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Background Radiology is an essential tool in the management of a patient. The aim of this manuscript was to build structured report (SR) Mammography based in Breast Cancer. Methods A working team of 16 experts (group A) was composed to create a SR for Mammography Breast Cancer. A further working group of 4 experts (group B), blinded to the activities of the group A, was composed to assess the quality and clinical usefulness of the SR final draft. Modified Delphi process was used to assess level of agreement for all report sections. Cronbach’s alpha (Cα) correlation coefficient was used to assess internal consistency and to measure quality analysis according to the average inter-item correlation. Results The final SR version was built by including n = 2 items in Personal Data, n = 4 items in Setting, n = 2 items in Comparison with previous breast examination, n = 19 items in Anamnesis and clinical context; n = 10 items in Technique; n = 1 item in Radiation dose; n = 5 items Parenchymal pattern; n = 28 items in Description of the finding; n = 12 items in Diagnostic categories and Report and n = 1 item in Conclusions. The overall mean score of the experts and the sum of score for structured report were 4.9 and 807 in the second round. The Cronbach’s alpha (Cα) correlation coefficient was 0.82 in the second round. About the quality evaluation, the overall mean score of the experts was 3.3. The Cronbach’s alpha (Cα) correlation coefficient was 0.90. Conclusions Structured reporting improves the quality, clarity and reproducibility of reports across departments, cities, countries and internationally and will assist patient management and improve breast health care and facilitate research.

The Italian College of Breast Radiologists by the Italian Society of Medical Radiology (SIRM) provides recommendations for breast care provision and procedural prioritization during COVID-19 pandemic, being aware that medical decisions must be currently taken balancing patient’s individual and community safety: (1) patients having a scheduled or to-be-scheduled appointment for in-depth diagnostic breast imaging or needle biopsy should confirm the appointment or obtain a new one; (2) patients who have suspicious symptoms of breast cancer (in particular: new onset palpable nodule; skin or nipple retraction; orange peel skin; unilateral secretion from the nipple) should request non-deferrable tests at radiology services; (3) asymptomatic women performing annual mammographic follow-up after breast cancer treatment should preferably schedule the appointment within 1 year and 3 months from the previous check, compatibly with the local organizational conditions; (4) asymptomatic women who have not responded to the invitation for screening mammography after the onset of the pandemic or have been informed of the suspension of the screening activity should schedule the check preferably within 3 months from the date of the not performed check, compatibly with local organizational conditions. The Italian College of Breast Radiologists by SIRM recommends precautions to protect both patients and healthcare workers (radiologists, radiographers, nurses, and reception staff) from infection or disease spread on the occasion of breast imaging procedures, particularly mammography, breast ultrasound, breast magnetic resonance imaging, and breast intervention procedures.

Ductal carcinoma in situ (DCIS) is a heterogeneous disease, for which the best adjuvant treatment is still uncertain. Many attempts of risk-groups stratification have been made over time, developing prognostic scores to predict risk of local recurrence (LR) on the basis of features such as age, final surgical margins (FSM) status, grade, and tumor size. The aim of our analysis was to evaluate the patterns of recurrence from a two large-institutional retrospective series.We collected data on 457 patients treated with BCS and adjuvant RT between 1990 and 2012. Final analysis was performed on 278 patients, due to missing data about hormonal status (HS). Patients were treated at the Radiation Oncology Unit of the University of Florence (n = 195), and S. Maria Annunziata Hospital (n = 83) (Florence, Italy).At a median follow up time of 10.8 years (range 3-25), we observed 20 LR (7.2%). The 5-year and 10-year LR rates were 4.9% and 10.2%, respectively. At Cox regression univariate analysis, estrogen receptor (ER) positive status (p = 0.001), HS positive (p = 0.003), and FSM1 mm (p = 0.0001) significantly impacted on LR. At Cox regression multivariate analysis positive ER status maintained a protective role (p = 0.003), and FSM status1 mm its negative impact (p = 0.0001) on LR rate.Our experience confirmed the wide heterogeneity of DCIS. Inadequate FSM and negative ER status negatively influenced LR rates. Tumor biology should be integrated in adjuvant treatment decision-making process.

