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Annals of Surgical Oncology 9:994-998 (2002)
© 2002 Society of Surgical Oncology

ORIGINAL ARTICLES

Ultrasound-Guided Lumpectomy of Nonpalpable Breast Cancer Versus Wire-Guided Resection: A Randomized Clinical Trial

Frans D. Rahusen, MD, Andre J. A. Bremers, MD, Hans F. J. Fabry, MD, A.H. M. Taets van Amerongen, MD, Rob P. A. Boom, MD and S. Meijer, MD, PhD

From the Department of Surgery (FDR), Medisch Centrum Leeuwarden, Leeuwarden, The Netherlands; Departments of Surgical Oncology (AJAB, HFJF, SM) and Radiology (AHMTvA), Vrije Universiteit Medical Center, Amsterdam, The Netherlands; and Department of Surgery (RPAB), District General Hospital, Amstelveen, The Netherlands.

Correspondence: Address correspondence and reprint requests to: S. Meijer, MD, PhD, VU Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam; Fax: 31-2-4444512; E-mail: s.meijer{at}vumc.nl


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: The wire-guided excision of nonpalpable breast cancer often results in tumor resections with inadequate margins. This prospective, randomized trial was undertaken to investigate whether intraoperative ultrasound (US) guidance enables a better margin clearance than the wire-guided technique in the breast-conserving treatment of nonpalpable breast cancers.

Methods: Patients with a preoperative histological diagnosis of nonpalpable breast cancer that could be visualized both with US and mammography were included. Patients were randomized to undergo either a wire-guided or a US-guided excision. Adequate margins were defined as >=1 mm.

Results: Of 49 included patients, 23 were assigned to undergo wire-guided excision and 26 to undergo US-guided excision. One patient crossed over to US-guided excision after inadvertent wire displacement. Mean tumor diameter, specimen weight, and operating time were similar in both groups. The excision was adequate in 24 (89%) of 27 US-guided excisions and 12 (55%) of 22 wire-guide excisions (P = .007).

Conclusions: US-guided excision seems to be superior to wire-guided excision with respect to margin clearance of mammographically detected and US-visible nonpalpable breast cancers. Patients do not have to undergo the unpleasant wire placement before surgery.

Key Words: Nonpalpable • Mammography • Ultrasonography • Breast neoplasms • Segmental mastectomy • Needle biopsy


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
With the introduction of screening mammography, the median tumor size has decreased considerably, and approximately half of breast cancers in surgical practice are nonpalpable.1 Traditionally, nonpalpable breast lesions have been excised with a hook wire as a guiding tool. This procedure served well for diagnostic purposes. However, with image-guided needle biopsies for a preoperative diagnosis now being the standard of care, the wire-guided excision has changed from a diagnostic to a therapeutic procedure.2 When percutaneous needle biopsy has established the diagnosis before surgery, the surgeon’s aim is to treat the patient with a one-stage surgical procedure. From this perspective, the wire-guided excision is a troublesome procedure. Adequate resection of a nonpalpable breast cancer is dependent both on the accuracy of wire placement by the radiologist and on the experience and three-dimensional imagination of the surgeon. Even when the diagnosis of breast cancer is known before surgery, the wire-guided excision is often inadequate, and the patient has to undergo a second surgical intervention in approximately 20% of cases.3,4 Re-excision for positive margins is indicated because an increase in the local recurrence rate is clearly related to tumors resected with involved margins.5,6 Another disadvantage of the wire placement is that the patient has to undergo an extra intervention before surgery. Wire placement is an unpleasant procedure and heightens the patient’s anxiety related to the surgical intervention.7

Ultrasound (US) has emerged as an attractive alternative guiding tool. US enables the surgeon to excise the nonpalpable malignancy under direct vision to obtain adequate margins.8 This study was undertaken to compare margin clearance and lumpectomy size with wire-guided and US-guided breast cancer excisions in a prospective, randomized fashion.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
This prospective, randomized, clinical trial was approved by the Investigational Review Board of the Free University Medical Center and was based on our preliminary experience with US-guided excisions of nonpalpable breast cancer.8 Between June 1998 and July 2001, patients were included from the departments of surgery of the Free University Medical Center in Amsterdam and of the District General Hospital in Amstelveen. All patients had nonpalpable mammographically detected breast lesions with an established diagnosis of invasive breast cancer after image-guided core needle biopsy. Patients were asked to participate in this study only if the nonpalpable breast cancer was also clearly identified by US. Both the wire-guided and the US-guided procedures were explained to the patient in detail. After informed consent had been obtained, patients were randomly assigned to either of the two surgical treatment modalities.

Surgery
Wires (Hawkins, MD Tech, Gainesville, FL) for mammographic localization of occult breast tumors were placed by a dedicated radiologist by using US guidance the day before surgery or on the morning of surgery. All wire placements were confirmed by repeat mammography. After excision, the specimen was sent to the radiology department for radiography.

