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AJR 2004; 183:1159-1168
© American Roentgen Ray Society

Breast Imaging

MRI for Surgical Planning in Patients with Breast Cancer Who Undergo Preoperative Chemotherapy

Fabienne Thibault1, Claude Nos2, Martine Meunier1, Carl El Khoury1, Liliane Ollivier1, Brigitte Sigal-Zafrani3 and Krishna Clough2 for the Institut Curie Breast Cancer Group

1 Department of Medical Imaging, Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
2 Department of Surgery, Institut Curie, 75248 Paris Cedex 05, France.
3 Department of Pathology, Institut Curie, 75248 Paris Cedex 05, France.

Received August 28, 2003; accepted after revision March 26, 2004.

 
Address correspondence to F. Thibault (fabienne.thibault{at}curie.net).


Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
OBJECTIVE. Accurate presurgical evaluation of residual disease appears essential for successful clinical outcome in patients with breast cancer who are undergoing chemotherapy. Our objective was to study the impact on surgical planning of adding serial MRI evaluations of the tumor to standard non–MRI assessments.

MATERIALS AND METHODS. MR images of breast tumors obtained before, during, and after preoperative chemotherapy were reviewed in 30 patients. Tumor response was assessed using both size and morphologic MRI criteria. We compared the actual surgical decisions made prospectively on the basis of standard (clinical, mammographic, and sonographic) assessments of response with decisions that would have been made had MRI findings also been considered. MRI investigators were blinded to the ultimate surgical results. Successful breast-conserving surgery was judged on pathologic confirmation of excision margins that were negative for cancer.

RESULTS. The standard evaluation led to 16 successful breast-conserving and 14 mastectomy procedures. Using MRI results would have led to major beneficial therapeutic changes in six (20%) of the 30 patients: five patients undergoing primary mastectomy (chemotherapy avoided) and one patient undergoing postchemotherapy mastectomy (unsuccessful breast-conserving surgery avoided). MRI would have added valuable information in 14 (46.7%) of the 30 patients. In seven (23.3%) of the 30 patients, the decision to perform postchemotherapy mastectomy would have been unchanged. In one patient (3.3%), MRI results would not have prevented unsuccessful breast-conserving surgery. In two patients (6.6%), MRI results would have prevented successful breast-conserving surgery from being performed.

CONCLUSION. Although the ultimate incidence of breast conservation was potentially similar for the patients (16/30, 53%) in whom the standard evaluation was used and for the patients (14/30, 47%) in whom the MRI-added evaluation was used, MRI was useful in establishing the final treatment earlier in the process, avoiding unnecessary preoperative chemotherapy, or selecting high-risk breast-conserving procedures.


Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
The standard surgical treatment for patients with large operable breast cancers is mastectomy. Preoperative (neoadjuvant) chemotherapy has been developed as a therapeutic option in the past decade [1–6]. The main benefit gained from preoperative chemotherapy is a reduction in tumor size, which permits breast-conserving surgery in patients who otherwise would have required a mastectomy. The reported rate of tumor downstaging obtained with neoadjuvant chemotherapy varies from 22.4% in the randomized National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 trial [7] to 34% in a recent study from The University of Texas M. D. Anderson Cancer Center [6]. In the NSABP B-18 trial [7], the rate of local relapse noted in patients whose surgical plan was changed from proposed mastectomy to lumpectomy after preoperative chemotherapy was 15.9% at 9 years. At our institution, a study of 257 patients with large breast tumors who had tumor reduction after preoperative chemotherapy and thus were eligible for breast-conserving surgery [4] showed high local relapse rates of 16% at 5 years and 21.5% at 10 years after surgery. In addition, this local relapse was a strong predictor for distant metastases [4]. The accurate evaluation of residual disease after neoadjuvant chemotherapy and before surgery appears essential for successful clinical outcome.

After induction therapy, the decision of whether to perform mastectomy versus breast-conserving surgery is typically based on clinical and radiologic assessment of tumor response [1, 5, 6]. Breast-conserving surgery is defined as successful if the margins on the final lumpectomy specimen are free from disease [4, 6].

