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Breast Imaging |
1 From the Department of Radiology, Georg-August University of Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany. Received June 17, 1998; revision requested August 13; final revision received March 3, 1999; accepted July 1. Address reprint requests to U.F.
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Abstract |
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 TOP Abstract IntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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MATERIALS AND METHODS: Preoperative contrast-enhanced MR imaging of the breast was performed in 463 patients with probably benign lesions (n = 63), suspicious lesions (n = 230), or lesions highly suggestive of malignancy (n = 170) per established clinical, mammographic, and/or ultrasonographic (US) criteria. T1-weighted fast low-angle shot MR imaging was performed before and after administration of gadopentetate dimeglumine. MR imaging findings were correlated with other imaging results and histopathologic findings. Special attention was paid to multifocality and multicentricity.
RESULTS: Histopathologic analysis revealed 143 benign and 405 malignant lesions. The sensitivity, specificity, and accuracy were 58%, 76%, and 62% for clinical examination; 86%, 32%, and 72% for conventional mammography; 75%, 80%, and 76% for US; and 93%, 65%, and 85% for contrast-enhanced MR imaging. Multifocality in 30 of 42 patients, multicentricity in 24 of 50 patients, and additional contralateral carcinomas in 15 of 19 patients were depicted with MR imaging alone. Due to the MR imaging findings, therapy was changed correctly in 66 patients (14.3%); unnecessary open biopsy was performed in 16 patients (3.5%).
CONCLUSION: Contrast-enhanced MR imaging of the breast is highly sensitive for invasive breast cancer. MR imaging may reveal unsuspected multifocal, multicentric, or contralateral breast carcinoma and result in therapy changes.
Index terms: Breast neoplasms, diagnosis, 00.30 • Breast neoplasms, MR, 00.12143, 00.121416 • Breast neoplasms, staging, 00.30 • Breast neoplasms, US, 00.1298 • Treatment planning
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Introduction |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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The advantage of contrast-enhanced MR imaging of the breast is its high sensitivity for invasive breast cancer. Limitations of breast MR imaging include low sensitivity in the detection of ductal carcinoma in situ (DCIS) (6–8) and low specificity (1,9). The described advantages and disadvantages favor the use of breast MR imaging in women with a high likelihood of occult invasive carcinomas.
In previous studies (10,11), breast MR imaging has been helpful in the differentiation between a scar and a carcinoma after open biopsy or a tumor recurrence after lumpectomy. Contrast-enhanced MR imaging has also been valuable in patients with occult primary breast carcinoma (12).
Options for the surgical treatment of breast carcinoma include breast-conserving surgery and mastectomy. Factors that influence the choice of surgical therapy include tumor size, ratio of tumor size to breast size, tumor location, tumor grade, histologic findings, and patient preference. Psychosocial and cosmetic considerations may also affect therapeutic decisions.
In this study, we evaluated preoperative contrast-enhanced MR imaging in a large group of patients with suspicious breast lesions to define the value of this modality with regard to the detection of multifocal or multicentric lesions and the effect on therapeutic decisions. The goal of the study was to determine if breast MR imaging could be helpful in determining the therapeutic approach in women with breast cancer.
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MATERIALS AND METHODS |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Clinical examination, bilateral axillary examinaton of the lymph nodes, and palpation of the breasts were performed. Pathologic changes in the skin, the areola, and the nipple and palpable masses ranging from hard, nonmovable, or irregular to discrete changes in the consistency of the breast parenchyma or thickening of the skin were evaluated. Irregular, hypoechoic masses with posterior acoustic shadowing were classified as suspicious at US. Mammographic evaluation criteria were based on the Breast Imaging Reporting and Data System (BI-RADS)(13).
