Mammography self-evaluation online test for screening readers: an Italian Society of Medical Radiology (SIRM) initiative.

OBJECTIVES: To report and analyse the characteristics and performance of the first cohort of Italian radiologists completing the national mammography self-evaluation online test established by the Italian Society of Medical Radiology (SIRM). METHODS: A specifically-built dataset of 132 mammograms (24 with screen-detected cancers and 108 negative cases) was preliminarily tested on 48 radiologists to define pass thresholds (62% sensitivity and 86% specificity) and subsequently made available online to SIRM members during a 13-month timeframe between 2018 and 2019. Associations between participants' characteristics, pass rates, and diagnostic accuracy were then investigated with descriptive statistics and univariate and multivariable regression analyses. RESULTS: A total of 342 radiologists completed the test, 151/342 (44.2%) with success. All individual variables, except gender, showed a significant correlation with pass rates and diagnostic sensitivity, confirmed by univariate logistic regression, while only involvement in organised screening programs and number of mammograms read per year showed a positive association with specificity at univariate logistic regression. In the multivariable regression analysis, fewer variables remained significant: > 3000 mammograms read per year for success rate; female gender, public practice setting, and higher experience self-judgement for sensitivity; no variables were significantly associated with specificity. CONCLUSIONS: This national self-evaluation test effectively differentiated multiple aspects of mammographic reading experience, but specific breast imaging experience was shown not to strictly guarantee good diagnostic accuracy. Due to its easy use and the validity of obtained results, this test could be extended to all Italian breast radiologists, regardless of their experience, also as a Breast Unit accreditation criterion. KEY POINTS: • This self-evaluation test was found to be able to differentiate various degrees of mammographic interpretation experience. • Breast cancer screening readers should undergo a self-assessment test, since experience parameters alone do not guarantee diagnostic ability.

8-Oxo-7,8-dihydro-2'-deoxyguanosine and other lesions along the coding strand of the exon 5 of the tumour suppressor gene P53 in a breast cancer case-control study.

The next-generation sequencing studies of breast cancer have reported that the tumour suppressor P53 (TP53) gene is mutated in more than 40% of the tumours. We studied the levels of oxidative lesions, including 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), along the coding strand of the exon 5 in breast cancer patients as well as in a reactive oxygen species (ROS)-attacked breast cancer cell line using the ligation-mediated polymerase chain reaction technique. We detected a significant 'in vitro' generation of 8-oxodG between the codons 163 and 175, corresponding to a TP53 region with high mutation prevalence, after treatment with xanthine plus xanthine oxidase, a ROS-generating system. Then, we evaluated the occurrence of oxidative lesions in the DNA-binding domain of the TP53 in the core needle biopsies of 113 of women undergoing breast investigation for diagnostic purpose. An increment of oxidative damage at the -G- residues into the codons 163 and 175 was found in the cancer cases as compared to the controls. We found significant associations with the pathological stage and the histological grade of tumours. As the major news of this study, this largest analysis of genomic footprinting of oxidative lesions at the TP53 sequence level to date provided a first roadmap describing the signatures of oxidative lesions in human breast cancer. Our results provide evidence that the generation of oxidative lesions at single nucleotide resolution is not an event highly stochastic, but causes a characteristic pattern of DNA lesions at the site of mutations in the TP53, suggesting causal relationship between oxidative DNA adducts and breast cancer.

Accuracy of needle biopsy of breast lesions visible on ultrasound: audit of fine needle versus core needle biopsy in 3233 consecutive samplings with ascertained outcomes.

