteristics of referred women with a diagnosis of bilateral breast cancer or unilateral breast cancer at workup. Bilateral or unilateral breast cancer had been diagnosed in respectively 40 (2.2%) and 1766 (97.8%) of 1806 referred women. Women with bilateral or unilateral breast cancer did not differ significantly in mean age, mammographic breast density, family history of breast cancer, or use of hormone replacement therapy. Compared with index cancers, contralateral cancers comprised significantly more lobular cancers (P = 0.02). Tumor size, mitotic activity, and estrogen receptor status were comparable for both groups, but contralateral cancers had a significantly lower risk of lymph node metastases (P = 0.03). Compared to unilateral breast cancer, contralateral malignancies in women with bilateral breast cancer comprised significantly more lobular cancers (P = 0.004) and lymph node negative cancers (P = 0.01). Contralateral breast cancers detected at screening comprise more lobular cancers and show less nodal involvement than index cancers or unilateral cancers. No differences are observed with respect to other patient and tumor characteristics.

Detection of bilateral breast cancer at biennial screening mammography in the Netherlands: a population-based study.

PURPOSE: To determine the incidence of bilateral breast cancer at biennial screening mammography and to assess the sensitivity of screening in the detection of bilateral breast cancer. MATERIALS AND METHODS: All women gave written informed consent, and the requirement to obtain review board approval was waived. The authors included all 302,196 screening mammograms obtained in 80,466 women aged 50-75 years in a southern breast screening region of the Netherlands between May 1998 and July 2008. During 2-year follow-up, the authors collected clinical data, breast imaging reports, biopsy results, and breast surgery reports from all patients with screening-detected and interval cancers. Two screening radiologists reviewed the screening and clinical mammograms of all bilateral screening-detected and interval cancers for mammographic abnormalities. The radiologists were initially blinded to each other's referral opinion, and discrepant assessments were followed by consensus reading. RESULTS: Of all women with screening-detected cancer (n = 1555) or interval cancer (n = 585), 52 (2.4%) had bilateral breast cancer. The sensitivity of screening mammography in the detection of bilateral breast cancer was 19% (10 of 52 women; 95% confidence interval: 8.5%, 29.9%). At blinded review, 18 of the 53 tumors not detected at screening (34%) were considered to be missed, 11 (21%) showed nonspecific minimal signs, and 24 (45%) had been mammographically occult at screening. Five women referred for further analysis experienced a 6-17-month delay in the diagnosis of the second breast cancer; in four of those women, the delay resulted from an incorrect Breast Imaging Reporting and Data System classification at clinical mammography. CONCLUSION: The sensitivity of screening mammography in the detection of bilateral breast cancer is disappointingly low. Both screening radiologists and clinical radiologists should pay vigorous attention to the contralateral breast to detect bilateral malignancies without diagnostic delay.

Experimental radioimmunotherapy of small peritoneal metastases of colorectal origin.

Radioimmunotherapy using radiolabeled monoclonal antibodies (MoAbs) directed against tumor-associated antigens might be an effective treatment modality for small volume disease. Our aim was to optimize an experimental model of radioimmunotherapy for small peritoneal metastases of colorectal origin using the anti-CEA MoAb MN-14. In nude mice with intraperitoneal (i.p.) LS174T tumors, a protein dose-escalation study was carried out to determine the maximal dose of radioiodinated MN-14 to be used in radioimmunotherapy. The biodistribution of radioiodinated MN-14 was determined after intravenous (i.v.) and i.p. administration. Finally, the therapeutic efficacy of escalating activity doses of (131)I-labeled MN-14 (62.5-500 microCi) was assessed and compared to that of unlabeled MN-14 or 500 microCi of (131)I-labeled irrelevant control antibody. At protein doses higher than 25 microg, uptake in tumor was reduced, presumably due to saturation of tumor antigen. During the first 24 hours i.p. administration led to higher tumor uptake and higher tumor:blood ratios than i.v. administration. Median survival of the control groups was 38 days (unlabeled MN-14) and 52 days ((131)I-labeled nonspecific antibody). Median survival of the groups treated with increasing activity doses of (131)I-labeled MN-14 was 42 days (62.5 microCi), 49 days (125 microCi), 63 days (250 microCi) and 101 days (500 microCi), respectively (p < 0.0001 compared to unlabeled MN-14). The present study shows that the anti-CEA-antibody MN-14 preferentially accumulates in i.p. LS174T tumor xenografts after both i.p. and i.v. administration. Intraperitoneal radioimmunotherapy using (131)I-labeled MN-14 delays significantly the outgrowth of peritoneal LS174T metastases, even at relatively low activity doses.