US-guided excision was performed together with an experienced radiologist in the operating room. The 10-MHz US probe (HAD 3000TM; Advanced Technology Laboratories, Bothell, WA) that was used for the procedure was held in a sterile plastic sheath that enabled its use in the surgical wound. The maximum diameter of the probe was 3 cm. Before incision, the lesion was visualized and the incision marked on the overlying skin with the breast held in a fixed position. During the procedure, repeat imaging with the US probe in the wound guided the surgeon and enabled the development of a surgical margin around the breast tumor (Fig. 1). The radiologist checked the resected specimen with US in the operating room (Fig. 2). All surgical procedures were performed by dedicated breast surgeons or by senior residents under their close supervision. The duration of the operation was noted from the start of disinfection to the application of the wound dressing. Included within this period was the performance of a sentinel node procedure. The time that was needed for the occasional axillary lymph node dissection (after the sentinel node was found to be positive with frozen section examination) was excluded from total operating room time. Cost analysis was performed on the basis of the cost of radiological procedures. Length of hospital stay was left out of the analysis because it was considered to depend on hospital-based logistics.



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  		FIG. 1. During the procedure, repeat imaging with the ultrasound probe in the wound will guide the surgeon to enable the development of an adequate surgical margin around the breast tumor.

 


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  		FIG. 2. In the operating room, the surgical specimen is checked with ultrasound for adequate margins.

 
Pathology
All specimens were weighed in the operating room and sent to the pathologist. Specimens were carefully inked and cut, after which the size of the tumor was determined first. Resections were described as being inadequate when microscopic tumor involvement of the (inked) resection border was present. A microscopically adequate margin was defined as >=1 mm. However, for all resected tumors, a distinction was made between involved margins and margins <1 mm.

Statistical Analysis
Chi-square analysis was performed for comparison of the number of resections with clear margins in both groups.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
A total of 49 patients were recruited for this study. Of these, 23 were assigned to undergo wire-guided excision and 26 to undergo US-guided excision. One patient had a wire displacement in the operating room and underwent a US-guided excision. Although the wire-guided excision must be considered to be a failure in this patient, we designated the patient to the US group because the aim of this study was to compare wire-guided with US-guided resections. Thus, ultimately two groups remained, one with 22 patients who underwent wire-guided excision and one with 27 patients who underwent US-guided excision.

The tumors excised in both groups were quite similar, and after resection, the average lumpectomy weight did not differ between the two surgical techniques (Table 1). Of 27 US-guided excisions, 1 was found to be with focally positive margins, 2 had close margins (<1 mm), and 24 (89%) had adequate margins. For wire-guided excisions, these figures were 4, 6, and 12 (55%), respectively (Table 2). From the outset, adequate margins were defined as >=1 mm. Therefore, US-guided excision did significantly better than wire-guided excision: 89% vs. 55%, respectively (P = .007 in {chi}2 analysis).


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  		TABLE 1. Comparison of tumor size, resection volume, and operating timea
 

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  		TABLE 2. Margins after ultrasound-guided versus wire-guided resections
 
The mean operating time for the lumpectomy and sentinel node procedure was the same for wire-guided excisions and ultrasonographic procedures (Table 1). After the diagnostic work-up, the US-guided excision adds a single US investigation procedure, which in our hospital is performed at a cost of 64.68 euros. The wire localization adds the cost of the wire localization placement (154.00 euros) and specimen radiogram (51.97 euros).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The fact that wire-guided excision too often results in inadequate margins is again illustrated in this prospective, randomized clinical trial. It became clear that US-guided resection resulted in more patients with an adequate (>1-mm) margin. Although it is being debated when margins are to be called inadequate and necessitate a re-resection, a re-excision seems to be clearly indicated for involved margins.5,6,9 The relationship between margin status and local recurrence is less clear for margins that measure <1 mm and even for margins that are only focally positive.10,11 If re-excisions are required only for positive margins, then this would be the case for "only" 18% of the wire-guided resections in this study. This is comparable with results of studies describing wire-guided excisions of preoperatively diagnosed breast cancer.3,12 Nevertheless, the effectiveness of the wire localization procedure leaves room for improvement, and the preoperative wire placement increases patient discomfort. It is, therefore, not surprising that alternative methods for tumor localization, such as radioactive tracer13 and dye,14 have been investigated. However, these modalities are similar to the wire-guided localization in the sense that the tumor is localized within the breast, but the surgeon is not informed about the tumor delineation within the breast parenchyma. This makes margin clearance a difficult undertaking. In addition, an unnecessarily large volume of breast tissue may be excised. US is unique as a guiding tool because it visualizes the tumor during the excision at all times.

