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Multicenter Comparative Multimodality Surveillance of Women at Genetic-Familial High Risk for Breast Cancer (HIBCRIT Study): Interim Results¹

¹ From the University of Milan School of Medicine, Department of Medical and Surgical Sciences, Unit of Radiology, IRCCS Policlinico San Donato, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy (F.S.); and Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy (F.P.). The remaining authors and their affiliations are listed at the end of this article. From the 2004 RSNA Annual Meeting. Received December 5, 2005; revision requested January 25, 2006; revision received February 28; accepted April 3; final version accepted June 30. The HIBCRIT study was supported by the Italian Ministry of Health (Ricerca Finalizzata 1% 98/JT/T) and Istituto Superiore di Sanità (ricerca corrente C3A3/2004) and coordinated by the Istituto Superiore di Sanità, Rome, Italy. Address correspondence to F.S. (e-mail: f.sardanelli{at}grupposandonato.it).

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE References

 
Purpose: To prospectively compare clinical breast examination (CBE), mammography, ultrasonography (US), and contrast material–enhanced magnetic resonance (MR) imaging for screening women at genetic-familial high risk for breast cancer and report interim results, with pathologic findings as standard.

Materials and Methods: Institutional review board of each center approved the research; informed written consent was obtained. CBE, mammography, US, and MR imaging were performed for yearly screening of BRCA1 or BRCA2 mutation carriers, first-degree relatives of BRCA1 or BRCA2 mutation carriers, or women enrolled because of a strong family history of breast or ovarian cancer (three or more events in first- or second-degree relatives in either maternal or paternal line; these included breast cancer in women younger than 60 years, ovarian cancer at any age, and male breast cancer at any age).

Results: Two hundred seventy-eight women (mean age, 46 years ± 12 [standard deviation]) were enrolled. Breast cancer was found in 11 of 278 women at first round and seven of 99 at second round (14 invasive, four intraductal; eight were 10 mm in diameter). Detection rate per year was 4.8% (18 of 377) overall; 4.3% (11 of 258) in BRCA1 or BRCA2 mutation carriers and first-degree relatives of BRCA1 or BRCA2 mutation carriers versus 5.9% (seven of 119) in women enrolled because of strong family history; and 5.3% (nine of 169) in women with previous personal breast and/or ovarian cancer versus 4.3% (nine of 208) in those without. In six (33%) of 18 patients, cancer was detected only with MR imaging. Sensitivity was as follows: CBE, 50% (95% confidence interval [CI]: 29%, 71%); mammography, 59% (95% CI: 36%, 78%); US, 65% (95% CI: 41%, 83%); and MR imaging, 94% (95% CI: 82%, 99%). Positive predictive value was as follows: CBE, 82% (95% CI: 52%, 95%); mammography, 77% (95% CI: 50%, 92%); US, 65% (95% CI: 41%, 83%); and MR imaging, 63% (95% CI: 43%, 79%).

Conclusion: Addition of MR imaging to the screening regimen for high-risk women may enable detection of otherwise unsuspected breast cancers.

© RSNA, 2007

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE References

 
The cumulative lifetime risk of breast cancer is greatly different for women with a hereditary predisposition for this disease from that for women in the general population. Although breast cancer affects a range of as many as one in seven to one in 11 women in Western countries (1,2), sporadic disease accounts for about 85%–95% of the occurrences. The remaining 5%–15% of breast cancers are clustered in families with high breast cancer incidence (3–5). For women in the latter group, an inherited predisposition may result in an early onset of the disease (typically in the premenopausal period) and in a lifetime risk greater than 50%–60% (3–7).

About 50% of the occurrences in high-risk families can be explained by the dominant autosomal inheritance of the deleterious BRCA1 or BRCA2 mutations on the 17q21 or the 13q12 chromosomal location, respectively, with incomplete penetrance (6,8,9). BRCA1 mutations are associated with an increased risk of ovarian cancer, whereas BRCA2 mutations may be associated with male breast cancer. Breast cancers in very young women (younger than 35 years) are frequently associated with BRCA1 mutations (10). Moreover, breast cancers in BRCA1 mutation carriers are more frequently high grade and estrogen receptor negative compared with sporadic cancers (11,12), and they are associated with less favorable survival (13,14).

The strategy for surveillance of high-risk women is different from that for surveillance of the general population (eg, annual mammography for women older than 40 years in the United States and biannual mammography for women older than 50 years in many European countries). Screening for high-risk women should begin at a younger age and with no more than a 1-year interval between examinations. As reported in a recent review (15), researchers determined that contrast material–enhanced magnetic resonance (MR) imaging is highly sensitive for identification of breast cancer in a large spectrum of clinical situations. Because of lower values for specificity and positive predictive value (PPV), with contrast-enhanced MR imaging, however, unnecessary breast biopsy has been reported because of false-positive findings (16,17), especially in premenopausal women (18,19) and also in high-risk women (20).

Findings from two retrospective (21,22) and five prospective studies (23–27) indicated that contrast-enhanced MR imaging is useful in the screening of high-risk women. These single- and multicenter studies differed in the number of diagnostic modalities used for comparative evaluation, in enrollment criteria, in selected age groups, and in levels of cumulative lifetime risk of breast cancer. The purpose of our multicenter trial was to prospectively compare the sensitivity of clinical breast examination (CBE), mammography, ultrasonography (US), and contrast-enhanced MR imaging for the screening of women at genetic-familial high risk for breast cancer and to report our interim results, with pathologic findings as the reference standard.

	MATERIALS AND METHODS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE References

 
Study Design and Population
An open prospective nonrandomized multicenter comparative trial was designed (7), and the institutional review board of each center approved the research. Informed written consent was obtained from each subject enrolled in the study. We planned to enroll asymptomatic subjects at high risk for breast cancer, women at least 25 years of age and men at least 50 years of age, who were (a) carriers of BRCA1 or BRCA2 mutations, as demonstrated with genetic testing, or subjects with personal unknown mutational status but who were first-degree relatives of BRCA1 or BRCA2 mutation carriers or (b) subjects with a strong family history of breast or ovarian cancer who had three or more events of breast or ovarian cancer in first- or second-degree relatives in either the maternal or the paternal line. These three or more events could have included female breast cancer in relatives younger than 60 years, ovarian cancer in relatives at any age, or male breast cancer in relatives at any age.

