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Published online before print April 19, 2007, 10.1148/radiol.2433060838
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(Radiology 2007;243:670-680.)
© RSNA, 2007

Breast Imaging

Contrast-enhanced MR Mammography for Evaluation of the Contralateral Breast in Patients with Diagnosed Unilateral Breast Cancer or High-Risk Lesions1

Federica Pediconi, MD, Carlo Catalano, MD, Antonella Roselli, MD, Simona Padula, MD, Fiorella Altomari, MD, Enrica Moriconi, MD, Anna Maria Pronio, MD, Miles A. Kirchin, PhD, and Roberto Passariello, MD

1 From the Departments of Radiological Sciences (F.P., C.C., A.R., S.P., F.A., E.M., R.P.) and Surgery (A.M.P.), University of Rome "La Sapienza," Viale Regina Elena, 324, 00161 Rome, Italy; and Department of Worldwide Medical Affairs, Bracco Imaging, Milan, Italy (M.A.K.). Received May 13, 2006; revision requested July 13; revision received July 24; accepted August 23; final version accepted October 5. Address correspondence to F.P. (e-mail: federica.pediconi{at}uniroma1.it).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 IMPLICATION FOR PATIENT CARE
 References
 
Purpose: To prospectively evaluate accuracy of gadobenate dimeglumine–enhanced magnetic resonance (MR) mammography for depiction of synchronous contralateral breast cancer in patients with newly diagnosed unilateral breast cancer or high-risk lesions, with histologic analysis or follow-up as reference.

Materials and Methods: The study had ethics committee approval; all patients provided written informed consent. One hundred eighteen consecutive women (mean age, 52 years) with unilateral breast cancer or high-risk lesions and negative findings in the contralateral breast at physical examination, ultrasonography, and conventional mammography underwent gadobenate dimeglumine–enhanced 1.5-T MR mammography. Transverse three-dimensional T1-weighted gradient-echo images were acquired before and at 0, 2, 4, 6, and 8 minutes after gadobenate dimeglumine administration (0.1 mmol per kilogram body weight). Breast Imaging Reporting and Data System (BI-RADS) was used to categorize breast density and the level of suspicion for malignant contralateral breast lesions. Results were compared with histologic findings. Sensitivity, specificity, accuracy, and positive and negative predictive values for contrast-enhanced MR mammography were evaluated.

Results: Contrast-enhanced MR mammography revealed contralateral lesions in 28 (24%) of 118 patients. Twenty-four lesions were detected in patients with dense breasts (BI-RADS breast density category III or IV). Lesions in eight (29%) of 28 patients were BI-RADS category 4; patients underwent biopsy. Lesions in 20 (71%) patients were BI-RADS category 5; patients underwent surgery. At histologic analysis, 22 lesions were confirmed as malignant; six lesions were fibroadenomas. No false-negative lesions were detected; none of the fibroadenomas were BI-RADS category 5. The sensitivity, specificity, accuracy, and positive and negative predictive values of contrast-enhanced MR mammography for depiction of malignant or high-risk contralateral lesions were 100%, 94%, 95%, 79%, and 100%, respectively. Follow-up findings (12–24 months) confirmed absence of contralateral lesions in 90 of 118 patients with negative contrast-enhanced MR mammographic findings in the contralateral breast.

Conclusion: Contrast-enhanced MR mammography is accurate for detection of synchronous contralateral cancer or high-risk lesions in patients with newly diagnosed breast cancer or high-risk lesions.

© RSNA, 2007


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 IMPLICATION FOR PATIENT CARE
 References
 
Women with a previous diagnosis of breast cancer are up to five times more likely to develop a second tumor in the contralateral breast than are women in the general population (1–3). Notably, up to 16% of metachronous contralateral cancers have been reported to metastasize, whereas 7% have proved fatal (4,5). Because of increased awareness of the higher risk, early detection of contralateral breast cancer is an important issue (6).

At the present time, conventional mammography, ultrasonography (US), and physical examination are the most widely employed noninvasive screening methods for the detection of contralateral cancer and are invariably an integral part of routine follow-up examinations. However, these techniques may have limited sensitivity and specificity for the detection and diagnosis of breast lesions, particularly in patients with dense breast parenchyma (7–16). In screening studies of the contralateral breast, the reported lesion detection rates range from 1%–3% for conventional mammography, 2%–3% for US, and 0.2%–1.0% for physical examination (17–19).

