Doralba Morrone

Solid nonpalpable breast lesions Success and failure of guided fine-needle aspiration cytology in a consecutive series of 2444 cases

Purpose: To evaluate the contribution of guided fine-needle aspiration cytology in reducing unnecessary biopsies of benign solid nonpalpable breast lesions with low suspicion of malignancy at mammography. Material and Methods: An evaluation was made of a consecutive series of 2444 solid nonpalpable breast lesions detected by mammography and undergoing guided (sonography or stereotaxy) fine-needle aspiration cytology. Surgical biopsy was made in the presence of strong suspicion of malignancy at mammography and/or of abnormal cytology. Results: The sensitivity was 96.7% and the specificity 77.7% (average follow-up 2.77 years). False-negative/inadequate cytology associated with low suspicion of malignancy at mammography resulted in a diagnostic delay in 27 cancer cases (invasive 20, intraductal 7). On the other hand, cytology led to surgical biopsy in 53 cancer cases which might not otherwise have been biopsied because of low radiological suspicion of cancer. Surgical biopsy of all cases, to avoid diagnostic delays, would have increased the benign biopsy rate by a factor of 4.5, with a rise in the benign: malignant biopsy ratio from 0.44:1 to 1.93:1. Conclusion: Stereotaxy- or ultrasound-guided fine-needle aspiration cytology of nonpalpable mammographic abnormalities can achieve a sharp reduction in unnecessary benign biopsies in cases of low suspicion of malignancy at mammography.

Indications for breast magnetic resonance imaging. Consensus document “Attualità in senologia”, Florence 2007

The clinical use of breast magnetic resonance (MR) imaging is increasing, especially for applications requiring paramagnetic contrast-agent injection. This document presents a synthetic list of acceptable indications with potential advantages for women according to evidence from the literature and the expert opinion of the panel that developed this statement. We generally recommend that breast MR imaging be performed in centres with experience in conventional breast imaging [mammography and ultrasonography (US)] and needle-biopsy procedures (under stereotactic or US guidance) as well as in breast MR imaging and second-look US for findings not revealed by conventional imaging performed before MR imaging. In our opinion, there is no evidence in favour of breast MR imaging as a diagnostic tool to characterise equivocal findings at conventional imaging when needle-biopsy procedures can be performed, nor for the study of asymptomatic, non-high-risk women with negative conventional imaging. After a description of technical and methodological requirements, we define the indications and limitations of breast MR imaging for surveillance of high-risk women, local staging before surgery, evaluation of the effect of neoadjuvant chemotherapy, breast previously treated for carcinoma, carcinoma of unknown primary syndrome, nipple discharge and breast implants.RiassuntoLa RM mammaria è in fase di crescente utilizzo clinico, soprattutto per le applicazioni che richiedono la somministrazione di mezzo di contrasto (MdC) paramagnetico. Il presente documento propone una codificazione sintetica delle indicazioni accettabili con potenziale vantaggio per le donne, secondo la valutazione delle evidenze presenti in letteratura e l’opinione del gruppo di esperti estensori del documento. In generale si raccomanda che l’indagine sia eseguita presso centri che siano in grado di combinare l’esperienza senologica relativa all’imaging convenzionale e ai prelievi agobioptici con quella specifica in RM mammaria e che garantiscano l’esecuzione del second look ecografico per i reperti non rilevati all’imaging convenzionale pre-RM. Non si ritiene che vi siano evidenze in favore dell’utilizzo della RM quale approccio diagnostico nella caratterizzazione di reperti equivoci all’imaging convenzionale in tutte le situazioni nelle quali sia praticabile il prelievo agobioptico sotto guida ecografica o stereotassica né in favore dello studio di donne non ad alto rischio asintomatiche e con imaging convenzionale negativo. Sono qui definiti i requisiti tecnici e metodologici di esecuzione dell’indagine e indicazioni e limiti relativi a: sorveglianza delle donne ad alto rischio di tumore mammario; stadiazione locale pretrattamento chirurgico; valutazione dell’effetto della chemioterapia neoadiuvante; mammella trattata per carcinoma; carcinoma unknown primary syndrome; mammella secernente; protesi mammarie.