When all examinations were concluded, 522 of the patients were considered to have a breast abnormality. Of these 522 patients, 463 (mean age, 54.3 years; age range, 21–89 years) underwent contrast-enhanced MR imaging preoperatively. Three of the remaining 59 patients were excluded from preoperative MR imaging due to inflammatory changes (swelling and reddening) of the entire breast. One of these three patients had mastitis, and two of these three patients had an inflammatory carcinoma.
The other 56 patients had different reasons not to undergo MR imaging preoperatively: Seven patients had a cardiac pacemaker, four patients were too large to fit within the MR system, three patients had claustrophobia, and 11 patients refused the examination; for five patients, the system was out of order for a day to be serviced; for three patients, the MR system was broken; and for 23 patients, there was no adequate examination date (open biopsy was performed on the following day after primary diagnostic testing).
With consideration of the results of clinical examination, mammography, and US, the lesions in the 463 patients were classified: Sixty-three patients had a probably benign abnormality (ie, compatible with adenoma or papilloma), and open biopsy was performed for reasons such as patient preference, cosmetics, or a recommendation from the referring outside radiologist. Of the remaining patients, 230 had suspicious findings, and 170 patients had findings highly suggestive of malignancy.
US examination was performed by using a 7.5-MHz transducer (Computer Sonograph CS 9300; Picker International, Munich, Germany). Conventional mammography was performed by using the Senographe DMR (GE Medical Systems, Milwaukee, Wis).
MR imaging of the breast was performed with a 1.5-T system (Magnetom SP 63 or Magnetom Vision; Siemens, Erlangen, Germany) with a dedicated bilateral breast surface coil. The entire breast was imaged before and five times after intravenous injection of 0.1 mmol gadopentetate dimeglumine (Magnevist; Schering, Berlin, Germany) per kilogram of body weight. A two-dimensional fast low-angle shot (FLASH) pulse sequence was used, with a repetition time of 336 msec and an echo time of 5 msec (336/5) and a flip angle of 90°. This sequence yielded 32 transverse sections of 4-mm section thickness in 1 minute 27 seconds without gaps. The field of view was 320 mm with a matrix of 256 x 256. The postprocessing procedure included the subtraction of the precontrast images from the images of the second measurement procedures after contrast medium injection. In addition, the postprocessing included the demonstration of a transverse maximum intensity projection image on the base of the subtraction images.
The semiquantitative analysis of the signal intensity–to–time relation was performed with the region-of-interest technique. The region of interest (2–5 pixels) was placed (by U.F.) within the tumor area with the highest signal intensity enhancement. The evaluation criterion was the peak percentage of signal intensity increase within the first 3 minutes after contrast material administration relative to the precontrast signal intensity (initial signal intensity increase). The percentage of signal intensity increase is defined as SI Increaselesion = [(SIpost - SIpre)/SIpre] x 100, where SI is signal intensity and "pre" and "post" mean before and after contrast material administration, respectively.
Furthermore, we evaluated the behavior of the signal intensity curve from the 3rd to the 8th minute: A signal intensity increase of more than 10% within this interval relative to the peak enhancement in the first 3 minutes was defined as "continued signal intensity increase." A signal intensity similar to the peak signal intensity was considered as a plateau, and a decrease of more than 10% was defined as a washout (14).
Finally, the morphology of a contrast-enhancing lesion (well defined vs ill defined) and the kinetic aspects of the contrast material enhancement (centrifugal vs centripetal [the ring sign]) were evaluated. In this context, each criterion for diagnosing malignancy was given a score of 0–2 points according to whether there was suspicion for malignancy (2 indicated high suspicion) (Table 1). The total number of points for all criteria was summed. According to this scoring system, lesions with at least 3 points and a size of more than 5 mm were considered to be suspicious for malignancy. The MR images were interpreted (by U.F.) in the presence of the original mammograms and the US images.
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Histopathologic examinations were performed with a thin-slice technique following hematoxylin-eosin staining. Nonproliferative lesions, including cysts, papillary apocrine changes, epithelium-related calcifications, and mild hyperplasia, were defined as grade I dysplasia. Grade II dysplasia was characterized by a moderate or florid hyperplasia, intraductal papillomas, and sclerosing adenosis. Atypical hyperplasia that possessed some of the features of carcinoma in situ was categorized as grade III dysplasia.