Contrast material–enhanced magnetic resonance (MR) mammography is increasingly considered an important imaging modality for the evaluation of breast cancer and a valuable complement to conventional methods for the detection of disease (7–12,15,16,18–23). Although investigators in numerous studies have confirmed the increased sensitivity of contrast-enhanced MR mammography compared with conventional methods for the detection of breast cancer (7–12,15), only those in a few studies have addressed the potential utility of this approach for evaluation of the contralateral breast (5,18,21,22,24). In these studies, the researchers used a conventional gadolinium-based contrast agent (gadopentetate dimeglumine [5,18,21,22]) or gadodiamide [24]) for contrast-enhanced MR mammography.

Recently, the sensitivity for detection of breast lesions, as well as the accuracy for identification of malignant breast lesions, at contrast-enhanced MR mammography has been shown to be significantly superior after administration of gadobenate dimeglumine rather than after administration of gadopentetate dimeglumine in a population of patients who were suspected of having a malignancy on the basis of conventional mammography and breast US (25). It is possible that contrast-enhanced MR mammography of the contralateral breast would benefit from the improved sensitivity for malignant lesion detection that is achievable with gadobenate dimeglumine. Thus, the purpose of our study was to prospectively evaluate the accuracy of gadobenate dimeglumine–enhanced MR mammography for the depiction of synchronous contralateral breast cancer in patients with a newly diagnosed unilateral breast cancer or high-risk lesion, with histologic analysis or follow-up as the reference standard.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 IMPLICATION FOR PATIENT CARE
 References
 
The study was approved by the ethics committee at our institution, and all patients provided written informed consent to participate in the study. The study was performed independently of any type of industry support (provision of contrast agents, equipment, financial support), and authors (F.P., C.C., A.R., S.P., F.A., E.M., A.M.P. and R.P.) had full control of all data and information submitted for publication. One author (M.A.K.), an employee of Bracco Imaging, Milan, Italy, played no part in patient enrollment or examination and had no control of the data and information submitted for publication.

Patients and Reference Standards
One hundred eighteen consecutive women (mean age, 52 years; range, 35–78 years) met our study criteria and had unilateral breast cancer or a high-risk lesion that was confirmed by means of cytologic or histologic analysis and apparent negative findings in the contralateral breast at physical examination, conventional mammography, and high-frequency-transducer US. These women were evaluated with bilateral contrast-enhanced MR mammography at our institution between October 2002 and January 2005. None of the patients had undergone chemotherapy or had received any other contrast material in the week prior to the contrast-enhanced MR mammographic study. Patients who were claustrophobic, required the use of a pacemaker, or had metallic implants were excluded from the study. Premenopausal patients were examined between the 2nd and 3rd weeks of their menstrual cycle, and those receiving hormone replacement therapy were examined 1 month after discontinuation of treatment (26,27).

The interval between conventional mammography and contrast-enhanced MR mammography ranged between 15 days and 1 month (mean, 21 days). Surgery or biopsy, with histologic evaluation of pathologic specimens, was performed in all patients from 24 hours to 1 month (mean, 12 days) after completion of the contrast-enhanced MR mammographic examination not only for the primary unilateral lesion but also for any contralateral breast lesions subsequently detected at contrast-enhanced MR mammography, as discussed later. Pathologic specimens (reference standard) were obtained from core biopsy, surgical biopsy, lumpectomy, or mastectomy. Core biopsy, as well as needle localization for lumpectomy and surgical biopsy, was performed by two interventional radiologists (F.P., with 5 years of experience as of 2001, and A.R., with 4 years of experience as of 2002) with imaging guidance (conventional mammography, US, or MR imaging) to better visualize the lesion.

Follow-up (reference standard) of women with contralateral breasts with negative findings at contrast-enhanced MR mammography was performed by using routine conventional mammography, high-frequency-transducer US, or contrast-enhanced MR mammography after an interval of 12–24 months, depending on the age of the patient. Typically, follow-up of younger patients (age range, 30–50 years) was performed after approximately 12–18 months, whereas follow-up of older patients (age, >50 years) was performed after approximately 18–24 months.