The occurrence of previous breast cancer and/or ovarian cancer in the subject to be enrolled could contribute to the number of events needed to meet the second criterion defined previously. A multifocal unilateral cancer was regarded as one event. A multicentric unilateral cancer was regarded as two events. An ipsilateral metachronous breast cancer was regarded as a new event if it was located at least at 5 cm from the previous cancer. Bilateral synchronous breast cancers were regarded as two different events.

Subjects with a history of personal breast cancer were included (28), provided that at least one breast was not completely excised. Exclusion criteria were pregnancy, breast-feeding, current chemotherapy, terminal illness, and contraindications to MR imaging. History of surveillance imaging prior to entry into the study was not specifically recorded. For each enrolled patient, we planned two annual rounds of assessment with CBE, mammography, US, and contrast-enhanced MR imaging and at least a 1-year follow-up with CBE, mammography, and US. At each screening event, each of these tests was performed by an independent physician who was unaware of the results obtained by the other three colleagues.

Centers were asked to plan the independent examinations for each screening event in the same day for as many enrolled subjects as possible. When we considered the need for planning contrast-enhanced MR imaging during the 2nd week of the menstrual cycle in premenopausal women and logistic problems (eg, different locations for mammography, US, and MR imaging facilities; members of the same family preferred to have the examination on the same day), a maximum time of 1 month for performance of the four diagnostic modalities was allowed. In some instances, justified by particular conditions, the central unit accepted a maximum delay of 2 months.

A national health institution (Istituto Superiore di Sanità, Rome, Italy) was responsible for multicenter project design, central coordination, and data management and funding (central unit). This institution was not directly involved in the enrollment or in the performance of genetic testing, CBE, mammography, breast US, and contrast-enhanced MR imaging. Seventeen centers in 14 Italian towns participated. The first center was activated in June 2000, and the 17th center was activated in November 2003; four institutes for cancer research and treatment, 12 university hospitals, and one general hospital were included. Quality assessment programs were regularly performed in the radiology departments of these institutions. At each center, examinations were performed, and findings from the examinations were interpreted with the supervision of a radiologist who had at least 10 years of experience in breast imaging; moreover, other physicians were involved in the trial at each center, and the centers and names of those involved appear at the end of this article.

During the first phase of the study (from June 2000 to December 2002), the enrollment was limited to the first criterion described before; preliminary results for this phase, which pertained to the first eight patients in whom breast cancer was detected, were reported during an international workshop in early 2002 (7). In January 2003, enrollment on the basis of the second criterion was also opened. The general plan of the trial was aimed at enrolling approximately 500 subjects in about 6 years, with about 50% fulfilling the first criterion and about 50% fulfilling the second criterion. For each of the three diagnostic imaging modalities (mammography, US, and contrast-enhanced MR imaging), performed in nonrandomized order, the results of local prospective independent readings are included in the data presented here. Each reader was aware of the high-risk condition of the women but was blinded to the results of the other three diagnostic modalities. During the second round, the readers were aware of the results from the first annual round.

Genetic Testing
Genetic testing for identification of deleterious BRCA1 and BRCA2 mutations included the use of individual or combined procedures, such as direct sequencing (29–31), protein truncation testing (29), single-strand conformation polymorphism (32), or mutation screening with denaturing chromatography (33).

Clinical Breast Examination
Thirty-nine physicians performed CBE in the 17 centers. Findings of each examination were coded as normal, suggestive of benign disease, indeterminate, suspicious for malignant disease, or highly suggestive of malignant disease. Palpable nodules that were judged as benign or indeterminate but were clearly benign at mammography and/or US (eg, cysts, calcified fibroadenomas) were not considered in the current report. In the present analysis, for each patient who had cancer during the trial, the cancer was considered palpable if at least one of the pathologically demonstrated malignant foci was coded at CBE as indeterminate, suspicious for malignant disease, or highly suggestive of malignant disease. Clinical findings were marked on a diagram and correlated with imaging findings after reporting.

Mammographic Examination
Bilateral two-view mammography (unilateral in women who previously had undergone one-breast mastectomy) was performed with screen-film units with a rotating anode, a 0.3–0.1-mm focus, a focus-film distance of 55 cm or greater, homogeneous breast compression, a mobile grid, and automatic exposure control. Dedicated daylight processing was performed. Standard mediolateral oblique and craniocaudal projections were acquired. Further dedicated mammograms (ie, magnification, spot compression, or other additional views) were obtained when necessary.

When an enrolled subject underwent a previous mammographic examination performed within the 2 months preceding enrollment, the mammogram from that examination was acquired as part of the study after a quality check; if mammography was performed more than 2 months before the enrollment, the first round of complete multimodality assessment was planned 12 months after the previous mammogram was obtained.

Images from mammographic examinations were evaluated by one reader. Evaluations were performed by radiologists with at least 10 years of experience in breast imaging, and findings were classified by using the five-point scale of the Breast Imaging Reporting and Data System (BI-RADS) (34). Thirty-nine radiologists interpreted the mammograms in the 17 centers. The density pattern was classified according to two categories: breasts with more than 50% of the breast occupied by fibroglandular density as a mean of the two mammographic views and breasts with 50% or less of the breast occupied by fibroglandular density as a mean of the two mammographic views.

US Examination
US examinations were performed by radiologists with at least 10 years of experience in breast imaging. Both breasts were systematically examined by using vertical, horizontal, radial, and antiradial scans obtained by a radiologist who reported the findings of the examination by using the five-point BI-RADS scale (35). Forty-one physicians performed and interpreted the US breast examinations in the 17 centers. Transducers with a frequency of 10 MHz or greater were used in 14 centers, transducers with a frequency of 7.5 MHz or greater were used in two centers, and only a transducer with a frequency of 7.5 MHz was used in one center; transverse resolution of 0.5 mm or less and lateral-transverse resolution of 1 mm or less were used.

Contrast-enhanced MR Imaging
Contrast-enhanced MR imaging was performed at 1.5 T (12 centers) or 1.0 T (four centers), whereas at one center both field strengths were used because of the change of equipment during the trial. The MR units, equipped with actively shielded gradients of 15 mT/m or greater, were purchased from three manufacturers (GE Medical Systems, Milwaukee, Wis; Philips Medical Systems, Best, the Netherlands; or Siemens Medical Solutions, Erlangen, Germany). Dedicated synchronous breast coils were used for bilateral studies (or unilateral studies when a mastectomy previously had been performed) with the patient in the prone position. The examination was planned on the 7th–14th day of the menstrual cycle in premenopausal women but without scheduling limitations in postmenopausal women.