The role of arbitration of discordant reports at double reading of screening mammograms

Objective: To asses the effectiveness of arbitration of discordant double readings in mammography screening. Design: A retrospective study of 1217 consecutive arbitrations. Setting: A subset of discordant double readings from the Florence screening programme underwent arbitration by a third reader. Results: Positive arbitration of 1217 discordant double readings prompted assessment in 476 cases (39.2%), detecting 30 cancers (6.3%). Of 741 negative arbitrations (60.8%), 311 have been followed up thus far, and two cancers (0.64%) occurred in the site previously suspected at one of the two independent readings. Arbitration had a sensitivity of 86.3% and a negative predictive value of 99.3%. Arbitration reduced the overall referral rates from 3.82% to 2.59% (relative decrease 32.1%). Due to false-negative arbitration, cancers detected per 1000 women screened would decrease from 4.58 to 4.50 (relative decrease 1.7%). For every cancer missed due to false-negative arbitration, 151 unnecessary recalls and €21,248 would have been saved, whereas the saved cost per screened woman due to arbitration was €1.72. Discussion: Arbitration of discordant double reading would substantially reduce referral rates with a limited reduction in cancer detection rate, and may be recommended as a routine procedure. Greater benefit from arbitration might be expected in the presence of high referral rates at independent double reading, a common scenario in a newly implemented service screening.

Founder mutations account for the majority of BRCA1-attributable hereditary breast/ovarian cancer cases in a population from Tuscany, Central Italy

Background Germline mutations in the BRCA1 and BRCA2 tumour-suppressor genes predispose to early-onset breast and ovarian cancer. Although both genes display a highly heterogeneous mutation spectrum, a number of alterations recur in some populations. Only a limited number of founder mutations have been identified in the Italian population so far. Objective To investigate the spectrum of BRCA1/BRCA2 mutations in a set of families originary from the Central–Eastern part of Tuscany and to ascertain the presence of founder effects. We also wanted to approximate the age of the most frequent BRCA1 founder mutation. Results Overall, four distinct BRCA1 mutations accounted for a large fraction (72.7%) of BRCA1-attributable hereditary breast/ovarian cancer in families originary from this area. We identified common haplotypes for two newly recognised recurrent BRCA1 mutations, c.3228_3229delAG and c.3285delA. The c.3228_3229delAG mutation was estimated to have originated about 129 generations ago. Interestingly, male breast cancer cases were present in 3 out of 11 families with the c.3228_3229delAG mutation. Conclusions The observation that a high proportion of families with BRCA1 alterations from Central–Eastern Tuscany harbours a limited number of founder mutations can have significant impact on clinical management of at risk subjects from this area. In addition, the identification of a large set of families carrying an identical mutation that predisposes to breast and ovarian cancer provides unique opportunities to study the effect of other genetic and environmental factors on penetrance and disease phenotype.

Proficiency test for screening mammography: results for 117 volunteer Italian radiologists

Objective To analyse the performance of a large sample of Italian radiologists undergoing a proficiency test for screening mammography. Design Evaluation of performance indicators according to reference standards determined by a panel of experts (sensitivity (reference standard ≥80%), recall rate (reference standard ≤15%)). Setting 117 Italian radiologists of varying experience (years of practice 0.5–18, average 5.9; mammograms read 500–51 000, average 13 000), all currently reporting clinical mammography and planning to take part in screening in the near future. Results Eighty four of 117 (72%) radiologists reached the standard for sensitivity, 88 (75%) reached the standard for recall rate, and only 59 (50%) reached both standards and passed the proficiency test. The probability of passing the test was significantly correlated with mammographic practice (p=0.015), mammograms read (p=0.024), and mammograms read/year (p=0.043). Discussion The performance of a large sample of Italian radiologists currently reporting clinical mammography was disappointing, indicating the need for proper training of at least 50% of the tested subjects. When implementing organised screening the health authority should set up a proper process for training and accrediting radiologists, and a proficiency test should be part of such a process.