Women who were previously treated for breast cancer (BC) are an important particular subgroup of women at intermediate BC risk. Their breast follow-up should be planned taking in consideration a 1.0-1.5 % annual rate of loco-regional recurrences and new ipsilateral or contralateral BCs during 15-20 years, and be based on a regional/district invitation system. This activity should be carried out by a Department of Radiology integrating screening and diagnostics in the context of a Breast Unit. We recommend the adoption of protocols dedicated to women previously treated for BC, with a clear definition of responsibilities, methods for invitation, site(s) of visits, methods for clinical and radiological evaluation, follow-up duration, role and function of family doctors and specialists. These women will be invited to get a mammogram in dedicated sessions starting from the year after the end of treatment. The planned follow-up duration will be at least 10 years and will be defined on the basis of patient's age and preferences, taking into consideration organizational matters. Special agreements can be defined in the case of women who have their follow-up planned at other qualified centers. Dedicated screening sessions should include: evaluation of familial/personal history (if previously not done) for identifying high-risk conditions which could indicate a different screening strategy; immediate evaluation of mammograms by one or, when possible, two breast radiologists with possible addition of supplemental mammographic views, digital breast tomosynthesis, clinical breast examination, breast ultrasound; and prompt planning of possible further workup. Results of these screening sessions should be set apart from those of general female population screening and presented in dedicated reports. The following research issues are suggested: further risk stratification and effectiveness of follow-up protocols differentiated also for BC pathologic subtype and molecular classification, and evaluation of different models of survivorship care, also in terms of cost-effectiveness.

This position paper, issued by ICBR/SIRM and GISMa, summarizes the evidence on DBT and provides recommendations for its use. In the screening setting, DBT in adjunct to digital mammography (DM) increased detection rate by 0.5-2.7‰ and decreased false positives by 0.8-3.6% compared to DM alone in observational and double-testing experimental studies. The reduction in recall rate could be less prominent in those screening programs which already have low recall rates with DM. The increase in radiation exposure associated with DM/DBT protocols has been solved by the introduction of synthetic mammograms (sDM) reconstructed from DBT datasets. Thus, whenever possible, sDM/DBT should be preferred to DM/DBT. However, before introducing DBT as a routine screening tool for average-risk women, we should wait for the results of randomized controlled trials and for a statistically significant and clinically relevant reduction in the interval cancer rate, hopefully associated with a reduction in the advanced cancer rate. Otherwise, a potential for overdiagnosis and overtreatment cannot be excluded. Studies exploring this issue are ongoing. Screening of women at intermediate risk should follow the same recommendations, with particular protocols for women with previous BC history. In high-risk women, if mammography is performed as an adjunct to MRI or in the case of MRI contraindications, sDM/DBT protocols are suggested. Evidence exists in favor of DBT usage in women with clinical symptoms/signs and asymptomatic women with screen-detected findings recalled for work-up. The possibility to perform needle biopsy or localization under DBT guidance should be offered when DBT-only findings need characterization or surgery.

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.

Women who underwent chest radiation therapy (CRT) during pediatric/young-adult age (typically, lymphoma survivors) have an increased breast cancer risk, in particular for high doses. The cumulative incidence from 40 to 45 years of age is 13–20 %, similar to that of BRCA mutation carriers for whom contrast-enhanced magnetic resonance imaging (MRI) is recommended. However, in women who underwent CRT, MRI sensitivity is lower (63–80 %) and that of mammography higher (67–70 %) than those observed in women with hereditary predisposition, due to a higher incidence of ductal carcinoma in situ with microcalcifications and low neoangiogenesis. A sensitivity close to 95 % can be obtained only using mammography as an adjunct to MRI. Considering the available evidence, women who underwent CRT before 30 receiving a cumulative dose ≥10 Gy should be invited after 25 (or, at least, 8 years after CRT) to attend the following program: 1. interview about individual risk profile and potential of breast imaging; 2. annual MRI using the same protocol recommended for women with hereditary predisposition; 3. annual bilateral two-view full-field digital mammography or digital breast tomosynthesis (DBT) with synthetic 2D reconstructions. Mammography and MRI can be performed at once or alternately every 6 months. In the case of MRI or contrast material contraindications, ultrasound will be performed instead of MRI. Reporting using BI-RADS is recommended. At the age for entering population screening, the individual risk profile will be discussed with the woman about opting for only mammography/DBT screening or for continuing the intensive protocol.