A long venous catheter access was obtained by using a plastic cannula in a cubital vein. After localizing scout views were obtained, a contrast-enhanced dynamic three-dimensional T1-weighted spoiled gradient-echo sequence was performed in the transverse or coronal plane. The parameters were as follows: repetition time, 13 msec or less; flip angle, 20°–30°; partition thickness, 3 mm or smaller; intersection gap, none; number of partitions, 40–128 (to cover both breasts entirely); and acquisition time, not longer than 120 seconds. The echo time was chosen to prevent fat-water signal opposition at 1.0 or 1.5 T (36). The field of view and image matrix were combined to obtain a pixel size of 1.4 x 1.4 mm or less.

An unenhanced sequence was performed before contrast agent injection. Then, 0.1 mmol/kg of one of the commercially available 0.5 mol/L two-compartment gadolinium chelates (gadopentetate dimeglumine, Magnevist, Schering, Berlin, Germany; gadoterate meglumine, Dotarem, Guerbet, Paris, France; gadodiamide, Omniscan, Amersham Health, Oslo, Norway; or gadoteridol, ProHance, Bracco, Milan, Italy) was intravenously administered at the rate of 2 mL/sec by using an automatic injector. Injection was followed by flushing with 20 mL of saline. Taking into account that the central lines of the k-space, mainly devoted to image contrast resolution, were acquired in the central third of the sequence time duration, the contrast agent injection was started at the same time as the first contrast-enhanced sequence was started. The number of contrast-enhanced sequences, typically five with a temporal resolution of 90 seconds, was sufficient to obtain dynamic information during at least the first 6 minutes after contrast agent injection.

Temporal subtraction (enhanced minus unenhanced images) was always performed for the first, second, and last contrast-enhanced sequences, and a maximum intensity projection algorithm was applied for the first and the second contrast-enhanced sequences. Signal intensity–time and percentage of enhancement–time dynamic curves were obtained for targeted small regions of interest positioned on the areas of homogeneous maximal enhancement within the enhancing lesion (37). Source and processed images were electronically stored on compact discs. Twenty-eight radiologists interpreted the contrast-enhanced MR images from breast examinations in the 17 centers.

Morphologic and dynamic parameters were combined according to the criteria first defined by Fischer et al (38) and tested by Baum et al (39) in 1031 breasts. In the study by Baum et al, sensitivity and specificity were both 92%. This eight-level scoring system was modified into a five-point scale according to the BI-RADS (40) classification (Table 1).

For any finding classified as BI-RADS 3 (probably benign) at each imaging modality without a higher classification (ie, BI-RADS 4 or 5) at other diagnostic modalities in the same round, a short-term (within 4 months) follow-up with the same modality with which the lesion was detected was planned. If the finding was confirmed (ie, a lesion with at least a BI-RADS 3 classification and was not reduced in diameter), an imaging-guided biopsy was performed according to the protocol defined previously. When the report for the fine-needle or core biopsy indicated that the lesion was suspicious for malignant disease or highly suggestive of malignancy, the patient always underwent surgery. When the findings in the report for the fine-needle or core biopsy suggested a diagnosis of lobular neoplasia (lobular carcinoma in situ), atypical ductal hyperplasia, radial scar, papilloma, or papillomatosis, the patient underwent surgery, and pathologic examination of the surgical specimen was performed. For all the lesions classified as BI-RADS 4 or 5 at any imaging modality, the patient underwent surgery, and pathologic examination was performed, even though the fine-needle or core biopsy yielded a negative, benign, or probably benign result.

All nonpalpable lesions were preoperatively localized by using a hook wire or a charcoal suspension, with the guidance of the imaging method used for biopsy.

At the 17 centers, 19 pathologists who had 9–35 years of experience with breast pathology classified the pathologic specimens according to the 1981 World Health Organization breast cancer classification (41). The maximal diameter of each malignant lesion was recorded. For invasive malignant lesions, axillary nodal status was explored with axillary dissection or sentinel lymph node biopsy, depending on the preference of each center involved in the study.

Statistical Analysis
Overall detection rate per year was calculated as the ratio between the number of patients with pathologically proved breast cancer and the sum of screening events at the first and the second rounds (278 + 99 = 377). The detection rate for each round was calculated as the ratio between the number of patients with pathologically proved breast cancer at each round and the number of women who underwent screening in the same round. The detection rate per year for subsets of enrolled women was calculated as the ratio between the number of patients who had a pathologically proved breast cancer in the subset of women and the number of screening events in the members of the subset of women in the analysis.

Sensitivity of each of the four modalities was calculated as the ratio between the number of true-positive findings (pathologically proved breast cancer detected by using each modality) and the number of true-positive findings plus false-negative findings (pathologically proved breast cancer examined with the same modality but not correctly diagnosed [ie, BI-RADS categories 1–3]). For each modality, the false-negative findings were defined as breast cancers detected by using one, two, or three of the remaining modalities and confirmed at pathologic examination.

PPV of each of the four modalities was calculated as the ratio between true-positive findings (defined as previously mentioned) and the number of true-positive findings plus false-positive findings (findings that needed to be explored with invasive procedures that defined a benign cytologic or pathologic diagnosis). Invasive procedures included fine-needle aspiration, core-needle biopsy, and surgical biopsy after imaging-guided localization (one patient opted for bilateral prophylactic mastectomy, which revealed a mammographic finding as false-positive).

In the evaluation of multiple malignant foci in the same breast, the total number of malignant foci demonstrated at pathologic examination was used as the standard of reference. The capability of each modality for depiction of multiple malignant foci was evaluated without considering the difference between multifocal and multicentric cancers.

For both sensitivity and PPV, 95% confidence intervals were calculated from the exact binomial distribution.

Differences in the mean age of the enrolled women or patients and in the mean pathologically determined diameter of the tumors were tested by using the two-tailed Mann-Whitney U test. Differences in detection rate, percentage of patients with invasive cancer, and percentage of patients with axillary nodal metastatic involvement were tested by using the ² test or the Fisher exact test, when the former was not applicable—that is, for small samples (fewer than 20 subjects sampled)—or when one or more of the so-called expected values was smaller than five (42). Statistical calculations were performed by using a software package (SPSS, version 6.0; SPSS, Chicago, Ill). A difference with P < .05 was considered significant.