A number of investigators have included MRI in the assessment of response to preoperative chemotherapy [8–13]. MRI was found to be more accurate than palpation and mammography in patients with extensive breast cancer [9, 11]. One study suggested a link between tumor morphology and the degree of response measured on breast MRI [14]. MRI findings, however, may lead to underestimation of the extent of residual disease after chemotherapy [10, 15].

The aim of our study was to determine how the addition of breast MRI to routine clinical and radiologic assessment of the tumor at presentation and under chemotherapy affects the overall surgical decision process. We studied the hypothesis that MRI assessment of both tumor size and morphology would help oncologists and surgeons select the appropriate therapeutic end point (breast-conserving surgery vs mastectomy) more directly than would conventional non–MRI assessment. The MR images of breast tumors in 30 patients undergoing preoperative chemotherapy were reviewed. We compared the actual decisions made on the basis of conventional assessment with the decisions that would have been made had MRI additionally been used in the planning of surgery. The investigators were blinded to the actual clinical outcomes when making the MRI-based decisions retrospectively.


Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Patient Population and Treatment
The MRI protocol was proposed to patients with operable breast cancers considered too large for breast-conserving surgery who underwent preoperative chemotherapy at our institution. In the protocol, breast MRI evaluation was scheduled before, during, and at the end of chemotherapy, producing a total of three MR examinations per patient. These were added to the clinical and radiologic evaluations used as the standard for therapeutic assessment. The study was set up with no direct benefit to patients because surgeons did not use the results of breast MRI to decide between postchemotherapy breast-conserving surgery and mastectomy. MRI as a method for assessing response was evaluated by correlation of the MRI results with pathologic findings in surgical specimens. The local ethics committee approved the study.

From November 1999 to December 2001, 30 consecutive patients (mean age, 49 years; range, 27–67 years) with stage II and III breast cancers confirmed at core biopsy were entered in the study after giving written consent. Tumor characteristics are shown in Table 1. Neoadjuvant chemotherapy consisted of four to six cycles of a combination of anthracyclines (epirubicin hydrochloride, 100 or 75 mg/m2), cyclophosphamide (500 mg/m2), and 5-fluorouracil (500 mg/m2) at 3- to 4-week intervals in 26 patients or of anthracyclines (doxorubicin hydrochloride, 50 mg/m2) and taxanes (docetaxel, 75 mg/m2) in four patients. Clinical response was evaluated by the medical oncologist before each course of chemotherapy and by the surgeon after two courses and at the end of induction therapy. Twenty-four patients underwent all three MRI examinations, and six patients only had the initial and final preoperative MRI evaluations.


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  		TABLE 1 Tumor Characteristics in 30 Patients

 

Breast-conserving surgery was considered for all patients after chemotherapy using the clinical, mammographic, and sonographic evaluations of tumor response as the guide for resection without knowledge of the MRI results. In patients with a limited response that precluded the possibility that breast-conserving surgery would produce acceptable cosmetic results, a mastectomy was performed. In patients with a complete or major response with no distinct residual tumor at palpation and no or minor residual abnormalities noted on conventional imaging, a wide lumpectomy at the initial tumor site was performed. In patients with a partial response, the surgeon could either perform a mastectomy or conserve the breast if the size of residual tumor relative to the volume of the breast allowed it. Patients with involved margins after breast-conserving surgery underwent a secondary mastectomy. All patients had postoperative external irradiation directed to the breast or thoracic wall and regional lymph nodes. Adjuvant chemotherapy was administered in 23 of 30 patients.

Mammography and Breast Sonography
Patients referred to our center had initial mammograms and breast sonograms obtained at outside facilities. Radiologists who performed the sonographic examinations were aware of the presence of a breast mass considered to be probably malignant either clinically or mammographically. After chemotherapy, patients underwent preoperative mammography and sonography at our institution.

Pathologic Analysis
All breast lumpectomy and mastectomy specimens were submitted for serial gross pathologic examination and subsequent histologic analysis. The longest diameter of residual gross abnormality and microscopic disease, histologic type of invasive tumor, and percentage of in situ components were noted. In lumpectomy cases, the distance from and location of any residual tumor focus relative to specimen margins were specified. The appropriateness of breast-conserving surgery was judged on pathologic confirmation of negative excision margins. Response to chemotherapy was evaluated using the percentage of residual tumor cells relative to tumor stroma and the mitotic index.