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.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.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%), p0.001, and specifically in malignant lesions (B1 = 0.9% vs. C1 = 4.5%; p0.001). 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%; p0.001) and complete sensitivity (97.4% vs. 93.8%; p = 0.001), however specificity was lower for CNB than FNAC (88.3% vs. 96.4%; p0.001). Absolute diagnostic accuracy was higher for CNB than FNAC (84.5% vs. 71.9; p0.001) while FNAC performed better than CNB for complete diagnostic accuracy (95.4% vs. 93.2; p0.008). 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.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.

This study has analysed the generation of 3-(2-deoxy-β-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 M1dG 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.

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 (χ2 = 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.

One-hundred-fourteen consecutive cases of breast ultrasound-guided 14-gauge needle core biopsy (14G NCB) performed from January 2001 to June 2013 and diagnosed as non-malignant papillary lesion (PL)-B3, were reviewed and compared with definitive histological diagnosis on surgical excision (SE) to evaluate the diagnostic accuracy of ultrasound-guided 14G NCB. PL with epithelial atypia on 14G NCB were associated to malignancy on definitive histological diagnosis on SE in 22 (7 DCIS and 15 invasive carcinomas) of 46 cases with an underestimation rate of 47.8 %, while 9 (4 DCIS and 5 invasive carcinomas) cases out of 68 cases of PL without epithelial atypia were upgraded to carcinoma with an underestimation rate of 13.2 %. In cases of PL with epithelial atypia on ultrasound-guided 14G NCB, SE appears mandatory due to the high risk of associated malignancy. The diagnosis of PL without epithelial atypia on ultrasound-guided 14G NCB does not exclude malignancy at subsequent SE, consequently further assessment (by surgical or vacuum-assisted excision) is recommended to avoid the risk of delaying a diagnosis of malignancy, although this tends to be lower (1 in 8 patients).

To compare breast density (BD) assessment provided by an automated BD evaluator (ABDE) with that provided by a panel of experienced breast radiologists, on a multivendor dataset.Twenty-one radiologists assessed 613 screening/diagnostic digital mammograms from nine centers and six different vendors, using the BI-RADS a, b, c, and d density classification. The same mammograms were also evaluated by an ABDE providing the ratio between fibroglandular and total breast area on a continuous scale and, automatically, the BI-RADS score. A panel majority report (PMR) was used as reference standard. Agreement (κ) and accuracy (proportion of cases correctly classified) were calculated for binary (BI-RADS a-b versus c-d) and 4-class classification.While the agreement of individual radiologists with the PMR ranged from κ = 0.483 to κ = 0.885, the ABDE correctly classified 563/613 mammograms (92 %). A substantial agreement for binary classification was found for individual reader pairs (κ = 0.620, standard deviation [SD] = 0.140), individual versus PMR (κ = 0.736, SD = 0.117), and individual versus ABDE (κ = 0.674, SD = 0.095). Agreement between ABDE and PMR was almost perfect (κ = 0.831).The ABDE showed an almost perfect agreement with a 21-radiologist panel in binary BD classification on a multivendor dataset, earning a chance as a reproducible alternative to visual evaluation.Individual BD assessment differs from PMR with κ as low as 0.483. An ABDE correctly classified 92 % of mammograms with almost perfect agreement (κ = 0.831). An ABDE can be a valid alternative to subjective BD assessment.