	RESULTS

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE References

 
Screening Population
The present interim analysis is based on the data available in March 2004 at the central data management unit in regard to the first round for the first 278 enrolled subjects and the second round for 99 subjects (ie, the first 99 subjects who underwent assessment in the second round), for a total of 377 screening events. The screening population (Table 2) consisted of 278 women (mean age, 46.0 years ± 12.0 [standard deviation]; range, 25–79 years) enrolled by 17 centers. All 278 women underwent assessment in the first round and, until March 2004, 99 women participated in the second round (35.6%). One hundred seventy-five (63%) of 278 women were enrolled because they were BRCA1 or BRCA2 mutation carriers or because they were first-degree relatives of BRCA1 or BRCA2 mutation carriers, whereas 103 (37%) were enrolled on the basis of family history, according to the criteria stated before; seven of them, all with a previous breast and/or ovarian cancer, had an inconclusive genetic test (BRCAX status).

View larger version (16K): [in this window] [in a new window] [Download PPT slide]   Figure 1: Flow diagram of the multicenter surveillance of women at high risk for breast cancer by using contrast-enhanced MR imaging, mammography, US, and CBE.

The overall maximal pathologically determined mean diameter was 13.3 mm ± 8.2, and eight of 18 patients had tumors 10 mm or smaller in diameter. Fourteen patients had at least one invasive cancer and four patients had only in situ cancers; considering the largest tumor for each patient in both groups, the mean diameter was 15.8 mm ± 7.6 for the invasive cancers and 4.8 mm ± 1.7 for the in situ cancers. Nine (50%) of 18 patients had multifocal, multicentric, or bilateral breast cancers. When we considered the most aggressive lesion in the nine patients with multifocal, multicentric, or bilateral cancers, we observed a percentage of patients with invasive cancers of 78% (14 of 18) (Table 3).

View larger version (52K): [in this window] [in a new window] [Download PPT slide]   Figure 2a: Asymptomatic 52-year-old woman with a strong family history of breast cancer that included a personal previous invasive ductal carcinoma of the right breast at 50 years of age had no suspicious finding at CBE. (a) Mediolateral oblique, (b) craniocaudal, and (c) magnified craniocaudal mammographic views of the right breast show a suspicious opacity with irregular borders associated with microcalcifications in central location (arrow on a and b). Less than 50% of the breast was occupied by fibroglandular density. Microcalcifications were confirmed with magnified spot compression (arrow on c). At first-look (ie, prospective) US examination (10-MHz probe), not shown, no suspicious findings were detected. (d) Second-look US scan (10-MHz probe) at final assessment showed hypoechoic suspicious mass (arrow) at same location as mammographic finding. (e) Coronal-subtracted (first enhanced minus unenhanced) contrast-enhanced T1-weighted gradient-echo MR image (repetition time msec/echo time msec, 11/4.8; flip angle, 25°; section thickness, 1 mm; matrix, 192 x 384; field of view, 192 x 384 mm) obtained with 0.1 mmol/kg gadoterate meglumine. (f) Percentage of enhancement–time dynamic curve for enhancing focus shown on c. (g) Coronal maximum intensity projection of both breasts shows spiculated enhancing focus in central location (arrow on e) associated with a strong initial enhancement with postinitial washout, visible on f. On the maximum intensity projection, the central lesion is well depicted (white arrow), whereas a second smaller enhancing focus 3 cm below (open arrow) is visible (percentage of enhancement–time dynamic curve with an initial enhancement greater than 100% and postinitial washout not shown) but was not detected at mammography and US. Note the prominent vascular supply of both lesions (arrowheads on g). Pathologic findings at mastectomy revealed bifocal invasive ductal carcinoma of 10 mm in diameter for one lesion (white arrow) and of 6 mm in diameter for the other (open arrow) of both lesions. At mammography, two other small masses were observed in both projections (a, b). They were known benign nodules that were unchanged in comparison with previous mammograms.

View larger version (60K): [in this window] [in a new window] [Download PPT slide]   Figure 2b: Asymptomatic 52-year-old woman with a strong family history of breast cancer that included a personal previous invasive ductal carcinoma of the right breast at 50 years of age had no suspicious finding at CBE. (a) Mediolateral oblique, (b) craniocaudal, and (c) magnified craniocaudal mammographic views of the right breast show a suspicious opacity with irregular borders associated with microcalcifications in central location (arrow on a and b). Less than 50% of the breast was occupied by fibroglandular density. Microcalcifications were confirmed with magnified spot compression (arrow on c). At first-look (ie, prospective) US examination (10-MHz probe), not shown, no suspicious findings were detected. (d) Second-look US scan (10-MHz probe) at final assessment showed hypoechoic suspicious mass (arrow) at same location as mammographic finding. (e) Coronal-subtracted (first enhanced minus unenhanced) contrast-enhanced T1-weighted gradient-echo MR image (repetition time msec/echo time msec, 11/4.8; flip angle, 25°; section thickness, 1 mm; matrix, 192 x 384; field of view, 192 x 384 mm) obtained with 0.1 mmol/kg gadoterate meglumine. (f) Percentage of enhancement–time dynamic curve for enhancing focus shown on c. (g) Coronal maximum intensity projection of both breasts shows spiculated enhancing focus in central location (arrow on e) associated with a strong initial enhancement with postinitial washout, visible on f. On the maximum intensity projection, the central lesion is well depicted (white arrow), whereas a second smaller enhancing focus 3 cm below (open arrow) is visible (percentage of enhancement–time dynamic curve with an initial enhancement greater than 100% and postinitial washout not shown) but was not detected at mammography and US. Note the prominent vascular supply of both lesions (arrowheads on g). Pathologic findings at mastectomy revealed bifocal invasive ductal carcinoma of 10 mm in diameter for one lesion (white arrow) and of 6 mm in diameter for the other (open arrow) of both lesions. At mammography, two other small masses were observed in both projections (a, b). They were known benign nodules that were unchanged in comparison with previous mammograms.

