title: Detection of breast cancer with addition of annual screening ultrasound or a single screening MRI to mammography in women with elevated breast cancer risk.
abstract: BACKGROUND
  Annual ultrasound screening may detect small, node-negative breast cancers that are not seen on mammography. Magnetic resonance imaging (MRI) may reveal additional breast cancers missed by both mammography and ultrasound screening.
  
  
  OBJECTIVE
  To determine supplemental cancer detection yield of ultrasound and MRI in women at elevated risk for breast cancer.
  
  
  METHODS
  From April 2004-February 2006, 2809 women at 21 sites with elevated cancer risk and dense breasts consented to 3 annual independent screens with mammography and ultrasound in randomized order. After 3 rounds of both screenings, 612 of 703 women who chose to undergo an MRI had complete data. The reference standard was defined as a combination of pathology (biopsy results that showed in situ or infiltrating ductal carcinoma or infiltrating lobular carcinoma in the breast or axillary lymph nodes) and 12-month follow-up.
  
  
  METHODS
  Cancer detection rate (yield), sensitivity, specificity, positive predictive value (PPV3) of biopsies performed and interval cancer rate.
  
  
  RESULTS
  A total of 2662 women underwent 7473 mammogram and ultrasound screenings, 110 of whom had 111 breast cancer events: 33 detected by mammography only, 32 by ultrasound only, 26 by both, and 9 by MRI after mammography plus ultrasound; 11 were not detected by any imaging screen. Among 4814 incidence screens in the second and third years combined, 75 women were diagnosed with cancer. Supplemental incidence-screening ultrasound identified 3.7 cancers per 1000 screens (95% CI, 2.1-5.8; P < .001). Sensitivity for mammography plus ultrasound was 0.76 (95% CI, 0.65-0.85); specificity, 0.84 (95% CI, 0.83-0.85); and PPV3, 0.16 (95% CI, 0.12-0.21). For mammography alone, sensitivity was 0.52 (95% CI, 0.40-0.64); specificity, 0.91 (95% CI, 0.90-0.92); and PPV3, 0.38 (95% CI, 0.28-0.49; P < .001 all comparisons). Of the MRI participants, 16 women (2.6%) had breast cancer diagnosed. The supplemental yield of MRI was 14.7 per 1000 (95% CI, 3.5-25.9; P = .004). Sensitivity for MRI and mammography plus ultrasound was 1.00 (95% CI, 0.79-1.00); specificity, 0.65 (95% CI, 0.61-0.69); and PPV3, 0.19 (95% CI, 0.11-0.29). For mammography and ultrasound, sensitivity was 0.44 (95% CI, 0.20-0.70, P = .004); specificity 0.84 (95% CI, 0.81-0.87; P < .001); and PPV3, 0.18 (95% CI, 0.08 to 0.34; P = .98). The number of screens needed to detect 1 cancer was 127 (95% CI, 99-167) for mammography; 234 (95% CI, 173-345) for supplemental ultrasound; and 68 (95% CI, 39-286) for MRI after negative mammography and ultrasound results.
  
  
  CONCLUSIONS
  The addition of screening ultrasound or MRI to mammography in women at increased risk of breast cancer resulted in not only a higher cancer detection yield but also an increase in false-positive findings.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00072501.
authors.affiliation: American College of Radiology Imaging Network, Philadelphia, Pennsylvania, USA. wendieberg@gmail.com
authors.forename: Wendie A
authors.initials: WA
authors.lastname: Berg
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Daniel
authors.initials: D
authors.lastname: Lehrer
authors.forename: Roberta A
authors.initials: RA
authors.lastname: Jong
authors.forename: Etta D
authors.initials: ED
authors.lastname: Pisano
authors.forename: Richard G
authors.initials: RG
authors.lastname: Barr
authors.forename: Marcela
authors.initials: M
authors.lastname: Böhm-Vélez
authors.forename: Mary C
authors.initials: MC
authors.lastname: Mahoney
authors.forename: W Phil
authors.initials: WP
authors.lastname: Evans
authors.forename: Linda H
authors.initials: LH
authors.lastname: Larsen
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Morton
authors.forename: Ellen B
authors.initials: EB
authors.lastname: Mendelson
authors.forename: Dione M
authors.initials: DM
authors.lastname: Farria
authors.forename: Jean B
authors.initials: JB
authors.lastname: Cormack
authors.forename: Helga S
authors.initials: HS
authors.lastname: Marques
authors.forename: Amanda
authors.initials: A
authors.lastname: Adams
authors.forename: Nolin M
authors.initials: NM
authors.lastname: Yeh
authors.forename: Glenna
authors.initials: G
authors.lastname: Gabrielli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008327:Mammography; D008875:Middle Aged; D011237:Predictive Value of Tests; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014463:Ultrasonography; D055815:Young Adult