For the purpose of the study, primary unilateral lesions subsequently confirmed at core biopsy to be lobular carcinoma in situ (LCIS), atypical lobular hyperplasia, or lymphoma were classified as malignant. These lesions are considered high-risk lesions because the diagnosis of frank carcinoma may be underestimated unless open biopsy is pursued (28–30).

MR Mammography
All contrast-enhanced MR mammographic examinations were performed with a 1.5-T magnet (Vision Plus; Siemens, Erlangen, Germany) by using a bilateral breast surface coil. Patients were placed in the prone position on the table. A transverse three-dimensional T1-weighted gradient-echo (GRE) dynamic sequence was performed before the administration of contrast agent, followed by repeat performance of this same sequence at 0, 2, 4, 6, and 8 minutes after the administration of contrast agent. The precontrast and postcontrast three-dimensional T1-weighted GRE dynamic MR images were acquired with repetition time msec/echo time msec, 8.1/4; flip angle, 30°; matrix, 512 x 396 pixels; field of view, 340 x 175 mm; and section thickness, 3 mm, with no intersection gap. The total acquisition time for the three-dimensional T1-weighted GRE dynamic sequence was 120 seconds. An additional T2-weighted short inversion time inversion-recovery sequence was performed before administration of contrast material with 9128/60; flip angle, 30°; matrix, 242 x 256 pixels; field of view, 400 mm; and section thickness, 3 mm. The acquisition time for the T2-weighted short inversion time inversion-recovery sequence was 200 seconds.

Postcontrast three-dimensional T1-weighted GRE dynamic MR images were acquired after administration of 0.1 mmol per kilogram body weight of gadobenate dimeglumine (MultiHance; Bracco Imaging) through an 18-gauge cannula positioned in an antecubital vein. Gadobenate dimeglumine was administered by using an automatic injector (Spectris; Medrad, Indianola, Pa) at a rate of 2 mL/sec and was followed by administration of 10 mL of saline at the same rate.

Image Evaluation
MR images were interpreted by two breast imaging specialists in consensus (F.P. and S.P., with 6 and 5 years of experience in breast MR imaging, respectively). During the study, images from the examinations were reviewed electronically by using a picture archiving and communication system (LifeWeb; Ferrania Technologies, London, England) that allowed manual windowing and optimization of parameters. Evaluations were performed directly at the system console by using the automated software available. Images from contrast-enhanced MR mammographic examinations were interpreted with knowledge of clinical history and were compared with findings from conventional mammography and high-frequency-transducer US, as is done in routine clinical practice.

Mammograms were reviewed retrospectively at the time of the contrast-enhanced MR mammographic interpretation to determine breast density according to the four-point scale from I to IV of the Breast Imaging Reporting and Data System (BI-RADS) classification (31). The MR imaging level of suspicion for the presence of malignant lesions was assigned a score from 0 to 5 by using the BI-RADS scale for suspicion of malignancy. Assessment of MR images was based on lesion morphologic characteristics and postcontrast enhancement patterns. Source images, subtracted images (postcontrast images minus precontrast images), and maximum intensity projection reconstructions were evaluated. Lesion enhancement patterns were determined on the basis of signal intensity–time curves obtained at up to three regions of interest placed on enhancing regions within lesions by the two readers in consensus. The signal intensity–time curves were classified according to shape from type I to III (32–35).

All lesions that were detected with conventional techniques and/or contrast-enhanced MR mammography and were classified as BI-RADS category 4 or 5 were evaluated histologically after biopsy or surgical resection. The size across the largest dimension (in millimeters) of all detected contralateral lesions was recorded.

Statistical Analysis
The sensitivity, specificity, accuracy, and positive and negative predictive values of contrast-enhanced MR mammography for depiction of malignant or high-risk contralateral breast lesions was determined. For these determinations, a breast with true-positive findings was a contralateral breast that was determined to harbor a malignant lesion at contrast-enhanced MR mammography that was confirmed to be malignant at histologic analysis. Conversely, a breast with false-positive findings was a contralateral breast that was determined to harbor a malignant lesion at contrast-enhanced MR mammography that was confirmed to be nonmalignant or benign at histologic analysis. Likewise, a breast with true-negative findings was a contralateral breast that was determined to have negative findings at contrast-enhanced MR mammography and the findings were confirmed to be negative at 12–24-month follow-up. A breast with false-negative findings was a contralateral breast that was determined to have negative findings at contrast-enhanced MR mammography but which was shown to harbor malignant lesions at 12–24-month follow-up.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 IMPLICATION FOR PATIENT CARE
 References
 