MRI
Breast MRI was performed on a 1.5-T whole-body imager (Signa, GE Healthcare) using a bilateral breast coil. First, an unenhanced axial 3D fast spoiled gradient-recalled echo T1-weighted sequence (TR/TE, 11.5/4.2; flip angle, 30°; slice thickness, 3 mm; no gap; field of view, 34 cm; matrix, 512 x 192; number of excitations, 1; scanning time, 1 min 25 sec) was acquired. Then the affected breast was imaged using sagittal 3D fast spoiled gradient-recalled echo T1-weighted sequences (11.5/4.2; flip angle, 30°; slice thickness, 4 mm; no gap; field of view, 24 cm; matrix, 512 x 192; number of excitations, 1; scanning time, 45 or 58 sec) (3D volume including all of the fibroglandular tissue) applied before and 10 times after bolus injection of contrast medium (0.1 mmol/kg of body weight of dimeglumine gadopentetate [Magnevist, Schering]) followed by a 20-mL saline IV flush. Finally, the axial sequence was repeated as a contrast-enhanced study. Postprocessing included unenhanced to enhanced image subtraction. The original and subtracted images were analyzed and interpreted by a radiologist who was aware of the mammographic and sonographic findings.

The diagnostic criterion for residual tumor after chemotherapy was the visual observation of residual enhancement at the location of the initial tumor as late as approximately 7–9 min after the injection of contrast medium. Time-to-signal-intensity curves obtained either in the area of highest or most homogeneous enhancement or in areas where visible residual enhancement was detected were used to help differentiate residual tumor from adjacent breast parenchyma. Enhancement profiles were also used to characterize concomitant enhancing foci located at a distance from the primary tumor, using diagnostic criteria described previously [16].

The sizes of initial and residual tumors visualized as 3D images were determined by the longest diameter in a given plane of a single tumor nodule or by a composite measurement of multiple tumor nodules when those were present. The European Organization for Research and Treatment of Cancer [17] guidelines were used to evaluate response to chemotherapy by changes of longest tumor diameters. A decrease of 30% or more was considered a partial response, an increase of 20% or more was considered progression, and a decrease of less than 30% or an increase of less than 20% was considered to indicate stability.

Retrospectively, soft copies of the MRI examinations were reviewed by two radiologists and a surgeon in consensus after the completion of all treatments. Reviewers, blinded to the actual treatment course of the patients, were presented with information on each MR examination individually. To achieve comparative tumor measurements and to discern the pattern of response, the reviewers first interpreted the current MRI examination for a given patient and then systematically compared the intra- and postchemotherapy MR images for that patient with initially obtained MR images. On prechemotherapy MR images, primary known tumors were classified as predominantly circumscribed nodular versus spiculated or infiltrating with jagged borders and as either unifocal (a single circumscribed mass or an infiltrating tumor area) (Figs. 1A, 1B, 1C, 2A, 2B, and 2C) or multifocal (with coexistence of two or more distinct tumor foci in the same quadrant) (Figs. 3A, 3B, and 3C). Suspicion of multicentric disease was noted. Multicentricity was defined as the presence of one or more suspicious enhancing foci in a quadrant different from that in which the index tumor was found (Figs. 4A, 4B, 4C, and 4D) or the extension of a tumor beyond the boundaries of the index quadrant. Tumor size was measured as described earlier, and the type of response was categorized as either shrinkage (concentric decrease of a tumor mass) or fragmentation into multiple smaller tumor foci.



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  		Fig. 1A. —42-year-old woman undergoing chemotherapy who had unifocal tumor seen on initial MR images. Initial MR images (native images) obtained before (A) and after (B) injection of contrast medium show one circumscribed tumor (arrows).

 


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  		Fig. 1B. —42-year-old woman undergoing chemotherapy who had unifocal tumor seen on initial MR images. Initial MR images (native images) obtained before (A) and after (B) injection of contrast medium show one circumscribed tumor (arrows).

 


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  		Fig. 1C. —42-year-old woman undergoing chemotherapy who had unifocal tumor seen on initial MR images. MR image obtained after chemotherapy shows marked concentric shrinkage of tumor (arrow) to single residue. Such process was considered to indicate most favorable or ideal situation for breast-conserving surgery, allowing complete tumor excision with standard lumpectomy.

