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Ann Surg. Nov 1999; 230(5): 680.
PMCID: PMC1420922

Prospective Comparison of Standard Triple Assessment and Dynamic Magnetic Resonance Imaging of the Breast for the Evaluation of Symptomatic Breast Lesions

Abstract

Objective

To compare the sensitivity and specificity of the traditional triple assessment of symptomatic breast lesions with contrast-enhanced dynamic magnetic resonance imaging.

Background

Although triple assessment is currently the gold standard for the assessment of symptomatic breast disease, its specificity is such that open biopsies are still required in many cases to be confident of the diagnosis. Contrast-enhanced dynamic magnetic resonance imaging of the breast represents an alternative diagnostic modality.

Methods

Patients were recruited from the symptomatic breast clinics. If any of the diagnostic modalities suggested malignancy, the lesion was excised. The remaining patients were followed clinically and radiologically.

Results

Two hundred eighty-five patients with a mean age of 43 years (range 21 to 77) were recruited. Malignant lesions were excised in 131 patients and benign lesions in 55 patients. The 99 patients who did not undergo surgery were followed clinically and radiologically for a median of 20 months. The sensitivity of each modality was as follows: clinical examination 84%, mammography 87.6%, fine-needle aspiration cytology 79.1%, triple assessment 99.2%, and magnetic resonance imaging 99.2%. In addition, histologically confirmed multifocal disease was detected in 40 patients on magnetic resonance imaging but in only 9 (22.5%) on mammography. The specificity for the diagnosis of benign disease was as follows: clinical examination 83.1%, ultrasound 88.9%, mammography 86.4%, fine-needle aspiration cytology 97%, triple assessment 59.1%, and magnetic resonance imaging 90.9%.

Conclusion

Contrast-enhanced dynamic magnetic resonance imaging of the breast is as sensitive and more specific than the combined traditional triple assessment for the diagnosis of malignant breast lesions.

Symptomatic breast lesions are traditionally evaluated by clinical, cytologic, and radiologic methods. Approximately 95% of symptomatic breast malignancies will be diagnosed using this so-called triple assessment. 1–3 Each of these diagnostic modalities, by itself, has an appreciable false-negative rate. Conventional x-ray mammography produces false-negative results in 5% to 15% of patients with palpable breast cancers, especially in younger patients with mammographically dense breast tissue and in the lobular cancers that are not normally associated with microcalcification. 4 Fine-needle aspiration cytology (FNAC) is a relatively accurate technique, but the false-negative rate is as high as 20%, especially in lobular cancer and carcinoma in situ. 5 This inaccuracy is compounded when the number of acellular aspirates is considered. 5 It is therefore necessary to combine these diagnostic modalities to achieve an acceptable level of sensitivity for the diagnosis of breast cancer. However, this improved sensitivity is often at the expense of specificity for the diagnosis of benign disease, and this results in an appreciable benign biopsy rate. 6 Further, it is increasingly recognized that multifocal breast cancer is frequently missed by traditional assessment. 7

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the breast is a recently developed imaging modality that has been shown to have a high sensitivity for the diagnosis of primary breast malignancy. 8 The aim of this study was to compare the sensitivity and specificity of DCE-MRI prospectively with the standard triple assessment of palpable breast lesions.

METHODS

Patients with palpable breast lesions were recruited from the symptomatic breast clinics. All underwent clinical examination by one of three consultant breast surgeons, who also performed the FNAC according to our standard protocol for symptomatic patients, which does not include image guidance. The results of the clinical examination were graded as P1, normal; P2, benign; P3, probably benign; P4, probably malignant; and P5, malignant. A classification of P4/5 was taken as positive for the diagnosis of malignancy. X-ray mammography, ultrasound, or both were performed by one of two specialist breast radiologists. DCE-MRI of the breast was then arranged. The resulting films were classified as no abnormality, benign, indeterminate/suspicious, or malignant. The classification of suspicious or malignant was taken as positive. The cytology and histology findings were all reported by a single dedicated breast pathologist. The cytology was graded conventionally from C1 to C5 (C1, inadequate; C2, benign; C3, probably benign; C4, probably malignant; C5, malignant); C4/5 was taken as positive for the diagnosis of malignancy. If the cytology was repeated after an indeterminate result, the most suspicious result was used for the analysis, because in clinical practice this would dictate further management. All lesions classified as suspicious or malignant clinically, mammographically, cytologically, or by MRI were excised. Patients not undergoing open surgical biopsy were followed clinically and radiologically for ≥18 months. Local ethical committee approval was granted for the study.