Conventional Mammography and High-Frequency-Transducer US
Overall, 169 unilateral primary tumors were detected in the 118 evaluated patients on the basis of combined physical examination, conventional mammography, and high-frequency-transducer US. Ninety-six patients had solitary unilateral lesions at mammography and/or US, 10 had multicentric unilateral lesions (36 lesions overall), and 12 patients had multifocal lesions (37 lesions overall) (Table 1). Histologic confirmation of these primary lesions was obtained in specimens obtained from surgical biopsy in 32 breasts, lumpectomy in 64 breasts, and mastectomy in 22 breasts. At histologic analysis, the primary malignant lesions in 118 evaluated patients comprised 36 (30.5%) IDCs, 27 (22.9%) cases of DCIS, 24 (20.3%) ILCs, and four (3.4%) medullary carcinomas. Additionally, histologic findings confirmed the presence of 17 (14.4%) LCIS lesions, six (5.1%) cases of atypical lobular hyperplasia, and four (3.4%) lymphomas. In none of these 118 patients did conventional mammography or high-frequency-transducer US depict a lesion in the contralateral breast.


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  		Table 1. Distribution of Primary Index Tumors according to Histologic Type among 118 Patients

 
Contrast-enhanced MR Mammography
With contrast-enhanced MR mammography, the presence of the unilateral primary tumors detected by using the conventional methods was confirmed in all 118 patients (Figs 1, 2), and, in addition, solitary contralateral breast lesions were detected in 28 (24%) of these patients (Table 2). The contralateral breast lesions detected at contrast-enhanced MR mammography but not at conventional mammography or high-frequency-transducer US ranged between 4 and 15 mm in size (mean size, 7.3 mm ± 2.3 [standard deviation]) and occurred predominantly (24 of 28 lesions) in patients with dense breasts (BI-RADS breast density category III in 10 patients and BI-RADS breast density category IV in 14 patients) (Fig 3). The four lesions detected at contrast-enhanced MR mammography that were not present in dense breasts (BI-RADS breast density category I in one patient, BI-RADS breast density category II in three patients) were all small lesions that ranged between 5 and 7 mm in size (Fig 4).


Figure 1
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  		Figure 1: Flow diagram depicts patient enrollment, diagnostic examinations performed, and major findings. CE-MRM = contrast-enhanced MR mammography.

 

Figure 2A
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  		Figure 2a: Multifocal ILC in the upper outer quadrant of the right breast and negative findings in contralateral breast at conventional mammography and US in a 54-year-old woman. (a) Craniocaudal and (b) mediolateral conventional mammograms show presence of three parenchymal distortions (arrows) in the upper outer quadrant of the right breast. (c) Transverse maximum intensity projection reconstruction of contrast-enhanced T1-weighted GRE MR image (8.1/4; flip angle, 30°) shows presence of three suspicious lesions (arrows) suggestive of multifocal lesions in the upper outer quadrant of the right breast. No lesions were evident at contrast-enhanced MR mammography of the contralateral left breast. This finding was confirmed at follow-up conventional mammography, US, and contrast-enhanced MR mammography.

 

Figure 2B
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  		Figure 2b: Multifocal ILC in the upper outer quadrant of the right breast and negative findings in contralateral breast at conventional mammography and US in a 54-year-old woman. (a) Craniocaudal and (b) mediolateral conventional mammograms show presence of three parenchymal distortions (arrows) in the upper outer quadrant of the right breast. (c) Transverse maximum intensity projection reconstruction of contrast-enhanced T1-weighted GRE MR image (8.1/4; flip angle, 30°) shows presence of three suspicious lesions (arrows) suggestive of multifocal lesions in the upper outer quadrant of the right breast. No lesions were evident at contrast-enhanced MR mammography of the contralateral left breast. This finding was confirmed at follow-up conventional mammography, US, and contrast-enhanced MR mammography.