 


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  		Fig. 2A. —67-year-old woman with unifocal tumor that fragmented while she underwent chemotherapy. Initial digitally subtracted MR image shows single tumor mass with spiculated margins.

 


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  		Fig. 2B. —67-year-old woman with unifocal tumor that fragmented while she underwent chemotherapy. MR images obtained after two courses (B) and at end of chemotherapy (C) show fragmentation of tumor, resulting in multiple residual foci. MRI measurement of longest tumor diameter underestimated residual 6-cm invasive ductal carcinoma tumor by 2 cm. This type of response was considered to indicate unfavorable situation for breast-conserving surgery. In this patient, MRI assessment would have led to postchemotherapy mastectomy and allowed her to avoid undergoing additional breast-conserving surgery that resulted in positive margins.

 


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  		Fig. 2C. —67-year-old woman with unifocal tumor that fragmented while she underwent chemotherapy. MR images obtained after two courses (B) and at end of chemotherapy (C) show fragmentation of tumor, resulting in multiple residual foci. MRI measurement of longest tumor diameter underestimated residual 6-cm invasive ductal carcinoma tumor by 2 cm. This type of response was considered to indicate unfavorable situation for breast-conserving surgery. In this patient, MRI assessment would have led to postchemotherapy mastectomy and allowed her to avoid undergoing additional breast-conserving surgery that resulted in positive margins.

 


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  		Fig. 3A. —In 57-year-old woman, multifocal tumor is seen on three successive slices (shown across each row) from lateral to medial parts of breasts. Initial MR images (A), MR images after two courses of chemotherapy (B), and preoperative MR images after completion of chemotherapy (C) all show two main central tumor nodules associated with smaller peripheral nodules (arrows, A) confined in one quadrant. B and C show nodule shrinkage in response to therapy but persistence of two small nodules on preoperative MR images (C). Patient is not suitable candidate for breast-conserving surgery.

 


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  		Fig. 3B. —In 57-year-old woman, multifocal tumor is seen on three successive slices (shown across each row) from lateral to medial parts of breasts. Initial MR images (A), MR images after two courses of chemotherapy (B), and preoperative MR images after completion of chemotherapy (C) all show two main central tumor nodules associated with smaller peripheral nodules (arrows, A) confined in one quadrant. B and C show nodule shrinkage in response to therapy but persistence of two small nodules on preoperative MR images (C). Patient is not suitable candidate for breast-conserving surgery.

 


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  		Fig. 3C. —In 57-year-old woman, multifocal tumor is seen on three successive slices (shown across each row) from lateral to medial parts of breasts. Initial MR images (A), MR images after two courses of chemotherapy (B), and preoperative MR images after completion of chemotherapy (C) all show two main central tumor nodules associated with smaller peripheral nodules (arrows, A) confined in one quadrant. B and C show nodule shrinkage in response to therapy but persistence of two small nodules on preoperative MR images (C). Patient is not suitable candidate for breast-conserving surgery.

 


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  		Fig. 4A. —51-year-old women who had multifocal tumor with multicentric disease suspected on initial MR images. Tumor nodules (arrowheads) extend widely within breast from lateral (A) to medial parts (D) beyond quadrant of index tumor, which was localized in retroareolar region (B) by standard evaluation. C shows section through nipple. Had MRI been considered, this patient would have undergone direct mastectomy, avoiding preoperative chemotherapy and unsuccessful breast-conserving surgery.

 


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  		Fig. 4B. —51-year-old women who had multifocal tumor with multicentric disease suspected on initial MR images. Tumor nodules (arrowheads) extend widely within breast from lateral (A) to medial parts (D) beyond quadrant of index tumor, which was localized in retroareolar region (B) by standard evaluation. C shows section through nipple. Had MRI been considered, this patient would have undergone direct mastectomy, avoiding preoperative chemotherapy and unsuccessful breast-conserving surgery.

 


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  		Fig. 4C. —51-year-old women who had multifocal tumor with multicentric disease suspected on initial MR images. Tumor nodules (arrowheads) extend widely within breast from lateral (A) to medial parts (D) beyond quadrant of index tumor, which was localized in retroareolar region (B) by standard evaluation. C shows section through nipple. Had MRI been considered, this patient would have undergone direct mastectomy, avoiding preoperative chemotherapy and unsuccessful breast-conserving surgery.

