Pietro Panizza

Magnetic resonance imaging of the breast: Recommendations from the EUSOMA working group

The use of breast magnetic resonance imaging (MRI) is rapidly increasing. EUSOMA organised a workshop in Milan on 20-21st October 2008 to evaluate the evidence currently available on clinical value and indications for breast MRI. Twenty-three experts from the disciplines involved in breast disease management - including epidemiologists, geneticists, oncologists, radiologists, radiation oncologists, and surgeons - discussed the evidence for the use of this technology in plenary and focused sessions. This paper presents the consensus reached by this working group. General recommendations, technical requirements, methodology, and interpretation were firstly considered. For the following ten indications, an overview of the evidence, a list of recommendations, and a number of research issues were defined: staging before treatment planning; screening of high-risk women; evaluation of response to neoadjuvant chemotherapy; patients with breast augmentation or reconstruction; occult primary breast cancer; breast cancer recurrence; nipple discharge; characterisation of equivocal findings at conventional imaging; inflammatory breast cancer; and male breast. The working group strongly suggests that all breast cancer specialists cooperate for an optimal clinical use of this emerging technology and for future research, focusing on patient outcome as primary end-point.

Multicenter surveillance of women at high genetic breast cancer risk using mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (the high breast cancer risk italian 1 study): final results.

Objectives:To prospectively compare clinical breast examination, mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (MRI) in a multicenter surveillance of high-risk women. Materials and Methods:We enrolled asymptomatic women aged ≥25: BRCA mutation carriers; first-degree relatives of BRCA mutation carriers, and women with strong family history of breast/ovarian cancer, including those with previous personal breast cancer. Results:A total of 18 centers enrolled 501 women and performed 1592 rounds (3.2 rounds/woman). Forty-nine screen-detected and 3 interval cancers were diagnosed: 44 invasive, 8 ductal carcinoma in situ; only 4 pT2 stage; 32 G3 grade. Of 39 patients explored for nodal status, 28 (72%) were negative. Incidence per year-woman resulted 3.3% overall, 2.1% <50, and 5.4% ≥50 years (P < 0.001), 4.3% in women with previous personal breast cancer and 2.5% in those without (P = 0.045). MRI was more sensitive (91%) than clinical breast examination (18%), mammography (50%), ultrasonography (52%), or mammography plus ultrasonography (63%) (P < 0.001). Specificity ranged 96% to 99%, positive predictive value 53% to 71%, positive likelihood ratio 24 to 52 (P not significant). MRI showed significantly better negative predictive value (99.6) and negative likelihood ratio (0.09) than those of the other modalities. At receiver operating characteristic analysis, the area under the curve of MRI (0.97) was significantly higher than that of mammography (0.83) or ultrasonography (0.82) and not significantly increased when MRI was combined with mammography and/or ultrasonography. Of 52 cancers, 16 (31%) were diagnosed only by MRI, 8 of 21 (38%) in women <50, and 8 of 31 (26%) in women ≥50 years of age. Conclusion:MRI largely outperformed mammography, ultrasonography, and their combination for screening high-risk women below and over 50.

The European Society of Breast Cancer Specialists recommendations for the management of young women with breast cancer.

EUSOMA (The European Society of Breast Cancer Specialists) is committed to writing recommendations on different topics of breast cancer care which can be easily adopted and used by health professionals dedicated to the care of patients with breast cancer in their daily practice. In 2011, EUSOMA identified the management of young women with breast cancer as one of the hot topics for which a consensus among European experts was needed. Therefore, the society recently organised a workshop to define such recommendations. Thirteen experts from the different disciplines met for two days to discuss the topic. This international and multidisciplinary panel thoroughly reviewed the literature in order to prepare evidence-based recommendations. During the meeting, two working groups were set up to discuss in detail diagnosis and loco-regional and systemic treatments, including both group aspects of psychology and sexuality. The conclusions reached by the working groups were then discussed in a plenary session to reach panel consensus. Whenever possible, a measure of the level of evidence (LoE) from 1 (the highest) to 4 (the lowest) degree, based on the methodology proposed by the US Agency for Healthcare Research and Quality (AHRQ), was assigned to each recommendation. The present manuscript presents the recommendations of this consensus group for the management of young women with breast cancer in daily clinical practice.