The tumor classification (the TNM system) was based on the Union Internationale Contre le Cancer, or UICC, system (19). In this classification, pT1 is defined as an invasive tumor smaller than 2 cm, pT2 is defined as a 2–5-cm tumor, and pT3 is defined as a tumor larger than 5 cm. pT4 is defined as tumor infiltration of the chest wall and/or the breast skin and an inflammatory carcinoma.
In accordance with the TNM system, multifocal and multicentric tumors were classified with consideration of the size of the largest single lesion. Two or more foci of cancer associated with one ductal network were defined as multifocal. Two or more foci in separate lobes or segments (ie, tumor manifestations in different quadrants) were classified as multicentric (20).
The standard surgical approach at our institution was lumpectomy in patients with a unifocal carcinoma smaller than 3 cm. However, patients with multifocality underwent quadrantectomy. Exceptions to this practice were patients with very small breasts. These patients underwent mastectomy even if the tumor was smaller than 3 cm. Most patients with a tumor larger than 3 cm and patients with multicentricity underwent mastectomy. Usually, this surgical approach was not influenced by the patient's age, tumor location, tumor grade, histologic findings, or immunohistologically defined prognostic factors (ie, presence of HER2/NEU, p55, etc). However, the patient's preference was considered in all cases.
Axillary lymph node dissection was performed in all women in whom histopathologic findings revealed an invasive breast carcinoma. Neoadjuvant chemotherapy was given to patients with inflammatory carcinoma of only the breast. However, these patients had been excluded from the study primarily. If histopathologic analysis revealed a benign lesion, the surgical intervention was limited to an excisional or incisional biopsy, depending on the type and size of the lesion.
Sensitivity, specificity, accuracy, and positive and negative predictive values were calculated for conventional and contrast-enhanced MR imaging.
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RESULTS |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Synchronous, contralateral carcinomas were found in 19 of the 336 patients who had a malignant tumor. In four of these 19 patients, tumors were depicted with US and/or mammography. However, in the remaining 15 of 19 patients, tumors were depicted with MR imaging alone (Fig 2). The histopathologic diagnosis of the contralateral tumors visible only on MR images was DCIS in three patients and pT1 invasive carcinoma in 12 patients (Table 7).
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MR imaging alone demonstrated false-positive lesions in 16 patients. In these 16 (3.5%) of the 463 patients, MR imaging depicted lesions seen only with MR that were proved to be benign with biopsy. In one patient, the false-positive finding was in the ipsilateral breast; in the remaining 15 patients, the lesions were in the contralateral breast. In these 16 patients, histopathologic findings were dysplasia in nine women, adenosis in three women, fibroadenoma in two women, focal mastitis in one woman, and papilloma in one woman (Table 4). In the remaining 34 of the 50 women with false-positive MR imaging findings, the clinical examination, mammographic, and US findings were also suspicious. In these women, biopsy was warranted independently of the MR imaging findings.
The sensitivity, specificity, accuracy, and positive and negative predictive values for the conventional methods and for contrast-enhanced MR imaging are shown in Table 8. These results contain both intraductal carcinomas and invasive growing tumors. When one considers only the invasive carcinomas, the sensitivity of contrast-enhanced MR imaging increases from 92.6% (375 of 405) to 97.7% (396 of 405). The low specificity of conventional mammography is explained by a high rate of suspicious microcalcifications without any correlation to findings of other diagnostic modalities. However, 32 DCIS lesions were primarily depicted with conventional mammography because of suspicious microcalcifications, whereas clinical examination and US findings were normal (Table 9).