Assessment of lesions detected at mammographic screening: performance at first or repeat screening in the Florence programme

Objective – To evaluate the assessment criteria and the results achieved in the detection of breast lesions at mammographic screening. Setting – Review of cases assessed in the last screening round of Florence city (FC.- first screening round: 29 522 subjects) and Florence district (FD — repeat screening round: 13 268 subjects) programmes. Methods – Referral and biopsy rates, predictive values, and prevalence of cancers detected by screening were determined, as well as the frequency of the diagnostic procedures used at assessment, and their contribution to the final diagnosis according to the mammographic appearance of the suspected lesion. Assessment costs were estimated. Results– Referral rate (FC 4.2%; FD 1.8%), referral positive predictive value (FC 18.7%; FD 28.3%), surgical biopsy rate (FC 0.96%; FD 0.6%), benign/malignant biopsy ratio (FC 0.20; FD 0.13), and prevalence of cancers detected by screening (FC 0.78%; FD 0.5%) were all within the European Community (EC) recommended standards for screening performance. The benign biopsy rate was considerably lower than that of recommended standards. The cost for each subject assessed was 179 000 Italian lire at the first and 116 000 lire at repeat screening. The cost for each subject screened that was attributable to assessment was 7600 lire at the first or 2100 lire at repeat screening. Conclusions – Limited referral rates and costs were achieved and the proportion of cancers detected by screening was high. The number of referrals was further reduced at repeat screening, and assessment had a limited impact on total screening costs. Detail or magnification mammography, palpation, sonography, and fine needle aspiration cytology all contributed to the final diagnosis and should be immediately available at the assessment clinic. The observed benign biopsy rate was particularly low and suggests that EC recommended standards should be modified.

Analysis of the results of a proficiency test in screening mammography at the CSPO of Florence: review of 705 tests

Purpose.The aim of this study was to evaluate the performance of a sample of Italian radiologists undergoing a proficiency test of screening mammography.Materials and methods.We retrospectively analysed the results of 705 tests (537 first tests, 168 repeat tests) taken during 1997–2005 by 537 Italian radiologists. The test, consisting of 17 screendetected cancer cases and 133 negative controls, was validated by a panel of expert readers defining a minimum standard as to sensitivity for cancer and recall rate of negative controls. Success rates were assessed as a function of previous experience in mammography (years of experience, total mammograms read, mammograms read in the last year).Results.A total of 176 radiologists successfully passed the test at their first attempt (32.7%). Success correlated with experience, measured in terms of years of experience (5-year cutoff: χ2 for trend=4.17, p=0.04), total mammograms read (χ2 for trend =11.8, p=0.002) or mammograms read in the last year (χ2 for trend=6.27, p=0.04). Training improves performance at repeat testing: after a first negative attempt, a second attempt was successful in 50.6% of cases (74/146) and a third in 68.1% (15/22).Conclusions.A substantial proportion of Italian radiologists taking the test showed limited proficiency in screening mammography. This finding is consistent with several reports of poor performance of service screening compared with reference standards. As expected, test performance is associated with experience, suggesting that the current policy of employing nondedicated, untrained, general radiologists in screening should be reconsidered. Test performance improves with training (courses, consultation of teaching atlases). Several screening programmes in Italy have been implemented without prior adequate radiologist training. Radiologist training needs to be considered a priority, at least in those screening programmes that are still to be implemented in one third of the country.

Digital breast tomosynthesis (DBT): recommendations from the Italian College of Breast Radiologists (ICBR) by the Italian Society of Medical Radiology (SIRM) and the Italian Group for Mammography Screening (GISMa)

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.