View larger version (106K): [in this window] [in a new window] [Download PPT slide]   Figure 2c: Asymptomatic 52-year-old woman with a strong family history of breast cancer that included a personal previous invasive ductal carcinoma of the right breast at 50 years of age had no suspicious finding at CBE. (a) Mediolateral oblique, (b) craniocaudal, and (c) magnified craniocaudal mammographic views of the right breast show a suspicious opacity with irregular borders associated with microcalcifications in central location (arrow on a and b). Less than 50% of the breast was occupied by fibroglandular density. Microcalcifications were confirmed with magnified spot compression (arrow on c). At first-look (ie, prospective) US examination (10-MHz probe), not shown, no suspicious findings were detected. (d) Second-look US scan (10-MHz probe) at final assessment showed hypoechoic suspicious mass (arrow) at same location as mammographic finding. (e) Coronal-subtracted (first enhanced minus unenhanced) contrast-enhanced T1-weighted gradient-echo MR image (repetition time msec/echo time msec, 11/4.8; flip angle, 25°; section thickness, 1 mm; matrix, 192 x 384; field of view, 192 x 384 mm) obtained with 0.1 mmol/kg gadoterate meglumine. (f) Percentage of enhancement–time dynamic curve for enhancing focus shown on c. (g) Coronal maximum intensity projection of both breasts shows spiculated enhancing focus in central location (arrow on e) associated with a strong initial enhancement with postinitial washout, visible on f. On the maximum intensity projection, the central lesion is well depicted (white arrow), whereas a second smaller enhancing focus 3 cm below (open arrow) is visible (percentage of enhancement–time dynamic curve with an initial enhancement greater than 100% and postinitial washout not shown) but was not detected at mammography and US. Note the prominent vascular supply of both lesions (arrowheads on g). Pathologic findings at mastectomy revealed bifocal invasive ductal carcinoma of 10 mm in diameter for one lesion (white arrow) and of 6 mm in diameter for the other (open arrow) of both lesions. At mammography, two other small masses were observed in both projections (a, b). They were known benign nodules that were unchanged in comparison with previous mammograms.

View larger version (118K): [in this window] [in a new window] [Download PPT slide]   Figure 2d: Asymptomatic 52-year-old woman with a strong family history of breast cancer that included a personal previous invasive ductal carcinoma of the right breast at 50 years of age had no suspicious finding at CBE. (a) Mediolateral oblique, (b) craniocaudal, and (c) magnified craniocaudal mammographic views of the right breast show a suspicious opacity with irregular borders associated with microcalcifications in central location (arrow on a and b). Less than 50% of the breast was occupied by fibroglandular density. Microcalcifications were confirmed with magnified spot compression (arrow on c). At first-look (ie, prospective) US examination (10-MHz probe), not shown, no suspicious findings were detected. (d) Second-look US scan (10-MHz probe) at final assessment showed hypoechoic suspicious mass (arrow) at same location as mammographic finding. (e) Coronal-subtracted (first enhanced minus unenhanced) contrast-enhanced T1-weighted gradient-echo MR image (repetition time msec/echo time msec, 11/4.8; flip angle, 25°; section thickness, 1 mm; matrix, 192 x 384; field of view, 192 x 384 mm) obtained with 0.1 mmol/kg gadoterate meglumine. (f) Percentage of enhancement–time dynamic curve for enhancing focus shown on c. (g) Coronal maximum intensity projection of both breasts shows spiculated enhancing focus in central location (arrow on e) associated with a strong initial enhancement with postinitial washout, visible on f. On the maximum intensity projection, the central lesion is well depicted (white arrow), whereas a second smaller enhancing focus 3 cm below (open arrow) is visible (percentage of enhancement–time dynamic curve with an initial enhancement greater than 100% and postinitial washout not shown) but was not detected at mammography and US. Note the prominent vascular supply of both lesions (arrowheads on g). Pathologic findings at mastectomy revealed bifocal invasive ductal carcinoma of 10 mm in diameter for one lesion (white arrow) and of 6 mm in diameter for the other (open arrow) of both lesions. At mammography, two other small masses were observed in both projections (a, b). They were known benign nodules that were unchanged in comparison with previous mammograms.

View larger version (126K): [in this window] [in a new window] [Download PPT slide]   Figure 2e: Asymptomatic 52-year-old woman with a strong family history of breast cancer that included a personal previous invasive ductal carcinoma of the right breast at 50 years of age had no suspicious finding at CBE. (a) Mediolateral oblique, (b) craniocaudal, and (c) magnified craniocaudal mammographic views of the right breast show a suspicious opacity with irregular borders associated with microcalcifications in central location (arrow on a and b). Less than 50% of the breast was occupied by fibroglandular density. Microcalcifications were confirmed with magnified spot compression (arrow on c). At first-look (ie, prospective) US examination (10-MHz probe), not shown, no suspicious findings were detected. (d) Second-look US scan (10-MHz probe) at final assessment showed hypoechoic suspicious mass (arrow) at same location as mammographic finding. (e) Coronal-subtracted (first enhanced minus unenhanced) contrast-enhanced T1-weighted gradient-echo MR image (repetition time msec/echo time msec, 11/4.8; flip angle, 25°; section thickness, 1 mm; matrix, 192 x 384; field of view, 192 x 384 mm) obtained with 0.1 mmol/kg gadoterate meglumine. (f) Percentage of enhancement–time dynamic curve for enhancing focus shown on c. (g) Coronal maximum intensity projection of both breasts shows spiculated enhancing focus in central location (arrow on e) associated with a strong initial enhancement with postinitial washout, visible on f. On the maximum intensity projection, the central lesion is well depicted (white arrow), whereas a second smaller enhancing focus 3 cm below (open arrow) is visible (percentage of enhancement–time dynamic curve with an initial enhancement greater than 100% and postinitial washout not shown) but was not detected at mammography and US. Note the prominent vascular supply of both lesions (arrowheads on g). Pathologic findings at mastectomy revealed bifocal invasive ductal carcinoma of 10 mm in diameter for one lesion (white arrow) and of 6 mm in diameter for the other (open arrow) of both lesions. At mammography, two other small masses were observed in both projections (a, b). They were known benign nodules that were unchanged in comparison with previous mammograms.