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DISCUSSION |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Compared with other imaging modalities, MR imaging of the breast has the highest sensitivity in the detection of invasive breast cancer. The rates reported range from 94% to 99% (1,3,9). MR imaging is a promising method for preoperative staging of breast cancer to exclude multifocality or multicentricity. Moreover, the simultaneous examination of the contralateral breast seems to be helpful since the high rate of bilateral tumor manifestations in patients with breast cancer ranges from 17% to over 50% (25,26).
Within the present study, MR imaging depicted additional multifocal or multicentric tumors in 6.5% or 5.2% of patients, respectively. Because of this increase in stage, the therapeutic procedure was changed from lumpectomy to quadrantectomy or mastectomy in 11% of the patients. Additional contralateral carcinomas not visible with US or conventional mammography were depicted with MR imaging alone in 3.2% of all patients. All of these patients underwent lumpectomy or mastectomy in addition to surgical intervention in the primary tumor. Homogeneously or heterogeneously structured dense fibroglandular tissue in a large percentage of the entire breast volume was the only mammographic or US finding to help define a subgroup of patients with multifocal or multicentric disease seen with MR imaging alone.
Our results are in accordance with the findings reported in the literature. Rieber et al (27) found four (11%) of 35 bifocal carcinomas with an interfocus distance of more than 2 cm visible with MR imaging alone. The detection rate of unrecognized contralateral carcinomas was 6% (27). Oellinger et al (28) reported on seven cases of multicentric lesions depicted with MR imaging alone in 25 patients. Harms et al (9) found additional multifocal and/or multicentric tumors in 11 (37%) of 30 patients. Findings of other studies (29,30) have also shown that preoperative MR imaging gives more reliable information about the tumor extent than does US or conventional mammography. All of these studies are, however, based on small patient groups.
In contrast with the promising rate of additional carcinomas found with MR imaging, false-positive findings have to be accepted in nearly 3.5% of patients. However, the number of biopsies of benign lesions seems to be acceptable because the patients have to undergo surgical removal of the detected primary lesion in any case. There is neither an increased risk due to anesthesia nor an extended postoperative time in the hospital. The development of technology to facilitate percutaneous biopsy of MR imaging–depicted lesions may diminish the effect of these false-positive findings.
Findings of the present study confirm reports about the limitations of contrast-enhanced MR imaging in the detection of intraductal carcinomas. The sensitivity for DCIS is reported to be approximately 50% (7). Nevertheless, intraductal carcinoma was depicted with contrast-enhanced MR imaging alone in three patients.
In conclusion, contrast-enhanced MR imaging has a relevant effect on decisions about therapy in patients with suspicious breast lesions. However, stereotactic equipment compatible with MR units is necessary to localize hypervascularized tumors visible with MR imaging alone. In this context, different breast biopsy and localization devices have been described (16,17,31–33).
In 336 women with breast cancer in this study, MR imaging depicted unsuspected multifocal lesions in 30 (8.9%), unsuspected multicentric lesions in 24 (7.1%), and unsuspected contralateral carcinoma in 15 (4.5%). MR imaging findings led to a change in the therapeutic approach in 66 (19.6%) of the 336 women with breast cancer. These data suggest that preoperative contrast-enhanced MR imaging of the breast is useful for staging breast carcinoma and for planning the appropriate therapy. In this situation, it is more important to perform preoperative contrast-enhanced MR imaging than it is to perform postoperative examinations to follow up after lumpectomy. Further study is needed to determine whether the use of breast MR imaging for staging and treatment planning leads to a decrease in tumor recurrence and to determine the cost-effectiveness of this approach.
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Footnotes |
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Author contributions: Guarantor of integrity of entire study, U.F.; study concepts, U.F., L.K.; study design, U.F.; definition of intellectual content, U.F.; literature research, U.F.; clinical studies, U.F.; data acquisition and analysis, U.F.; manuscript preparation, U.F.; manuscript editing, U.F., L.K.; manuscript review, U.F., L.K., E.G.
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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 K. J. Macura, R. Ou |