Letter to the Editor regarding the paper by F. Cardoso et al. ‘European Breast Cancer Conference manifesto on breast centres/units’

a Senology Unit, Bellaria Hospital, Bologna, Italy b Department of Health, Regione Emilia-Romagna, Bologna, Italy c Zadig Scientific Communication Agency, Rome, Italy d Department of Health, Veneto Region, Venice, Italy e Centre for Cancer Prevention, Turin, Italy f Local Health Authority, Modena, Italy g Cancer Research and Prevention Institute, Florence, Italy h Local Health Authority, Sassari, Italy i Local Health Authority, Asolo, Italy j Romagna Cancer Registry, Romagna Cancer Institute (Istituto Scientifico Romagnolo per Lo Studio e La Cura Dei Tumori, IRST, IRCCS), 47014 Meldola, Forlı̀, Italy

Post‐Treatment Follow‐Up of Screen‐Detected Breast Cancer Patients: A National Survey from Italy

To the Editor: Follow-up (FU) practices after primary treatment of breast cancer vary to a great extent and are often nonstandard. One the one hand, different schedules are suggested by guidelines for the performance of mammography and physical examination (1–3), and a variety of practical protocols are in common use (4). On the other hand, laboratory and instrumental tests for the detection of distant recurrences are widely used despite the lack of any good evidence of their effectiveness (5). In 2015, the Italian Group for Mammography Screening (GISMa), the scientific society that gathers the professionals involved in mammography screening programs in Italy, has carried out a questionnaire survey of the patterns of FU of breast cancer patients detected by screening. The reason for this restriction is that screening programs have direct responsibility over these women. The unit of investigation was the local screening program. Since Italian health services, including mammography screening, are delivered on a healthcare district basis, the questionnaire was composed of 11 items relating to the presence and major characteristics of the FU service at the healthcare district level. The questions were simple and unambiguous. An active FU service was defined as using an active personal invitation strategy for eligible patients. Minimal and intensive FU were defined as including mammography and physical examination and, respectively, one or more among tumor markers, chest radiography, liver ultrasound, bone scan, computed tomography scan, and positron emission tomography. The questionnaire was saved as a Microsoft Excel file with locked cells and was sent via e-mail to all screening centers known to the GISMa. Replies were received from 70 local screening programs, equivalent to 62% of the 113 active programs currently known to the Italian National Center for Screening Monitoring. Data were analyzed descriptively. Table 1 shows that only 46, or two-thirds, of programs provide a FU service, and that only 56% provide an active service. In most programs with FU service, there is a specially appointed multi-disciplinary team with all relevant expertise areas represented. The greater part of FU teams are not directed by a radiologist. Primary care physicians are assigned no role in two-thirds of programs. Also noteworthy, most multi-disciplinary teams are not supported by a common platform for data collection and integration. Table 2 shows the high degree of variation in FU protocols, with similar numbers of programs following the three possible approaches. Minimal FU protocols are generally based on combined mammography and physical examination. Intensive protocols are used in more than 60% FU services. A little less than half of intensive protocols include tumor markers, chest radiography, liver ultrasound, bone scan, computed tomography scan, and positron emission tomography. The last three questions addressed whether, and when, breast cancer survivors are returned to normal screening. Again, a striking variation was observed. In 48% programs with FU service, their exclusion is permanent. In the remaining ones, patients are returned to normal screening, although this occurs only for a part of them in 9% programs. When women are returned to screening, the duration of FU is 10 years in 75% FU services. Bearing in mind that programs with efficient and appropriate FU practices are likely to be overrepresented in the sample due to selection bias, the following points need to be stressed. First, at least half of screen-detected breast cancer patients in Italy are not assisted by an active FU service, which puts them at risk of not undergoing their checks regularly. Second, screening radiologists have a secondary role in multidisciplinary teams, which could predict an insufficient consideration for the value of mammography in surveillance protocols. Studies from other countries have noted that mammography rates decrease rapidly Address correspondence and reprint requests to: Lauro Bucchi, Romagna Cancer Institute (IRST) IRCCS, 47014 Meldola, Forl ı, Italy, or e-mail: lauro.bucchi@irst.emr.it