View larger version (11K): [in this window] [in a new window] [Download PPT slide]   Figure 2f: Asymptomatic 52-year-old woman with a strong family history of breast cancer that included a personal previous invasive ductal carcinoma of the right breast at 50 years of age had no suspicious finding at CBE. (a) Mediolateral oblique, (b) craniocaudal, and (c) magnified craniocaudal mammographic views of the right breast show a suspicious opacity with irregular borders associated with microcalcifications in central location (arrow on a and b). Less than 50% of the breast was occupied by fibroglandular density. Microcalcifications were confirmed with magnified spot compression (arrow on c). At first-look (ie, prospective) US examination (10-MHz probe), not shown, no suspicious findings were detected. (d) Second-look US scan (10-MHz probe) at final assessment showed hypoechoic suspicious mass (arrow) at same location as mammographic finding. (e) Coronal-subtracted (first enhanced minus unenhanced) contrast-enhanced T1-weighted gradient-echo MR image (repetition time msec/echo time msec, 11/4.8; flip angle, 25°; section thickness, 1 mm; matrix, 192 x 384; field of view, 192 x 384 mm) obtained with 0.1 mmol/kg gadoterate meglumine. (f) Percentage of enhancement–time dynamic curve for enhancing focus shown on c. (g) Coronal maximum intensity projection of both breasts shows spiculated enhancing focus in central location (arrow on e) associated with a strong initial enhancement with postinitial washout, visible on f. On the maximum intensity projection, the central lesion is well depicted (white arrow), whereas a second smaller enhancing focus 3 cm below (open arrow) is visible (percentage of enhancement–time dynamic curve with an initial enhancement greater than 100% and postinitial washout not shown) but was not detected at mammography and US. Note the prominent vascular supply of both lesions (arrowheads on g). Pathologic findings at mastectomy revealed bifocal invasive ductal carcinoma of 10 mm in diameter for one lesion (white arrow) and of 6 mm in diameter for the other (open arrow) of both lesions. At mammography, two other small masses were observed in both projections (a, b). They were known benign nodules that were unchanged in comparison with previous mammograms.

View larger version (53K): [in this window] [in a new window] [Download PPT slide]   Figure 2g: Asymptomatic 52-year-old woman with a strong family history of breast cancer that included a personal previous invasive ductal carcinoma of the right breast at 50 years of age had no suspicious finding at CBE. (a) Mediolateral oblique, (b) craniocaudal, and (c) magnified craniocaudal mammographic views of the right breast show a suspicious opacity with irregular borders associated with microcalcifications in central location (arrow on a and b). Less than 50% of the breast was occupied by fibroglandular density. Microcalcifications were confirmed with magnified spot compression (arrow on c). At first-look (ie, prospective) US examination (10-MHz probe), not shown, no suspicious findings were detected. (d) Second-look US scan (10-MHz probe) at final assessment showed hypoechoic suspicious mass (arrow) at same location as mammographic finding. (e) Coronal-subtracted (first enhanced minus unenhanced) contrast-enhanced T1-weighted gradient-echo MR image (repetition time msec/echo time msec, 11/4.8; flip angle, 25°; section thickness, 1 mm; matrix, 192 x 384; field of view, 192 x 384 mm) obtained with 0.1 mmol/kg gadoterate meglumine. (f) Percentage of enhancement–time dynamic curve for enhancing focus shown on c. (g) Coronal maximum intensity projection of both breasts shows spiculated enhancing focus in central location (arrow on e) associated with a strong initial enhancement with postinitial washout, visible on f. On the maximum intensity projection, the central lesion is well depicted (white arrow), whereas a second smaller enhancing focus 3 cm below (open arrow) is visible (percentage of enhancement–time dynamic curve with an initial enhancement greater than 100% and postinitial washout not shown) but was not detected at mammography and US. Note the prominent vascular supply of both lesions (arrowheads on g). Pathologic findings at mastectomy revealed bifocal invasive ductal carcinoma of 10 mm in diameter for one lesion (white arrow) and of 6 mm in diameter for the other (open arrow) of both lesions. At mammography, two other small masses were observed in both projections (a, b). They were known benign nodules that were unchanged in comparison with previous mammograms.

View larger version (78K): [in this window] [in a new window] [Download PPT slide]   Figure 3a: Asymptomatic 69-year-old BRCA1 carrier with previous left mastectomy for invasive ductal carcinoma at 55 years old had no suspicious finding at CBE of right breast. (a) Mediolateral and (b) craniocaudal mammographic views of right breast without any detected suspicious abnormality; less than 50% of breast was occupied by fibroglandular density. No suspicious finding was detected at US (not shown). (c) Transverse and (d) lateral maximum intensity projections of subtracted (first enhanced minus unenhanced) coronal T1-weighted gradient-echo contrast-enhanced MR images (8.9/4.3, 25° flip angle) after administration of 0.1 mmol/kg gadopentetate dimeglumine. Two small enhancing suspicious foci (solid arrows on c and d) are visible on the lateral quadrants of the right breast. (e) Transverse fast spin-echo MR imaging–guided (204/20, 90° flip angle) biopsy of one of the two foci confirmed presence of a malignant lesion. Arrow shows the amagnetic needle, with the tip at the site of the enhancing focus. Pathologic examination of the breast after mastectomy demonstrated multiple foci of ductal carcinoma in situ (maximum diameter, 3 mm); two were located where MR imaging showed enhancing lesions. In the inner posterior part of the breast, the transverse MR subtracted maximum intensity projection image shows enhancement caused by the superimposition of internal mammary vessels (open arrow on c).

View larger version (78K): [in this window] [in a new window] [Download PPT slide]   Figure 3b: Asymptomatic 69-year-old BRCA1 carrier with previous left mastectomy for invasive ductal carcinoma at 55 years old had no suspicious finding at CBE of right breast. (a) Mediolateral and (b) craniocaudal mammographic views of right breast without any detected suspicious abnormality; less than 50% of breast was occupied by fibroglandular density. No suspicious finding was detected at US (not shown). (c) Transverse and (d) lateral maximum intensity projections of subtracted (first enhanced minus unenhanced) coronal T1-weighted gradient-echo contrast-enhanced MR images (8.9/4.3, 25° flip angle) after administration of 0.1 mmol/kg gadopentetate dimeglumine. Two small enhancing suspicious foci (solid arrows on c and d) are visible on the lateral quadrants of the right breast. (e) Transverse fast spin-echo MR imaging–guided (204/20, 90° flip angle) biopsy of one of the two foci confirmed presence of a malignant lesion. Arrow shows the amagnetic needle, with the tip at the site of the enhancing focus. Pathologic examination of the breast after mastectomy demonstrated multiple foci of ductal carcinoma in situ (maximum diameter, 3 mm); two were located where MR imaging showed enhancing lesions. In the inner posterior part of the breast, the transverse MR subtracted maximum intensity projection image shows enhancement caused by the superimposition of internal mammary vessels (open arrow on c).

