title: 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.
abstract: OBJECTIVE
  : To prospectively compare clinical breast examination, mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (MRI) in a multicenter surveillance of high-risk women.
  
  
  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.
  
  
  CONCLUSIONS
  : MRI largely outperformed mammography, ultrasonography, and their combination for screening high-risk women below and over 50.
authors.affiliation: Dipartimento di Scienze Medico-Chirurgiche, Università degli Studi di Milano, IRCCS Policlinico San Donato, Unità di Radiologia, San Donato Milanese, Milano, Italy. f.sardanelli@grupposandonato.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Sardanelli
authors.forename: Franca
authors.initials: F
authors.lastname: Podo
authors.forename: Filippo
authors.initials: F
authors.lastname: Santoro
authors.forename: Siranoush
authors.initials: S
authors.lastname: Manoukian
authors.forename: Silvana
authors.initials: S
authors.lastname: Bergonzi
authors.forename: Giovanna
authors.initials: G
authors.lastname: Trecate
authors.forename: Daniele
authors.initials: D
authors.lastname: Vergnaghi
authors.forename: Massimo
authors.initials: M
authors.lastname: Federico
authors.forename: Laura
authors.initials: L
authors.lastname: Cortesi
authors.forename: Stefano
authors.initials: S
authors.lastname: Corcione
authors.forename: Sandro
authors.initials: S
authors.lastname: Morassut
authors.forename: Cosimo
authors.initials: C
authors.lastname: Di Maggio
authors.forename: Anna
authors.initials: A
authors.lastname: Cilotti
authors.forename: Laura
authors.initials: L
authors.lastname: Martincich
authors.forename: Massimo
authors.initials: M
authors.lastname: Calabrese
authors.forename: Chiara
authors.initials: C
authors.lastname: Zuiani
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Preda
authors.forename: Bernardo
authors.initials: B
authors.lastname: Bonanni
authors.forename: Luca A
authors.initials: LA
authors.lastname: Carbonaro
authors.forename: Alma
authors.initials: A
authors.lastname: Contegiacomo
authors.forename: Pietro
authors.initials: P
authors.lastname: Panizza
authors.forename: Ernesto
authors.initials: E
authors.lastname: Di Cesare
authors.forename: Antonella
authors.initials: A
authors.lastname: Savarese
authors.forename: Marcello
authors.initials: M
authors.lastname: Crecco
authors.forename: Daniela
authors.initials: D
authors.lastname: Turchetti
authors.forename: Maura
authors.initials: M
authors.lastname: Tonutti
authors.forename: Paolo
authors.initials: P
authors.lastname: Belli
authors.forename: Alessandro Del
authors.initials: AD
authors.lastname: Maschio
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000235:genetics; D016009:Chi-Square Distribution; D016001:Confidence Intervals; D003287:Contrast Media; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007558:Italy; D008279:Magnetic Resonance Imaging; D008327:Mammography; D008875:Middle Aged; D011159:Population Surveillance / Q000379:methods*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D018570:Risk Assessment; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013223:Statistics as Topic; D018709:Statistics, Nonparametric; D014463:Ultrasonography; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; D003287:Contrast Media