MRI of the Breast

We have published the full details of our dynamic MRI technique previously. 9 In brief, a 1.5 T whole-body imager (Signa Advantage, GE Medical Systems, Milwaukee, WI) with phased array bilateral breast coils was used to obtain T1-weighted images (TR/TE 640/11 ms, section thickness 4 mm, gap 1 mm) followed by T2-weighted fat-suppressed images (TR/TE 4000/144 ms). A fast radiofrequency spoiled gradient-echo technique (TR/TE 11.1/4.2 ms, section thickness 5 to 7 mm, gap 1.5 to 3 mm, temporal resolution 3 to 12 seconds) was then used to obtain the dynamic images after the infusion of 0.1 mmol/kg dimeglumine gadopentetate (Magnevist, Schering AG, Berlin, Germany). Finally, postcontrast T1-weighted fat-suppressed images were obtained covering the same scan locations as the precontrast images. For this particular sequence, the total scanning time is approximately 30 minutes, during which the woman lies prone in the machine with her breasts lying freely within the receiver, with no compression applied.

The MR images were then analyzed qualitatively by a specialist MR radiologist blinded to the results of the x-ray mammography and cytology. Quantitative analysis of the enhancement profile of a whole tumor slice and maximal area of enhancement was also performed to obtain information about the benign or malignant nature of the lesion. 9 The final result was classified in a similar manner to the mammogram reports.

Statistical Analysis

Sensitivity, specificity, and positive and negative predictive values were calculated where appropriate.

RESULTS

Two hundred eighty-five patients with a mean age of 43 years (range 21 to 77) were recruited. Malignant lesions were confirmed histologically in 131 patients and benign breast disease in 55, in whom on one or more of the diagnostic modalities was the lesion considered suspicious or the patient requested excision. The distribution of the final histology is shown in Table 1. MRI proved to be the most sensitive modality for the diagnosis of malignancy, at 99.2%; FNAC, mammography, and clinical examination produced sensitivities of 79.1%, 87.6%, and 84%, respectively. The corresponding positive predictive values were MRI 0.902, clinical examination 0.809, mammography 0.862, and FNAC 0.962. (Only 30 ultrasound scans were performed on malignant breast lesions [sensitivity 75%] and therefore positive and negative predictive values were not calculated for this modality, although the results of ultrasound, where performed, were included in the evaluation of the accuracy of triple assessment.) When the clinical, cytologic, and x-ray mammographic/ultrasound results were taken together, a sensitivity of 99.2% was achieved. However, this was associated with a marked reduction in specificity to 59.1%, with a corresponding decrease in the positive predictive value to 0.674. One patient with an initially negative evaluation on both triple assessment and DCE-MRI insisted on her lump being removed. Histology subsequently showed the lesion to be a small focus of lobular carcinoma in situ.

Table thumbnail
Table 1. HISTOLOGIC DIAGNOSIS OF EXCISED LESIONS

There were 40 cases of histologically confirmed multifocal disease; all were correctly diagnosed by MRI but only 9 (22.5%) were detected on traditional mammography. However, MRI predicted the presence of multifocal disease in a further 19 patients; this was not confirmed with standard histologic examination, although the foci were small, and no specific pathologic investigation of the whole breast was performed once the primary tumor had been characterized. As a consequence, within the limits of the standard pathologic examination performed, the calculated specificity of MRI for the detection of multifocal disease was only 67.8%, although studies that have specifically looked for multifocal disease detected on MRI have revealed that this is probably an underestimate.

Fourteen false-positive results were reported by MRI, giving a specificity of 90.9%. These lesions were shown histologically to be fibroadenomas (n = 4), a radial scar (n = 1), intraductal papillomas (n = 2), fibrocystic disease (n = 6), and a chronic breast abscess (n = 1). The corresponding specificity of FNAC, x-ray mammography, ultrasound, and clinical examination were 97%, 86.4%, 88.9%, and 83.1%, respectively. The negative predictive values were MRI 0.993, clinical examination 0.86, mammography 0.877, FNAC 0.828, and triple assessment 0.989. No malignancies were identified in the group not undergoing open biopsy despite continued clinical and radiologic follow-up over a median of 20 months (interquartile range 18 to 24 months). No patients were lost to follow-up.