Contrast-Enhanced Breast MRI in Patients with Suspicious Microcalcifications on Mammography: Results of a Multicenter Trial

OBJECTIVE The objective of our study was to test dynamic MRI in evaluating mammographically detected suspicious microcalcifications. MATERIALS AND METHODS One hundred twelve patients with mammographically detected microcalcifications with BI-RADS category 5 (n = 78) or 4 (n = 34) lesions were studied at 17 centers a using 3D gradient-echo dynamic coronal technique (< or = 3 mm thickness) and 0.1 mmol/kg of gadoteridol. A pathologic sample was obtained in all cases. Agreement between the major diameter measured on mammography, MRI, or both and the major diameter measured at pathologic examination was calculated in 62 cases. RESULTS Of the 112 lesions, pathologic examination revealed 37 benign lesions, 33 ductal carcinoma in situ (DCIS), and 42 invasive carcinomas. The specificity of MRI for benign lesions was 68%. Considering the subgroups of calcifications alone and calcifications associated with masses, the specificity values became 79% and 33%, respectively. The sensitivity of MRI for DCIS was 79%. Analysis of the two subgroups showed sensitivity values of 68% for calcifications alone and of 1% for calcifications associated with masses. The sensitivity for invasive carcinomas was 93%. Analysis of the two subgroups showed sensitivity values to be 92% for calcifications alone and 94% for calcifications associated with masses. Considering the overall results, the sensitivity of MRI was 87%; specificity, 68%; positive predictive value, 84%; negative predictive value, 71%; and accuracy, 80%. Considering the subgroups of calcifications alone and calcifications associated with masses, the sensitivity values became 80% and 97%; the positive predictive values, 86% and 82%; the negative predictive values, 71% and 75% (95% confidence interval [CI], 0.19-0.99); and the accuracy values, 80% and 82% (95% CI, 0.66-0.92), respectively. An odds ratio (OR) of 13.54 (95% CI, 5.20-35.28) showed a raised risk of malignant breast tumor in subjects with positive MR examination of mammographically detected suspicious clusters of microcalcifications. The statistical analysis on each subgroup showed an OR of 15.07 (95% CI, 4.73-48.08) for calcifications alone and an OR of 14.00 (95% CI, 1.23-158.84) for calcifications associated with masses. Any significant improvement in the predictive ability of dynamic MRI depending on the extent of calcifications on mammography was not proved. Considering the 62 cases of proved malignancy with measured maximal diameter at pathologic examination, both mammography and MR examination seem to overestimate tumor extent. CONCLUSION The not-perfect sensitivity of MRI (87%), when applying our interpretation criteria and imaging sequences, is a crucial point that prevents us from clinical use of MRI in the diagnosis of mammographically detected microcalcifications.

Breast MRI: EUSOBI recommendations for women's information.

AbstractThis paper summarizes information about breast MRI to be provided to women and referring physicians. After listing contraindications, procedure details are described, stressing the need for correct scheduling and not moving during the examination. The structured report including BI-RADS® categories and further actions after a breast MRI examination are discussed. Breast MRI is a very sensitive modality, significantly improving screening in high-risk women. It also has a role in clinical diagnosis, problem solving, and staging, impacting on patient management. However, it is not a perfect test, and occasionally breast cancers can be missed. Therefore, clinical and other imaging findings (from mammography/ultrasound) should also be considered. Conversely, MRI may detect lesions not visible on other imaging modalities turning out to be benign (false positives). These risks should be discussed with women before a breast MRI is requested/performed. Because breast MRI drawbacks depend upon the indication for the examination, basic information for the most important breast MRI indications is presented. Seventeen notes and five frequently asked questions formulated for use as direct communication to women are provided. The text was reviewed by Europa Donna–The European Breast Cancer Coalition to ensure that it can be easily understood by women undergoing MRI.Key Points• Information on breast MRI concerns advantages/disadvantages and preparation to the examination • Claustrophobia, implantable devices, allergic predisposition, and renal function should be checked • Before menopause, scheduling on day 7–14 of the cycle is preferred • During the examination, it is highly important that the patient keeps still • Availability of prior examinations improves accuracy of breast MRI interpretation

