Combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer.
BACKGROUND
Screening ultrasound may depict small, node-negative breast cancers not seen on mammography.


OBJECTIVE
To compare the diagnostic yield, defined as the proportion of women with positive screen test results and positive reference standard, and performance of screening with ultrasound plus mammography vs mammography alone in women at elevated risk of breast cancer.


METHODS
From April 2004 to February 2006, 2809 women, with at least heterogeneously dense breast tissue in at least 1 quadrant, were recruited from 21 sites to undergo mammographic and physician-performed ultrasonographic examinations in randomized order by a radiologist masked to the other examination results. Reference standard was defined as a combination of pathology and 12-month follow-up and was available for 2637 (96.8%) of the 2725 eligible participants.


METHODS
Diagnostic yield, sensitivity, specificity, and diagnostic accuracy (assessed by the area under the receiver operating characteristic curve) of combined mammography plus ultrasound vs mammography alone and the positive predictive value of biopsy recommendations for mammography plus ultrasound vs mammography alone.


RESULTS
Forty participants (41 breasts) were diagnosed with cancer: 8 suspicious on both ultrasound and mammography, 12 on ultrasound alone, 12 on mammography alone, and 8 participants (9 breasts) on neither. The diagnostic yield for mammography was 7.6 per 1000 women screened (20 of 2637) and increased to 11.8 per 1000 (31 of 2637) for combined mammography plus ultrasound; the supplemental yield was 4.2 per 1000 women screened (95% confidence interval [CI], 1.1-7.2 per 1000; P = .003 that supplemental yield is 0). The diagnostic accuracy for mammography was 0.78 (95% CI, 0.67-0.87) and increased to 0.91 (95% CI, 0.84-0.96) for mammography plus ultrasound (P = .003 that difference is 0). Of 12 supplemental cancers detected by ultrasound alone, 11 (92%) were invasive with a median size of 10 mm (range, 5-40 mm; mean [SE], 12.6 [3.0] mm) and 8 of the 9 lesions (89%) reported had negative nodes. The positive predictive value of biopsy recommendation after full diagnostic workup was 19 of 84 for mammography (22.6%; 95% CI, 14.2%-33%), 21 of 235 for ultrasound (8.9%, 95% CI, 5.6%-13.3%), and 31 of 276 for combined mammography plus ultrasound (11.2%; 95% CI. 7.8%-15.6%).


CONCLUSIONS
Adding a single screening ultrasound to mammography will yield an additional 1.1 to 7.2 cancers per 1000 high-risk women, but it will also substantially increase the number of false positives.


BACKGROUND
clinicaltrials.gov Identifier: NCT00072501.
Berg
Wendie A
WA
American Radiology Services Inc, Johns Hopkins Green Spring, Lutherville, Maryland, USA. wendieberg@gmail.com
Blume
Jeffrey D
JD
Cormack
Jean B
JB
Mendelson
Ellen B
EB
Lehrer
Daniel
D
Böhm-Vélez
Marcela
M
Pisano
Etta D
ED
Jong
Roberta A
RA
Evans
W Phil
WP
Morton
Marilyn J
MJ
Mahoney
Mary C
MC
Larsen
Linda Hovanessian
LH
Barr
Richard G
RG
Farria
Dione M
DM
Marques
Helga S
HS
Boparai
Karan
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D001943:Breast Neoplasms / Q000175:diagnosis*; D005260:Female; D006801:Humans; D008327:Mammography; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D011237:Predictive Value of Tests; D012307:Risk Factors; D012680:Sensitivity and Specificity; D016217:Ultrasonography, Mammary