The inter- and intraobserver agreement (kappa-statistic) in reporting according to Breast Imaging Reporting and Data System (BI-RADS((R))) breast density categories was tested in 12 dedicated breast radiologists reading a digitized set of 100 two-view mammograms. Average intraobserver agreement was substantial (kappa=0.71, range 0.32-0.88) on a four-grade scale (D1/D2/D3/D4) and almost perfect (kappa=0.81, range 0.62-1.00) on a two-grade scale (D1-2/D3-4). Average interobserver agreement was moderate (kappa=0.54, range 0.02-0.77) on a four-grade scale and substantial (kappa=0.71, range 0.31-0.88) on a two-grade scale. Major disagreement was found for intermediate categories (D2=0.25, D3=0.28). Categorization of breast density according to BI-RADS is feasible and consistency is good within readers and reasonable between readers. Interobserver inconsistency does occur, and checking the adoption of proper criteria through a proficiency test and appropriate training might be useful. As inconsistency is probably due to erroneous perception of classification criteria, standard sets of reference images should be made available for training.

Two consecutive series of 107 invasive carcinomas and 108 carcinomas in situ of the breast were considered retrospectively. The main symptomatic, clinical and cytological features were retrieved from clinical records, whereas the features at mammography and/or ultrasonography were reclassified at a blinded review by an expert radiologist. The power of predicting invasion on the basis of these features was then evaluated. The accuracy of such a prediction was compared to that of a mathematical model using the same diagnostic features by multivariate logistic regression analysis. Neither approach reached a satisfactory accuracy, but the radiologist's judgment (sensitivity 97.1%, specificity 81.9%, positive predictive value 98.4%, negative predictive value 71.6%, overall accuracy 95.8%) was slightly superior to the mathematical model (sensitivity 93.2%, specificity 87.9% positive predictive value 98.8%, negative predictive value 53.7%, overall accuracy 92.8%). Although some presentations are significantly associated with invasive or in situ status, diagnostic features alone are not sufficiently accurate to bypass histological confirmation, although they might give useful clinical indications.

Nipple discharge (ND) is a common symptom with a reported incidence of 2% to 5% of patients referred to breast cancer clinics. Approximately 90% of ND is of benign etiology. An underlying carcinoma is present with a rate of 6% to 21%. This is more frequent if it is associated with clinical or radiologic abnormality. ND after nipple-sparing mastectomy (NSM) is a rare event as the whole retroareolar glandular tissue is usually completely removed with mastectomy. ND is otherwise possible if a small amount of tissue is accidentally left by the surgeon or with the aim of reducing the risk of the nipple-areola complex (NAC) necrosis. This condition can be of concern as it may imply a local recurrence and therefore implicate NAC removal. Herein we report a case of a ND in an NSM in which only a selective duct excision allowed NAC preservation.

Radial scar/complex sclerosing lesion (RS/CSL) of the breast has become more frequently detected with the increasing performance of mammography as a screening test. The clinical, mammographic, and cytologic features of 22 cases of histologically proved breast RS/CSL, 3 of which associated with carcinoma arising at the periphery of the lesion, were reviewed. Clinical examination and mammography did not show specific features in differentiating RS/CSL from carcinoma of the breast. Cytology of RS/CSL without associated malignant changes was dominated by bland epithelial clusters and bipolar naked nuclei. Apocrine cells, papillary clusters, foam cells, and fibrillary elastoid material were also frequently seen. At the cytologic review, only one case of RS with apocrine adenosis, showing atypical cells, was diagnosed as suspicious. Two of the three cases of CSL with associated carcinoma in situ were cytologically characterized by the presence of single atypical cells. In the third case, characterized by a small tubular carcinoma near to CSL, fine-needle aspiration cytology revealed few tubular clusters without myoepithelial cells. Although cytology of RS/CSL without associated carcinoma does not seem characteristic, in most cases a diagnosis of benignancy can be performed correctly. The application of fine-needle aspiration cytology to mammographic lesions with features suggesting RS/CSL may permit a better planning of these lesions.