INTRODUCTION: Core needle biopsy (CNB) has progressively replaced fine needle aspiration cytology (FNAC) in the diagnosis of breast lesions. Less information is available on how these tests perform for biopsy of ultrasound (US) visible breast lesions. This study examines the outcomes of CNB and FNAC in a large series ascertained with surgical histology or clinical-imaging follow-up. MATERIALS AND METHODS: Retrospective five-year audit of 3233 consecutive US-guided needle samplings of solid breast lesions, from self-referred symptomatic or asymptomatic subjects, performed by six radiologists in the same time-frame (2003-2006): 1950 FNAC and 1283 CNB. The probability of undergoing CNB as a first test instead of FNAC was evaluated using logistic regression. Accuracy and inadequacy were calculated for each of CNB and FNAC performed as first test. Accuracy measures included equivocal or borderline/atypical lesions as positive results. RESULTS: The probability of CNB as a first test instead of FNAC increased significantly over time, when there was a pre-test higher level of suspicion, in younger (relative to older) women, with increasing lesion size on imaging, and for palpable (relative to impalpable) lesions. Inadequacy rate was lower for CNB (B1 = 6.9%) than for FNAC (C1 = 17.7%), p < 0.001, and specifically in malignant lesions (B1 = 0.9% vs. C1 = 4.5%; p < 0.001). False negative rate was equally low for both CNB and FNAC (1.7% each test). CNB performed significantly better than FNAC for absolute sensitivity (93.1% vs. 74.4%; p < 0.001) and complete sensitivity (97.4% vs. 93.8%; p = 0.001), however specificity was lower for CNB than FNAC (88.3% vs. 96.4%; p < 0.001). Absolute diagnostic accuracy was higher for CNB than FNAC (84.5% vs. 71.9; p < 0.001) while FNAC performed better than CNB for complete diagnostic accuracy (95.4% vs. 93.2; p < 0.008). In the small subgroup assessed with CNB after an inconclusive initial FNAC (231 cases) there was improved complete sensitivity (from 93.8% to 97.0%) however this also increased costs. CONCLUSION: FNAC and CNB were generally performed in different patients, thus our study reported indirect comparisons of these tests. Although FNAC performed well (except for relatively high inadequacy), CNB had significantly better performance based on measures of sensitivity, but this was associated with lower specificity for CNB relative to FNAC. Overall, CNB is the more reliable biopsy method for sonographically-visible lesions; where FNAC is used as the first-line test, inadequate or inconclusive FNAC can be largely resolved by using repeat sampling with CNB.

Breast fine-needle aspiration malondialdehyde deoxyguanosine adduct in breast cancer.

This study has analysed the generation of 3-(2-deoxy-ß-D-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine adduct [M1dG], a biomarker of oxidative stress and lipid peroxidation, in breast fine-needle aspirate samples of 22 patients with breast cancer, at different clinical stages, in respect to 13 controls. The multivariate analysis show that M(1)dG adduct was higher in cases than in controls (Mean Ratio (MR) = 5.26, 95% CI = 3.16-8.77). Increased M1dG was observed in women with a tumour grade 3 and a pathological diameter 2 (MR = 7.61, 95% CI = 3.91-14.80 and MR = 5.75, 95% CI = 3.13-10.59, respectively). A trend with increasing tumour grade and pathological diameter was present (MR = 1.98, 95% CI = 1.57-2.50 and MR = 2.44, 95% CI = 1.71-3.48, respectively). Not significant effects of age and smoking habit were found (MR = 1.58, 95% CI = 0.92-2.72 and MR = 1.68, 95% CI 0.88-3.20, respectively). An increment over the background frequency of M1dG can contribute to breast cancer development. Increasing severity of breast tumour can influence DNA damage level.

Does computer-aided detection (CAD) contribute to the performance of digital mammography in a self-referred population?