 


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  		Fig. 4D. —51-year-old women who had multifocal tumor with multicentric disease suspected on initial MR images. Tumor nodules (arrowheads) extend widely within breast from lateral (A) to medial parts (D) beyond quadrant of index tumor, which was localized in retroareolar region (B) by standard evaluation. C shows section through nipple. Had MRI been considered, this patient would have undergone direct mastectomy, avoiding preoperative chemotherapy and unsuccessful breast-conserving surgery.

 

Surgical Decisions Based on Standard Evaluation Versus Standard Evaluation Plus MRI
On the basis of the MRI review, the surgeon reevaluated the pre- and postchemotherapy surgical decisions. Patients with suspected multicentric disease on initial MRI should have undergone histologic evaluation so that the extent of disease could be determined. In cases in which multicentric disease was confirmed, a primary mastectomy should have been performed. Patients with unicentric tumors were considered candidates for neoadjuvant chemotherapy. The ideal situation corresponded to the progressive shrinkage of a circumscribed tumor that made breast-conserving surgery feasible via standard lumpectomy. The less-than-ideal situation corresponded to the fragmentation of a unifocal mass or partial shrinkage of an initial multifocal tumor, both leading to multiple residual tumor foci after chemotherapy. In patients with large breasts, breast-conserving surgery would have necessitated a wide adapted lumpectomy or quadrantectomy for complete tumor excision. In our protocol, such patients undergo immediate breast reshaping with unilateral or bilateral mammaplasty [18].


Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Surgical Decisions Based on Standard Evaluation
Results are summarized in Table 2. After chemotherapy, 11 patients (40%) with poor tumor response underwent a mastectomy and 19 patients (60%) eligible for breast-conserving surgery were treated conservatively. Three of the 19 were subsequently shown to have positive specimen margins and therefore underwent a secondary mastectomy. Thus, the rate of radical surgery was 47% (14/30 patients).


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  		TABLE 2 Surgical Procedures Based on Standard or Standard Plus MRI Evaluation of Tumor Response in 30 Patients

 



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  		Fig. 6A. —44-year-old woman with large unifocal breast tumor. Initial MR image shows unifocal tumor.

 


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  		Fig. 6B. —44-year-old woman with large unifocal breast tumor. MR image obtained after two courses of chemotherapy shows marked fragmentation of tumor but little change in its longest composite diameter.

 


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  		Fig. 6C. —44-year-old woman with large unifocal breast tumor. MR image obtained after chemotherapy shows only two or three low-enhancing residual foci (arrows). Patient underwent secondary mastectomy after breast-conserving surgery resulted in positive margins. Size of residual tumor at histology (3.5-cm invasive lobular carcinoma) was underestimated by 1.5 cm. MRI evaluation would not have prevented additional breast-conserving surgery in this patient.

 
Histologically, there were one complete response with no residual tumor cells, six partial responses (malignant cells ≤ 20%), and 23 minor or absent responses (malignant cells > 20%). The mean gross and microscopic sizes of residual tumors measured on surgical specimens were 2.7 and 2.8 cm, respectively (range, 0–7 cm). Of the 16 patients treated via breast-conserving surgery with no further surgery, one patient had a complete response. The other 15 patients with residual disease underwent complete surgical excision.

The length of follow-up of the surviving 26 patients ranges from 19 to 42 months (mean, 30 months). One patient had local relapse 15 months after breast-conserving surgery. Three patients died from breast cancer metastases 20, 25, and 30 months after surgery. One patient was lost to follow-up 20 months after surgery, with no recurrent disease at that time.

MRI Review
Tumor features observed on the prechemotherapy MR images are reported in Table 3. Multicentric disease was suspected in seven of 30 patients. The suspicious areas were undetected on either mammography or breast sonography. The remaining 23 patients had unicentric tumors. The mean size of the 30 primary tumors measured on initial MR images was 4.5 cm (range, 2.4–9.0 cm).