 

Figure 2C
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  		Figure 2c: Multifocal ILC in the upper outer quadrant of the right breast and negative findings in contralateral breast at conventional mammography and US in a 54-year-old woman. (a) Craniocaudal and (b) mediolateral conventional mammograms show presence of three parenchymal distortions (arrows) in the upper outer quadrant of the right breast. (c) Transverse maximum intensity projection reconstruction of contrast-enhanced T1-weighted GRE MR image (8.1/4; flip angle, 30°) shows presence of three suspicious lesions (arrows) suggestive of multifocal lesions in the upper outer quadrant of the right breast. No lesions were evident at contrast-enhanced MR mammography of the contralateral left breast. This finding was confirmed at follow-up conventional mammography, US, and contrast-enhanced MR mammography.

 

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  		Table 2. Characteristics of Breasts, Primary Index Tumors, and Contralateral Breast Lesions among 28 Patients with Contralateral Lesions Detected at Contrast-enhanced MR Mammography

 

Figure 3A
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  		Figure 3a: ILC in the lower quadrant of the right breast and a DCIS lesion in the contralateral breast in a 39-year-old woman. (a) Craniocaudal conventional mammogram shows presence of a round high-density mass with indistinct margin (arrow) in the middle of the right breast. (b) Transverse contrast-enhanced T1-weighted GRE subtracted MR image (8.1/4; flip angle, 30°) confirms the presence of a suspicious lobulated lesion (arrow) in the lower outer quadrant of the right breast with a type III signal intensity–time curve. (c) Transverse contrast-enhanced GRE subtracted MR image of the contralateral breast reveals additional suspicious lesion (arrow) with a type III signal intensity–time curve.

 

Figure 3B
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  		Figure 3b: ILC in the lower quadrant of the right breast and a DCIS lesion in the contralateral breast in a 39-year-old woman. (a) Craniocaudal conventional mammogram shows presence of a round high-density mass with indistinct margin (arrow) in the middle of the right breast. (b) Transverse contrast-enhanced T1-weighted GRE subtracted MR image (8.1/4; flip angle, 30°) confirms the presence of a suspicious lobulated lesion (arrow) in the lower outer quadrant of the right breast with a type III signal intensity–time curve. (c) Transverse contrast-enhanced GRE subtracted MR image of the contralateral breast reveals additional suspicious lesion (arrow) with a type III signal intensity–time curve.

 

Figure 3C
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  		Figure 3c: ILC in the lower quadrant of the right breast and a DCIS lesion in the contralateral breast in a 39-year-old woman. (a) Craniocaudal conventional mammogram shows presence of a round high-density mass with indistinct margin (arrow) in the middle of the right breast. (b) Transverse contrast-enhanced T1-weighted GRE subtracted MR image (8.1/4; flip angle, 30°) confirms the presence of a suspicious lobulated lesion (arrow) in the lower outer quadrant of the right breast with a type III signal intensity–time curve. (c) Transverse contrast-enhanced GRE subtracted MR image of the contralateral breast reveals additional suspicious lesion (arrow) with a type III signal intensity–time curve.

 

Figure 4A
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  		Figure 4a: IDC in the left breast and a fibroadenoma in the right breast in a 74-year-old woman. (a) Mediolateral oblique conventional mammogram reveals parenchymal distortion (arrow) in the upper inner quadrant of the left breast. (b, c) Transverse contrast-enhanced T1-weighted GRE subtracted MR images (8.1/4; flip angle, 30°) (b) confirm presence of a lesion (arrow) with suspicious morphologic and enhancement characteristics in the upper inner quadrant of the left breast and (c) show presence of another lesion (arrow) in the contralateral right breast, with homogeneous enhancement and type I signal intensity–time curve suggestive of a benign lesion.

 

Figure 4B
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  		Figure 4b: IDC in the left breast and a fibroadenoma in the right breast in a 74-year-old woman. (a) Mediolateral oblique conventional mammogram reveals parenchymal distortion (arrow) in the upper inner quadrant of the left breast. (b, c) Transverse contrast-enhanced T1-weighted GRE subtracted MR images (8.1/4; flip angle, 30°) (b) confirm presence of a lesion (arrow) with suspicious morphologic and enhancement characteristics in the upper inner quadrant of the left breast and (c) show presence of another lesion (arrow) in the contralateral right breast, with homogeneous enhancement and type I signal intensity–time curve suggestive of a benign lesion.