This study was undertaken to assess the role of real-time reading in the mammography screening programme carried out at the Hospital of Marzana, Verona, Italy.During the 5-year period 1999-2004, 54,472 women attended the screening programme (32,291 first calls: unadjusted uptake 41.4%, adjusted uptake 50.3%; 21,551 2- year routine recalls: unadjusted uptake 86.4%, adjusted uptake 89.9%). Further diagnostic investigations [(FDI), imaging and cytohistological] were performed immediately after real-time reading of the screening mammograms (FDI rate among first calls 10.9%; FDI rate among 2-year recalls 5.4%). Overall, cytohistological FDI were requested in 27% of imaging FDI, with a clear prevalence of cytological [fine-needle aspiration cytology (FNAC) 87%] over histological procedures [core needle biopsy (CNB) 11%; vacuum aspiration biopsy (VAB) 2%].Imaging FDI proved to be conclusive in 73%. Cytohistological FDI led to the use of surgical biopsy (SB) in 39.5% (ratio between benign and malignant SB: 0.19/first calls, 0.14/2-year recalls). There were a total of 427 screen-detected breast cancers (BC), with a very good breast cancer detection rate (BCDR/first calls 9.7 per thousand; BCDR/2-year recalls 5.1 per thousand). In the 427 screen-detected BC, the incidence of pTis, pT1a,b cancers was 59.6% (diagnostic anticipation); the incidence of pN0 cancers was 61.2%; the incidence of conservative surgical procedures was 78.6%. In interval cancers, the false negative rate was 8.3% only, whereas the proportional incidence was very low indeed (14% first year; 38% second year).The high sensitivity exhibited by the Marzana mammography screening programme suggests that the value of real-time reading should be validated by other programmes adopting a similar approach.

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.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).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.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.

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.

To evaluate the sensitivity for breast cancer of different diagnostic tests performed in a consecutive series of women aged under 36 years.The study analyses 155 women with breast cancer incident in the Tuscany Cancer Registry from 1985 to 2000. The sensitivity of each method was evaluated in relation to the most recent test performed during the year before diagnosis and to different variables, such as tumour size and calendar period.Sensitivity was 70.3 % for physical examination, 76.0% for mammography, 69.1% for ultrasonography and 80.6% for cytology (86.2% if inadequate samples are excluded). Sensitivity was associated to pT category for physical examination (pT1=60.6%; pT2-4=86.4%; chi squared=10.2, p= 0.001) and for ultrasonography (pT1=61.9%; pT2-4=92.0%; chi squared=5.7, p=0.01) and to breast radiological density for mammography (50-100% density=75.5%; 0-50% density=91.3%; chi squared=1.85, p0.17). Among 112 cases examined with palpation, mammography and cytology, these methods had a sensitivity of 78.5%, 75.8% and 91.9%, respectively, and an overall sensitivity of 98.2%. Among 65 cases examined with palpation, ultrasonography and cytology, these methods had a sensitivity of 67.6%, 70.7% and 92.3%, respectively, and an overall sensitivity of 95.3%. Among 123 cases examined with palpation, imaging (mammography and/or ultrasonography) and cytology, these methods had a sensitivity of 76.4%, 78.0% and 90.2%, respectively, and an overall sensitivity of 96.7%. Cancer was suspected by one method only in 2.4% of cases with palpation, 1.6% with imaging and 7.3% with cytology. Comparison between mammography and ultrasonography was possible in 58 cases undergoing both tests: sensitivity was 79.3% for ultrasonography and 74.1% for mammography, respectively chi squared=0.1, p=0.66). If sensitivity had been determined according to the test performed immediately before diagnosis it would have been higher, that is 74.4% for palpation, 76.8% for mammography, 73.5% for ultrasonography and 90.9% for cytology (97.7% if inadequate samples were excluded), and overall sensitivity would be 96.1%.Differential diagnosis of breast cancer in women aged under 36 years is difficult, sensitivity being lower as compared to older women, with the only exception of cytology. The association of multiple tests (diagnostic imaging and cytology) is crucial to achieve an acceptable false negative rate. In particular, the extensive use of cytology in the presence of an even minimal doubt at palpation and/or imaging is strongly recommendable. Sensitivity must be calculated on the basis of an independent pathology registry, and false negatives must be defined within a given period after the test. Analysis limited to tests performed immediately before diagnosis leads to a biased overestimation of sensitivity.