Multicenter, Double-Blind, Randomized, Intraindividual Crossover Comparison of Gadobenate Dimeglumine and Gadopentetate Dimeglumine for Breast MR Imaging (DETECT Trial)

PURPOSE To intraindividually compare 0.1 mmol/kg doses of gadobenate dimeglumine and gadopentetate dimeglumine for contrast material-enhanced breast magnetic resonance (MR) imaging by using a prospective, multicenter double-blind, randomized protocol. MATERIALS AND METHODS Institutional review board approval and patient informed consent were obtained. One hundred sixty-two women (mean age, 52.8 years ± 12.3 [standard deviation]) enrolled at 17 sites in Europe and China between July 2007 and May 2009 underwent at least one breast MR imaging examination at 1.5 T by using three-dimensional spoiled gradient-echo sequences. Of these, 151 women received both contrast agents in randomized order in otherwise identical examinations separated by more than 2 but less than 7 days. Images, acquired at 2-minute or shorter intervals after contrast agent injection, were evaluated independently by three blinded radiologists unaffiliated with enrollment centers. Histopathologic confirmation was available for all malignant lesions (n = 144), while benign lesions were confirmed either by using histopathologic examination (n = 52) or by at least 12-month diagnostic follow-up (n = 20) with mammography and/or ultrasonography. Determinations of malignant lesion detection rates and diagnostic performance (sensitivity, specificity, accuracy, positive predictive value [PPV], and negative predictive value [NPV]) were performed and compared (McNemar and Wald tests). A full safety assessment was performed. RESULTS Significant superiority for gadobenate dimeglumine was noted by readers 1, 2, and 3 for malignant lesion detection rate (91.7%, 93.1%, 94.4% vs 79.9%, 80.6%, 83.3%, respectively; P ≤ .0003). Readers 1, 2, and 3 reported significantly superior diagnostic performance (sensitivity, specificity, and accuracy) for breast cancer detection with gadobenate dimeglumine (91.1%, 94.5%, 95.2% vs 81.2%, 82.6%, 84.6%; 99.0%, 98.2%, 96.9% vs 97.8%, 96.9%, 93.8%; 98.2%, 97.8%, 96.7% vs 96.1%, 95.4%, 92.8%, respectively; P ≤ .0094) and significantly superior PPV (91.1%, 85.2%, 77.2% vs 80.7%, 75.5%, 60.9%, respectively; P ≤ .0002) and NPV (99.0%, 99.4%, 99.4% vs 97.8%, 98.0%, 98.1%, respectively; P ≤ .0003). No safety concerns were noted with either agent. CONCLUSION Gadobenate dimeglumine is superior to gadopentetate dimeglumine for breast cancer diagnosis.

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.

What is the sensitivity of mammography and dynamic MR imaging for DCIS if the whole-breast histopathology is used as a reference standard?