US has already proven to be of great value in the diagnostic setting of breast lesions. In one study, for instance, US was used as a screening tool to assess its added value to screening mammography. When the detection rates were compared, it seemed that of all US-detected and mammographically detected nonpalpable malignancies, 25% were detected by US only.15 Pamilo et al.16 showed that US will visualize 62% of nonpalpable mammographically detected breast cancers. If mammographic lesions that consist entirely of microcalcifications are excluded, the sensitivity of US increases to 76%.

Furthermore, US has a substantial added benefit to mammography in the differential diagnosis of mammographically detected breast lesions.17,18 When US is able to visualize a nonpalpable breast lesion, it is preferred by radiologists and surgeons as a guiding tool for performing image-guided breast biopsies19 and for guide-wire placement.20 It is, therefore, not surprising that this real-time imaging modality has found a place in the operative setting. The use of intraoperative US has been elegantly described by Schwartz et al.21 Like the wire-guided excisions, intraoperative US-guided excisions have since been used by several investigators for diagnostic purposes.22–24 Smith et al.25 showed that US is a very practical tool in the operative setting, not only for nonpalpable, but also for poorly palpable, breast tumors. Patients with tumors with dubious palpability constitute a significant part of all patients who have been referred to the surgeon after a screening round. In this study, however, these patients were not included. US is able to delineate a margin around a nonpalpable breast cancer, which makes adequate resection possible without the unnecessary sacrifice of healthy breast tissue. In this respect, Davies et al.22 showed that US was quite accurate in determining the true tumor size when they compared the US diameter with the microscopic diameter of the breast tumors.

The results of US-guided excisions in this study are quite similar to those of our first series, in which we assessed margin clearance with this technique for the first time.8 However, in the age of evidence-based medicine, we found it necessary to perform a prospective, randomized trial comparing operative US with the gold standard. Several studies have shown that when a preoperative diagnosis is known, the margin clearance with wire-guided excisions is markedly increased.4,26 In this series, all patients had a preoperative diagnosis of breast cancer and were, therefore, operated on with curative intent. This constituted a solid basis for the comparison of both techniques.

One could theorize that real-time imaging with US allows for a more accurate determination of a margin around the tumor and that, therefore, specimen size will be smaller. With wire-guided resections, the surgeon will conceivably resect more tissue "just to be sure" that the pathologist will later (after the patient has been discharged) determine that enough healthy tissue around the tumor has been resected. Indirectly, this study has confirmed this hypothesis. US-guided excisions were more often adequate, whereas the mean specimen size was the same. This is important not only for the success rate of the procedure, but also for cosmetic outcome in breast-conserving treatment. To the resected tissue must be added the amount of tissue that is resected with a re-resection after involved margins. Resected tissue volume and cosmetic outcome have been shown to be inversely related.27

Another important aspect of more accurate resection is that patients are not required to undergo a second operation. This will improve the patient’s well-being and reduce hospital costs.

The presence of the radiologist in the operating room is not optimal for the health economics of this procedure, although this was less costly than the wire-localization procedure. However, the practice in our hospital is a reflection of how this technique was first introduced. It was performed in close collaboration with a very dedicated radiologist. Other studies with intraoperative US for breast surgery have shown that the radiologist’s presence after a certain learning phase is no longer required for a successful operation.28

In conclusion, US-guided excision seems to be superior to wire-guided excision with respect to margin clearance of mammographically detected nonpalpable breast cancers. This will lead to a decrease in necessary re-excisions. Furthermore, patients benefit from the fact that they do not have to undergo the unpleasant wire placement before surgery.


   Footnotes
 
After a positive core needle biopsy, patients with nonpalpable breast cancer were randomized to undergo either an ultrasound-guided or a wire-guided resection. Ultrasound-guided excision resulted in more resections with adequate margins, and specimen weights were the same in both groups.

Received for publication April 8, 2002. Accepted for publication July 24, 2002.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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  12. King TA, Cederbom GJ, Champaign JL, et al. A core breast biopsy diagnosis of invasive carcinoma allows for definitive surgical treatment planning. Am J Surg 1998; 176: 497–501.[CrossRef][Medline]
  13. Luini A, Zurrida S, Paganelli G, et al. Comparison of radioguided excision with wire localization of occult breast lesions. Br J Surg 1999; 86: 522–5.[CrossRef][Medline]
  14. Berridge DL, Mastey LA, Eckstrom PC, Czarnecki DJ. Indocyanine green dye as a tissue marker for localization of nonpalpable breast lesions. AJR Am J Roentgenol 1995; 164: 1299.[Medline]
  15. Kolb TM, Lichy J, Newhouse JH. Occult cancer in women with dense breasts: detection with screening US—diagnostic yield and tumor characteristics. Radiology 1998; 207: 191–9.[Abstract/Free Full Text]
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  17. Ciatto S, Rosselli DT, Catarzi S, Morrone D. The contribution of ultrasonography to the differential diagnosis of breast cancer. Neoplasma 1994; 41: 341–5.[Medline]
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