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  		TABLE 3 MRI Features of Tumors at Presentation

 

Morphologic Changes from Chemotherapy
The patterns of response observed on MRI are summarized in Tables 4 and 5. Results in patients with unicentric tumors are separated into two groups according to findings on the standard evaluation (Table 4): 15 patients were considered responders, and eight were considered nonresponders. In the responder group, five patients had unifocal tumors that displayed marked shrinkage on MRI and were considered ideal candidates for breast-conserving surgery (Figs. 1A, 1B, and 1C). In contrast, four patients with unifocal tumors that fragmented (Figs. 2A, 2B, and 2C) and six patients with multifocal tumors that showed either shrinkage (Figs. 3A, 3B, and 3C) or fragmentation were considered less appropriate candidates for breast-conserving surgery. None of the eight tumors in the group of standard nonresponders showed a significant decrease in size on MRI. In these patients, limited changes toward shrinkage were noted in six patients and toward fragmentation in two patients. Considering all unicentric tumors (uni- and multifocal cases), 13 of the 15 nodular forms shrank, and two fragmented; five of the eight spiculated or infiltrating forms fragmented, whereas three shrank (Table 5). Thus, nodular tumors tended to shrink rather than fragment and spiculated and irregular masses tended to fragment rather than shrink. This result was statistically significant (Fisher's exact test, p = 0.03). When the pattern of response in all 30 primary tumors (i.e., uni- and multicentric cases, Table 5) was considered, the findings were confirmed with even higher significance (Fisher's exact test, p = 0.005).


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  		TABLE 4 Morphologic Pattern of Response Observed on MRI in 23 Unicentric Tumors, Including 15 Responding and Eight Nonresponding, by Standard Evaluation

 

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  		TABLE 5 Morphologic Pattern of Response in Relation to Initial Tumor Presentation

 

Changes in Largest Diameter of the Tumor
The mean size of the 30 primary tumors measured on postchemotherapy MRI was 2.6 cm (range, 0–7.7 cm). The MRI and histologic sizes of residual tumor after chemotherapy correlated with a Spearman rank correlation coefficient of 0.79 (p = 0.001) (Fig. 5). MRI underestimations of residual disease ranged from 0.1 to 3.5 cm in eight patients, including two false-negative cases (complete MRI response but residual tumor found at pathology). MRI overestimations of residual tumor ranged from 0.1 to 1.3 cm in 17 patients and reached 2.0 cm in one patient. No false-positive finding was noted on MRI (residual suspicious enhancement on MRI but complete response at pathology).



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  		Fig. 5. —Graph shows MRI and histopathologic correlation of residual tumor sizes after chemotherapy. MRI-measured longest diameters in centimeters (x-axis) is compared with greatest dimensions of microscopic disease on surgical specimens in centimeters (y-axis). Spearman rank correlation coefficient = 0.79, p = 0.001.

 

Retrospective Decisions Based on Standard Plus MRI Evaluation Versus Standard Evaluation
The MRI-aided evaluation is summarized Table 2. If MRI results had been considered at presentation, seven patients with suspected multicentric disease would have undergone a mastectomy if their histologic evaluation was positive. The addition of MRI assessment would have allowed them to avoid preoperative chemotherapy. The 23 remaining patients with unicentric tumors would have received neoadjuvant chemotherapy. Because of the absence or insufficiency of tumor response on standard plus MRI evaluation, eight of these patients would have undergone postchemotherapy mastectomy. Five other patients would have undergone a lumpectomy on the basis of the shrinkage of a unifocal tumor (the ideal situation). The remaining 10 patients with multiple tumor foci on preoperative MRI would have been assessed for the feasibility of breast-conserving surgery on the basis of breast size. In fact, these patients' breasts were large enough relative to residual tumor size to allow complete tumor excision by wide quadrantectomy and breast reshaping. Otherwise, multifocal tumor residue on preoperative MRI would have indicated that mastectomy should be performed. Nine of these patients actually had negative margins of resection, and one patient with positive margins underwent a secondary mastectomy.