 

Figure 4C
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  		Figure 4c: IDC in the left breast and a fibroadenoma in the right breast in a 74-year-old woman. (a) Mediolateral oblique conventional mammogram reveals parenchymal distortion (arrow) in the upper inner quadrant of the left breast. (b, c) Transverse contrast-enhanced T1-weighted GRE subtracted MR images (8.1/4; flip angle, 30°) (b) confirm presence of a lesion (arrow) with suspicious morphologic and enhancement characteristics in the upper inner quadrant of the left breast and (c) show presence of another lesion (arrow) in the contralateral right breast, with homogeneous enhancement and type I signal intensity–time curve suggestive of a benign lesion.

 
On the basis of lesion morphologic characteristics and enhancement patterns, contralateral breast lesions in eight (29%) of 28 patients were classified as BI-RADS category 4 for suspicion of malignancy, and these patients underwent core biopsy. Lesions in the remaining 20 (71%) patients were classified as BI-RADS category 5 (highly suggestive of malignancy), and these patients underwent surgery. Subsequent histologic findings confirmed that detected contralateral breast lesions in 22 of 28 patients were malignant or high-risk lesions (10 cases of DCIS, six IDCs, four cases of LCIS, two ILCs) (Figs 3, 5) and that six lesions were fibroadenomas (Fig 4). Each of the six fibroadenomas detected in contralateral breasts was designated as BI-RADS category 4 for suspicion of malignancy. The lesions in contralateral breasts in the remaining two of eight patients that were designated as BI-RADS category 4 comprised one 4-mm LCIS lesion and one 8-mm DCIS lesion.


Figure 5A
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  		Figure 5a: DCIS and a benign nodule (fibroadenolipoma) in the left breast and a DCIS lesion in the contralateral right breast in a 46-year-old woman. (a) Mediolateral oblique conventional mammogram reveals a parenchymal distortion (white arrow) and a benign nodule (black arrow) in the upper outer quadrant of the left breast. Transverse contrast-enhanced T1-weighted GRE subtracted MR images (8.1/4; flip angle, 30°) (b) confirm the presence of the malignant lesion (arrow) in the upper outer quadrant of left breast and (c) reveal the presence of another lesion (arrow) in the contralateral right breast, with morphologic characteristics suggestive of malignancy (DCIS).

 

Figure 5B
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  		Figure 5b: DCIS and a benign nodule (fibroadenolipoma) in the left breast and a DCIS lesion in the contralateral right breast in a 46-year-old woman. (a) Mediolateral oblique conventional mammogram reveals a parenchymal distortion (white arrow) and a benign nodule (black arrow) in the upper outer quadrant of the left breast. Transverse contrast-enhanced T1-weighted GRE subtracted MR images (8.1/4; flip angle, 30°) (b) confirm the presence of the malignant lesion (arrow) in the upper outer quadrant of left breast and (c) reveal the presence of another lesion (arrow) in the contralateral right breast, with morphologic characteristics suggestive of malignancy (DCIS).

 

Figure 5C
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  		Figure 5c: DCIS and a benign nodule (fibroadenolipoma) in the left breast and a DCIS lesion in the contralateral right breast in a 46-year-old woman. (a) Mediolateral oblique conventional mammogram reveals a parenchymal distortion (white arrow) and a benign nodule (black arrow) in the upper outer quadrant of the left breast. Transverse contrast-enhanced T1-weighted GRE subtracted MR images (8.1/4; flip angle, 30°) (b) confirm the presence of the malignant lesion (arrow) in the upper outer quadrant of left breast and (c) reveal the presence of another lesion (arrow) in the contralateral right breast, with morphologic characteristics suggestive of malignancy (DCIS).

 
Findings at follow-up examinations at 12–24 months confirmed the absence of contralateral breast lesions in the 90 patients with negative findings at contrast-enhanced MR mammography in contralateral breasts. Follow-up (reference standard) for all patients was performed by using routine conventional mammography, high-frequency-transducer US, or contrast-enhanced MR mammography. Follow-up was performed at 12 months in 11 patients (mean age, 42 years), 18 months in 27 patients (mean age, 53 years), and 24 months in 80 patients (mean age, 57 years).

Accuracy for Detection of Malignant Contralateral Breast Lesions
The malignant or high-risk lesions that were found in 22 contralateral breasts and were confirmed as such were considered true-positive findings, whereas the confirmed fibroadenomas that were found in six breasts and were classified as malignant at contrast-enhanced MR mammography were considered false-positive findings. Similarly, the lesions in 90 contralateral breasts that were negative and were confirmed to be so at 12–24-month follow-up were considered true-negative findings. Because none of the breasts with negative findings at contrast-enhanced MR mammography were shown to harbor malignant lesions at 12–24-month follow-up, there were no breasts with false-negative findings.