Purpose. Our purpose was to compare mammography and dynamic contrast-enhanced magnetic resonance imaging (MRI) in the detection of ductal carcinoma in situ (DCIS)Materials and methods. Ninety patients (aged 58.6±16.1 years) who were candidates for unilateral (n=81) or bilateral (n=9) mastectomy underwent mammography and dynamic contrast-enhanced breast MRI using a coronal three-dimensional gradient-echo sequence with slice thickness ≤3 mm before and after intravenous injection of gadoteridol (0.1 mmol/kg). Mammographic and MR images were evaluated by two offsite readers working in consensus. Pathological examination performed on 5-mm sections covering the whole breast was used as a reference standardResults. Out of 99 breasts, pathology revealed 26 DCIS in 14 breasts of 14 patients, aged 52.0+_9.6 years. Lesion diameter at pathology was <5 mm (n=4); ≥5 and <10 mm (n=7); ≥10 and <20 mm (n=3); ≥20 mm (n=2); not assessed (n=10). Sensitivity was 35% (9/26) for mammography and 38% (10/26) for MRI (not significant difference, McNemar test). Both mammography and MRI provided a true positive result in seven cases (four of them measured at pathology, with a diameter of 20.0±12.9 mm; median 20 mm) and a false negative result in 14 cases (10 of them measured at pathology, with a diameter of 4.2±1.9 mm; median 4.6 mm) (p=0.024, Mann-Whitney U test). Only 46% (12/26) of DCIS were detected at mammography and/or MRI; the remaining 54% (14/26) were diagnosed only at pathological examinationConclusions. When the whole breast is used as the histopathological reference standard, both mammography and MRI show low sensitivity for DCISRiassuntoObiettivo . Confrontare la sensibilità per il carcinoma duttale in situ (DCIS) della mammografia e della risonanza magnetica (RM) con mezzo di contrastoMateriali e metodi . Novanta pazienti (età 58.6±16.1 anni) candidate alla mastectomia monolaterale (n=81) o bilaterale (n=9) sono state sottoposte a mammografia e RM a contrasto dinamico mediante sequenza tridimensionale coronale gradient-echo con spessore di strato ≤3 mm, prima e dopo iniezione endovenosa di gadoteridolo (0.1 mmol/kg). Mammografia e RM sono state valutate da due lettori off-site, in consenso. L’;esame istologico dell’;intera mammella (strati di 5 mm di spessore) ha rappresentato lo standard di riferimentoRisultati . L’esame istologico delle 99 mammelle ha evidenziato 26 DCIS in 14 mammelle di 14 pazienti (età 52.0±9.6 anni). All’esame istologico il diametro della lesione è risultato <5 mm (n=4); ≥5 e <10 mm (n=7); ≥10 e <20 mm (n=3); ≥20 mm (n=2); non valutato (n=10). La sensibilità è risultata del 35% (9/26) per la mammografia e del 38% (10/26) per la RM (differenza non significativa, test di McNemar). Mammografia e RM sono risultate entrambe vere positive in 7 casi (4 dei quali con diametro misurato istologicamente, pari a 20.0±12.9 mm, mediana 20 mm) ed entrambe false negative in 14 casi (10 dei quali con diametro misurato istologicamente, pari a 4.2±1.9 mm, mediana 4.6) (p=0.024, test U di Mann-Whitney). Solo il 46% (12/26) dei DCIS sono stati identificati alla mammografia e/o alla RM mentre il rimanente 54% (14/26) è stato riconosciuto solo all’esame istologicoConclusioni . Allorquando l’intera mammella è assunta come standard di riferimento istologico, sia la mammografia che la RM mostrano ridotta sensibilità per il DCIS

Tailored Breast Cancer Screening Program with Microdose Mammography, US, and MR Imaging: Short-term Results of a Pilot Study in 40–49-Year-Old Women

