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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

Sardanelli, Francesco MD*; Podo, Franca DrSci†; Santoro, Filippo DrSci†; Manoukian, Siranoush MD‡; Bergonzi, Silvana MD§; Trecate, Giovanna MD¶; Vergnaghi, Daniele MD¶; Federico, Massimo MD‖; Cortesi, Laura MD‖; Corcione, Stefano MD**; Morassut, Sandro MD††; Di Maggio, Cosimo MD‡‡; Cilotti, Anna MD§§; Martincich, Laura MD¶¶; Calabrese, Massimo MD‖‖; Zuiani, Chiara MD***; Preda, Lorenzo MD†††; Bonanni, Bernardo MD‡‡‡; Carbonaro, Luca A. MD*; Contegiacomo, Alma MD§§§; Panizza, Pietro MD¶¶¶; Di Cesare, Ernesto MD‖‖‖; Savarese, Antonella MD****; Crecco, Marcello MD††††; Turchetti, Daniela MD‡‡‡‡; Tonutti, Maura MD§§§§; Belli, Paolo MD¶¶¶¶; Maschio, Alessandro Del MD¶¶¶; for the High Breast Cancer Risk Italian 1 (HIBCRIT-1) Study

doi: 10.1097/RLI.0b013e3181f3fcdf
Original Article

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.

From the *Dipartimento di Scienze Medico-Chirurgiche, Università degli Studi di Milano, IRCCS Policlinico San Donato, Unità di Radiologia, San Donato Milanese, Milano, Italy; †Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Roma, Italy; Units of ‡Medical Genetics, §Breast Imaging, and ¶Diagnostic Radiology A, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy; ‖Department of Oncology and Haematology, University of Modena and Reggio Emilia, Modena, Italy; **Breast Imaging Unit, University Hospital of Ferrara, Ferrara, Italy; ††Department of Radiology, Centro di Riferimento Oncologico, Aviano, Italy; ‡‡Department of Oncology and Surgical Sciences, IRCCS Istituto Oncologico Veneto, Padova, Italy; §§Radiological Section, Ospedale Santa Chiara, University of Pisa, Pisa, Italy; ¶¶Unit of Diagnostic Imaging, IRCC Institute for Cancer Research and Treatment, Candiolo, Torino, Italy; ‖‖Unit of Breast Imaging, University of Genoa and San Martino Hospital, Genova, Italy; ***Institute of Radiology, Azienda Ospedaliero-Universitaria Santa Maria della Misericordia, Udine, Italy; †††Department of Radiology, European Institute of Oncology, Milan, Italy; ‡‡‡Division of Cancer Prevention and Genetics, European Institute of Oncology, Milan, Italy; §§§Department of Endocrinology and Molecular and Clinical Oncology, Federico II University, Napoli, Italy; ¶¶¶Department of Radiology, Vita-Salute University, San Raffaele Hospital, Milano, Italy; ‖‖‖Department of Radiology, University of L'Aquila, L'Aquila, Italy; Departments of ****Medical Oncology and ††††Radiology, Regina Elena National Cancer Institute, Roma, Italy; ‡‡‡‡Unit of Medical Genetics, Policlinico Sant'Orsola Malpighi, University of Bologna, Bologna, Italy; §§§§Department of Radiology, University of Trieste, Trieste, Italy; and ¶¶¶¶Department of Bio-Imaging and Radiological Sciences, Catholic University, Roma, Italy.

Received April 3, 2010, and accepted for publication, after revision, July 10, 2010.

Massimo Calabrese is currently at Department of Breast Imaging, National Institute for Cancer Research, Genova, Italy.

F.S. and F.P. authors contributed equally for this study.

Supported by Italian Ministry of Health, Ricerca Finalizzata 1% 98/JT/T; Istituto Superiore di Sanità, Ricerca Corrente C3A3/2004; Italian Ministry of Health, Research Project on Cancer Screening, Law No. 138/2004; Special Project in Oncology 2006—Art. 3 “Rete Solidale e Collaborazioni Internazionali (ISS per ACC),” Project ACC2-InTEF.

Reprints: Francesco Sardanelli, MD, Dipartimento di Scienze Medico-Chirurgiche, Università degli Studi di Milano, IRCCS Policlinico San Donato, Unità di Radiologia, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy. E-mail:; or

© 2011 Lippincott Williams & Wilkins, Inc.