View larger version (96K): [in this window] [in a new window] [Download PPT slide]   Figure 3c: Asymptomatic 69-year-old BRCA1 carrier with previous left mastectomy for invasive ductal carcinoma at 55 years old had no suspicious finding at CBE of right breast. (a) Mediolateral and (b) craniocaudal mammographic views of right breast without any detected suspicious abnormality; less than 50% of breast was occupied by fibroglandular density. No suspicious finding was detected at US (not shown). (c) Transverse and (d) lateral maximum intensity projections of subtracted (first enhanced minus unenhanced) coronal T1-weighted gradient-echo contrast-enhanced MR images (8.9/4.3, 25° flip angle) after administration of 0.1 mmol/kg gadopentetate dimeglumine. Two small enhancing suspicious foci (solid arrows on c and d) are visible on the lateral quadrants of the right breast. (e) Transverse fast spin-echo MR imaging–guided (204/20, 90° flip angle) biopsy of one of the two foci confirmed presence of a malignant lesion. Arrow shows the amagnetic needle, with the tip at the site of the enhancing focus. Pathologic examination of the breast after mastectomy demonstrated multiple foci of ductal carcinoma in situ (maximum diameter, 3 mm); two were located where MR imaging showed enhancing lesions. In the inner posterior part of the breast, the transverse MR subtracted maximum intensity projection image shows enhancement caused by the superimposition of internal mammary vessels (open arrow on c).

View larger version (85K): [in this window] [in a new window] [Download PPT slide]   Figure 3d: Asymptomatic 69-year-old BRCA1 carrier with previous left mastectomy for invasive ductal carcinoma at 55 years old had no suspicious finding at CBE of right breast. (a) Mediolateral and (b) craniocaudal mammographic views of right breast without any detected suspicious abnormality; less than 50% of breast was occupied by fibroglandular density. No suspicious finding was detected at US (not shown). (c) Transverse and (d) lateral maximum intensity projections of subtracted (first enhanced minus unenhanced) coronal T1-weighted gradient-echo contrast-enhanced MR images (8.9/4.3, 25° flip angle) after administration of 0.1 mmol/kg gadopentetate dimeglumine. Two small enhancing suspicious foci (solid arrows on c and d) are visible on the lateral quadrants of the right breast. (e) Transverse fast spin-echo MR imaging–guided (204/20, 90° flip angle) biopsy of one of the two foci confirmed presence of a malignant lesion. Arrow shows the amagnetic needle, with the tip at the site of the enhancing focus. Pathologic examination of the breast after mastectomy demonstrated multiple foci of ductal carcinoma in situ (maximum diameter, 3 mm); two were located where MR imaging showed enhancing lesions. In the inner posterior part of the breast, the transverse MR subtracted maximum intensity projection image shows enhancement caused by the superimposition of internal mammary vessels (open arrow on c).

View larger version (170K): [in this window] [in a new window] [Download PPT slide]   Figure 3e: Asymptomatic 69-year-old BRCA1 carrier with previous left mastectomy for invasive ductal carcinoma at 55 years old had no suspicious finding at CBE of right breast. (a) Mediolateral and (b) craniocaudal mammographic views of right breast without any detected suspicious abnormality; less than 50% of breast was occupied by fibroglandular density. No suspicious finding was detected at US (not shown). (c) Transverse and (d) lateral maximum intensity projections of subtracted (first enhanced minus unenhanced) coronal T1-weighted gradient-echo contrast-enhanced MR images (8.9/4.3, 25° flip angle) after administration of 0.1 mmol/kg gadopentetate dimeglumine. Two small enhancing suspicious foci (solid arrows on c and d) are visible on the lateral quadrants of the right breast. (e) Transverse fast spin-echo MR imaging–guided (204/20, 90° flip angle) biopsy of one of the two foci confirmed presence of a malignant lesion. Arrow shows the amagnetic needle, with the tip at the site of the enhancing focus. Pathologic examination of the breast after mastectomy demonstrated multiple foci of ductal carcinoma in situ (maximum diameter, 3 mm); two were located where MR imaging showed enhancing lesions. In the inner posterior part of the breast, the transverse MR subtracted maximum intensity projection image shows enhancement caused by the superimposition of internal mammary vessels (open arrow on c).

View larger version (112K): [in this window] [in a new window] [Download PPT slide]   Figure 4a: Asymptomatic 56-year-old woman with a strong family history of breast cancer. (a) Craniocaudal mammographic view shows asymmetric opacity (arrow) in left breast (fibroglandular density greater than 50%). (b) US scan shows hypoechoic mass (arrow) of 3 mm in diameter with partly irregular borders. Both mammogram and US scan were judged as suggestive of malignancy. (c, e) Two contrast-enhanced coronal subtracted (first enhanced minus unenhanced) T1-weighted gradient-echo MR images (8/4, 25° flip angle, 2.5-mm section thickness; 128 x 256 matrix; 175 x 350-mm field of view) obtained after administration of 0.1 mmol/kg gadopentetate dimeglumine. Each shows a round enhancing lesion (arrow). (d, f) Percentage of enhancement–time dynamic curves show continuous increase. Both enhancing lesions were judged as benign at MR imaging. Pathologic examination revealed two foci of invasive lobular carcinoma of 3 and 9 mm in diameter.

View larger version (179K): [in this window] [in a new window] [Download PPT slide]   Figure 4b: Asymptomatic 56-year-old woman with a strong family history of breast cancer. (a) Craniocaudal mammographic view shows asymmetric opacity (arrow) in left breast (fibroglandular density greater than 50%). (b) US scan shows hypoechoic mass (arrow) of 3 mm in diameter with partly irregular borders. Both mammogram and US scan were judged as suggestive of malignancy. (c, e) Two contrast-enhanced coronal subtracted (first enhanced minus unenhanced) T1-weighted gradient-echo MR images (8/4, 25° flip angle, 2.5-mm section thickness; 128 x 256 matrix; 175 x 350-mm field of view) obtained after administration of 0.1 mmol/kg gadopentetate dimeglumine. Each shows a round enhancing lesion (arrow). (d, f) Percentage of enhancement–time dynamic curves show continuous increase. Both enhancing lesions were judged as benign at MR imaging. Pathologic examination revealed two foci of invasive lobular carcinoma of 3 and 9 mm in diameter.