BACKGROUND: Recent evidence suggests that computer-aided detection (CAD) may have a negative impact on the interpretation of mammography-this necessitates timely evaluation of CAD in practice. We report a retrospective study of the incremental effect of CAD on the accuracy of full-field digital mammography (DM) as applied prospectively in breast assessment. METHODS: Subjects were all consecutive women attending a self-referral breast centre in Florence between September 2005 and January 2007 (N = 3,425). DM was reported without, then with, CAD according to a standard protocol; all mammograms recalled on the basis of either the radiologist's reading alone, or the radiologist's reading after viewing CAD, were recalled to assessment. RESULTS: Overall recall rate (RR) was 13.1% and 107 cancers were diagnosed (90 invasive cancers, 8 DCIS, 9 malignant on cytology). The use of CAD allowed the additional detection of 5 cancers (three invasive cancers, one DCIS, one malignant on cytology) and caused one additional benign surgical biopsy, with a relative RR of 4.9%, and an incremental RR of 1.17%. The cancer detection rate (CDR) of DM interpreted with the use of CAD was 3.12% and did not significantly differ from the CDR of 2.9% based on DM without CAD (chi(2) = 3.2, P = 0.07). CONCLUSION: While the increase in CDR with the use of CAD only approached statistical significance, representing modest gains in absolute terms, the incremental number of cancers detected justifies the incremental recall and benign surgical biopsy attributable to CAD use. In our clinical setting, these data suggest more benefit than harm in using CAD with DM, and we will continue the use of CAD with ongoing monitoring of patient outcomes.

Interval breast cancers in screening: the effect of mammography review method on classification.

Surveillance of interval cancers (IC) lacks standardisation of review methodologies. We investigated the extent to which 'informed' or 'blinded' review may affect IC classification. This is a retrospective study of 100 validated screening mammograms (20 IC, 80 negative screens) independently reviewed by six radiologists. Three sequenced review methods with increasing information were used: (1) blinded (no IC information, case mix), (2) partially informed, and (3) fully informed. IC 'screening error' (SE) reports averaged 24% (10-40), 33% (20-55), and 42% (35-50) for phases 1, 2, and 3, while 'minimal signs' (MS) reports averaged 6% (5-15), 10% (10-20), and 20% (15-30), respectively. Negative mammograms classification was MS in 18% (7-39) or SE in 19% (11-29), respectively. MS or SE classification was more likely for method 2 (OR=1.78, p=0.033) and method 3 (OR=3.91, p=0.000) relative to method 1, but no reader effect was evident. Inter-observer agreement in classifying at method 1 was slight (k 0.20), lowest (k 0.06) for MS, and fair (k 0.25) for negative and SE categories. More 'informed' review is more likely to yield an IC classification as MS or SE. Due to expected variability, review methods need standardisation to improve screening quality. Our data support blinded review of IC in mammography screening.

Accuracy and underestimation of malignancy of breast core needle biopsy: the Florence experience of over 4000 consecutive biopsies.

Breast core needle biopsy (CNB) is used for sampling breast lesions in both the screening and diagnostic context. We present the accuracy of breast CNB from a consecutive series of 4035 core biopsies, using methods that minimise selection and verification bias. We calculate accuracy and underestimation of malignancy for both automated (14G) and directional vacuum-assisted (11G) CNB performed under stereotactic or sonographic guidance. Overall sensitivity of CNB is 94.2% (92.9-95.5%) and specificity is 88.1% (86.6-89.6%), positive and negative predictive values are 84.8% (82.9-86.7%) and 95.6% (94.6-96.6%), respectively. In sampling microcalcification, the overall underestimation of malignancy is 26.6% (22.9-30.3%): underestimation is significantly higher for automated CB relative to VAB (chi2 ((df = 1)) = 8.90 , P = 0.002), the absolute difference in underestimation being 14% (5-23%); sensitivity is higher for VAB than automated CB (chi2 ((df = 1)) = 3.28, P = 0.06) but specificity is significantly higher for automated CB (14G) relative to VAB (11G) (chi2 ((df = 1)) = 6.37, P = 0.01), and the overall accuracy of the two methods is similar. Sensitivity of CNB improved with experience (over time and in relation to caseload). Accuracy was not substantially affected by lesion palpability or image-guidance method, and was similar for both masses and calcification but lower for lesions depicted as distortions on mammography. Inadequacy was very low and decreased with greater operator caseload, and was not associated with core gauge or image-guidance method. False negatives occurred in 4.4% (3.4-5.4%) of cases, and where core histology was benign but discordant with (suspicious) imaging and/or clinical findings the likelihood of malignancy was 33.1% (18.5-47.7%), emphasising the importance of correlating all test information in breast diagnosis.

Accuracy of fine needle aspiration cytology (FNAC) of axillary lymph nodes as a triage test in breast cancer staging.