Table 2 also summarizes the comparison between therapeutic decisions based on the standard evaluation and on the standard plus MRI evaluation. Using MRI results, seven (23%) patients would have undergone primary mastectomy. The MRI-added evaluation would also have prevented one patient from having to undergo unsuccessful breast-conserving surgery after chemotherapy (Figs. 4A, 4B, 4C, and 4D). However, another two of these seven patients (2/30 total patients, 6.6%) eventually had successful breast-conserving surgery with no recurrence detected at 34- and 29-months follow-up. Using MRI-added evaluation for the 23 patients undergoing chemotherapy would have resulted in a direct posttreatment mastectomy for a stable fragmented tumor (Figs. 2A, 2B, and 2C) in one (1/30, 3.3%) but would have not prevented unsuccessful breast-conserving surgery in another (3.3%) with a fragmented tumor that showed marked—but overestimated—response on MRI (Figs. 6A, 6B, and 6C). Overall, the standard evaluation led to 16 successful breast-conserving surgeries and 14 mastectomy procedures. Potentially, the standard plus MRI evaluation would have led to 14 successful breast-conserving surgeries (five lumpectomies and nine quadrantectomies) and 16 mastectomies. The surgical alternative chosen in patients with smaller breast volumes would have been five breast-conserving surgeries by standard lumpectomy and 25 mastectomies.


Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Initial MRI
Because unsuspected multicentric disease would have been detected at presentation, seven of our 30 patients would have had their primary treatment converted from chemotherapy to mastectomy, although two of these patients ultimately had successful breast-conserving surgery and have had recurrence-free survival after breast irradiation. In four patients, the tumor extended beyond the volume of a single quadrant, and in three patients, MRI showed distant suspicious foci. If multicentricity had been histologically confirmed, a mastectomy would have been performed. The study was designed to evaluate breast MRI but not direct surgical treatment; thus, the prospective surgical decision was made without using the MRI information. Three patients eventually had marked response to chemotherapy at standard assessment. One patient in whom the tumor extended beyond a quadrant both initially (Figs. 4A, 4B, 4C, and 4D) and after treatment could have avoided undergoing additional breast-conserving surgery after chemotherapy. The other two patients with distant suspicious foci and successful breast-conserving surgery at the index tumor site were mentioned earlier. The suspicious foci were no longer visible on postchemotherapy MRI. The remaining four patients with poor responses on standard evaluation underwent mastectomy and thoracic wall irradiation. Three also had stable tumors on MRI, but one patient with residual infiltrating lobular carcinoma at histology had a false-negative MRI result.

The ability of breast MRI to reveal additional tumor foci not suspected from the results on conventional imaging has been shown previously [19–23]. In these reports, multifocal or multicentric cancer was found in 18–37% of mastectomy or lumpectomy specimens, similar to our findings of 23% (7/30). Investigators also addressed the impact of MRI on surgical treatment in women with primary operable [24] or early-stage [25, 26] breast cancer. In one report [26], most treatment changes that stemmed from MRI evaluations were found to be clinically favorable. Some unfavorable effects, however, were linked to the lack of specificity of breast MRI for cancer diagnosis.

As discussed earlier, the patients in our study in whom multicentric disease was suspected should have undergone preoperative histologic confirmation of tumor extent. The clinical benefit gained from using MRI-guided localization and biopsy devices to assess "MRI-only" lesions before treatment planning is a major advance [27–30]. At the time of our study, we did not have an MRI-compatible biopsy device at our center. The expected diffusion of such commercially available systems should further improve the therapeutic management of patients in this setting.

Assessing Response to Neoadjuvant Chemotherapy with MRI
Residual tumor extent.—In our series, the MRI and histologic sizes of residual tumor after chemotherapy correlated well. Only minor overestimations of residual disease were noted on MRI, except in one nonresponding patient (nonresponsive according to both standard and MRI assessments) in whom a 2-cm overestimation of residual tumor would have had no impact on treatment plans. Two false-negative cases included a 3.5-cm invasive lobular carcinoma with fragmentation pattern on MRI and a 1-cm invasive ductal carcinoma with only 10% residual tumor cells that showed shrinkage. In addition, MRI measurements underestimated 4.5- and 6-cm residual infiltrating ductal carcinomas by 3.5 and 2 cm, respectively. Both tumors displayed fragmentation. Histologically, malignant cells were arranged in multiple foci separated by normal fibrous tissue. Both patients, showing complete clinical and major radiologic responses, underwent breast-conserving surgery. The patient (in Figs. 2A, 2B, and 2C) with a 6-cm residue had positive margins of resection that necessitated a secondary mastectomy. The patient with a 4.5-cm residue had negative margins. In a third patient (in Figs. 6A, 6B, and 6C) in whom MRI showed fragmentation and led to 1.5-cm underestimation of tumor size, breast-conserving surgery would have been unsuccessful despite a marked decrease in tumor diameter on MRI. Histology showed a 3.5-cm invasive lobular carcinoma.