PURPOSE To evaluate the feasibility, performance, and cost of a breast cancer screening program aimed at 40-49-year-old women and tailored to their risk profile with supplemental ultrasonography (US) and magnetic resonance (MR) imaging. MATERIALS AND METHODS The institutional review board approved this study, and informed written consent was obtained. A total of 3017 40-49-year-old women were invited to participate. The screening program was tailored to lifetime risk (Gail test) and mammographic density (according to Breast Imaging Reporting and Data Systems [BI-RADS] criteria) with supplemental US or MR imaging and bilateral two-view microdose mammography. The indicators suggested by European guidelines, US incremental cancer detection rate (CDR), and estimated costs were evaluated. RESULTS A total of 1666 women (67.5% participation rate) were recruited. The average lifetime risk of breast cancer was 11.6%, and nine women had a high risk of breast cancer; 917 women (55.0%) had a high density score (BI-RADS density category 3 or 4). The average glandular dose for screening examinations was 1.49 mGy. Screening US was performed in 835 study participants (50.1%), mostly due to high breast density (800 of 1666 women [48.0%]). Screening MR imaging was performed in nine women (0.5%) at high risk for breast cancer. Breast cancer was diagnosed in 14 women (8.4 cases per 1000 women). Twelve diagnoses were made with microdose mammography, and two were made with supplemental US in dense breasts (2.4 cases per 1000 women). All patients were submitted for surgery, and 10 underwent breast-conserving surgery. The sentinel lymph node was evaluated in 11 patients, resulting in negative findings in six. Pathologic analysis resulted in the diagnosis of four ductal carcinomas in situ and 10 invasive carcinomas (five at stage I). CONCLUSION A tailored breast cancer screening program in 40-49-year-old women yielded a greater-than-expected number of cancers, most of which were low-stage disease.

Nonpalpable breast lesions: preoperative radiological guidance in radioguided occult lesion localisation (ROLL)

PurposeThis study evaluated the methods, technical aspects and impact of preoperative radiological guidance in radioguided occult lesion localisation (ROLL) for single nonpalpable breast lesions.Materials and methodsA total of 288 patients underwent ROLL before surgery. Human serum albumin macroaggregates labelled with 3.7–7.4 MBq of technetium99 were injected into the lesion. In the case of ultrasonographic guidance (221/288 patients), inoculum positioning resulted in a change of echogenicity at the lesion site. In the case of mammographic guidance (67/288 patients), iodinated contrast medium was injected following the radiotracer for subsequent mammographic evaluation. Patients underwent surgery within 24 h from ROLL. A gamma-detecting probe was used to locate the lesion during surgery and guide its removal. After excision, the specimen was examined by either ultrasonography or mammography to verify complete lesion removal before histological evaluation.ResultsThe lesion was correctly localised in 281/288 patients (97.5%). One ROLL procedure failed because surgery could not be performed within 24 h and the radioactivity decayed. Of the six incorrect localisations, 2 were due to the radiological guidance and 4 to technetium99 dispersion.ConclusionsRadiological guidance in ROLL ensured the outcome of the procedure of localisation and removal of single, nonpalpable breast lesions in the majority of cases.RiassuntoObiettivoScopo del presente lavoro è stato quello di valutare metodi, aspetti tecnici ed impatto della guida radiologica preoperatoria nella radioguided occult lesion localisation (ROLL) per lesioni mammarie singole non palpabili.Materiali e metodiDuecentottantotto pazienti sono state sottoposte a ROLL prima dell’intervento. All’interno della lesione sono stati iniettati macro-aggregati di albumina umana marcata con tecnezio99; nel caso di guida ecografica (221/288 soggetti), l’inoculo ha prodotto iperecogenicità in corrispondenza della lesione; nel caso di guida mammografica (67/288 soggetti), dopo il radiotracciante è stato inoculato mezzo di contrasto iodato per il successivo controllo mammografico. Le pazienti sono state sottoposte ad intervento chirurgico entro 24 ore dalla ROLL. Per localizzare la lesione e guidarne la rimozione chirurgica, è stata utilizzata una sonda per la rilevazione dei raggi gamma. Dopo l’escissione, il pezzo operatorio è stato esaminato con ecografia o mammografia per verificare la completa rimozione della lesione.RisultatiLa lesione è stata localizzata correttamente in 281/288 pazienti (97,5%). Una ROLL non ha avuto successo poiché non è stato possibile effettuare l’intervento chirurgico entro 24 ore. Delle 6 localizzazioni non riuscite, 2 sono da mettere in relazione alla guida radiologica e 4 alla dispersione del tecnezio99.ConclusioniLa guida radiologica nella ROLL ha garantito l’esito della localizzazione e rimozione di lesioni mammarie singole non palpabili nella maggioranza dei casi.