INTRODUCTION: Axillary node fine needle aspiration cytology (FNAC) has the potential to triage women with operable breast cancer to initial nodal surgical procedure. Because of variability in the reported accuracy of this test its role and clinical utility in pre-operative staging remains controversial. METHODS: We retrospectively evaluated the accuracy of ultrasound-guided axillary FNAC in all consecutive clinically T1-2 N0-1 breast cancers that had undergone this test (491 biopsies). We included subjects with clinically or sonographically indeterminate or suspicious nodes. Pathological node status was used as the reference standard (based on axillary dissection or sentinel node biopsy). RESULTS: Sensitivity of node FNAC was 72.6% (67.3-77.9) and specificity was 95.7% (92.5-98.8) for all cases, sensitivity was lower at 64.6% (59.3-70.0) if inadequate cytology was included as a negative result. FNAC sensitivity was highest in women with clinically suspicious nodes [92.5% (88.2-96.7)] and lowest in women with sonographically abnormal and clinically negative nodes [50.0% (41.3-58.7)]. Specificity was high in both groups, 81.2% (54.5-96.0) and 97.2% (94.6-99.9), respectively. The false-negative rate was 15.3% (12.1-18.5), the false-positive rate was 1.4% (0.4-2.5), and the inadequacy rate was 10.8% (8.0-13.5). The likelihood of node FNAC being positive was significantly associated with tumour grade and stage, and the number of nodes involved with metastases. DISCUSSION: Our data show that axillary FNAC has moderate sensitivity (which varies according to selection criteria for the test) and consistently high specificity, is associated with low inadequacy and very few false positives. We estimate that its use would have improved triage to initial nodal procedure in about one quarter of our cases. If one accepts the premise that initial surgical staging of the axilla should be based on all information available through pre-operative diagnosis, then axillary FNAC should be adopted routinely into clinical practice.

Negligible advantages and excess costs of routine addition of breast ultrasonography to mammography in dense breasts.

AIM: To assess the role of breast ultrasonography as a complement to negative mammography in radiologically dense breasts. MATERIAL AND METHODS: Out of a total series of 49,044 consecutive mammograms reported as negative in asymptomatic women, 25,665 (52.3%) were coded as dense (BI-RADS D3-4) and ultrasonography was recommended. Due to organizational problems, ultrasonography was performed immediately or within 1 month only in 5,227 cases, representing the study series. RESULTS: Two cancers were detected at immediate ultrasonography (0.03%). The cancer detection rate in women aged 40-49 and 50-69 years was 0.002% and 0.07%, respectively. The benign biopsy rate was 0.5% for core biopsies and 0.02% for surgical biopsies. The cost per ultrasonography-assessed woman was Euro 56.05, whereas the cost per additional mammographically occult but ultrasonography-detected cancer was Euro 146,496.53. The mammograms of the 2 cancer cases underwent blind review by an expert reader and were confirmed as negative. DISCUSSION: Our findings show a low cancer detection rate, substantially lower compared to other clinical studies of ultrasonography in dense breasts, though in accordance with preliminary evidence from an Italian randomized clinical trial within a population-based screening program. The policy of adding ultrasonography to negative mammography in dense breasts seems to have very limited cost-effectiveness, and should not be adopted in routine practice before results of ongoing clinical trials are available.

Role of ultrasound-guided fine needle cytology of axillary lymph nodes in breast carcinoma staging.