The results are summarized in Tables 2 and 3.

DISCUSSION

Triple assessment with clinical, cytologic, and mammographic investigations has become established as the gold standard for the diagnosis of malignant breast lesions. It is generally accepted that >95% of palpable malignant breast lesions can be diagnosed in this way. 1–3 However, the specificity of this method of diagnosis continues to give rise to concerns that false-positive results will lead to both psychological and physical problems. Attempts at improving the accuracy of triple assessment have focused principally on three areas: scoring systems, core needle biopsy, and improvements in the quality of imaging. 10–13 There is little doubt that improving the objectivity of triple assessment with a suitable scoring system would increase its overall accuracy. 10 Using core needle biopsy to obtain a histologic rather than a cytologic result, although it has produced some promising early results, has not resulted in a marked diagnostic improvement over traditional FNAC. 14 This accepted, the use of image-guided FNAC and core techniques has been shown to reduce costs considerably compared with open biopsy. 15 Digital mammography can provide significantly more information than traditional film/screen mammography, but the essential method of imaging remains the same, with the principal improvement being in contrast resolution and the ability to manipulate and analyze the image; however, spatial resolution remains a technological limitation when compared with film/screen mammography. 12

Dynamic contrast-enhanced MRI relies on fundamentally different methods of image acquisition and processing than x-ray mammography. 8,9 Mammography relies on tissue density; contrast-enhanced MRI is dependent on tumor vascularity and permeability. 16 This gives it a theoretical advantage to identify breast lesions and to distinguish benign from malignant disease. Dimeglumine gadopentetate (Gd-DTPA), the contrast agent most commonly used, was first applied to breast imaging in the 1980s. However, in these early scans it was found that although excellent sensitivity was obtained, the specificity was poor because both benign and malignant lesions enhanced on postcontrast images. 13

In an attempt to improve the specificity of the breast MRI, fast scanning sequences were introduced to facilitate dynamic imaging of breast tissue. With this technique, the actual uptake curve of the Gd-DTPA can be analyzed, improving the differentiation of benign from malignant tissue—malignant tissue enhances rapidly and heterogeneously, and benign tissue enhances more slowly and homogeneously 9 (Figs. 1 and 2). Of course, these techniques represent a more advanced level of MRI technology and some centers still use pre- and postcontrast images, accepting the associated reduction in specificity. 17

The patient undergoing MRI of the breast does not suffer the discomfort associated with the compression plates used in traditional mammography. There is no associated problem with radiation exposure, and in general MRI is as well tolerated as other comparable methods of x-ray imaging, such as computed tomography. 18 However, there is a significant cost disadvantage: breast MRI is approximately 10 times more expensive than a traditional mammogram. 8

In this series, a median of 20 months of follow-up is obviously not long enough to be sure that no cancers were missed in the follow-up–only group. Nevertheless, both MRI and triple assessment are known to be oversensitive for the detection of cancer; given the policy of excising suspicious lesions shown on any of the diagnostic modalities, we are confident that no cancers were left undiagnosed. The difficulties in using DCE-MRI to evaluate infections of the breast are well documented, 19 and in this series, including the indeterminate/suspicious category as positive led to the excision of a chronic breast abscess. Further, even with our techniques, the enhancement profiles of fibroadenomas and papillomas can occasionally be equivocal or suspicious. 9

The excellent sensitivity achieved by the traditional triple assessment in this study is to be expected, given the established accuracy of this method of diagnosis. However, the relatively low specificity underlines the problem of increasing sensitivity by performing multiple tests, which inevitably leads to a reduction in specificity due to the increased number of false-positive results. A recent review of the results of FNAC for palpable masses found a range of sensitivity of 0.65 to 0.98 and specificity of 0.34 to 1.0, which is not out of keeping with our results. 20 The addition of ultrasound or stereotactic guidance to either the FNAC or core biopsy of palpable abnormalities has been reported to improve the sensitivity to 94% to 97% and the specificity to 98% to 100%. 21 However, these studies must be interpreted with caution because inadequate samples are generally not included in the analysis, histologic correlation is not always available for the benign lesions, and follow-up is often inadequate. 22 In this study, the addition of MRI to the standard triple assessment did not significantly improve the sensitivity, but it did provide a significant improvement in diagnostic specificity. This suggests that in certain selected cases, dynamic MRI of the breast may be able to reduce the number of inappropriate surgical biopsies, with their attendant cost and complications, by accurately ruling out malignant disease.