On the basis of these findings, the sensitivity, specificity, and accuracy for the depiction of malignant or high-risk lesions in contralateral breasts were determined to be 100% (22/[22 + 0]), 94% (90/[90 + 6]), and 95% ([22 + 90]/[22 + 90 + 6 + 0]), respectively (Table 3). Similarly, the positive predictive value and negative predictive value were determined to be 79% (22/[22 + 6]) and 100% (90/[90 + 0]), respectively.


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  		Table 3. Sensitivity, Specificity, Accuracy, and Positive and Negative Predictive Values for Detection of Malignant or High-Risk Contralateral Breast Lesions among 118 Patients

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
IMPLICATION FOR PATIENT CARE
 References
 
During the past decade, findings in numerous reports have confirmed that contrast-enhanced MR mammography offers high sensitivity for the detection of breast cancer (7–11). In addition, it offers pathophysiologic information that cannot be obtained by using conventional imaging methods alone (20,35,36). However, the reported moderate specificity of contrast-enhanced MR mammography for the diagnosis of breast cancer has always been a concern (32–34,37–39). On the other hand, contrast-enhanced MR mammography may be a useful screening procedure in selected women who are at high risk for breast cancer, such as women who have had prior breast cancer, those who have a genetic predisposition or strong family history of breast cancer, or those who have had a prior diagnosis of atypia or LCIS at biopsy (28,29). A further specific application of contrast-enhanced MR mammography may be for screening the contralateral breast in women with a malignancy in one breast that was diagnosed by means of conventional screening mammography or US (5,18).

Findings in our study indicate that 28 (24%) of 118 patients with malignant breast lesions at conventional mammography and/or high-frequency-transducer US also had solitary contralateral breast lesions that were detected only at contrast-enhanced MR mammography. Of these 28 lesions, 22 (18.6% overall) were subsequently confirmed to be malignant after histologic evaluation. Researchers in previous studies have reported contralateral lesion detection rates for contrast-enhanced MR mammography that range from 8.2% (15 of 182 patients) (16) to 32% (72 of 223 patients) (5). The corresponding rates for confirmed contralateral malignant lesions among these populations were 3.8% (seven of 182 patients) and 5% (12 of 223 patients), respectively.

An important advantage of MR imaging compared with conventional techniques (mammography and US) for the detection of breast cancer is that it is applicable in patients with dense breast parenchyma; investigators in several studies have shown that the depiction of lesions in dense breasts is significantly improved with contrast-enhanced MR mammography compared with conventional breast imaging modalities (14–16,40). Our findings concur with the findings of others; 24 of 28 lesions that were not seen at conventional mammography and high-frequency-transducer US were present in breasts that were classified as BI-RADS category III or IV for breast density. Notably, all of the larger (10–15 mm) lesions that were not seen at conventional imaging occurred in dense breasts.

The sensitivity, specificity, and accuracy of contrast-enhanced MR mammography for the depiction of malignant or high-risk contralateral breast lesions among 118 patients with negative findings in contralateral breasts at conventional mammography and US were 100%, 94%, and 95%, respectively. Similarly, the positive predictive value that detected lesions were malignant was 79%, whereas the corresponding negative predictive value that the absence of detected lesions was truly indicative of a negative finding in a contralateral breast was 100%. These values compare favorably with values of 91% (sensitivity), 90% (specificity), 90% (accuracy), 43% (positive predictive value), and 99% (negative predictive value) that were reported by Viehweg et al (22) for a patient cohort of 119 patients.