View larger version (29K): [in this window] [in a new window] [Download PPT slide]   Figure 4c: Asymptomatic 56-year-old woman with a strong family history of breast cancer. (a) Craniocaudal mammographic view shows asymmetric opacity (arrow) in left breast (fibroglandular density greater than 50%). (b) US scan shows hypoechoic mass (arrow) of 3 mm in diameter with partly irregular borders. Both mammogram and US scan were judged as suggestive of malignancy. (c, e) Two contrast-enhanced coronal subtracted (first enhanced minus unenhanced) T1-weighted gradient-echo MR images (8/4, 25° flip angle, 2.5-mm section thickness; 128 x 256 matrix; 175 x 350-mm field of view) obtained after administration of 0.1 mmol/kg gadopentetate dimeglumine. Each shows a round enhancing lesion (arrow). (d, f) Percentage of enhancement–time dynamic curves show continuous increase. Both enhancing lesions were judged as benign at MR imaging. Pathologic examination revealed two foci of invasive lobular carcinoma of 3 and 9 mm in diameter.

View larger version (17K): [in this window] [in a new window] [Download PPT slide]   Figure 4d: Asymptomatic 56-year-old woman with a strong family history of breast cancer. (a) Craniocaudal mammographic view shows asymmetric opacity (arrow) in left breast (fibroglandular density greater than 50%). (b) US scan shows hypoechoic mass (arrow) of 3 mm in diameter with partly irregular borders. Both mammogram and US scan were judged as suggestive of malignancy. (c, e) Two contrast-enhanced coronal subtracted (first enhanced minus unenhanced) T1-weighted gradient-echo MR images (8/4, 25° flip angle, 2.5-mm section thickness; 128 x 256 matrix; 175 x 350-mm field of view) obtained after administration of 0.1 mmol/kg gadopentetate dimeglumine. Each shows a round enhancing lesion (arrow). (d, f) Percentage of enhancement–time dynamic curves show continuous increase. Both enhancing lesions were judged as benign at MR imaging. Pathologic examination revealed two foci of invasive lobular carcinoma of 3 and 9 mm in diameter.

View larger version (21K): [in this window] [in a new window] [Download PPT slide]   Figure 4e: Asymptomatic 56-year-old woman with a strong family history of breast cancer. (a) Craniocaudal mammographic view shows asymmetric opacity (arrow) in left breast (fibroglandular density greater than 50%). (b) US scan shows hypoechoic mass (arrow) of 3 mm in diameter with partly irregular borders. Both mammogram and US scan were judged as suggestive of malignancy. (c, e) Two contrast-enhanced coronal subtracted (first enhanced minus unenhanced) T1-weighted gradient-echo MR images (8/4, 25° flip angle, 2.5-mm section thickness; 128 x 256 matrix; 175 x 350-mm field of view) obtained after administration of 0.1 mmol/kg gadopentetate dimeglumine. Each shows a round enhancing lesion (arrow). (d, f) Percentage of enhancement–time dynamic curves show continuous increase. Both enhancing lesions were judged as benign at MR imaging. Pathologic examination revealed two foci of invasive lobular carcinoma of 3 and 9 mm in diameter.

View larger version (17K): [in this window] [in a new window] [Download PPT slide]   Figure 4f: Asymptomatic 56-year-old woman with a strong family history of breast cancer. (a) Craniocaudal mammographic view shows asymmetric opacity (arrow) in left breast (fibroglandular density greater than 50%). (b) US scan shows hypoechoic mass (arrow) of 3 mm in diameter with partly irregular borders. Both mammogram and US scan were judged as suggestive of malignancy. (c, e) Two contrast-enhanced coronal subtracted (first enhanced minus unenhanced) T1-weighted gradient-echo MR images (8/4, 25° flip angle, 2.5-mm section thickness; 128 x 256 matrix; 175 x 350-mm field of view) obtained after administration of 0.1 mmol/kg gadopentetate dimeglumine. Each shows a round enhancing lesion (arrow). (d, f) Percentage of enhancement–time dynamic curves show continuous increase. Both enhancing lesions were judged as benign at MR imaging. Pathologic examination revealed two foci of invasive lobular carcinoma of 3 and 9 mm in diameter.

False-Positive Diagnoses and PPVs
A total of 15 invasive procedures were performed in 13 patients without breast cancer who had a mean age of 43.9 years ± 10.3; five of them were enrolled because they were BRCA1 mutation carriers, one was enrolled as a first-degree relative of a BRCA1 mutation carrier, and seven were enrolled because of a strong family history of breast and/or ovarian cancer. Only two of them had a previous personal history of breast cancer. The following 20 false-positive findings led to invasive diagnostic procedures: two at CBE, three at mammography, six at US, and nine at contrast-enhanced MR imaging. Because three invasive diagnostic procedures were determined with a concordant false-positive finding at two modalities and one invasive diagnostic procedure was determined with a concordant false-positive finding at three modalities, 20 false-positive findings led to only 15 invasive diagnostic procedures. These 15 invasive procedures were US-guided fine-needle aspiration or core-needle biopsy (n = 11), US-guided fine-needle aspiration and local excision (n = 2), fine-needle aspiration with mammographic stereotactic guidance (n = 1), and mastectomy (n = 1). The woman who underwent mastectomy decided to undergo bilateral prophylactic mastectomy, which did not reveal any malignant lesions at pathologic examination; thus, one false-positive finding occurred at mammography. Of the 11 US-guided procedures, seven were performed as the result of second-look US findings detected only with contrast-enhanced MR imaging. The cytologic or pathologic benign diagnosis obtained with these 15 invasive procedures included one or two of the following findings: single or multiple fibroadenomas (n = 4), papilloma (n = 2), adenosis or fibroadenosis (n = 2), intraparenchymal lymph node (n = 1), and fibrocystic changes or other benign findings (n = 8). On this basis, we calculated the PPVs (Table 4).

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE References

 
The detection rate for breast cancer in high-risk women (in our study, 4.8%) was more than 10-fold that obtained in the screening of a general female population. The first-screening detection rate recently reported by Caines et al (43) by using mammography in the general female population was 0.37% for women aged 40–49 years and 0.58% for women aged 50–59 years. We believe our high detection rate was caused by not only the high disease prevalence in the population but also the multimodality approach, which included contrast-enhanced MR imaging. In fact, in the trial by Brekelmans et al (44