Purpose The use of full field digital mammography (FFDM) in alternative to conventional screen film mammography (SFM) in the current practice is delayed by the high costs of FFDM. The present study, performed at the Centro per lo Studio e la Prevenzione Oncologica of Florence, using both FFDM and SFM, was aimed at estimating the impact of introducing the new FFDM technique on overall mammography costs. Material and methods We estimated the differential costs of both methods, based on real expenditures, as provided by the administrative department, and on radiologists, radiographers and other staff's working time. Two different workload scenarios (5000 and 10,000 tests/year per mammography equipment) were considered. Common costs of both techniques were censored for study purpose. Results Beside a higher cost due to purchase and hire/leasing costs of equipment, FFDM implies a greater workload for radiologists (reading time almost doubled). SFM implies a greater workload for the administrative staff to run the archive and for loading/unloading films of the roller viewer, whereas no different workload has been observed for radiographers. Overall FFDM costs €24.22–26.46 for examination more than SFM for the 5000 tests scenario and €9.91–12.15 more for the 10,000 tests scenario. Discussion Although present study estimates cannot easily be generalised to any local setting, the model for cost calculation is easy to be exported to another scenario by applying different local parameters. The advantages made available by FFDM (computerised data recording, tele-transmission, tele-reporting, tele-consulting, automatic display on monitor of previous exams and use of CAD) may justify the higher cost, but a limited reduction in purchase and assistance costs could easily allow a turnover, with FFDM being more convenient than SFM even on the cost side.

Aims and Background Screening mammography has been shown to be effective in reducing breast cancer mortality in several randomized clinical trials. One major side effect of screening is the diagnosis of benign breast disease (BBD), which is considered as a nonprogressive lesion, except for a small percentage of lesions considered at high risk. We present data referring to service screening programs active in Italy in 2000 and 2001 and participating in the national survey carried out by the Italian Group for Mammography Screening (GISMa). Methods To all centers participating in the GISMa National Survey, we submitted a questionnaire regarding the service screening protocol and main indicators of performance of the local program in the years 2000 and 2001. Results A total of 657 detected BBD cases, registered by 23 Italian breast cancer screening centers in women 50 to 69 years of age, are included in this study. The BBD detection rate was 2.5 per 1000 at the first screening test and 1.05 per 1000 at repeated tests. The benign/malignant ratio was 0.34 at the first and 0.22 at the repeated test. Conclusions Detection of BBD occurred frequently in breast screening programs, and prognostic implications should be further investigated. Women should be individually informed at screening, and with greater detail at the moment of the recall for assessment, of the implications of BBD detection and receive the necessary, also psychological, counseling to avoid the possible harm related to breast cancer screening.

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.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).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).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.

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.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.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).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.

To evaluate the role of computer aided diagnosis (CAD) to improve screening mammograms interpretation.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.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, p0.001) 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).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.