Of interest is that, whereas Viehweg et al (22) used a double dose (0.2 mmol/kg) of gadopentetate dimeglumine, we used only a single dose of 0.1 mmol/kg of gadobenate dimeglumine. Previously, it has been shown that the enhancement of breast lesions achieved with a single 0.1 mmol/kg dose of gadobenate dimeglumine is superior to that achieved with an equivalent 0.1 mmol/kg dose of gadopentetate dimeglumine (41). More recently, Pediconi et al (25) reported significantly greater sensitivity for breast lesion detection and greater confidence and accuracy for the identification of malignant breast lesions at contrast-enhanced MR mammography with 0.1 mmol/kg gadobenate dimeglumine than at contrast-enhanced MR mammography with an equivalent dose of gadopentetate dimeglumine. Equivalence between a single dose of gadobenate dimeglumine and a double dose of gadopentetate dimeglumine has previously been demonstrated for other MR imaging applications, most notably contrast-enhanced MR angiography (42), and has been ascribed to a twofold greater T1 relaxation rate in blood deriving from weak and transient interactions of the gadobenate dimeglumine contrast-effective moiety of gadobenate dimeglumine with serum albumin (43,44).

In regard to the 28 lesions detected at contrast-enhanced MR mammography in the contralateral breast, all but six were subsequently confirmed to be malignant at histologic analysis. The six lesions that were not revealed to be malignant at histologic analysis were small (5–10 mm) fibroadenomas. Notably, each of these lesions was classified as BI-RADS category 4 for suspicion of malignancy. Conversely, the 22 confirmed malignant lesions comprised 20 lesions that were classified as BI-RADS category 5 and only two that were classified as BI-RADS category 4. Misdiagnosis of fibroadenoma at contrast-enhanced MR mammography on the basis of morphologic characteristics alone is well known (21,37,41,45). This is particularly problematic in the case of small (<10 mm) lesions. Recently, the use of breast vascular mapping has been proposed as a corollary to contrast-enhanced MR mammography to demonstrate the increased vascularity associated with the neoangiogenesis of malignant breast lesions (46,47). Specifically, one-sided increased breast vascularity at contrast-enhanced MR mammography often is an indirect sign of invasive breast cancer that can be used as an additional means to differentiate malignant from nonmalignant breast lesions. Although determination of ipsilateral increased vascularity was not performed in our study, an example of its potential for the differentiation of fibroadenomas from invasive cancer has been reported (48). Future contrast-enhanced MR mammographic screening procedures might usefully incorporate breast vascular mapping into the examination protocol to provide an additional potential means of detecting breast malignancy.

Of the 28 detected contralateral breast lesions, only two (7%) shared the same histologic features as the primary index tumor. Histologic differences between index and contralateral breast lesions have previously been reported for up to 67% of patients (2,5,49), and this finding indicates that such differences are a common feature among patients with contralateral breast cancer.

A limitation of our study is that data were not available about family history or the genetic predisposition to breast cancer of the evaluated patients. As a result, it was not possible to correlate our findings with a potential elevated risk for breast cancer or to compare our findings with findings in studies for which genetic predisposition was known (5,18). On the other hand, the results of our study are encouraging in that all synchronous cancers that were present were detected at contrast-enhanced MR mammography; none of the patients with negative findings in contralateral breasts at contrast-enhanced MR mammography were shown to have contralateral breast lesions at 12–24-month follow-up. Further work is clearly warranted before firm conclusions can be drawn about the potential of contrast-enhanced MR mammography as a breast cancer screening modality. Our study was performed solely in patients scheduled for biopsy or surgical intervention because of highly suspicious unilateral breast lesions detected at conventional mammography and high-frequency-transducer US. Further work might conceivably look more specifically at patients with dense breasts for whom conventional techniques often are inadequate and at patients with a confirmed genetic predisposition to breast cancer or a strong family history of breast cancer.

In summary, our study findings indicate that contrast-enhanced MR mammography is superior to conventional mammography and high-frequency-transducer US for the depiction of contralateral breast cancer or high-risk lesions in patients with a newly diagnosed unilateral breast cancer or high-risk lesions depicted with conventional techniques.


   IMPLICATION FOR PATIENT CARE
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 IMPLICATION FOR PATIENT CARE
References
 


   FOOTNOTES
 

Abbreviations: BI-RADS = Breast Imaging Reporting and Data System • DCIS = ductal carcinoma in situ • GRE = gradient echo • IDC = infiltrating ductal carcinoma • ILC = infiltrating lobular carcinoma • LCIS = lobular carcinoma in situ

See Materials and Methods for pertinent disclosures.

Author contributions: Guarantors of integrity of entire study, F.P., C.C., M.A.K., R.P.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, all authors; clinical studies, all authors; statistical analysis, all authors; and manuscript editing, all authors


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 IMPLICATION FOR PATIENT CARE
 References
 

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