In patients with an established cytologic diagnosis of malignancy, the preoperative detection of multifocal disease with DCE-MRI (see Fig. 1) would facilitate the planning of appropriate surgery and would reduce the necessity for a further procedure after attempted local excision. Although it is possible to localize lesions with MRI, 23 there was no instance where this was required: either the women with multifocal disease diagnosed on DCE-MRI had requested a mastectomy, or the multiple lesions were all contained within the same quadrant and were therefore amenable to local surgery in the form of a quadrantectomy or wide local excision. The lesions identified on the DCE-MRIs classified as false positive for multifocal disease were all contained within the same quadrant, and therefore no patient underwent unnecessary mastectomy on the basis of the DCE-MRI. It is, however, interesting to note that although MRI detected multifocal disease in approximately 30% of patients in this series, we have previously reported that, even when using MRI for follow-up after breast-conserving therapy without preoperative MRI, recurrent disease develops in only 8.5% of patients. 7 Given the standard pathologic methods we used to analyze the breast after mastectomy, the apparent specificity for the detection of multifocal disease by DCE-MRI is lower than is clinically desirable. However, when the small enhancing foci that indicate multifocality on DCE-MRI are actively sought, the specificity of the imaging technique has been shown to be significantly enhanced. 24 In light of the relatively low recurrence rate after breast-conserving surgery and radiotherapy, these small foci of carcinoma that are detected only on MRI may prove clinically irrelevant. They may be adequately treated by radiotherapy and tamoxifen or might be contributing to local failure. The answers to these questions are currently unknown and remain a considerable source of controversy; this issue requires urgent further investigation. 7

The proportion of benign to malignant lesions (1.18:1) reflects the need to obtain informed consent from the patient before arranging the MRI scan. Despite our ability to obtain scans within 1 week and therefore not to delay treatment, patients who were informed of their benign diagnosis on standard assessment were less keen to proceed to further additional investigations; therefore, the number of patients recruited in this group was smaller than would be anticipated from a symptomatic clinic population. Further bias was introduced by the fact that patients with benign lesions that were equivocal on cytology, mammography, or both were more likely to agree to an MRI examination. However, the ability of MRI to rule out cancer in this group is an important conclusion that can be drawn from this study.

Ultimately, the cost of the necessary MRI technology, the backup required, and the time taken to perform a scan means that DCE-MRI is as yet unacceptable for the routine assessment of symptomatic breast lesions. However, there is the potential to target women who would benefit from such a scan. Young women with dense breast tissue and those who have undergone previous surgery could benefit substantially; in these patients, the routine use of breast MRI may be warranted in addition to the standard triple assessment. 8,25 In addition, with the technical advances in data acquisition and analysis resulting in increased specificity of the dynamic phase of breast MRI, it may soon be possible to exclude malignancy confidently in women with lesions classified as suspicious but not diagnostic of malignancy on traditional triple assessment. As such, breast MRI is likely to find a role as an adjunct to standard triple assessment in selected groups of patients, thus avoiding unnecessary surgical biopsies with their attendant cost and complications. Indeed, guidelines for the integration of this technology into the clinical scenario have recently been suggested. 26 The role of DCE-MRI in the delineation of multifocal breast cancer has yet to be evaluated fully and awaits a formal randomized trial.

Footnotes

Correspondence: Michael J. Kerin, MD, FRCSI, FRCS(Ed), FRCS(Gen), The University of Hull, Academic Surgical Unit, Castle Hill Hospital, Castle Road, Hull HU16 5JQ, United Kingdom.

P.J. Drew was a Northern & Yorkshire Regional Health Authority Research Fellow. The Centre for MR Investigations is funded jointly by the Yorkshire Cancer Research Campaign and Royal Hull Hospitals NHS Trust.

Accepted for publication June 14, 1999.

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