Rationale: Women with breast IEN have an annual risk of invasive disease equal to 8-10 times the general population, thus representing an important target for chemoprevention. In the NSABP-P1 trial, tamoxifen use at 20 mg/day was associated with an 86% reduction of invasive breast cancer in women with previous ADH (RR=0.14, 95% IC, 0.03-0.47) and with a 56% risk reduction in women with previous LCIS (RR=0.44, 0.16-1.06). However, the increased risk of endometrial cancer and of venous thromboembolism, have significantly limited its broad use in chemoprevention. To improve the risk-benefit ratio, the use of lower doses of the drug has been proposed. Recent trials from our group have shown that a dose of 5 mg/day does not increase endometrial proliferation and is associated with a decrease of the estrogenic activity of tamoxifen on IGF-I, SHBG and antithrombin-III, with a potential decrease of venous thromboembolic events. Moreover, tamoxifen exhibits a high tissue distribution, so that a dose of 5 mg/day attains at the breast tissue level a concentration 10 times higher than that needed to inhibit cell growth in vitro. The CYP2D6 enzyme mediates oxidation of N-desmethyl tamoxifen to endoxifen, the most active metabolite of tamoxifen. The SNP CYP2D6*4 (1846G>A) allele accounts for 75% of CYP2D6 poor metabolizer phenotype which have been associated with a higher risk to develop a breast event compared to wildtype (Serrano D et al. Pharmacogenomics J. 2010 Mar 23). Study design and enrollment report: This is a multicenter randomized double-blind placebo-controlled phase III trial with two parallel arms: tamoxifen at daily dose of 5 mg or placebo for a total treatment time of 3 years, to assess the efficacy and the safety of 5 mg/day tamoxifen to reduce breast cancer incidence in women with previous IEN (LIN 2-3 and ER-positive or unknown DIN 1b-3). At present no standard treatment exists to treat these women, particularly in Europe, where tamoxifen is not registered in women with prior DCIS (DIN 2-3). A total of 1400 women will be recruited in 3 years to detect a 50% reduction (Hazard Ratio = 0.5) in the incidence of breast cancer in the tamoxifen arm with an 80% power and a 1-sided 5% alpha level. Secondary endpoints include: incidence of other non-invasive breast disorders (i.e., LIN, ductal atypical hyperplasia), endometrial cancer, clinical bone fractures, cardiovascular events, venous thromboembolic events, and clinically manifest cataract. The pharmacogenetic endpoints include to assess whether CYP2D6 genotype can explain modulation on surrogate biomarkers of tamoxifen efficacy and safety, including circulating IGF-I, hormones, mammographic density, endometrial thickness and hot flashes, but also on clinical events. As of July 27, 2010, 10 enrolment centers have been activated, n=128 women have been screened and n=44 have been randomized. 58 women refused to participate and 26 women were excluded for the following ineligibility reasons: 6 women for use of raloxifene, tamoxifen or other SERMs; 4 women for ER negative primary breast cancer; 3 women for bilateral mastectomy, 2 for previous thromboembolic events, 2 for age limits and 9 for other reasons. No serious adverse events or suspected unexpected serious adverse reactions were registered. Citation Information: Cancer Prev Res 2010;3(12 Suppl):A70.

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 € 56.05, whereas the cost per additional mammographically occult but ultrasonography-detected cancer was € 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.

To evaluate the role of double reading of screening mammograms by expert radiologists.We analyzed the results of independent readings of a proficiency test of screening mammography (140 cases, 32 cancers) performed by four expert radiologists. Double reading was simulated by matching the four original readings in 6 possible combinations. The impact of double reading over single reading was evaluated in terms of increased sensitivity and increased recall rate.Of 32 carcinomas 22, 6, or 4 were identified by 4, 3, or 2 readers, respectively. Of 108 cases negative for cancer a recall for further investigations was suggested by 4, 3, 2, 1 or no reader(s) in 3, 3, 9, 14, or 79 cases, respectively. Inter-reader diagnostic repeatability was good (k = 0.65). Single readers achieved an average sensitivity of 89% (range 87.5-90.6%) and an average recall rate of 12.2% (range 7.4-16.6%). Simulated double reading achieved an average increase in sensitivity of 8.8% (range 6.2-10.95%) and an average increase of recall rate of 6.2% (range 3.8-8.3%).Even though the relative increase of recall rate is relevant (+53.2%), the corresponding gain in sensitivity justifies the use of double reading, which was confirmed to be worthwhile also when expert radiologists are involved. This study confirms the opportunity of adopting double reading as a routine procedure in mammographic screening.