PURPOSE: To evaluate the efficacy of cytology on axillary lymph node ultrasound-guided aspiration biopsy in the reduction of inappropriate surgery, such as the sentinel node (SN) procedure if positive, or axillary dissection if negative. MATERIALS AND METHODS: Cytology was performed on 159 consecutive cases, on the ultrasonographically most suspicious lymph node. Lymph node histology was used as a reference standard to determine accuracy. Four different scenarios were simulated: routine axillary ultrasonography with cytology of the lymph nodes visible at ultrasonography (A), or of only the lymph nodes suspicious at ultrasonography (B), with ultrasonography limited to clinically negative axillae and cytology of the lymph nodes visible at ultrasonography (C), or only of the lymph nodes suspicious at ultrasonography only (D). RESULTS: Cytologic sensitivity was 58.6%, specificity 100%. Immediate axillary dissection only in the case of positive cytology would have avoided 6/6 inappropriate axillary dissections and 5/34 (14.7%) inappropriate SN, compared to routine practice (immediate dissection for palpable adenopathy, SN in the remaining cases). Each of the simulated scenarios saved inappropriate surgical procedures (A: 6 dissections, 5 SNs; B: 6 dissections, 3 SNs; C: 13 SNs; D: 11 SNs) at no expense (A and B) or limited expense (C: Euro 348, D: Euro 232 for each inappropriate surgical procedure saved). CONCLUSIONS: Axillary lymph node cytology can save axillary dissections or sentinel node procedures and is recommended as routine practice. Routine axillary ultrasonography, with cytology of sonographically visible lymph nodes, followed by immediate axillary dissection only in case of positive cytology proved to be the best approach in terms of cost-benefit ratio.

Comparison of two commercial systems for computer-assisted detection (CAD) as an aid to interpreting screening mammograms.

PURPOSE: To compare the diagnostic accuracy of two commercial CAD systems (CADx and R2) and their impact as an aid to conventional reading of screening mammograms. MATERIALS AND METHODS: The image set considered consisted of 120 mammograms, 89 confirmed negative and 31 with subsequent interval cancers (11 classified as false negatives (FN), 20 as "minimal signs" (MS)). The set was digitised and processed with CAD, and printouts obtained of the mammograms with indications of the areas warranting review. Six expert radiologists read the mammograms three times, once using conventional reading and twice using CAD reading with CADx and R2, respectively. The two CAD systems were compared in terms of diagnostic accuracy of the marks and the impact of CAD reading compared to conventional reading and to the use of independent second reading simulated by combining pairs of single conventional readings. RESULTS: R2 highlighted more calcifications (218 vs 132, +65%) and CADx highlighted more masses (208 vs 105, +98%). CADx and R2 marked 15 and 17 out of 31 cancers, respectively (sensitivity 48.3% vs 54.8%, chi squared=6.4, p=0.79), 10 and 6 out of 11 FN (90.9% vs 54.5%, chi squared=2.0, p=0.15), respectively, and 5 and 11 out of 20 MS (25.0% vs 55.0%, chi squared=2.6, p=0.10), respectively. As for specificity, the false positive markings for masses were on average (per case) 1.60 for CADx and 0.75 for R2, those for calcifications were 1.08 for CADx and 1.77 for R2 and the total false positive markings were 2.68 for CADx and 2.52 for R2. CADx and R2 marked 73 and 63 of 89 negative controls (specificity = 0.18 vs 0.29, chi squared=2.52, p=0.11), respectively. All the radiologists showed greater sensitivity with CAD reading compared to conventional reading. On average, sensitivity with conventional reading was 58.6% (109/186), as against 70.9% (132/186) for CADx or R2 (chi squared=5.71, p=0.016). Sensitivity for FN cases was 71.2% (47/66) with conventional reading, 84.8% (56/66) with CADx (chi squared=2.82, p=0.09) and 80.3% (53/66) for R2 (chi squared=1.03, p=0.30) (CADx vs R2, chi squared=0.21, p=0.64). Sensitivity for MS cases was 51.6% (62/120) for conventional reading, 63.3% (76/120) for CADx (chi squared=2.88, p=0.08) and 65.8% (79/120) for R2 (chi squared=4.40, p=0.03) (CADx vs R2, chi squared=0.07, p=0.78). The recall rates were 18.1% (97/534) for conventional reading, 29.7% (159/534) for CADx (chi squared=5.72, p=0.01) and 24.3% (130/534) for R2 (chi squared=10.11, p=10-5) (CADx vs R2, chi squared=3.71, p=0.05). Double reading was significantly more sensitive than conventional reading (chi squared=29.6, p=10-6), CADx (chi squared=5.33, p=0.02) and R2 (chi squared=5.33, p=0.02). The recall rate for double reading was significantly higher than for conventional reading (chi squared=21.5, p=10-6) whereas no significant difference was detected when compared to CADx (chi squared=0.16, p=0.68) or R2 (chi squared=3.4, p=0.06). CONCLUSIONS: Despite using different algorithms, the two CAD systems exhibit comparable levels of diagnostic accuracy and a similar positive impact on sensitivity when used as an aid to conventional reading. Single reading with either CAD system is as specific but not as sensitive to double independent reading: its use as an alternative to double reading cannot be recommended and should be investigated further by means of controlled prospective studies.