These results suggest that breast MRI is less accurate for assessing residual tumor in patients in whom fragmentation has occurred during chemotherapy. We think that surgeons should be aware of the risk of error associated with MRI measurement of tumor with this type of response. Previous reports have shown that residual disease can be underestimated on MRI after induction therapy, particularly invasive lobular carcinomas [10, 15].

Contribution to surgical planning.—Considering the actual clinical outcome in our patients, both initial and subsequent intra- and posttherapeutic MR images carried valuable information with regard to therapeutic management. In six patients (6/30, 20%), this information would have led to major appropriate changes in the course of treatment: five patients with multicentric disease would have undergone immediate mastectomy without neoadjuvant chemotherapy, and one patient with stable, fragmented tumor on MRI would have avoided additional breast-conserving surgery by undergoing direct postchemotherapy mastectomy. In another fourteen patients (46.7%), MRI information would have helped surgeons plan breast surgery in more detail or with more confidence. Five of the patients with a single, circumscribed tumor residue assessed on serial MR images would have been candidates for breast conservation with a standard lumpectomy. The other nine patients with multiple residual foci and limited reduction in tumor size after chemotherapy were less appropriate candidates for breast-conserving surgery. These findings would have, in retrospect, changed treatment choice to a wider excision (e.g., quadrantectomy) or a mastectomy. One patient (3.3%), who had ipsilateral local recurrence 15 months after successful breast-conserving surgery performed without using the MR images, displayed a multifocal residue on preoperative MRI. It is possible that this recurrence was linked to disease left in the breast outside the excisional volume. In another patient (3.3%), however, MRI would not have prevented unsuccessful breast conservation before ultimate mastectomy. Two patients (6.6%) in whom the MRI results would have favored primary mastectomy because of the multicentric extent of the disease were able to undergo postchemotherapy breast-conserving surgery with no local regional relapse at follow-up. Finally, seven patients (23.3%) with similarly poor tumor response on standard and MRI assessments would have undergone postchemotherapy mastectomy with no changes made to the surgical plan.

Pattern of response to chemotherapy.—One recent study of patients treated by neoadjuvant chemotherapy suggested a link between tumor morphology and the degree of response measured on breast MRI [14]. Dominant nodular presentation with circumscribed borders generally responded by shrinking to a smaller mass, was predictive of a partial or complete response, and was likely to be resectable after induction therapy. Other MRI patterns such as multiple tumor nodules, diffuse tissue infiltration, and sparse enhancement of a tumor mass were either predictive of a poorer response with no significant shrinkage or little change in tumor size. In this series, we found a similar link between initial tumor morphology and the type of response (e.g., overall nodular vs spiculated shape and a tendency to respond by shrinking vs fragmenting, respectively). However, shrinkage did not necessarily lead to a complete response on MRI because some peripheral nodules seen at presentation in the vicinity of a main tumor mass were still present after chemotherapy. Particularly in cases with marked response on standard evaluation, visualization of a multifocal residue on MRI adds useful information for surgical planning. Then, a wider excision than that planned using non-MRI assessment might have been required to achieve complete removal of the tumor.

In summary, in this series of large operable breast cancers, MRI was useful in establishing the final treatment earlier in the treatment process. Initial MR images obtained before chemotherapy would have been useful in revealing potential multicentric disease, thus obviating unnecessary chemotherapy and, in one patient, unsuccessful breast-conserving surgery. Preoperatively, the morphologic assessment of tumor response would have helped surgeons to select patients most likely to have successful breast conservation after resection of a unifocal residue and optimize the extent of surgical treatment necessary to remove all residual tumor in multifocal situations.


Acknowledgments
 
We thank all the radiologists, clinicians, and pathologists who participated in this study.


References
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 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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