Comparison of standard reading and computer aided diagnosis (CAD) on a proficiency test of screening mammography.

PURPOSE: To evaluate the role of computer aided diagnosis (CAD) to improve screening mammograms interpretation. MATERIALS AND METHODS: Six radiologists underwent a screening mammography proficiency test first by conventional, then by CAD assisted reading. Sensitivity and recall rate at conventional and CAD reading were compared. Independent conventional double reading was simulated (15 pair combinations) and compared to single CAD reading. RESULTS: CAD marked 31 of 32 cancers (case-based sensitivity=96.8%). On a film and lesion basis, CAD identified 31 of 32 (96.8%) malignant calcifications and 29 of 42 (69.0%) malignant opacities, the only cancer not identified by CAD being depicted as an isolated opacity. CAD marked 348 areas (153 microcalcifications and 195 opacities) in 88 of 108 non cancer cases, with a case-based specificity of 18.5% (20/108). Considering all six readings, cancer was identified in 164 or 174 of 192 readings (85.4 vs 90.6%, c2 2.03, df=1, p=0.15) and recalls of non-cancer cases were 108 or 159 of 648 readings (16.6 vs 24.5%, c2 11.7, df=1, p<0.001) at conventional or CAD reading, respectively. CAD reading (average of 6 readings, 192 cancer, 648 non-cancer readings) was slightly, non significantly less sensitive (sensitivity 90.6 vs 92.9%, c2 0.73, df=1, p=0.39) and slightly, but not significantly more specific (recall rate 24.5 vs 26.1%, c2 0.56, df=1, p=0.45) as compared to simulated independent double reading (average of 15 combinations, 480 cancer, 1620 non-cancer readings). CONCLUSION: CAD seems to allow for a limited absolute increase (+5.2%) in sensitivity and for a limited absolute increase (+7.9%) in recall rate, the latter difference only reaching statistical significance. CAD reading showed no significant difference in diagnostic accuracy as compared to conventional (simulated) double reading, although further studies are needed to confirm it as possible alternative to double reading in the current screening practice.

Comparison of standard reading and computer aided detection (CAD) on a national proficiency test of screening mammography.

OBJECTIVE: To evaluate the role of computer aided detection (CAD) in improving the interpretation of screening mammograms MATERIAL AND METHODS: Ten radiologists underwent a proficiency test of screening mammography first by conventional reading and then with the help of CAD. Radiologists were blinded to test results for the whole study duration. Results of conventional and CAD reading were compared in terms of sensitivity and recall rate. Double reading was simulated combining conventional readings of four expert radiologists and compared with CAD reading. RESULTS: Considering all ten readings, cancer was identified in 146 or 153 of 170 cases (85.8 vs. 90.0%; chi(2)=0.99, df=1, P=0.31) and recalls were 106 or 152 of 1330 cases (7.9 vs. 11.4%; chi(2)=8.69, df=1, P=0.003) at conventional or CAD reading, respectively. CAD reading was essentially the same (sensitivity 97.0 vs. 96.0%; chi(2)=7.1, df=1, P=0.93; recall rate 10.7 vs. 10.6%; chi(2)=1.5, df=1, P=0.96) as compared with simulated conventional double reading. CONCLUSION: CAD reading seems to improve the sensitivity of conventional reading while reducing specificity, both effects being of limited size. CAD reading had almost the same performance of simulated conventional double reading, suggesting a possible use of CAD which needs to be confirmed by further studies inclusive of cost-effective analysis.